acid-phosphatase and Osteoporosis

Bone turnover markers (BTMs) are known the bone formation marker, the bone resorption marker and the bone matrix related marker participating in bone quality, respectively. In the Guidelines for the Use of Bone Metabolic Markers in the Diagnosis and Treatment of Osteoporosis (2012 Edition) from publishing Japan Osteoporosis Society Committee, the newly and commonly BTMs were considered to give the normal reference value in Japanese people, the reevaluation of MSC, and the influence of renal function on BTMs, respectively. The flow chart of the measurement of bone resorption markers and bone formation markers when selecting drug treatment for osteoporosis, the measurement of ucOC and bone resorption markers when selecting drug treatment in osteoporosis, and the evaluation of therapeutic effects of bone antiresorption drugs using bone resorption markers were corrected newly in the guideline 2012 edition. It is thought that the BTMs have been continued more developing as essential biomarker with the treatment of osteoporosis in the future.

Topics: Acid Phosphatase; Alkaline Phosphatase; Amino Acids; Biomarkers; Bone and Bones; Bone Matrix; Bone Remodeling; Bone Resorption; Collagen Type I; Humans; Isoenzymes; Osteocalcin; Osteogenesis; Osteoporosis; Peptide Fragments; Peptides; Practice Guidelines as Topic; Procollagen; Tartrate-Resistant Acid Phosphatase

The importance of measurement of bone metabolic markers has been increasingly recognized in the treatment of osteoporosis. Bone is a dynamic organ in which bone formation and resorption continuously occurs. Biochemical marker for bone metabolism is an non-invasive measure to assess bone metabolic state. Although the purpose of its measurement was initially hypothesized to predict rate of bone loss, the increase of bone marker by itself provides a clinically relevant marker for bone fragility. Furthermore, measurement of bone marker is known to help improve drug compliance. Recent sophistication of bone marker measurement and the increasing kinds of bone markers increase the importance of its measurement to improve osteoporosis treatment.

Topics: Acid Phosphatase; Alkaline Phosphatase; Amino Acids; Biomarkers; Bone and Bones; Bone Density; Bone Remodeling; Collagen Type I; Forecasting; Fractures, Spontaneous; Humans; Isoenzymes; Osteocalcin; Osteogenesis; Osteoporosis; Patient Compliance; Peptide Fragments; Peptides; Practice Guidelines as Topic; Procollagen; Risk Factors; Tartrate-Resistant Acid Phosphatase; Time Factors

Recent advances of the measurement of bone turn over markers contribute to non-invasive assessment of bone-metabolic disorders. We can detect the cause of the metabolic disorders with bone turn over markers and hormonal profiles more easily than before. Today, we can diagnose and treat metabolic bone diseases without invasive procedure such as bone biopsy.

Topics: Acid Phosphatase; Alkaline Phosphatase; Arginine; Biomarkers; Biopsy; Bone and Bones; Bone Diseases, Metabolic; Collagen Type I; Diagnosis, Differential; Homocysteine; Humans; Isoenzymes; Lysine; Osteoporosis; Peptide Fragments; Peptides; Procollagen; Tartrate-Resistant Acid Phosphatase

Raloxifene is the only SERM available in Japan. The effect on bone metabolism is relatively mild and slow compared with that of bisphosphonates, and reaches plateau after 6th month or later. As diurnal variations of metabolic markers, especially urinary markers are large, it is often difficult to confirm the effect of raloxifen on bone by individual base. The strict sampling time before and after treatment, and/or selection of patients with high turnover bone may help to increase the chance to confirm the raloxifene effect. A new type of SERM bone marker such as tartrate resistant acid phosphatase fraction 5b is expected to improve the chance. Some papers suggest the relation between suppression of bone markers by raloxifene and vertebral fractures, but the relation is not usually confirmed due to wide variations of the markers.

Topics: Acid Phosphatase; Biomarkers; Bone and Bones; Bone Density Conservation Agents; Bone Remodeling; Bone Resorption; Clinical Trials as Topic; Diphosphonates; Humans; Isoenzymes; Osteoporosis; Raloxifene Hydrochloride; Selective Estrogen Receptor Modulators; Tartrate-Resistant Acid Phosphatase

The purposes hypothesized for the determination of bone metabolic markers, among which we can measure serum BAP, NTX, TRAP-5b or urinary NTX, DPD, CTX in routine clinical practice, are to predict the rate of bone loss and the resultant fracture risk, and to estimate bone quality. The higher value of bone markers, which might reflect high turnover bone disease, allows us to discriminate those who require early introduction of drug therapy such as bisphosphonate, and raloxifene. Furthermore, early reduction of bone resorption markers, but not bone formation markers, possibly 3-6 month after initiation of bone anti-resorptive drugs, enables us to predict bone gain thereafter. Among various bone resorption markers, TRAP-5b might be the best in that it is not susceptible to between-day variation, day-to-day variation, and renal dysfunction resulting from chronic kidney disease which often occurs in osteoporosis-prone elderly women.

Topics: Acid Phosphatase; Alkaline Phosphatase; Amino Acids; Biomarkers; Bone and Bones; Bone Density Conservation Agents; Bone Resorption; Collagen Type I; Diphosphonates; Female; Fractures, Bone; Humans; Isoenzymes; Osteoporosis; Peptides; Raloxifene Hydrochloride; Risk Assessment; Tartrate-Resistant Acid Phosphatase

Numerous experimental and clinical observations suggest that overall changes in bone resorption during menopause or treatment with hormone replacement therapy (HRT) are combined effects of changes in osteoclast number and function. Moreover, due to a coupling between osteoclastic bone resorption and osteoblastic bone formation, pronounced alteration of osteoclast number will eventually lead to alteration of osteoblastic bone formation. Fragments of type I collagen, such as the C- and N-terminal telopeptides of collagen type I (CTX and NTX, respectively), are generated during bone resorption and hence can be used as surrogate markers of osteoclast function. Circulating levels of different enzymes in the serum, such as TRAP 5b and cathepsin K are proportional to the number of osteoclasts, and hence can be used as surrogate markers of osteoclast number. Since antiresorptive effects can be obtained in different ways, we felt it was timely to discuss the different scenarios, highlight differences specific to different pharmacological interventions with different mechanisms of action, and discuss how these bone markers can assist us in a deeper analysis of the pharmacodynamics and safety profile of existing and upcoming drug candidates.

Topics: Acid Phosphatase; Biomarkers; Bone Density Conservation Agents; Bone Resorption; Cathepsin K; Cathepsins; Cell Count; Cell Differentiation; Collagen Type I; Female; Humans; Isoenzymes; Osteoclasts; Osteopetrosis; Osteoporosis; Peptides; Tartrate-Resistant Acid Phosphatase

Fluoride (F) is an essential trace element which is involved in the skeletal systems of teeth and bone. F increases proliferation of osteoblastic cells and stimulates bone formation. F inhibits acid phosphatase activity in osteoblastic cells and induces an increases in tyrosin phosphorylated protein, leading to cell proliferation. Also, the activation of G protein by F is important in the cellular mechanism of F action in osteoblastic cells. F also has inhibitory effects on osteoclastic bone resorption. The oral administration of F solution has stimulatory effects on bone formation in various animal models. Moreover, the intake of F with comparatively low doses may have beneficial effects in the development of bone mineral density and fracture in human.

Topics: Acid Phosphatase; Animals; Bone and Bones; Bone Density; Bone Resorption; Cell Proliferation; Fluorides; Fractures, Bone; GTP-Binding Proteins; Humans; Osteoblasts; Osteogenesis; Osteoporosis; Stimulation, Chemical

Topics: Acid Phosphatase; Alkaline Phosphatase; Amino Acids; Arthritis, Rheumatoid; Biomarkers; Bone Resorption; Collagen Type I; Humans; Isoenzymes; Osteocalcin; Osteogenesis; Osteoporosis; Osteoprotegerin; Peptide Fragments; Peptides; Procollagen; RANK Ligand; Tartrate-Resistant Acid Phosphatase

Topics: Acid Phosphatase; Alkaline Phosphatase; Amino Acids; Biomarkers; Bone and Bones; Bone Diseases, Metabolic; Collagen Type I; Humans; Isoenzymes; Osteocalcin; Osteoporosis; Peptide Fragments; Peptides; Procollagen; Tartrate-Resistant Acid Phosphatase

Topics: Acid Phosphatase; Alkaline Phosphatase; Amino Acids; Biomarkers; Bone and Bones; Bone Remodeling; Collagen Type I; Fractures, Bone; Humans; Isoenzymes; Osteocalcin; Osteoporosis; Peptides; Risk; Risk Assessment; Tartrate-Resistant Acid Phosphatase

Bone markers are aimed to assess bone cells activity. Some are specific of bone formation (osteocalcin, bone alkaline phosphatase, extension peptides of type I procollagen); others are specific of bone resorption (deoxypyridinoline and peptidebound forms.). Their main applications are: evaluation of fracture risk and follow-up of antiosteoporotic treatments. Their use in clinical practice is difficult: choice of the most appropriate bone marker, relevance of changes, and may require the specialist's opinion.

Topics: Acid Phosphatase; Alkaline Phosphatase; Biomarkers; Bone Remodeling; Bone Resorption; Collagen; Collagen Type I; Female; Fractures, Bone; Humans; Menopause; Osteocalcin; Osteoporosis; Peptides; Risk Factors

Acid phosphatases (APs) are a family of enzymes that are widespread in nature, and can be found in many animal and plant species. Mystery surrounds the precise functional role of these molecular facilitators, despite much research. Yet, paradoxically, human APs have had considerable impact as tools of clinical investigation and intervention. One particular example is tartrate resistant acid phosphatase, which is detected in the serum in raised amounts accompanying pathological bone resorption. This article seeks to explore the identity and diversity of APs, and to demonstrate the relation between APs, human disease, and clinical diagnosis.

Topics: Acid Phosphatase; alpha-Macroglobulins; Biomarkers; Bone Resorption; Favism; Gaucher Disease; Humans; Intracellular Fluid; Isoenzymes; Leukemia, Hairy Cell; Male; Osteoclasts; Osteoporosis; Prostate; Prostatic Neoplasms; Protein Binding; Reactive Oxygen Species; Tartrate-Resistant Acid Phosphatase

Topics: Acid Phosphatase; Alkaline Phosphatase; Biomarkers; Bone and Bones; Bone Density; Bone Remodeling; Collagen; Humans; Hydroxyproline; Integrin-Binding Sialoprotein; Isoenzymes; Organ Specificity; Osteocalcin; Osteoporosis; Sialoglycoproteins

An overview of biochemical markers of bone metabolism is presented along with indications for their clinical utilization.. The structure, cyclical metabolism, and hormone regulation of bone is reflected by markers of resorption, formation and/or turnover. Markers of resorption representing degradation of type 1 collagen, include N-telopeptides, C-telopeptides, hydroxyproline, and the collagen crosslinks pyridinoline and deoxypyridinoline; acid phosphatase, a marker of osteoclast activity, and urinary calcium are also indicators of bone resorption. Bone formation markers indicate osteoblast activity; bone-specific alkaline phosphatase and the N-terminal and C-terminal extension peptides of procollagen reflect formation of organic matrix in bone. Osteocalcin, produced by osteoblasts but also released during osteoclastic degradation, may indicate either formation when resorption and formation are coupled or turnover when they are uncoupled.. Bone markers respond to intervention more rapidly than techniques such bone mineral density. Resorption markers respond approximately 1 to 3 months after intervention; markers of formation respond later, after 6 to 9 months. Bone markers may add useful information for assessing fracture risk and for monitoring osteoporosis, Paget's disease of bone, cancer metastasis, and metabolic disease. Various therapeutic interventions may affect release of some bone markers.. Bone disease has high prevalence in adults so bone markers will become even more important for assessing fracture risk and monitoring therapy as populations age. Characteristics of bone markers are dependent on biology and the assay used. Substantial work remains in characterizing existing assays, identifying better markers and performing the clinical studies to define which bone markers should be measured and when.

Topics: Acid Phosphatase; Alkaline Phosphatase; Biomarkers; Bone and Bones; Bone Resorption; Calcium; Humans; Osteocalcin; Osteoporosis

Topics: Acid Phosphatase; Alkaline Phosphatase; Biomarkers; Bone Resorption; Calcium; Humans; Osteocalcin; Osteoporosis; Procollagen

Topics: Acid Phosphatase; Alkaline Phosphatase; Calcium; Collagen; Humans; Hydroxyproline; Osteocalcin; Osteoporosis

In this article we review the biochemical basis for markers of bone metabolism and comment on their bone specificity and representativeness for bone tissue. Major developments have recently taken place particularly with respect to markers of bone collagen metabolism; accordingly, they are in the focus of this review. We also attempt to relate the various collagenous and non-collagenous markers to each other and to the phases of the osteoblast phenotype.

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Biomarkers; Bone and Bones; Humans; Osteoblasts; Osteocalcin; Osteoclasts; Osteoporosis; Procollagen; Sensitivity and Specificity

During the last few years non-invasive methods to measure bone metabolism have been the object of intensive studies, chiefly because of the need for sensitive and specific markers to be used in the exploration of osteoporosis. Bone formation can be evaluated by assays of serum alkaline phosphatase, osteocalcin and collagen extension peptides. Bone resorption can be quantified by assays of urinary hydroxyproline and urinary pyridinoline excretion, and by assay of tartrate-resistant acid phosphatase in plasma. These markers have different sensitivity and specificity. At present, serum osteocalcin and urinary pyridinoline are the most effective markers, notably to evaluate bone metabolism in menopausal women and in patients with vertebral osteoporosis. In the near future a battery of tests based on a combination of the most effective markers will probably be used to study the complex abnormalities of bone metabolism which occur in bone diseases, and in particular in osteoporosis.

Topics: Acid Phosphatase; Alkaline Phosphatase; Amino Acids; Biomarkers; Bone and Bones; Calcium; Female; Humans; Hydroxyproline; Male; Osteocalcin; Osteoporosis; Osteoporosis, Postmenopausal; Peptides; Procollagen

The conventional model that bisphosphonates bind to the bone surface and inhibit mature osteoclasts does not convincingly explain the prolonged duration of action of zoledronate. We hypothesized that zoledronate on the bone surface adjacent to marrow cells impairs osteoclastogenesis, contributing to sustained inhibition of resorption. In this case, numbers of circulating preosteoclasts may be reduced after zoledronate treatment. This study assessed this possibility in subjects from a clinical trial. Twenty-two osteopenic women participating in a randomized, controlled trial comparing zoledronate 5 mg with placebo were recruited, 18 months after administration of study drug. Peripheral blood mononuclear cells were analyzed for the presence of osteoclast precursors using flow cytometry for preosteoclast markers and the ability to form osteoclast-like cells in culture with RANKL and M-CSF. There was no difference in the percentage of CD14(+)/CD11b(+) cells in peripheral blood between the two groups. The numbers of TRAP(+) multinucleated cells in cultures in the absence of RANKL and M-CSF were very low in both groups, but a significantly higher number of these cells was observed in the zoledronate group compared with the placebo group (p = 0.01). The number of TRAP(+) multinucleated cells and resorption pits following culture with RANKL and M-CSF did not differ between the two groups. Serum P1NP was reduced 53 % at 18 months in the zoledronate group but unchanged in the placebo group. These results do not support the hypothesis that the inhibitory action of zoledronate contributes to its prolonged action on preosteoclasts within bone marrow.

Topics: Acid Phosphatase; Aged; Bone Density Conservation Agents; Bone Resorption; CD11b Antigen; Diphosphonates; Female; Flow Cytometry; Humans; Imidazoles; Isoenzymes; Leukocytes, Mononuclear; Lipopolysaccharide Receptors; Macrophage Colony-Stimulating Factor; Middle Aged; Osteoclasts; Osteoporosis; Placebos; RANK Ligand; Tartrate-Resistant Acid Phosphatase; Zoledronic Acid

Vitamin D and vitamin B deficiency are common in elderly subjects and are important risk factors for osteoporosis and age-related diseases. Supplementation with these vitamins is a promising preventative strategy. The objective of this study was to evaluate the effects of vitamins D3 and B supplementation on bone turnover and metabolism in elderly people.. Healthy subjects (n=93; >54 years) were randomly assigned to receive either daily vitamin D3 (1200 IU), folic acid (0.5 mg), vitamin B12 (0.5 mg), vitamin B6 (50 mg), and calcium carbonate (456 mg) (group A) or only vitamin D3 plus calcium carbonate (group B) in a double blind trial. We measured at baseline and after 6 and 12 months of supplementation vitamins, metabolites, and bone turnover markers.. At baseline mean plasma 25-hydroxy vitamin D [25(OH)D] was low (40 or 30 nmol/L) and parathormone was high (63.7 or 77.9 pg/mL). 25(OH)D and parathormone correlated inversely. S-Adenosyl homocysteine and S-adenosyl methionine correlated with bone alkaline phosphatase, sclerostin, and parathormone. One year vitamin D3 or D3 and B supplementation increased plasma 25(OH)D by median 87.6% (group A) and 133.3% (group B). Parathormone was lowered by median 28.3% (A) and 41.2% (B), bone alkaline phosphatase decreased by 2.8% (A) and 16.2% (B), osteocalin by 37.5% (A) and 49.4% (B), and tartrate-resistant-acid-phosphatase 5b by 6.1% (A) and 36.0% (B). Median total homocysteine (tHcy) was high at baseline (group A: 12.6, group B: 12.3 µmol/L) and decreased by B vitamins (group A) to 8.9 µmol/L (29.4%). tHcy lowering had no additional effect on bone turnover.. One year vitamin D3 supplementation with or without B vitamins decreased the bone turnover significantly. Vitamin D3 lowered parathormone. The additional application of B vitamins did not further improve bone turnover. The marked tHcy lowering by B vitamins may modulate the osteoporotic risk.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Alkaline Phosphatase; Biomarkers; Bone and Bones; Cholecalciferol; Dietary Supplements; Double-Blind Method; Drug Administration Schedule; Female; Humans; Isoenzymes; Male; Middle Aged; Osteoporosis; Parathyroid Hormone; S-Adenosylhomocysteine; S-Adenosylmethionine; Tartrate-Resistant Acid Phosphatase; Vitamin B Complex; Vitamin D

Whole-body vibration (WBV) presents as osteogenic in animal models and young patients, but the effect remains unclear in senior people. The use of alternative tilting during WBV to ameliorate bone mass and bone metabolism, particularly in senior people, has not previously been reported. This study assessed changes in bone mineral density (BMD) and bone metabolism in senior people after six-month treatment of whole-body vibration with alternative tilting (WBVAT).. Fifty-three senior people (11M/42F, >65 yrs, mean age 77) and 15 adults (4M/11F, 50-60 yrs, mean age 53) were enrolled and assigned randomly to WBVAT (senior: n=27; adult: n=7) and control groups (senior: n=26; adult: n=7), respectively. The WBVAT groups were subjected to vertical vibration (0.5-0.8 g, 45-55 Hz) and alternative tilting (2° tilting angle or 8 mm displacement at 0.4 Hz) 20 minutes per day, 3 days a week, for 6 months. BMD in the lumbar spine and femoral neck was measured at 0, 3 and 6 months, respectively, as well as biochemical markers of bone metabolism, including serum calcium, phosphorus, alkaline phosphatase (ALP), osteocalcin and tartrate resistance acid phosphatase at 0, 1, 3 and 6 months, respectively.. After 6-month WBVAT treatment, BMD in the lumbar spine and femoral neck increased significantly by 2.52% and 3.22% for senior people, and 1.63% and 2.05% for adults, respectively. The 6-month WBVAT treatment increased BMD in the senior people, both with and without osteoporosis (OP) and in both men and women, but led to a BMD gain greater in people with OP (p<0.01) and women (p<0.01), respectively. The serum ALP level increased significantly by a net 24.4% in seniors after WBVAT treatment at 3 months; other biochemical markers showed non-significant differences between the WBVAT and control groups.. WBVAT treatment may increase BMD in senior people, particularly those with OP and women. Changes in bone metabolism after WBVAT treatment were not observed in most cases.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Alkaline Phosphatase; Bone Density; Calcium; Equipment Design; Female; Femur Neck; Humans; Isoenzymes; Lumbar Vertebrae; Male; Middle Aged; Osteocalcin; Osteogenesis; Osteoporosis; Phosphorus; Posture; Tartrate-Resistant Acid Phosphatase; Vibration

As there is little evidence of the efficacy of 25-hydroxyvitamin D3 (25-HCC) in reducing the risk of new fractures in osteoporotic women, we performed an open, prospective study with a follow-up of 1 yr in 58 females over 65 yr of age with osteoporosis and proximal femoral fractures. The patient group received 1 g calcium per day and 10 640 IU 25-HCC per week, while the control group received 1 g calcium daily. Biochemical markers of bone remodelling, serum calcium and parathyroid hormone were determined. Bone mineral density was assessed in the lumbar spine and in the proximal femur by two methods. After 1 yr of treatment, 25-HCC corrected secondary hyperparathyroidism, increased urine calcium excretion, and increased bone mass in the femoral neck, but had no effect upon the appearance of new fractures.

Topics: Absorptiometry, Photon; Acid Phosphatase; Aged; Aged, 80 and over; Alkaline Phosphatase; Biomarkers; Bone Density; Calcifediol; Calcium; Creatinine; Female; Femoral Neck Fractures; Follow-Up Studies; Humans; Isoenzymes; Osteoporosis; Parathyroid Hormone; Phosphorus; Prospective Studies; Tartrate-Resistant Acid Phosphatase; Urea

Purple acid phosphatases (PAPs) are ubiquitous binuclear metallohydrolases that have been isolated from various animals, plants and some types of fungi. In humans and mice, elevated PAP activity in osteoclasts is associated with osteoporosis, making human PAP an attractive target for the development of anti-osteoporotic drugs. Based on previous studies focusing on phosphonate scaffolds, as well as a new crystal structure of a PAP in complex with a derivative of a previously synthesized α-aminonaphthylmethylphosphonic acid, phosphonates 24-40 were designed as new PAP inhibitor candidates. Subsequent docking studies predicted that all of these compounds are likely to interact strongly with the active site of human PAP and most are likely to interact strongly with the active site of pig PAP. The seventeen candidates were synthesized with good yields and nine of them (26-28, 30, 33-36 and 38) inhibit in the sub-micromolar to nanomolar range against pig PAP, with 28 and 35 being the most potent mammalian PAP inhibitors reported with K

Topics: Acid Phosphatase; Animals; Glycoproteins; Humans; Mammals; Mice; Organophosphonates; Osteoporosis; Plants; Swine

Osteoporosis is a common bone disorder characterized by reduced bone density and increased risk of fractures. The modulation of bone cell functions, particularly the inhibition of osteoclastic differentiation, plays a crucial role in osteoporosis treatment. Polyphosphoesters (PPEs) have shown the potential in reducing the function of osteoclast cells, but the effect of their chemical structure on osteoclastic differentiation remains largely unexplored. In this study, we evaluated the effect of PPE's chemical structure on the inhibition of osteoclastic differentiation of murine bone marrow mononuclear cells (BMNCs). PPEs containing phosphotriester and phosphodiester units at varying compositions were synthesized. Cytotoxicity testing confirmed the biocompatibility of the copolymers at concentrations below 0.5 mg/mL. Isolated from long bones, BMNCs were cultured in a differentiation medium supplemented with different PPE concentrations. Osteoclast formation was assessed through tartrate-resistant acid phosphatase and phalloidin staining. A significant decrease in the size of osteoclast cells formed upon BMNC contact with PPEs was observed, with a more pronounced effect observed at higher PPE concentrations. In addition, an increased composition of phosphodiester units in the PPEs yielded a decreased density of differentiated osteoclasts. Furthermore, real-time PCR analysis of major osteoclastic markers provided gene expression data that correlated with microscopic observations, confirming the effect of phosphodiester units in suppressing osteoclast differentiation of BMNCs from the early stages. These findings highlight the potential of PPEs as polymers are capable of modulating bone cell functions through their chemical structures.

Topics: Acid Phosphatase; Animals; Bone Marrow; Bone Marrow Cells; Cell Differentiation; Cells, Cultured; Humans; Mice; Osteoclasts; Osteoporosis

The effect of milk on bone health is controversial. In this study, the effects of yak milk in mice with retinoic acid-induced osteoporosis (OP) were evaluated. Yak milk was provided to OP mice as a nutrition supplement for 6 wk. The results showed that yak milk significantly reduced bone turnover markers (tartrate acid phosphatase and alkaline phosphatase). The yak milk treatment was also associated with remarkably increased bone mineral density, bone volume, trabecular thickness, and trabecular number, as well as improved biomechanical properties (maximum load and stress) of the tibia. Furthermore, yak milk mitigated the deterioration of the network and thickness of trabecular bone in treated OP mice compared with the OP model group. The results indicated that yak milk could improve bone mass and microarchitecture through the inhibition of bone resorption in OP mice.

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Bone Density; Cattle; Cattle Diseases; Mice; Milk; Osteoporosis; Rodent Diseases; Tartrates; Tretinoin

Purple acid phosphatases (PAPs) are binuclear hydrolases that catalyze the hydrolysis of phosphorylated substrates under acidic to neutral conditions. Elevated serum concentrations of PAP are observed in patients suffering from osteoporosis, identifying this enzyme as a potential target for the development of novel therapeutic agents to treat this disease. α-Alkoxy-substituted naphthylmethylphosphonic acid derivatives have been identified previously as molecules that bind with high affinity to PAPs, and docking studies suggest that longer alkyl chains may increase the binding affinities of such compounds. Here, we synthesized several derivatives and tested their inhibitory effect against pig and red kidney bean PAPs. The most potent inhibitor within this series is the octadecyl derivative, which has a K

Topics: Acid Phosphatase; Animals; Crystallography, X-Ray; Dose-Response Relationship, Drug; Enzyme Inhibitors; Humans; Models, Molecular; Molecular Structure; Osteoporosis; Phaseolus; Structure-Activity Relationship; Swine

Topics: Acid Phosphatase; Animals; Binding Sites; Biphenyl Compounds; Catalysis; Cattle; Copper; Electron Spin Resonance Spectroscopy; Kinetics; Osteoporosis; Oxidation-Reduction; Peroxidases; Picrates; Protective Agents; Reactive Oxygen Species; Serum Albumin, Bovine; Spectrometry, Fluorescence; Superoxide Dismutase; Thermodynamics; Time Factors

The aim of this study was to investigate the effect of evodiamine (EV) on dexamethasone-induced osteoporosis in zebrafish. Zebrafish larvae were exposed to different concentrations of dexamethasone to obtain the osteoporosis in zebrafish. Calcium, phosphorus, and alizarin red staining determination were performed to evaluate the effects of EV on bone mineralization. Alkaline phosphatase (ALP), hydroxyproline (HP), and tartrate resistant acid phosphatase (TRAP) were also measured by commercial kits. The expression of MMP3-OPN-MAPK pathway in zebrafish was measured by Western blot. RT-PCR was used to determine mRNA levels of MMP3, OPN, and MAPK. EV could significantly increase the content of calcium and phosphorus. The results of alizarin red staining showed that EV could significantly increase the calcium sink of horse fish, increasing the area of bone formation. EV could increase the content of hydroxyproline in zebrafish. EV also increased ALP and TRAP in zebrafish. Western blot and RT-PCR results showed that EV restored the MMP3-OPN-MAPK pathway in zebrafish. In conclusion, we found that EV can alleviate dexamethasone-induced osteoporosis in zebrafish. The mechanism is related to activating MMP3-OPN-MAPK pathway and then activating bone remodeling.

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Bone Remodeling; Calcification, Physiologic; Calcium; Dexamethasone; Glucocorticoids; Hydroxyproline; Larva; Matrix Metalloproteinase 3; Mitogen-Activated Protein Kinases; Osteoblasts; Osteoclasts; Osteogenesis; Osteoporosis; Quinazolines; Signal Transduction; Tartrate-Resistant Acid Phosphatase; Zebrafish

Purple acid phosphatases (PAPs) are metalloenzymes that catalyse the hydrolysis of phosphate esters under acidic conditions. Their active site contains a Fe(III)Fe(II) metal centre in mammals and a Fe(III)Zn(II) or Fe(III)Mn(II) metal centre in plants. In humans, elevated PAP levels in serum strongly correlate with the progression of osteoporosis and metabolic bone malignancies, which make PAP a target suitable for the development of chemotherapeutics to combat bone ailments. Due to difficulties in obtaining the human enzyme, the corresponding enzymes from red kidney bean and pig have been used previously to develop specific PAP inhibitors. Here, existing lead compounds were further elaborated to create a series of inhibitors with K

Topics: Acid Phosphatase; Animals; Antineoplastic Agents; Dose-Response Relationship, Drug; Enzyme Inhibitors; Glycoproteins; Molecular Docking Simulation; Molecular Structure; Osteoporosis; Phaseolus; Structure-Activity Relationship; Swine

Previous genome-wide association studies have identified common variants in genes associated with bone mineral density (BMD) and risk of fracture. Recently, we identified single nucleotide polymorphisms (SNPs) in Wingless-type mouse mammary tumor virus integration site (WNT)16 that were associated with peak BMD in premenopausal women. To further identify the role of Wnt16 in bone mass regulation, we created transgenic (TG) mice overexpressing human WNT16 in osteoblasts. We compared bone phenotypes, serum biochemistry, gene expression, and dynamic bone histomorphometry between TG and wild-type (WT) mice. Compared with WT mice, WNT16-TG mice exhibited significantly higher whole-body areal BMD and bone mineral content (BMC) at 6 and 12 weeks of age in both male and female. Microcomputer tomography analysis of trabecular bone at distal femur revealed 3-fold (male) and 14-fold (female) higher bone volume/tissue volume (BV/TV), and significantly higher trabecular number and trabecular thickness but lower trabecular separation in TG mice compared with WT littermates in both sexes. The cortical bone at femur midshaft also displayed significantly greater bone area/total area and cortical thickness in the TG mice in both sexes. Serum biochemistry analysis showed that male TG mice had higher serum alkaline phosphatase, osteocalcin, osteoprotegerin (OPG), OPG to receptor activator of NF-kB ligand (tumor necrosis family ligand superfamily, number 11; RANKL) ratio as compared with WT mice. Also, lower carboxy-terminal collagen cross-link (CTX) to tartrate-resistant acid phosphatase 5, isoform b (TRAPc5b) ratio was observed in TG mice compared with WT littermates in both male and female. Histomorphometry data demonstrated that both male and female TG mice had significantly higher cortical and trabecular mineralizing surface/bone surface and bone formation rate compared with sex-matched WT mice. Gene expression analysis demonstrated higher expression of Alp, OC, Opg, and Opg to Rankl ratio in bone tissue in the TG mice compared with WT littermates. Our data indicate that WNT16 is critical for positive regulation of both cortical and trabecular bone mass and structure and that this molecule might be targeted for therapeutic interventions to treat osteoporosis.

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Bone and Bones; Bone Density; Collagen Type I; Female; Femur; Humans; Isoenzymes; Male; Mice; Mice, Transgenic; Osteoblasts; Osteocalcin; Osteogenesis; Osteoporosis; Osteoprotegerin; Peptides; RANK Ligand; Real-Time Polymerase Chain Reaction; RNA, Messenger; Tartrate-Resistant Acid Phosphatase; Wnt Proteins; Wnt Signaling Pathway; X-Ray Microtomography

The endocannabinoid system (which includes fatty acid derivatives, receptors, and metabolizing enzymes) is involved in a variety of physiological processes, including bone metabolism in which it regulates the function of osteoblasts and osteoclasts, as well as differentiation of their precursors. The zebrafish (Danio rerio) provides a useful animal model for bone research since zebrafish bones develop rapidly and are anatomically similar to mammalian bones. Putative orthologues and paralogs of endocannabinoid genes have recently been identified in zebrafish, demonstrating the presence of cannabinoid type 1 (CB1) and type 2 (CB2) receptors with affinity to endocannabinoid ligands. To identify therapeutic molecules potentially useful in bone-related diseases, we evaluated the in vivo effects of exposure to long-chain fatty acid amides in adult zebrafish. Using a well-established zebrafish scale model, we found that anandamide and N-linoleoylethanolamine are able to stimulate bone formation by increasing alkaline phosphatase activity in physiological conditions. In addition, they prevent the alteration of bone markers in a prednisolone-induced osteoporosis model in adult zebrafish scales, whereas their esterified forms do not. These data suggest that long-chain fatty acid amides are involved in regulating bone metabolism in zebrafish scales and that the CB2 receptor is a key mediator in this process.

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Bone and Bones; Endocannabinoids; Gene Expression Regulation; Glucocorticoids; Male; Osteoporosis; Polyunsaturated Alkamides; Prednisolone; Receptor, Cannabinoid, CB2; Zebrafish

The aim of this study was to evaluate skeletal pain associated with osteoporosis and to examine the inhibitory effect of bisphosphonate (BP) on pain in an ovariectomized (OVX) mouse model. We evaluated skeletal pain in OVX mice through an examination of pain-like behavior as well as immunohistochemical findings. In addition, we assessed the effects of alendronate (ALN), a potent osteoclast inhibitor, on those parameters. The OVX mice showed a decrease in the pain threshold value, and an increase in the number of c-Fos immunoreactive neurons in laminae I-II of the dorsal horn of the spinal cord. Alendronate caused an increase in the pain threshold value and inhibited c-Fos expression. The serum level of tartrate-resistant acid phosphatase 5b, a marker of osteoclast activity, was significantly negatively correlated with the pain threshold value. Furthermore, we found that an antagonist of the transient receptor potential channel vanilloid subfamily member 1, which is an acid-sensing nociceptor, improved pain-like behavior in OVX mice. These results indicated that the inhibitory effect of BP on osteoclast function might contribute to an improvement in skeletal pain in osteoporosis patients.

Topics: Acid Phosphatase; Alendronate; Animals; Diphosphonates; Disease Models, Animal; Female; Isoenzymes; Mice; Mice, Inbred C57BL; Osteoclasts; Osteoporosis; Ovariectomy; Pain; Pain Threshold; Posterior Horn Cells; Proto-Oncogene Proteins c-fos; Tartrate-Resistant Acid Phosphatase; Transient Receptor Potential Channels

The therapeutic effects of vitamin K3 (VK3) on osteoporosis are still unknown. In this study, we hypothesized that VK3 possesses therapeutic effects on osteoporosis; to verify this hypothesis, the ovariectomized rat was used as an osteoporosis model. Fifty-six Sprague-Dawley female rats aged 8 to 9 months were randomly assigned to 4 groups: sham surgery, ovariectomy with saline, ovariectomy with low-dose VK3, and ovariectomy with high-dose VK3. Intramuscular injection of VK3 was performed every other day beginning 1 month postoperatively. The therapeutic effects of VK3 on osteoporosis were evaluated by measurement of bone mineral density (BMD), bone biochemical markers, biomechanical properties, and bone morphometric parameters. The overall average BMD in VK3-treated groups increased to a level between those of the ovariectomy group and the sham surgery group. The procollagen I N-terminal peptide level peaked at 2 months after surgery in all groups except in the group that had undergone ovariectomy with low-dose VK3. The tartrate-resistant acid phosphatase 5b level increased more slowly at 4 months after surgery than at 2 months after surgery in the VK3-treated groups. The ovariectomy with high-dose VK3 group had the highest maximum stress of the middle femur of all groups. With VK3 treatment, the trabecular bone area percentage increased. All morphometric indicators for the middle tibia in the VK3-treated groups reached the levels found in the sham surgery group. In summary, VK3 therapy increased BMD at 1 and 2 months postsurgery and the maximum stress of the middle femur. In addition, VK3 therapy slowed the increase in bone turnover in ovariectomized rats. Furthermore, VK3 can improve morphometric indicators for the middle tibia. Our preliminary study indicates that VK3 has a potential therapeutic effect on osteoporosis and is worthy of further investigation.

Topics: Acid Phosphatase; Animals; Bone Density; Dose-Response Relationship, Drug; Female; Femur; Isoenzymes; Osteoporosis; Ovariectomy; Peptide Fragments; Procollagen; Rats; Rats, Sprague-Dawley; Tartrate-Resistant Acid Phosphatase; Time Factors; Treatment Outcome; Vitamin K 3

Bone protective effects of withaferin A (WFA) from leaves of Withania somnifera (L.) were evaluated in preventive model of Balb/c mice with 17 β-estradiol (E2) and alendronate (ALD).. Adult female Balb/c mice, 7 to 9 wk, were bilaterally ovariectomized (OVx) to mimic the state of E2 deficiency. Immediately after surgery mice were administrated WFA at doses of 1, 5, 10 mg/kg/d while other two OVx groups received ALD or E2 for 2 mo. Sham and OVx groups with vehicle and no treatment served as controls.. WFA administration increased new bone formation, as well as improving microarchitecture and biomechanical strength of the bones. It prevented bone loss by reducing expression of osteoclastic genes tartrate resistant acid phosphatase (TRAP) and receptor activator of nuclear factor κ B (RANK). Increase in bone turnover marker, osteocalcin (OCN) and inflammatory cytokine tumor necrosis factor-alpha (TNF-α) because of ovariectomy were reduced with WFA treatment, with effects comparable to E2 administration. Histomorphometric analysis of uterus shows that WFA was not fraught with estrogenic or antiestrogenic effects. At cellular level, WFA promoted differentiation of bone marrow cells (BMCs) and increased mineralization by inducing expression of osteogenic genes. WFA has bone protective potential as its treatment prevents bone loss that is comparable to ALD and E2.. It is surmised that WFA in preclinical setting is effective in preserving bone loss by both inhibition of resorption and stimulation of new bone formation before onset of osteoporosis with no uterine hyperplasia.

Topics: Acid Phosphatase; Alendronate; Animals; Biomarkers; Bone and Bones; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Estradiol; Female; Isoenzymes; Mice; Mice, Inbred BALB C; Osteocalcin; Osteoclasts; Osteoporosis; Ovariectomy; Plant Leaves; Plants, Medicinal; Receptor Activator of Nuclear Factor-kappa B; Tartrate-Resistant Acid Phosphatase; Tumor Necrosis Factor-alpha; Withania; Withanolides

Two new compounds, chrysinoneside A (1) and (-)-trans-chrysanthenol-6-O-β-D-glucopyranoside (2), along with 17 known compounds (3-19) were isolated from Chrysanthemum indicum flowers. The total phenolic and flavonoid contents of various fractions were determined. The EtOAC fraction had the highest total phenolic content (525.84 ± 23.51 mg GAE/g DR) and the total flavonoid content (63.49 ± 3.32 mg QE/g DR). The EtOAc and water fractions showed the greatest peroxyl radical-scavenging capacity and the ability to reduce Cu(I) ions, with ORAC and CUPRAC values ranging from 24.00 ± 0.44 to 28.06 ± 1.35 and 16.90 ± 0.51 to 49.77 ± 0.97 μM, respectively. Compounds 5-11, 18, and 19 displayed strong effects in both peroxyl radical-scavenging and reducing capacity assays at a concentration of 10 μM. The anti-osteoporosis activity of these compounds was also evaluated. Compounds 10, 13, and 19 exhibited the most potent tartrate-resistant acid phosphatase activity in receptor activator of nuclear factor-κB ligand-induced osteoclastic RAW 264.7 cells with values of 105.95 ± 1.18, 110.32 ± 3.95, and 112.58 ± 6.42%, respectively.

Topics: Acid Phosphatase; Animals; Antioxidants; Cell Differentiation; Cell Line; Chrysanthemum; Flavonoids; Flowers; Isoenzymes; Mice; Molecular Structure; Osteoclasts; Osteoporosis; Oxidation-Reduction; Phenols; Plant Extracts; RANK Ligand; Tartrate-Resistant Acid Phosphatase

Long-term effects of glucocorticoid treatment in humans induce bone loss and increase the risk of fracture in the skeleton. The pathogenic mechanisms of glucocorticoid-induced osteoporosis (GIOP) are still unclear. The GIOP and its effects have been reproduced in several animal models including Danio rerio (zebrafish) embryo. The treatment of adult fish with prednisolone (PN) has shown a dose-dependent decrease of mineralized matrix in the scales. Large resorption lacunae are characterized by single TRAP-positive cells which migrate to the margin of the scale merging into a multinucleated structures. The treatment with PN of cultured scales did not increase TRAP activity suggesting that the massive presence of osteoclasts in the resorption sites could be likely the result of a systemic recruitment of monocyte-macrophage precursors. We observed that treatment with PN induced a significant decrease of the alkaline phosphatase (ALP) activity in scale scleroblasts if compared with untreated controls. Then, we investigated the total mineral balance under prednisolone treatment using a time-dependent double live staining. The untreated fish fully repaired the resorption lacuna induced by prednisolone, whereas treated fish failed. The presence of osteoclast resorption fingerprints on new matrix suggested that the osteoclast activity counterbalances the osteodepositive activity exerted by scleroblasts. The treatment with PN in association with alendronate (AL) has surprisingly resulted in a significant decrease of TRAP activity and increase of ALP compared to PN-treated fish in biochemical and histological assays confirming the action of alendronate against GIOP in fish as well in humans.

Topics: Acid Phosphatase; Alendronate; Alkaline Phosphatase; Animals; Biomarkers; Bone Density Conservation Agents; Bone Matrix; Bone Remodeling; Disease Models, Animal; Glucocorticoids; Isoenzymes; Male; Osteoclasts; Osteoporosis; Phenotype; Prednisolone; Tartrate-Resistant Acid Phosphatase; Time Factors; Tissue Culture Techniques; Zebrafish; Zebrafish Proteins

Our study aimed to investigate the antiosteoporotic properties of the ethanol extract of Podocarpium podocarpum (DC.) Yang et Huang (PE) in ovariectomized (OVX) rats and to characterize the active constituents. As a result, PE significantly inhibited the increased urinary Ca excretion and activity of bone resorption markers including tartrate-resistant acid phosphatase (TRAP), deoxypyridinoline crosslinks and cathepsin K in OVX rats, whereas exhibited little effects on the body, uterus and vagina weight. Detailed micro-CT analysis showed that PE notably enhanced bone quality, with increased bone mineral content (BMC), bone volume fraction (BVF), connectivity density (CD), tissue mineral content (TMC), tissue mineral density (TMD) and trabecular number (Tb. N), and decreased trabecular separation (Tb. Sp), in OVX animal. Those findings implied that PE had notable antiosteoporotic effect, especially effective in preventing bone resorption, with little side-effects on reproductive tissue. Further chemical investigation led to the isolation of 17 flavonoids, most of which showed significantly stimulatory effect on osteoblastic proliferation, ALP activity and mineralized nodes formation as well as inhibitory effect on osteoclastic TRAP activity in osteoblastic and osteoclastic cells. Our results indicated that PE, with abundant flavonoids, had remarkable antiosteoporotic activity and therefore can be a promising candidate for the treatment of postmenopausal osteoporosis induced by estrogen deficiency through herbal remedy.

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Bone Density; Cells, Cultured; Disease Models, Animal; Fabaceae; Female; Femur; Flavonoids; Isoenzymes; Molecular Structure; Osteoblasts; Osteoclasts; Osteoporosis; Ovariectomy; Plant Extracts; Rats; Rats, Sprague-Dawley; Tartrate-Resistant Acid Phosphatase

The roles of different immune cell populations and cytokines in bone metabolism have been extensively investigated. However, the influence of whole immune organ removal on osteopathology remains unknown. In the current study, we investigated the effects of splenectomy on bone metabolism and microarchitecture in rats with or without concurrent ovariectomy. Ovariectomized (OVX) rats were used as osteoporosis model. Sixty 12-week-old female rats were randomized into 4 groups (n = 15): sham, splenectomized (SP), ovariectomized, as well as ovariectomized and splenectomized (OVX + SP). Bone microarchitecture was assessed by micro CT analysis at 4 week and 12 week post-operation, respectively. Bone pathology and metabolism were evaluated via immunohistochemical staining. The serum levels of alkaline phosphatase (ALP), tumor necrosis factor-alpha (TNF-α), tartrate-resistant acid phosphatase 5b (Tracp5b), and C-terminal telopeptide (CTx) were analyzed at 4 and 12 weeks post-operation. Removal of the spleen led to alterations in the homeostasis of bone metabolism and increased bone formation in rats. In this study, our findings indicate that the spleen is involved in skeletal metabolism.

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Body Weight; Bone and Bones; Bone Diseases, Metabolic; Collagen Type I; Female; Immunohistochemistry; Isoenzymes; Osteoclasts; Osteogenesis; Osteoporosis; Ovariectomy; Peptides; Random Allocation; Rats; Rats, Sprague-Dawley; Splenectomy; Tartrate-Resistant Acid Phosphatase; Time Factors; Tumor Necrosis Factor-alpha; X-Ray Microtomography

Heng-Gu-Gu-Shang-Yu-He-Ji, also known as OsteoKing, is used as a herbal Traditional Chinese Medicine for the treatment of bone disease, including femoral head necrosis and osteoarthritis. However, whether OsteoKing has anti-osteoporotic properties has remained to be elucidated. The purpose of the present study was therefore to investigate the effects of OsteoKing on ovariectomy-induced osteoporosis in rabbits. Female New Zealand white rabbits were randomly divided into an ovariectomized (OVX) group and a sham-surgery group. The rabbits in the OVX group were subjected to an ovariectomy, while the rabbits in the sham group were subjected to the removal of an area of fat near the two ovaries. Bone mineral density, mechanical properties, serum biochemical parameters and micro-architecture were examined at 150 days post-OVX to characterize the experimental animal model. Once the osteoporotic rabbit model had been established, the rabbits in the OVX group were divided into the following groups: Model group, nilestriol group and 300 and 600 mg/kg OsteoKing groups, containing 16 rabbits in each group. OsteoKing and nilestriol were administered orally. The bone mineral density, mechanical properties, serum biochemical parameters, histology and micro-architecture were examined using dual-energy X-ray absorptiometric analysis, mechanical assessments, enzyme-linked immunosorbent assays, histopathological evaluation and micro-computerized tomography examination following 60 days and 120 days of treatment, respectively. Treatment with OsteoKing led to an elevation in the bone mineral density of the vertebra and serum phosphorus levels, reduced serum concentrations of osteocalcin, procollagen type I N-terminal peptide, tartrate-resistant acid phosphatase 5b and cross-linked N-telopeptide of type I collagen, improved mechanical properties (maximum load, stiffness and energy absorption capacity), and micro-architecture of the lumbar vertebra in the OVX osteoporotic rabbit model following treatment for 120 days. In conclusion, it was demonstrated that OsteoKing is effective in the prevention of estrogen deficiency-associated bone loss and may be a promising drug for the treatment of post-menopausal osteoporosis.

Topics: Absorptiometry, Photon; Acid Phosphatase; Administration, Oral; Animals; Bone Density; Bone Density Conservation Agents; Drugs, Chinese Herbal; Estriol; Estrogens; Female; Isoenzymes; Lumbar Vertebrae; Osteocalcin; Osteoporosis; Ovariectomy; Peptide Fragments; Phosphorus; Procollagen; Quinestrol; Rabbits; Tartrate-Resistant Acid Phosphatase; Tomography, Emission-Computed

To study the relevance of PTH, 25(OH)D3, CT, bone resorption markers C-terminal telopeptide of type I (CTX-1), and tartrate-resistant acid phosphatase (TRACP), bone formation markers bone gla protein (BGP), bone alkaline phosphatase (BALP) with the femoral neck BMD in females.. PTH, 25(OH)D3, CT, CTX-1, TRACP, BGP, and BALP were detected by an enzyme immunoassay analyzer and femoral neck BMD were measured by a BMD detector. The results of 860 females were divided into several groups according to standard of five-year age intervals. SPSS 13.0 software was used for statistical analysis.. The measured values of PTH, 25(OH) D3 and CT had no differences in 35-50 age group. The measured values of 25(OH) D3 began to decline after the age of 50, and 25(OH)D3 had positive relevance with BMD. The values of CT were decreased in the age groups from 65 to 79 years old, and were significant positive correlated with BMD. The CTX-1 and TRACP had negative relevance with BMD in 35-45 age group and BGP and BALP had positive relevance with BMD in 35-45 age group. The BGP, BALP increased significantly in 50-60 age group, and CTX-1, TRACP, BGP, and BALP had negative relevance with BMD in 50-60 age group. BGP and BALP began to decline and had positive relevance with BMD after the age of 65, and CTX-1 and TRACP had negative relevance with BMD after the age of 65.. PTH, 25(OH)D3, CT, CTX-1, TRACP, BGP, and BALP were the important technical means for monitoring the level of bone metabolism and the diagnosis and differential diagnosis of osteoporosis.

Topics: Acid Phosphatase; Adult; Aged; Alkaline Phosphatase; Antineoplastic Agents, Hormonal; Biomarkers; Bone Density; Calcitonin; Female; Humans; Hydroxycholecalciferols; Isoenzymes; Middle Aged; Osteocalcin; Osteoporosis; Parathyroid Hormone; Tartrate-Resistant Acid Phosphatase

The potential of increasing bone mass and preventing fractures in osteoporosis using stem cell therapy is currently an area of intense focus. However, there are very little data available regarding the postfracture bony defect healing efficacy under osteoporotic conditions. This study aims to investigate whether critical-sized segmental bone defects in a rabbit model of osteoporosis could be repaired using an allogenic stem cell-based tissue engineering (TE) approach and to investigate the potential influence of osteoporosis on the treatment efficacy. Rabbit fetal bone marrow mesenchymal stem cells (BMSCs) were harvested and expanded in vitro. Decalcified bone matrix (DBM) scaffolds were then seeded with allogenic fetal BMSCs and cultivated in osteogenic media to engineer BMSC/DBM constructs. Critical-sized radial defects were created in ovariectomized (OVX) rabbits and the defects were repaired either by insertion of BMSC/DBM constructs or by DBM scaffolds alone. Also, nonovariectomized age-matched (non-OVX) rabbits were served as control. At 3 months post-treatment under the osteoporotic condition (OVX rabbits), the BMSC/DBM constructs inserted within the defect generated significantly more bone tissue when compared to the DBM scaffold as demonstrated by the X-ray, microcomputed tomography, and histological analyses. In addition, when compared to a normal nonosteoporotic condition (age-matched non-OVX rabbits), the defect treatment efficacy was adversely affected by the osteoporotic condition with significantly less bone regeneration. This study demonstrated the potential of allogenic fetal BMSC-based TE strategy for repairing bone defects in an osteoporotic condition. However, the treatment efficacy could be considerably compromised in the OVX animals. Therefore, a more sophisticated strategy that addresses the complicated pathogenic conditions associated with osteoporosis is needed.

Topics: Acid Phosphatase; Animals; Bone Matrix; Cell Shape; Disease Models, Animal; Female; Isoenzymes; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Osteoporosis; Ovariectomy; Rabbits; Radiography; Radius; Sus scrofa; Tartrate-Resistant Acid Phosphatase; Tissue Engineering; Treatment Outcome; Wound Healing

Milk is known as a safe food and contains easily absorbable minerals and proteins, including whey protein, which has demonstrated antiosteoporotic effects on ovariectomized rats. This study evaluated the antiosteoporotic effect of whey protein concentrate hydrolysate (WPCH) digested with fungal protease and whey protein concentrate (WPC). Two experiments were conducted to determine (1) efficacy of WPCH and WPC and (2) dose-dependent impact of WPCH in ovariectomized rats (10 weeks old). In Experiment I, ovariectomized rats (n=45) were allotted into three dietary treatments of 10 g/kg diet of WPC, 10 g/kg diet of WPCH, and a control diet. In Experiment II, ovariectomized rats (n=60) were fed four different diets (0, 10, 20, and 40 g/kg of WPCH). In both experiments, sham-operated rats (n=15) were also fed a control diet containing the same amount of amino acids and minerals as dietary treatments. After 6 weeks, dietary WPCH prevented loss of bone, physical properties, mineral density, and mineral content, and improved breaking strength of femurs, with similar effect to WPC. The bone resorption enzyme activity (tartrate resistance acid phosphatase) in tibia epiphysis decreased in response to WPCH supplementation, while bone formation enzyme activity (alkaline phosphatase) was unaffected by ovariectomy and dietary treatment. Bone properties and strength increased as the dietary WPCH level increased (10 and 20 g/kg), but there was no difference between the 20 and 40 g/kg treatment. WPCH and WPC supplementation ameliorated bone loss induced by ovariectomy in rats.

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Bone Density; Dietary Supplements; Female; Femur; Fungi; Isoenzymes; Osteoporosis; Ovariectomy; Peptide Hydrolases; Protein Hydrolysates; Rats, Sprague-Dawley; Tartrate-Resistant Acid Phosphatase; Tibia; Whey Proteins

To explore the significance of serum bone metabolic markers in the diagnosis and monitoring of multiple myeloma bone disease(MBD).. Thirty-six newly diagnosed multiple myeloma (MM) patients who were treated in Department of Hematology, Tianjin Medical University General Hospital from January 2013 to December 2014 were collected. Bone morbidity was graded into two stages according to the radiographic evaluation of the skeleton: stage A (n=12) included patients with no lytic lesions or with osteoporosis alone; stage B (n=24) included patients with osteolytic lesions and/or a pathological fracture. All the patients achieved partial or complete remission after treated with bortezomib + dexamethasone + zoledronic acid regimen. A total of 25 aged- and gender-matched healthy individuals were enrolled in this study as controls. The levels of serum tartrate-resistant acid phosphatase isoform 5b (TRACP-5b), carboxy-terminal cross-linking telopeptide of type I collagen (CTX), osteocalcin (OCN), and procollagen I amino-terminal propeptide (PINP) were investigated by ELISA and electrochemiluminescence immunoassay (ECLIA). The differences of these bone metabolic markers before and after treatment, and at different stages of bone disease were observed.. The value of TRACP-5b in the newly diagnosed MM was significantly higher than that in the healthy controls and after treatment(median 4.16 vs 2.63 U/L, P=0.014; 4.16 vs 2.61 U/L, P=0.037). Serum level of CTX in the newly diagnosed MM patients was significantly decreased after treatment (median: 0.26 vs 1.05 µg/L, P=0.003). The ratio of CTX/OCN and CTX/PINP decreased after treatment, but there were no significant differences (both P>0.05). The pretreatment level of serum TRACP-5b in stage B patients was higher than that of the healthy controls (median: 4.20 vs 2.63 U/L, P=0.015). The levels of serum CTX in stage A and stage B patients were both higher than that of the healthy controls (median: 1.16 vs 0.48 µg/L, P=0.002; 0.88 vs 0.48 µg/L, P=0.040). The levels of serum OCN and PINP were higher in stage A patients compared with stage B patients, but there were no significant differences (both P>0.05). The ratio of CTX/OCN and CTX/PINP of stage A and stage B patients all increased compared with those of the healthy controls, but there were no significant differences (all P>0.05).. Bone damage of MM patients is improved after effective treatment, but bone imbalance still exists, indicating that the treatment of MBD is a long process. Abnormal serum levels of TRACP-5b and CTX are found before positive X-ray findings in MBD, suggesting that these biochemical markers could be used as indices for early diagnosis of MBD.

Topics: Acid Phosphatase; Biomarkers; Collagen Type I; Diphosphonates; Humans; Imidazoles; Isoenzymes; Multiple Myeloma; Osteoporosis; Procollagen; Tartrate-Resistant Acid Phosphatase; Zoledronic Acid

Tartrate-resistant acid phosphatase isoform 5b (TRACP5b) is a serum bone resorption marker. Our aim was to investigate its utility in monitoring metabolic bone disease.. Serum TRACP5b, C-terminal cross-linking telopeptide of type I collagen, urine N-terminal cross-linking telopeptide of type I collagen and free deoxypyridinoline were measured pre- and post-treatment with a parathyroid hormone analogue [PTH (1-34)] (n = 14) or a bisphosphonate (N-BP) (n = 8). TRACP5b, bone alkaline phosphatase (bone ALP), 25-hydroxyvitamin D (25OHD) and parathyroid hormone (PTH) were measured in 100 osteoporosis patients on prolonged bisphosphonate therapy.. Changes in TRACP5b were smaller in magnitude but mimicked those of other bone resorption markers. Absolute changes in TRACP5b and the other resorption markers correlated significantly (p < 0.001). In patients on long-term bisphosphonates, TRACP5b and bone ALP levels were not suppressed. Vitamin D status was consistent with the level of supplementation.. TRACP5b has limited utility as a single marker of metabolic bone disease treatment.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Alkaline Phosphatase; Amino Acids; Biomarkers; Bone Density Conservation Agents; Bone Resorption; Collagen Type I; Diphosphonates; Female; Humans; Isoenzymes; Male; Middle Aged; Osteoporosis; Parathyroid Hormone; Peptides; Predictive Value of Tests; Tartrate-Resistant Acid Phosphatase; Teriparatide; Time Factors; Treatment Outcome; Vitamin D

The purpose of this study was to evaluate the effect of parathyroid hormone (PTH) (1-84) in a model of male osteoporosis induced by orchidectomy in rats.. Six-month-old Wistar rats were used as follows: SHAM (simulated orchidectomy), orchidectomized (ORX), ORX + PTH1 (ORX and treated with 10 µg/Kg/d of PTH 1-84) and ORX + PTH2 (ORX and treated with 50 µg/Kg/d of PTH 1-84) over 3 months, with treatment beginning three months after orchidectomy.. Orchidectomy resulted in a decreased of femoral and lumbar bone mineral density (BMD), a worsening of trabecular and cortical microarchitecture and a decrease in biomechanical properties. Both doses of PTH (1-84) partially (low dose) or totally (high dose) restored the ORX-induced changes. Serum C-telopeptide of type I collagen/5b isoenzyme of tartrate-resistant acid phosphatase (CTX/TRAP) resorption index increased after orchidectomy. Osteocalcin (bone Gla protein; BGP) levels were not affected by orchidectomy. PTH (1-84) treatment did not produce any changes in the levels of CTX/TRAP with respect to the ORX group. BGP levels increased with PTH treatment.. PTH (1-84) is able to restore the adverse effects of orchidectomy on bone as measured by BMD, microstructural and biomechanical properties and bone remodeling markers.

Topics: Absorptiometry, Photon; Acid Phosphatase; Animals; Biomarkers; Biomechanical Phenomena; Bone Density; Collagen Type I; Enzyme-Linked Immunosorbent Assay; Isoenzymes; Male; Orchiectomy; Osteocalcin; Osteoporosis; Parathyroid Hormone; Peptides; Random Allocation; Rats; Rats, Wistar; Tartrate-Resistant Acid Phosphatase; X-Ray Microtomography

Studies have demonstrated that a moderate intake of amino acids is associated with development of bone health. Methionine, a sulphur-containing essential amino acid, has been largely implicated for improving cartilage formation, however its physiological significance on bone integrity and functionality have not been elucidated. We investigated whether methionine can prevent osteoporotic bone loss.. The anti-resorptive effect of methionine, (250 mg kg(-1) body wt administered in drinking water for 10 weeks), was evaluated in ovariectomized (OVX) rats by monitoring changes in bone turnover, formation of osteoclasts from blood-derived mononuclear cells and changes in the synthesis of pro-osteoclastogenic cytokines.. Methionine improved bone density and significantly decreased the degree of osteoclast development from blood mononuclear cells in OVX rats, as indicated by decreased production of osteoclast markers tartarate resistant acid phosphatase b (TRAP5b) and MIP-1α. siRNA-mediated knockdown of myeloid differentiation primary response 88 [MyD88], a signalling molecule in the toll-like receptor (TLR) signalling cascade, abolished the synthesis of both TRAP5b and MIP-1α in developing osteoclasts. Methionine supplementation disrupted osteoclast development by inhibiting TLR-4/MyD88/NF-κB pathway.. TLR-4/MyD88/NF-κB signalling pathway is integral for osteoclast development and this is down-regulated in osteoporotic system on methionine treatment. Methionine treatment could be beneficial for the treatment of postmenopausal osteoporosis.

Topics: Acid Phosphatase; Administration, Oral; Alendronate; Animals; Bone Density; Bone Density Conservation Agents; Bone Remodeling; Cells, Cultured; Chemokine CCL3; Disease Models, Animal; Dose-Response Relationship, Drug; Down-Regulation; Drug Therapy, Combination; Female; Inflammation Mediators; Isoenzymes; Methionine; Myeloid Differentiation Factor 88; NF-kappa B; Osteoclasts; Osteoporosis; Ovariectomy; Rats; Rats, Sprague-Dawley; RNA Interference; Signal Transduction; Tartrate-Resistant Acid Phosphatase; Time Factors; Toll-Like Receptor 4

A decrease of bone mass is a major risk factor for fracture. Several natural products have traditionally been used as herbal medicines to prevent and/or treat bone disorders including osteoporosis. Praeruptorin A is isolated from the dry root extract of Peucedanum praeruptorum Dunn and has several biological activities, but its anti-osteoporotic activity has not been studied yet.. The effect of praeruptorin A on the differentiation of bone marrow-derived macrophages into osteoclasts was examined by phenotype assay and confirmed by real-time PCR and immunoblotting. The involvement of NFATc1 in the anti-osteoclastogenic action of praeruptorin A was evaluated by its lentiviral ectopic expression. Intracellular Ca(2+) levels were also measured.. Praeruptorin A inhibited the RANKL-stimulated osteoclast differentiation accompanied by inhibition of p38 and Akt signaling, which could be the reason for praeruptorin A-downregulated expression levels of c-Fos and NFATc1, transcription factors that regulate osteoclast-specific genes, as well as osteoclast fusion-related molecules. The anti-osteoclastogenic effect of praeruptorin A was rescued by overexpression of NFATc1. Praeruptorin A strongly prevented the RANKL-induced Ca(2+) oscillation without any changes in the phosphorylation of PLCγ.. Praeruptorin A could exhibit its anti-osteoclastogenic activity by inhibiting p38/Akt-c-Fos-NFATc1 signaling and PLCγ-independent Ca(2+) oscillation.

Topics: Acid Phosphatase; Calcium; Cell Differentiation; Coumarins; DNA Primers; Humans; Immunoblotting; Isoenzymes; Macrophages; MAP Kinase Signaling System; Molecular Structure; NFATC Transcription Factors; Oncogene Protein v-akt; Osteoclasts; Osteoporosis; Phospholipase C gamma; Proto-Oncogene Proteins c-fos; Real-Time Polymerase Chain Reaction; Tartrate-Resistant Acid Phosphatase

The present study investigated the antioxidant and anti-osteoporosis activities of phytochemicals in the fruits of Prunus mume. From the methanol extract, three new acylated sucroses, mumeoses P-R (1-3), were isolated together with 20 known compounds (4-23). Compounds 1-3 showed potent peroxyl radical-scavenging activities and 12-19 showed both potent peroxyl radical-scavenging and reducing activities. The anti-osteoporosis activity was evaluated using murine pre-osteoblastic MC3T3-E1 cells and pre-osteoclastic RAW 264.7 cells. Compounds 2 and 3 (cis-trans isomers), 5, 7, 8, and 10 significantly stimulated the differentiation of pre-osteoblastic MC3T3-E1 cells to increase collagen synthesis or mineralization functions of osteoblasts, while compounds 5, 6, 9, 10, 12, 14-16, 18, 20, and 22 significantly suppressed tartrate-resistant acid phosphatase activity in receptor activator of nuclear factor-κB ligand-induced osteoclastic RAW 264.7 cells. These results indicated that the fruits of P. mume are an excellent source of antioxidant and anti-osteoporosis phytochemicals.

Topics: 3T3 Cells; Acid Phosphatase; Acylation; Animals; Antioxidants; Cell Differentiation; Collagen; Fruit; Isoenzymes; Mice; Osteoblasts; Osteoporosis; Plant Extracts; Prunus; Tartrate-Resistant Acid Phosphatase

Osteoporosis is a silent disease, characterized by a porous bone micro-structure that enhances risk for fractures and associated disabilities. Senile, or age-related osteoporosis (SO), affects both men and women, resulting in increased morbidity and mortality. However, cellular and molecular mechanisms underlying senile osteoporosis are not fully known. Recent studies implicate the accumulation of reactive oxygen species (ROS) and increased oxidative stress as key factors in SO. Herein, we show that loss of caspase-2, a cysteine aspartate protease involved in oxidative stress-induced apoptosis, results in total body and femoral bone loss in aged mice (20% decrease in bone mineral density), and an increase in bone fragility (30% decrease in fracture strength). Importantly, we demonstrate that genetic ablation or selective inhibition of caspase-2 using zVDVAD-fmk results in increased numbers of bone-resorbing osteoclasts and enhanced tartrate-resistant acid phosphatase (TRAP) activity. Conversely, transfection of osteoclast precursors with wild type caspase-2 but not an enzymatic mutant, results in a decrease in TRAP activity. We demonstrate that caspase-2 expression is induced in osteoclasts treated with oxidants such as hydrogen peroxide and that loss of caspase-2 enhances resistance to oxidants, as measured by TRAP activity, and decreases oxidative stress-induced apoptosis of osteoclasts. Moreover, oxidative stress, quantified by assessment of the lipid peroxidation marker, 4-HNE, is increased in Casp2-/- bone, perhaps due to a decrease in antioxidant enzymes such as SOD2. Taken together, our data point to a critical and novel role for caspase-2 in maintaining bone homeostasis by modulating ROS levels and osteoclast apoptosis during conditions of enhanced oxidative stress that occur during aging.

Topics: Acid Phosphatase; Aldehydes; Animals; Apoptosis; Bone and Bones; Caspase 2; Homeostasis; Isoenzymes; Lipid Peroxidation; Mice; Osteoclasts; Osteoporosis; Oxidative Stress; Reactive Oxygen Species; Superoxide Dismutase; Tartrate-Resistant Acid Phosphatase

Whole body vibration (WBV) stimulation has a beneficial effect on the recovery of osteoporotic bone. We aimed to investigate the immediate effect of WBV on lipopolysaccharide (LPS)-mediated inflammatory bone loss by varying the exposure timing. Balb/C mice were divided into the following groups: control, LPS (L), and LPS with vibration (LV). The L and LV groups received LPS (5 mg/kg) by 2 intraperitoneal injections on days 0 and 4. The LV group was exposed to WBV (0.4 g, 45 Hz) either during LPS treatment (LV1) or after cessation of LPS injection (LV2) and then continued WBV treatment for 10 min/d for 3 d. Evaluation based on micro-computed tomography was performed 7 d after the first injection, when the L group showed a significant decrease in bone volume (-25.8%) and bone mineral density (-33.5%) compared with the control group. The LV2 group recovered bone volume (35%) and bone mineral density (19.9%) compared with the L group, whereas the LV1 group showed no improvement. This vibratory signal showed a suppressive effect on the LPS-mediated induction of inflammatory cytokines such as IL-1β or TNF-α in human mesenchymal stem cells in vitro. These findings suggest that immediate exposure to WBV after the conclusion of LPS treatment efficiently reduces trabecular bone loss, but WBV might be less effective during the course of treatment with inflammatory factor.

Topics: Acid Phosphatase; Adult; Animals; Bone Density; Bone Regeneration; Cells, Cultured; Disease Models, Animal; Femur; Humans; Interleukin-1beta; Isoenzymes; Lipopolysaccharides; Male; Mesenchymal Stem Cells; Mice; Mice, Inbred BALB C; Organ Size; Osteoporosis; Tartrate-Resistant Acid Phosphatase; Tibia; Time Factors; Tumor Necrosis Factor-alpha; Vibration; X-Ray Microtomography

Due to some severe side effects or lack of efficacy of currently used synthetic drugs, such as bisphosphonates (BPs), the search for new therapeutic agents that can more effectively prevent and treat osteoporosis (OP) has been an increasingly important topic of research. In this study, the low-molecular weight hyaluronan (LMW-HA, 50 kDa) produced by enzymatic degradation of high-molecular weight hyaluronan (HMW-HA, 1922 kDa) from Streptococcus zooepidemicus was evaluated in vitro for its anti-osteoclastogenic potentials using RAW 264.7 murine macrophage cells. LMW-HA (25-200 μg/ml) dose-dependently inhibited the receptor activator of NF-κB ligand (RANKL)-induced tartrate-resistance acid phosphatase (TRAP) activity and the formation of multinucleated osteoclasts. Western blot analysis showed that LMW-HA reduced the RANKL-induced expression of tumor necrosis factor receptor-associated factor 6 (TRAF6), gelsolin and c-Src-proline-rich tyrosine kinase 2 suggesting that it could inhibit actin ring formation of osteoclast cells. In addition, LMW-HA inhibited the bone resorption activity of osteoclastic cells by dose-dependently attenuating the RANKL-induced expression of carbonic anhydrase II and integrin β3. RT-PCR analysis showed that LMW-HA dose-dependently decreased the expression of osteoclast-specific genes, such as matrix metalloproteinase 9 (MMP-9) and cathepsin K, suggesting that it has potential to inhibit the differentiation of osteoclastic cells. Taken collectively, these results suggested that LMW-HA (50 kDa) has significant anti-osteoporotic activity in vitro and may be used as a potent functional ingredient in health beneficial foods or as a therapeutic agent to prevent or treat OP.

Topics: Acid Phosphatase; Animals; Cathepsin K; Cell Differentiation; Cell Line; Hyaluronic Acid; Isoenzymes; Macrophages; Matrix Metalloproteinase 9; Mice; Molecular Weight; Osteoclasts; Osteoporosis; RANK Ligand; Tartrate-Resistant Acid Phosphatase; TNF Receptor-Associated Factor 6

Recently, involvement of the sympathetic nervous system in bone metabolism has attracted attention. β2-Adrenergic receptor (β2-AR) is presented on osteoblastic and osteoclastic cells. We previously demonstrated that β-AR blockers at low dose improve osteoporosis with hyperactivity of the sympathetic nervous system via β2-AR blocking, while they may have a somewhat inhibitory effect on osteoblastic activity at high doses. In this study, the effects of butoxamine (BUT), a specific β2-AR antagonist, on tooth movement were examined in spontaneously hypertensive rats (SHR) showing osteoporosis with hyperactivity of the sympathetic nervous system. We administered BUT (1 mg/kg) orally, and closed-coil springs were inserted into the upper-left first molar. After sacrifice, we calculated the amount of tooth movement and analyzed the trabecular microarchitecture and histomorphometry. The distance in the SHR control was greater than that in the Wistar-Kyoto rat group, but no significant difference was found in the SHR treated with BUT compared with the Wistar-Kyoto rat control. Analysis of bone volume per tissue volume, trabecular number, and osteoclast surface per bone surface in the alveolar bone showed clear bone loss by an increase of bone resorption in SHR. In addition, BUT treatment resulted in a recovery of alveolar bone loss. Furthermore, TH-immunoreactive nerves in the periodontal ligament were increased by tooth movement, and BUT administration decreased TH-immunoreactive nerves. These results suggest that BUT prevents alveolar bone loss and orthodontic tooth movement via β2-AR blocking.

Topics: Acid Phosphatase; Adrenergic beta-2 Receptor Antagonists; Alveolar Process; Animals; Butoxamine; Imaging, Three-Dimensional; Isoenzymes; Male; Organ Size; Orthodontic Wires; Osteocalcin; Osteoclasts; Osteoporosis; Periodontal Ligament; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Sympathetic Nervous System; Tartrate-Resistant Acid Phosphatase; Tooth Movement Techniques; Tyrosine 3-Monooxygenase; X-Ray Microtomography

JSOG-6 is used as a traditional medicine to relieve the symptoms associated with inflammation, rheumatism, and osteoporosis in Korea. In the present study, we investigated the effects of JSOG-6 on bone loss prevention both in in vitro and in vivo as well as its underlying mechanism of action.. Protection against bone loss was assessed in an ovariectomized (OVX) mouse model. Bone microarchitecture was measured using a micro-computed tomography to detect the parameters of three-dimensional structure of a trabecular bone. Serum biomarkers were also evaluated in an OVX-induced model. Osteoclasts derived from mouse bone marrow cells (BMCs) and osteoblastic MC3T3-E1 cells were also employed to investigate the mechanism of action.. Oral administration of JSOG-6 significantly increased the bone mineral density (BMD) of the femur in OVX mice in vivo. Especially, the reduced Tb.No (trabecular bone number) in the OVX group was significantly recovered by JSOG-6 treatment. The serum levels of alkaline phosphatase (ALP), osteocalcin, C-terminal telopeptide, and tartrate-resistant acid phosphatase, biomarkers of bone resorption, were significantly elevated in OVX mice, but JSOG-6 effectively inhibited the increase in OVX mice. JSOG-6 was also found to enhance the osteoblastic differentiation and maturation with the increase of the density and ALP activity, a marker of osteoblastic differentiation, as well as calcium deposition, a marker of osteoblastic maturation in MC3T3-E1 cells. The effects of JSOG-6 on osteoblastic differentiation were also associated in part with the increase of ALP and OPN mRNA expressions and the decrease of RANKL mRNA expression in MC3T3-E1 cells.. The findings demonstrate that JSOG-6 induced protection against bone loss in OVX mice, and its anti-osteoporotic property might be, in part, a function of the stimulation of osteoblast differentiation and the inhibition of osteoclast formation. These findings suggest that JSOG-6 might be an applicable therapeutic traditional medicine for the regulation of the osteoporotic response.

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Bone and Bones; Bone Density; Bone Resorption; Cell Differentiation; Cell Line; Female; Femur; Gene Expression; Humans; Isoenzymes; Mice; Mice, Inbred ICR; Osteoblasts; Osteocalcin; Osteoclasts; Osteogenesis; Osteoporosis; Ovariectomy; Phytotherapy; Plant Extracts; RANK Ligand; Republic of Korea; Tartrate-Resistant Acid Phosphatase; X-Ray Microtomography

Use of bone mineral density (BMD) by dual-energy x-ray absorptiometry (DXA) is controversial for diagnosing bone loss in CKD patients on dialysis. The alternative quantitative computed tomography (QCT) is expensive and requires high radiation exposure. This study compared the two techniques and evaluated serum biochemical parameters for prediction of bone loss.. This prospective study enrolled patients from dialysis centers throughout Kentucky. BMD of the spine and hip was measured at baseline and after 1 year by DXA and QCT. Customary and novel serum biochemical parameters were obtained at the same times, including calcium, phosphorus, whole and intact parathyroid hormone, bone-specific alkaline phosphatase, procollagen type 1 N-terminal propeptide, tartrate-resistant acid phosphatase-5b, Dickkopf-1, fibroblast growth factor, and sclerostin. Rates of detection of osteoporosis by DXA and QCT were compared. Correlations were calculated between baseline biochemical parameters and BMD at baseline and changes over 1 year. Multivariable regression was performed to adjust for age, sex, body mass index, and race.. Eighty-one patients completed the study (mean age=52.6 ± 12.3 years, 56% men, 53% African American, and median dialysis vintage=41 months). At baseline, QCT and DXA of the spine identified similar rates of osteoporosis (13.6% and 13.6%), but at the hip, DXA identified more osteoporosis (22.2% versus 13.6%). At any site and by either method, 33.3% of the patients were osteoporotic. Baseline BMD correlated with sclerostin, intact parathyroid hormone, bone-specific alkaline phosphatase, tartrate-resistant acid phosphatase-5b, and fibroblast growth factor. At 1 year, hip QCT identified a higher number of patients experiencing bone loss (51.3%) than DXA (38.5%). After multivariable adjustment, baseline sclerostin and tartrate-resistant acid phosphatase-5b predicted bone loss measured by QCT of the hip; procollagen type 1 N-terminal propeptide predicted cortical spine bone gain by QCT.. QCT identified prospectively more bone loss at the hip than DXA. The baseline serum biochemical parameters sclerostin and tartrate-resistant acid phosphatase-5b were noninvasive independent predictors of bone loss in CKD patients on dialysis.

Topics: Absorptiometry, Photon; Acid Phosphatase; Adaptor Proteins, Signal Transducing; Adult; Aged; Biomarkers; Bone Density; Bone Morphogenetic Proteins; Cross-Sectional Studies; Female; Genetic Markers; Hip Joint; Humans; Isoenzymes; Kentucky; Linear Models; Male; Middle Aged; Multivariate Analysis; Osteoporosis; Peptide Fragments; Predictive Value of Tests; Procollagen; Prospective Studies; Renal Dialysis; Renal Insufficiency, Chronic; Risk Factors; Tartrate-Resistant Acid Phosphatase; Time Factors; Tomography, X-Ray Computed; Treatment Outcome

A new pterocarpan glycoside, glycinol-3-O-β-D-glucopyranoside (1), and a new dihydrochalcone glycoside, ismaeloside A (2), were isolated together with 13 known compounds, including several flavonoids (3-8), lignans (9-11), and phenolic compounds (12-15), from the methanol extract of the aerial parts of Ducrosia ismaelis. The chemical structures of these compounds were elucidated from spectroscopic data and by comparison of these data with previously published results. The anti-osteoporotic and antioxidant activities of the isolated compounds were assessed using tartrate-resistant acid phosphatase (TRAP), oxygen radical absorbance capacity (ORAC), and reducing capacity assays. Compound 15 exhibited a dose-dependent inhibition of osteoclastic TRAP activity with a TRAP value of 86.05±6.55% of the control at a concentration of 10 μM. Compounds 1, 3-5, and 8 showed potent peroxyl radical-scavenging capacities with ORAC values of 22.79±0.90, 25.57±0.49, 20.41±0.63, 26.55±0.42, and 24.83±0.12 μM Trolox equivalents (TE) at 10 μM, respectively. Only compound 9 was able to significantly reduce Cu(I) with 23.44 μM TE at a concentration of 10 μM. All of the aforementioned compounds were isolated for the first time from a Ducrosia species.

Topics: Acid Phosphatase; Antioxidants; Apiaceae; Dose-Response Relationship, Drug; Humans; Isoenzymes; Molecular Structure; Osteoporosis; Plant Components, Aerial; Reactive Oxygen Species; Structure-Activity Relationship; Tartrate-Resistant Acid Phosphatase

The pathogenesis of bone resorption in β-thalassemia major is multifactorial and our understanding of the underlying molecular and cellular mechanisms remains incomplete. Considering the emerging importance of the endocannabinoid/endovanilloid system in bone metabolism, it may be instructive to examine a potential role for this system in the development of osteoporosis in patients with β-thalassemia major and its relationship with iron overload and iron chelation therapy. This study demonstrates that, in thalassemic-derived osteoclasts, tartrate-resistant acid phosphatase expression inversely correlates with femoral and lumbar bone mineral density, and directly correlates with ferritin levels and liver iron concentration. The vanilloid agonist resiniferatoxin dramatically reduces cathepsin K levels and osteoclast numbers in vitro, without affecting tartrate-resistant acid phosphatase expression. The iron chelators deferoxamine, deferiprone and deferasirox decrease both tartrate-resistant acid phosphatase and cathepsin K expression, as well as osteoclast activity. Taken together, these data show that transient receptor potential vanilloid type 1 activation/desensitization influences tartrate-resistant acid phosphatase expression and activity, and this effect is dependent on iron, suggesting a pivotal role for iron overload in the dysregulation of bone metabolism in patients with thalassemia major. Our applied pharmacology provides evidence for the potential of iron chelators to abrogate these effects by reducing osteoclast activity. Whether iron chelation therapy is capable of restoring bone health in humans requires further study, but the potential to provide dual benefits for patients with β-thalassemia major -preventing iron-overload and alleviating associated osteoporotic changes - is exciting.

Topics: Acid Phosphatase; Adult; beta-Thalassemia; Biomarkers; Blotting, Western; Case-Control Studies; Cathepsin K; Cells, Cultured; Female; Fluorescent Antibody Technique; Follow-Up Studies; Humans; Iron Chelating Agents; Iron Overload; Isoenzymes; Male; Osteoclasts; Osteoporosis; Prognosis; Real-Time Polymerase Chain Reaction; Receptor, Cannabinoid, CB1; Receptor, Cannabinoid, CB2; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Tartrate-Resistant Acid Phosphatase; TRPV Cation Channels

Through researching the relationship among osteoporosis and inflammatory reaction besides angiogenesis, to compare pharmacological differences between icariin and genistein to inhibit bone loss.. 6 months old female SD rats were randomly divided into SHAM group, model group, ICA group, GEN group and E group. The bone mineral density of total, femur and lumbar, serum OC, TRACP 5b, IL-6 and VEGF, biomechanics of femur and tibia microarchitecture were analyzed.. Compared with SHAM group, model group of body weight, uterine weight, bone mineral density of total, femur and lumbar, serum OC, TRACP 5b, IL-6 and VEGF, biomechanics of femur and lumbar and tibia microarchitecture were significantly changed (P < 0.05). Compared with model group, ICA group of body weight, bone mineral density of total and femur, serum TRACP 5b and femural biomechanics were significantly changed (P < 0.05). GEN group of bone mineral density of total, femur and lumbar, serum OC, TRACP 5b, IL-6 and VEGF, biomechanics of femur and lumbar and tibia microarchitecture were significantly changed (P < 0.05).. Icariin inhibits bone loss on model rat through suppressing bone resorption. Genistein prevents bone loss on model rat by the pathway of inhibiting inflammatory reaction, activating angiogenesis, enhancing bone formation and inhibiting bone resorption. Moreover, pharmacological activity of genistein is more potential than icariin.

Topics: Acid Phosphatase; Administration, Oral; Angiogenesis Inducing Agents; Animals; Anti-Inflammatory Agents; Bone and Bones; Bone Density; Bone Density Conservation Agents; Bone Resorption; Epimedium; Fabaceae; Female; Flavonoids; Genistein; Interleukin-6; Isoenzymes; Osteocalcin; Osteoporosis; Ovariectomy; Random Allocation; Rats; Rats, Sprague-Dawley; Tartrate-Resistant Acid Phosphatase; Vascular Endothelial Growth Factor A

Isoflavones are naturally occurring plant chemicals belonging to the "phytoestrogen" class. The aim of the present study was to examine the effects of isoflavones obtained from Cordyceps sinensis (CSIF) on development of estrogen deficiency-induced osteoporosis in ovariectomized rats.. After the rats were treated orally with CSIF, serum alkaline phosphatase (ALP), tartarate resistant acid phosphatase (TRAP), serum osteocalcin (OC), homocysteine (HCY), C-terminal crosslinked telopeptides of collagen type I (CTX), estradiol and interferonγ (IFN-γ) level were examined. At the same time, the urine calcium, plasma calcium, plasma phosphorus and the mass of uterus, thymus and body were also examined.. The beneficial effects of CSIF on improvement of osteoporosis in rats were attributable mainly to decrease ALP activity, TRAP activity, CTX level and IFN-γ level. At the same time, CSIF also increase the OC and estradiol level in ovariectomized osteopenic rats. The histological examination clearly showed that dietary CSIF can prevent bone loss caused by estrogen deficiency.. The significant estrogenic activity of CSIF demonstrated that CSIF has significant estrogenic effects in OVX rats.

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Biological Products; Bone Density Conservation Agents; Bone Diseases, Metabolic; Collagen Type I; Cordyceps; Estradiol; Estrogens; Female; Humans; Interferon-gamma; Isoflavones; Osteocalcin; Osteoporosis; Ovariectomy; Phosphorus; Phytoestrogens; Phytotherapy; Rats; Rats, Wistar; Uterus

In response to various stresses including viral infection, nutrient deprivation, and stress to the endoplasmic reticulum, eukaryotic translation initiation factor 2 alpha (eIF2α) is phosphorylated to cope with stress induced apoptosis. Although bone cells are sensitive to environmental stresses that alter the phosphorylation level of eIF2α, little is known about the role of eIF2α mediated signaling during the development of bone-resorbing osteoclasts. Using two chemical agents (salubrinal and guanabenz) that selectively inhibit de-phosphorylation of eIF2α, we evaluated the effects of phosphorylation of eIF2α on osteoclastogenesis of RAW264.7 pre-osteoclasts as well as development of MC3T3 E1 osteoblast-like cells. The result showed that salubrinal and guanabenz stimulated matrix deposition of osteoblasts through upregulation of activating transcription factor 4 (ATF4). The result also revealed that these agents reduced expression of the nuclear factor of activated T cells c1 (NFATc1) and inhibited differentiation of RAW264.7 cells to multi-nucleated osteoclasts. Partial silencing of eIF2α with RNA interference reduced suppression of salubrinal/guanabenz-driven downregulation of NFATc1. Collectively, we demonstrated that the elevated phosphorylation level of eIF2α not only stimulates osteoblastogenesis but also inhibit osteoclastogenesis through regulation of ATF4 and NFATc1. The results suggest that eIF2α-mediated signaling might provide a novel therapeutic target for preventing bone loss in osteoporosis.

Topics: Acid Phosphatase; Activating Transcription Factor 4; Animals; Cells, Cultured; Cinnamates; Down-Regulation; Eukaryotic Initiation Factor-2; Genes, fos; Guanabenz; Isoenzymes; Mice; NFATC Transcription Factors; Osteoblasts; Osteocalcin; Osteoclasts; Osteogenesis; Osteoporosis; Phosphorylation; Receptors, Cell Surface; RNA, Messenger; Tartrate-Resistant Acid Phosphatase; Thiourea

Coenzyme Q10 (CoQ10), a powerful antioxidant, is a key component in mitochondrial bioenergy transfer, generating energy in the form of ATP. Many studies suggest that antioxidants act as inhibitors of osteoclastogenesis and we also have previously demonstrated the inhibitory effect of CoQ10 on osteoclast differentiation. Despite the significance of this effect, the molecular mechanism when CoQ10 is present at high concentrations in bone remodeling still remains to be elucidated. In this study, we investigated the inhibitory effect of CoQ10 on osteoclastogenesis and its impact on osteoblastogenesis at concentrations ranging from 10 to 100 μM. We found that nontoxic CoQ10 markedly attenuated the formation of receptor activator of nuclear factor κB ligand (RANKL)-induced tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells in both bone-marrow-derived monocytes (BMMs) and RAW 264.7 cells. Osteoclastogenesis with CoQ10 was significantly suppressed the gene expression of NFATc1, TRAP, and osteoclast-associated immunoglobulin-like receptor, which are genetic markers of osteoclast differentiation and scavenged intracellular reactive oxygen species, an osteoclast precursor, in a dose-dependent manner. Furthermore, CoQ10 strongly suppressed H2 O2 -induced IκBα, p38 signaling pathways for osteoclastogenesis. In bone formation study, CoQ10 acted to enhance the induction of osteoblastogenic biomarkers including alkaline phosphatase, type 1 collagen, bone sialoprotein, osteoblast-specific transcription factor Osterix, and Runt-related transcription factor 2 and, also promoted matrix mineralization by enhancing bone nodule formation in a dose-dependent manner. Together, CoQ10 acts as an inhibitor of RANKL-induced osteoclast differentiation and an enhancer of bone-forming osteoblast differentiation. These findings highlight the potential therapeutic applications of CoQ10 for the treatment of bone disease.

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Bone Marrow Cells; Bone Regeneration; Bone Resorption; CD40 Antigens; Cell Differentiation; Cell Line, Tumor; Core Binding Factor Alpha 1 Subunit; Gene Expression Regulation; Hydrogen Peroxide; I-kappa B Proteins; Isoenzymes; Mice; Monocytes; NF-KappaB Inhibitor alpha; NFATC Transcription Factors; Osteoblasts; Osteoclasts; Osteoporosis; p38 Mitogen-Activated Protein Kinases; RANK Ligand; Reactive Oxygen Species; Signal Transduction; Sp7 Transcription Factor; Tartrate-Resistant Acid Phosphatase; Transcription Factors; Ubiquinone

Reduced bone mineral density and hip fracture are frequently observed in patients with Alzheimer's disease (AD). However, mechanisms underlying their association remain poorly understood. Amyloid precursor protein (APP) is a transmembrane protein that is ubiquitously expressed in bone marrow stromal cells (BMSCs), osteoblasts (OBs), macrophages (BMMs), and osteoclasts (OCs). Mutations in the APP gene identified in early-onset AD patients are believed to cause AD. But little is known about APP's role in bone remodeling. Here, we present evidence for Swedish mutant APP (APPswe) in suppression of OB differentiation and function in culture and in mouse. APP expression in BMSCs increases during aging. Ubiquitous expression of APPswe in young adult Tg2576 transgenic mice (under the control of a prion promoter) recaptured skeletal "aging-like" deficits, including decreased OB genesis and bone formation, increased adipogenesis and bone marrow fat, and enhanced OC genesis and bone resorption. Remarkably, selective expression of APPswe in mature OB-lineage cells in TgAPPswe-Ocn mice (under the control of osteocalcin [Ocn] promoter-driven Cre) also decreased OB genesis and increased OC formation, resulting in a trabecular bone loss. These results thus suggest a cell-autonomous role for APPswe in suppressing OB formation and function, but a nonautonomous effect on OC genesis. Notably, increased adipogenesis and elevated bone marrow fat were detected in young adult Tg2576 mice, but not in TgAPPswe-Ocn mice, implying that APPswe in BMSCs and/or multicell types in bone marrow promotes bone marrow adipogenesis. Intriguingly, the skeletal aging-like deficits in young adult Tg2576 mice were prevented by treatment with N-acetyl-L-cysteine (NAC), an antioxidant, suggesting that reactive oxygen species (ROS) may underlie APPswe-induced osteoporotic deficits. Taken together, these results demonstrate a role for APPswe in suppressing OB differentiation and bone formation, implicate APPswe as a detrimental factor for AD-associated osteoporotic deficit, and reveal a potential clinical value of NAC in the treatment of osteoporotic deficits. © 2013 American Society for Bone and Mineral Research.

Topics: Acetylcysteine; Acid Phosphatase; Adipogenesis; Aging; Amyloid beta-Peptides; Animals; Animals, Newborn; Bone and Bones; Bone Resorption; Cell Differentiation; Cell Lineage; Cells, Cultured; Cricetinae; Humans; Isoenzymes; Mesenchymal Stem Cells; Mice; Mice, Inbred C57BL; Mice, Transgenic; Mutation; Organ Size; Osteoblasts; Osteogenesis; Osteoporosis; Tartrate-Resistant Acid Phosphatase

Bone integrity abnormality and imbalance between bone formation by osteoblasts and bone resorption by osteoclasts are known to result in metabolic bone diseases such as osteoporosis. Silymarin-rich milk thistle extract (MTE) and its component silibinin enhanced alkaline phosphatase activity of osteoblasts but reduced tartrate-resistant acid phosphatase (TRAP) activity of osteoclasts. The osteoprotective effects of MTE were comparable to those of estrogenic isoflavone. Low-dose combination of MTE and isoflavone had a pharmacological synergy that may be useful for osteogenic activity. This study attempted to reveal the suppressive effects of MTE on bone loss. C57BL/6 female mice were ovariectomized (OVX) as a model for postmenopausal osteopenia and orally administered 10 mg/kg MTE or silibinin for 8 weeks. The sham-operated mice served as estrogen controls. The treatment of ovariectomized mice with nontoxic MTE and silibinin improved femoral bone mineral density and serum receptor activator of nuclear factor- κB ligand/osteoprotegerin ratio, an index of osteoclastogenic stimulus. In addition, the administration of MTE or silibinin inhibited femoral bone loss induced by ovariectomy and suppressed femoral TRAP activity and cathepsin K induction responsible for osteoclastogenesis and bone resorption. Collectively, oral dosage of MTE containing silibinin in the preclinical setting is effective in preventing estrogen deficiency-induced bone loss.

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Cathepsin K; Chromatography, High Pressure Liquid; Estradiol; Estrogens; Female; Femur; Glycine max; Isoenzymes; Mice; Mice, Inbred C57BL; Organ Size; Osteoblasts; Osteoclasts; Osteogenesis; Osteoporosis; Ovariectomy; Phytotherapy; Plant Extracts; Silybin; Silybum marianum; Silymarin; Tartrate-Resistant Acid Phosphatase; Uterus

Intake of multivitamin preparations is very common in developed countries. However, excessive intake of vitamin A was associated with increased bone fragility. The aim of this study was to determine if chronic administration of the active metabolite of vitamin A all-trans-retinoic acid (ATRA) in slight excess is associated with changes of bone turnover and density in intact and castrated mice.. Three mo old male mice (C57B1/6) intact and castrated were injected intraperitonealy with 10 mg/kg/d of the ATRA or vehicle (control) once daily for 3 wk. The bone density, ash weights, calcium, and phosphorus content of the femur were measured. Plasma tartrate-resistant acid phosphatase (Tr-ACP) and serum bone alkaline phosphatase (B-ALP) were determined.. ATRA decreased bone density in both groups; however, this effect was more pronounced in castrated animals (1.487 ± 0.04 to 1,360 ± 0.05 g/cm(3)) than in intact mice (1.570 ± 0.03 to 1.510 ± 0.03 g/cm(3)). Bone density correlated with decreased B-ALP and increased Tr-ACP in ATRA-treated mice. ATRA treatment led to significantly lower thickness of cortical bone both in the intact and castrated animals.. Our results indicate that repeated administration of ATRA in slight excess leads to significant bone loss both in intact and castrated mice. This effect was more pronounced in testosterone-deficient animals. Testosterone deficiency as occurs following castration may sensitize the bone to resorption mediated by ATRA. Therefore, chronic vitamin A administration may be a risk factor for osteoporosis, especially in older and testosterone-depleted subjects.

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Bone Density; Calcium; Femur; Isoenzymes; Male; Mice; Mice, Inbred C57BL; Orchiectomy; Osteoporosis; Phosphorus; Risk Factors; Tartrate-Resistant Acid Phosphatase; Testosterone; Toxicity Tests; Tretinoin

To explore the risk factors of acute-phase response (APR) following the first-dose administration of zoledronic acid in the treatment of osteoporosis.. We reviewed the clinical data of the patients receiving the first use of zoledronic acid 5 mg treatment of osteoporosis from January 2009 to November 2012, and divided the patients into acute phase response group (APR+) and no response group (APR-). The age, body mass index (BMI), concomitant medications, comorbidities, laboratory parameters between the two groups were compared and analyzed.. A total of 178 patients were eligible for inclusion in the study, of which 108 patients experienced APR. In APR group, there were 80 (44. 9%) patients developed fever, 14 (9. 6%) chills, 48 (27.0%) musculoskeletal pain, 19 (10.7%) gastrointestinal symptoms, 10 (5.6%) headache and dizziness, 7 (3.9%) palpitation,and 3 (1.7%) rash. APR was more common in the patients with higher baseline tartrate-resistant acid phosphatase 5b (TRACP-5b) and new-onset vertebral compression fractures (new-onset VCF). Stepwise logistic regression showed that the odds ratio (OR) of APR in higher baseline TRACP-5b and new VCF was 3. 3 and 2. 5 respectively.. The first use of zoledronic acid in the treatment of osteoporosis appears high incidence of APR. High TRACP-5b levels and new vertebral fracture are risk factors for APR.

Topics: Acid Phosphatase; Acute-Phase Reaction; Aged; Diphosphonates; Female; Humans; Imidazoles; Isoenzymes; Male; Middle Aged; Osteoporosis; Risk Factors; Tartrate-Resistant Acid Phosphatase; Zoledronic Acid

Progressive bone mineral loss and increasing bone fragility are hallmarks of osteoporosis. A combination of minerals isolated from the red marine algae, Lithothamnion sp. was examined for ability to inhibit bone mineral loss in female mice maintained on either a standard rodent chow (control) diet or a high-fat western diet (HFWD) for 5, 12, and 18 months. At each time point, femora were subjected to μ-CT analysis and biomechanical testing. A subset of caudal vertebrae was also analyzed. Following this, individual elements were assessed in bones. Serum levels of the 5b isoform of tartrate-resistant acid phosphatase (TRAP) and procollagen type I propeptide (P1NP) were also measured. Trabecular bone loss occurred in both diets (evident as early as 5 months). Cortical bone increased through month 5 and then declined. Cortical bone loss was primarily in mice on the HFWD. Inclusion of the minerals in the diet reduced bone mineral loss in both diets and improved bone strength. Bone mineral density was also enhanced by these minerals. Of several cationic minerals known to be important to bone health, only strontium was significantly increased in bone tissue from animals fed the mineral diets, but the increase was large (5-10 fold). Serum levels of TRAP were consistently higher in mice receiving the minerals, but levels of P1NP were not. These data suggest that trace minerals derived from marine red algae may be used to prevent progressive bone mineral loss in conjunction with calcium. Mineral supplementation could find use as part of an osteoporosis-prevention strategy.

Topics: Acid Phosphatase; Animals; Bone Density; Dietary Supplements; Female; Isoenzymes; Mice; Minerals; Osteoporosis; Peptide Fragments; Procollagen; Rhodophyta; Tartrate-Resistant Acid Phosphatase

To explore the effect of combination of Epimedii Folium and Ligustri Lucidi Fructus on osteoporosis rats induced by retinoic acid.. Sixty three-month-old male Wistar rats were randomly divided into the normal control group, the model group, the Epimedii Folium group, the Ligustri Lucidi Fructus group, the combination group of Epimedii Folium and Ligustri Lucidi Fructus and the raloxifene group. The osteoporosis model was established through oral administration with retinoic acid for two weeks. Meanwhile, all of treatment groups were administered with corresponding drugs for three weeks. The contents of serum calcium (Ca), phosphorus (P), alkaline phosphatase (AKP) and tartrate-resistant acid phosphatase (StrACP) were detected, and the pathomorphological changes of femurs were observed.. The model control group showed much lower contents of serum Ca and P than the normal control group, but with significantly higher AKP and StrACP activity than the normal control group. The femoral head area showed reduced, narrow and sparse trabecular bones, with typical osteoporosis-like changes. Compared with the model control group, all of treated groups showed significant increase in Ca and P contents in serum, and down-regulate AKP and StrACP levels, while trabecular bones became more and wider, and densely interweaved as a reticular formation. Among them, the combination group showed the most significant effect.. Epimedii Folium and Ligustri Lucidi Fructus could effectively correct the abnormal bone metabolism and improve pathological conditions of bone tissues, so as to show the anti-osteoporosis effect. The combined application of the two drugs showed a better efficacy.

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Body Weight; Calcium; Drug Interactions; Drugs, Chinese Herbal; Epimedium; Femur; Isoenzymes; Ligustrum; Male; Osteoporosis; Phosphorus; Rats; Rats, Wistar; Tartrate-Resistant Acid Phosphatase; Tretinoin

Pulsed electromagnetic field (PEMF) has been shown to increase bone mineral density in osteoporosis patients and prevent bone loss in ovariectomized rats. But the mechanisms through which PEMF elicits these favorable biological responses are still not fully understood. Receptor activator of nuclear factor κB ligand (RANKL) and osteoprotegerin (OPG) are cytokines predominantly secreted by osteoblasts and play a central role in differentiation and functional activation of osteoclasts. The purpose of this study was to investigate the effects of PEMF on RANKL and OPG expression in ovariectomized rats. Thirty 3-month-old female Sprague-Dawley rats were randomly divided into three groups: sham-operated control (Sham), ovariectomy control (OVX), and ovariectomy with PEMF treatment (PEMF). After 12-week interventions, the results showed that PEMF increased serum 17β-estradiol level, reduced serum tartrate-resistant acid phosphatase level, increased bone mineral density, and inhibited deterioration of bone microarchitecture and strength in OVX rats. Furthermore, PEMF could suppress RANKL expression and improve OPG expression in bone marrow cells of OVX rats. In conclusion, this study suggests that PEMF can prevent ovariectomy-induced bone loss through regulating the expression of RANKL and OPG.

Topics: Absorptiometry, Photon; Acid Phosphatase; Animals; Biomarkers; Biomechanical Phenomena; Bone and Bones; Bone Density; Bone Marrow Cells; Disease Models, Animal; Down-Regulation; Electromagnetic Fields; Estradiol; Female; Isoenzymes; Osteoporosis; Osteoprotegerin; Ovariectomy; RANK Ligand; Rats; Rats, Sprague-Dawley; RNA, Messenger; Tartrate-Resistant Acid Phosphatase; Time Factors; Up-Regulation

To evaluate the roles or effects of oviductus ranae (OR) or oviductus ranae eggs (ORE) in preventing and treating postmenopausal osteoporosis.. In vivo experiment: Sixty female adult Wistar rats were randomly divided into 5 groups of 12. To provide an osteoporosis model 4 groups of rats were ovariectomized (OVX), with the 5th being sham operated. Medication commenced 7 days after the operation and lasted continuously for 12 weeks. Sham operated and OVX groups were given equivalent volumes of 5% Tween-80. The other three groups intragastrically received conjugated estrogens (CE), OR or ORE of the corresponding doses. At the 12th week, serum estrogen, bone gla protein (BGP), serum calcium, phosphorus, and alkaline phosphatase (ALP) were assayed; bone mineral densities (BMD) were measured and bone scanning was conducted; uteri were weighed, and weight, volume and length of the femoral bones were determined; and cortical thickness of femoral heads and area of bone trabecula were measured by image analyzer. In vitro experiment: Eighty 10-month old SD rats, with equal numbers of males and females, were randomly divided into 8 groups. Osteoblasts were isolated from neonatal rat calvariae, and the cells were exposed to various concentrations of serum from OR and ORE groups to study the impact of these sera on osteoblastic proliferation, ALP activity and mineralization. Osteoclastic numbers were determined using tartrate resistant acid phosphatase (TRAP).. In vivo experiment: The body weight of the four OVX groups increased significantly (P<0.01). Uterine weight of the CE group was the highest (P<0.01); Compared with the model group, estrogen level, BMD, bone scanning/bone imaging index weight of the femoral bones, cortical thickness of femoral heads in the OR and ORE groups increased significantly (P<0.05, P<0.01); femoral volume in the ORE group increased significantly (P<0.05); and the content of osteocalcin, phosphorus, and ALP in serum decreased significantly (P<0.05, P<0.01). In vitro experiment: Sera from OR and ORE groups had notable effects on the proliferation of osteoblasts (P<0.05 and P<0.01, repsectively) and stimulated the formation of calcium nodes (P<0.05, P<0.01), while the enhancement of ALP activity in osteoblasts was significant (P<0.05, P<0.01). The number of TRAP-positive cells was significantly reduced as well (P<0.01).. OR and its eggs could effectively suppress OVX-induced osteoporosis in rats, and increase bone turnover possibly by both an increase in osteoblastic activity and a decrease in osteoclastic activity. The present study provides evidence that OR and its eggs could be considered a complementary and alternative medicine for the treatment of postmenopausal osteoporosis.

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Biomarkers; Body Weight; Bone and Bones; Bone Density; Calcification, Physiologic; Cell Count; Cell Differentiation; Cell Proliferation; Female; Femur; Isoenzymes; Male; Materia Medica; Organ Size; Osteoblasts; Osteoclasts; Osteoporosis; Ovariectomy; Ovum; Rats; Rats, Wistar; Tartrate-Resistant Acid Phosphatase; Uterus

Osteoporosis is characterized by poor bone quality. However, it is still controversially discussed whether osteoporosis compromises fracture healing. Herein, we studied whether the course of healing of a femur fracture is affected by osteoporosis or age.. Using the senescence-accelerated osteoporotic mouse, strain P6 (SAMP6), and a closed femur fracture model, we studied the process of fracture healing in 5- and 10-month-old animals, including biomechanical, histomorphometric, and protein biochemical analysis.. In five-month-old osteoporotic SAMP6 mice, bending stiffness, callus size, and callus tissue distribution as well as the concentrations of the bone formation marker osteocalcin and the bone resorption markers tartrate-resistant acid phosphatase form 5b (TRAP) and deoxypyridinoline (DPD) did not differ from that of non-osteoporotic, senescence-resistant, strain 1 (SAMR1) controls. In contrast, femur fractures in 10-month-old SAMP6 mice showed a significantly reduced bending stiffness and an increased callus size compared to fractures in age-matched SAMR1 controls. This indicates a delayed fracture healing in advanced age SAMP6 mice. The delay of fracture healing was associated with higher concentrations of TRAP and DPD. Significant differences in osteocalcin concentrations were not found between SAMP6 animals and SAMR1 controls.. In conclusion, the present study indicates that fracture healing in osteoporotic SAMP6 mice is not affected in five-month-old animals, but delayed in animals with an age of 10 months. This is most probably due to the increased osteoclast activity in advanced age SAMP6 animals.

Topics: Acid Phosphatase; Aging; Amino Acids; Animals; Bone Resorption; Femoral Fractures; Fracture Healing; Fractures, Closed; Isoenzymes; Mice; Mice, Mutant Strains; Osteocalcin; Osteoclasts; Osteoporosis; Tartrate-Resistant Acid Phosphatase; Weight-Bearing

Serum preptin levels among subjects with different bone mineral densities (BMD) were measured and investigated to determine the correlation between BMD and bone-metabolic markers.. Approximately 52 elderly male patients with osteoporosis, 50 elderly men with osteopaenia, and 31 age-matched normal bone mass controls participated in the study. The serum preptin levels and bone metabolic markers were measured by enzyme-linked immunosorbent assay. The relationships between preptin levels, BMD, and metabolic parameters were also assessed.. The serum preptin level was the lowest in the osteoporosis group and positively correlated with BMD. All the bone formation markers in the osteoporosis and osteopaenia groups were significantly reduced compared with those in the normal group. Serum preptin level was positively correlated with all the bone formation markers, whereas no correlation was observed with the bone resorption marker TRACP-5b.. Serum preptin levels are decreased in osteoporosis and osteopaenia patients and positively correlated with BMD. Therefore, preptin is involved in the pathogenesis of osteoporosis, probably through bone formation rather than bone resorption.

Topics: Absorptiometry, Photon; Acid Phosphatase; Aged; Aged, 80 and over; Biomarkers; Bone Density; Bone Diseases, Metabolic; Case-Control Studies; Down-Regulation; Enzyme-Linked Immunosorbent Assay; Femur Neck; Hip Joint; Humans; Insulin-Like Growth Factor II; Isoenzymes; Linear Models; Lumbar Vertebrae; Male; Multivariate Analysis; Osteogenesis; Osteoporosis; Peptide Fragments; Tartrate-Resistant Acid Phosphatase

In men, idiopathic osteoporosis (IOP) is often associated with low serum insulin-like growth factor (IGF-1) and reduced bone formation. The characteristics of premenopausal women with IOP are not well defined. We aimed to define the clinical, reproductive, and biochemical characteristics of premenopausal women with unexplained osteoporosis.. This is a cross-sectional study of 64 women with unexplained osteoporosis, 45 with fragility fractures, 19 with low bone mineral density (BMD; Z-score less than or equal to -2.0) and 40 normal controls. The following are the main outcome measures: clinical and anthropometric characteristics, reproductive history, BMD, gonadal and calciotropic hormones, IGF-1, and bone turnover markers (BTMs).. Subjects had lower BMI and BMD than controls, but serum and urinary calcium, serum estradiol, vitamin D metabolites, IGF-1, and most BTMs were similar. Serum parathyroid hormone (PTH) and the resorption marker, tartrate-resistant acid phosphatase (TRAP5b), were significantly higher in both groups of subjects than controls and directly associated in all groups. Serum IGF-1 and all BTMs were directly associated in controls, but the association was not significant after controlling for age. There was no relationship between serum IGF-1 and BTMs in subjects. There were few differences between women with fractures and low BMD.. Higher serum TRAP5b and PTH suggest that increased bone turnover, possibly related to subclinical secondary hyperparathyroidism could contribute to the pathogenesis of IOP. The absence of differences between women with fractures and those with very low BMD indicates that this distinction may not be clinically useful to categorize young women with osteoporosis.

Topics: Absorptiometry, Photon; Acid Phosphatase; Adolescent; Adult; Anthropometry; Biomarkers; Body Mass Index; Bone Density; Bone Remodeling; Case-Control Studies; Cross-Sectional Studies; Diet; Female; Humans; Insulin-Like Growth Factor I; Isoenzymes; Middle Aged; Osteoporosis; Osteoporotic Fractures; Parathyroid Hormone; Premenopause; Reproductive History; Tartrate-Resistant Acid Phosphatase; Young Adult

Previous studies have shown that fracture healing depends on gender and that in females, ovariectomy-induced osteoporosis impairs the healing process. There is no information, however, whether the alteration of fracture healing in osteoporosis also depends on gender.. Therefore, we herein studied fracture healing in female and male senescence-accelerated osteoporotic mice, strain P6 (SAMP6), including biomechanical, histomorphometric, and protein biochemical analysis.. Bending stiffness was reduced in male and female SAMP6 mice compared with senescence-resistant strain 1 (SAMR1) controls. This was associated with elevated serum concentrations of tartrate-resistent acid phosphatase form 5b (TRAP) in both female and male SAMP6 mice. Callus size, however, was significantly larger in female SAMP6 mice compared with male SAMP6 mice and female SAMR1 controls. This indicates a delayed remodeling process in female SAMP6 mice. The delay of callus remodeling in female SAMP6 mice was associated with a significantly higher osteoprotegerin (OPG) callus tissue expression and increased serum concentrations of osteocalcin (OC) and deoxypyridinoline (DPD), indicating elevated osteoblast and osteoclast activities.. The present study shows that remodeling during fracture healing in female, but not in male, SAMP6 mice is delayed, most probably due to an increased osteoblast and osteoclast activity.

Topics: Acid Phosphatase; Aging; Amino Acids; Animals; Biomechanical Phenomena; Bone Remodeling; Bony Callus; Disease Models, Animal; Female; Fracture Healing; Isoenzymes; Male; Mice; Mice, Mutant Strains; Osteoblasts; Osteocalcin; Osteoclasts; Osteoporosis; Osteoprotegerin; Sex Characteristics; Tartrate-Resistant Acid Phosphatase

Type 1 diabetic osteoporosis results from impaired osteoblast activity and death. Therefore, anti-resorptive treatments may not effectively treat bone loss in this patient population. Intermittent parathyroid hormone (PTH) treatment stimulates bone remodeling and increases bone density in healthy subjects. However, PTH effects may be limited in patients with diseases that interfere with its signaling. Here, we examined the ability of 8 and 40 µg/kg intermittent PTH to counteract diabetic bone loss. PTH treatment reduced fat pad mass and blood glucose levels in non-diabetic PTH-treated mice, consistent with PTH-affecting glucose homeostasis. However, PTH treatment did not significantly affect general body parameters, including the blood glucose levels, of type 1 diabetic mice. We found that the high dose of PTH significantly increased tibial trabecular bone density parameters in control and diabetic mice, and the lower dose elevated trabecular bone parameters in diabetic mice. The increased bone density was due to increased mineral apposition and osteoblast surface, all of which are defective in type 1 diabetes. PTH treatment suppressed osteoblast apoptosis in diabetic bone, which could further contribute to the bone-enhancing effects. In addition, PTH treatment (40 µg/kg) reversed preexisting bone loss from diabetes. We conclude that intermittent PTH may increase type 1 diabetic trabecular bone volume through its anabolic effects on osteoblasts.

Topics: Acid Phosphatase; Animals; Bone Density; Bone Remodeling; Bone Resorption; Cell Survival; Diabetes Complications; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Humans; Isoenzymes; Male; Mice; Mice, Inbred BALB C; Osteoblasts; Osteogenesis; Osteoporosis; Parathyroid Hormone; RNA, Messenger; Tartrate-Resistant Acid Phosphatase

This study examined the efficacy of hydroalcoholic extract of dried clove buds, which is rich in phenolic compounds namely eugenol and eugenol derivatives (precursors of flavones, isoflavones and flavonoids), on different primary and secondary osteoporotic marker changes in an ovariectomised (OVX) rat model of osteoporosis. Female Wistar rats were randomly divided into three groups: sham-operated control (A), OVX (B) and OVX plus 50% hydroalcoholic extract of dried clove buds for 4 weeks (C). Results indicated that, compared to control, serum alkaline phosphatase (AP; 48.25%, p < 0.01), serum tartrate-resistant acid phosphatase (TRAP; 63.48%, p < 0.01), urinary calcium (14.70%, p < 0.01), urinary phosphate (50.30%, p < 0.01) and urinary creatinine (122.44%, p < 0.01) were significantly altered in OVX rats. All these altered responses were significantly restored (AP: 27.53%, p < 0.01; TRAP: 33.51%, p < 0.01; calcium: 53.15%, p < 0.01; phosphate: 27.49%, p < 0.01; creatinine: 46.40%, p < 0.01) by supplementation with hydroalcoholic extract of dried clove buds. Results of bone density, bone mineral content, bone tensile strength and histological analysis also showed similar trend of results, which supported initial observations of this study. It is proposed that hydroalcoholic extract of dried clove buds has bone-preserving efficacy against hypogonadal osteoporosis.

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Bone Density; Calcium; Clove Oil; Creatinine; Disease Models, Animal; Drug Evaluation, Preclinical; Eugenol; Female; Isoenzymes; Osteoporosis; Ovariectomy; Phosphates; Rats; Rats, Wistar; Tartrate-Resistant Acid Phosphatase; Tensile Strength; Tibia

This paper demonstrates the use of TissueQuant - an image analysis tool for quantification of color intensities which was developed for use in medical research where the stained biological specimen such as tissue or antigen needs to be quantified. TissueQuant provides facilities for user interaction to choose and quantify the color of interest and its shades. Gaussian weighting functions are used to provide a color score which quantifies how close the shade is to the user specified reference color. We describe two studies in medical research which use TissueQuant for quantification. The first study evaluated the effect of petroleum-ether extract of Cissus quadrangularis (CQ) on osteoporotic rats. It was found that the analysis results correlated well with the manual evaluation, p < 0.001. The second study evaluated the nerve morphometry and it was found that the adipose and non adipose tissue content was maximum in radial nerve among the five nerves studied.

Topics: Acid Phosphatase; Algorithms; Alkaline Phosphatase; Animals; Cissus; Color; Female; Humans; Image Processing, Computer-Assisted; Isoenzymes; Male; Osteoporosis; Peripheral Nerves; Phytotherapy; Plant Extracts; Rats; Rats, Wistar; Software; Software Design; Tartrate-Resistant Acid Phosphatase

Osteoclasts are macrophage-related bone resorbing cells of hematopoietic origin. Factors that regulate osteoclastogenesis are of great interest for investigating the pathology and treatment of bone diseases such as osteoporosis. In mammals, receptor activator of NF-κB ligand (Rankl) is a regulator of osteoclast formation and activation: its misexpression causes osteoclast stimulation and osteoporotic bone loss. Here, we report an osteoporotic phenotype that is induced by overexpression of Rankl in the medaka model. We generated transgenic medaka lines that express GFP under control of the cathepsin K promoter in osteoclasts starting at 12 days post-fertilization (dpf), or Rankl together with CFP under control of a bi-directional heat-shock promoter. Using long-term confocal time-lapse imaging of double and triple transgenic larvae, we monitored in vivo formation and activation of osteoclasts, as well as their interaction with osteoblasts. Upon Rankl induction, GFP-positive osteoclasts are first observed in the intervertebral regions and then quickly migrate to the surface of mineralized neural and haemal arches, as well as to the centra of the vertebral bodies. These osteoclasts are TRAP (tartrate-resistant acid phosphatase) and cathepsin K positive, mononuclear and highly mobile with dynamically extending protrusions. They are exclusively found in tight contact with mineralized matrix. Rankl-induced osteoclast formation resulted in severe degradation of the mineralized matrix in vertebral bodies and arches. In conclusion, our in vivo imaging approach confirms a conserved role of Rankl in osteoclastogenesis in teleost fish and provides new insight into the cellular interactions during bone resorption in an animal model that is useful for genetic and chemical screening.

Topics: Acid Phosphatase; Animals; Animals, Genetically Modified; Bone Resorption; Cathepsin K; Green Fluorescent Proteins; Isoenzymes; Microscopy, Confocal; Oryzias; Osteoclasts; Osteoporosis; Promoter Regions, Genetic; RANK Ligand; Tartrate-Resistant Acid Phosphatase; Time-Lapse Imaging

Previous studies have demonstrated the dual effects of strontium ranelate (SR) on osteoporotic and undisturbed bone. However, reports of its effect on titanium implant osseointegration in osteoporotic bodies were limited. This study was designed to investigate the effects of SR on osseointegration of titanium implant in ovariectomized rats.. Twelve weeks after bilateral ovariectomy in female Sprague-Dawley rats, each animal received two titanium implants in the distal metaphysis of femur. All rats were then randomly divided into two groups: Control and SR (625 mg/kg/day). Twelve weeks after implantation, serum levels of osteocalcin (OCN) and tartrate-resistant acid phosphatase (TRAP) 5b, implant osseointegration and peri-implant trabecular microarchitecture were analyzed by histomorphometry, micro-computerized tomography (micro-CT), and biomechanical test.. Compared with control, SR treatment increased serum levels of OCN by 29.2%, and decreased the levels of TRAP 5b by 25.5% in serum analysis; SR treatment increased percent bone volume by 63.1% and percent osseointegration by 48.3% in micro-CT assessment, and increased bone area density by 55.6% and bone-to-implant contact by 49.0% in histomorphometry; SR treatment also increased the maximal push-out force by 117.7% and the ultimate shear strength by 103.5% in push-out test.. Strontium ranelate treatment could improve titanium implant osseointegration in osteoporotic rats.

Topics: Acid Phosphatase; Animals; Biomechanical Phenomena; Bone Density Conservation Agents; Coated Materials, Biocompatible; Female; Femur; Isoenzymes; Microscopy, Electron, Scanning; Organometallic Compounds; Osseointegration; Osteocalcin; Osteoporosis; Ovariectomy; Prosthesis Implantation; Rats; Rats, Sprague-Dawley; Tartrate-Resistant Acid Phosphatase; Thiophenes; Titanium; X-Ray Microtomography

The prophylactic effects of Hijikia fusiforme on bone metabolism were examined using in vitro indices of bone formation and resorption. As the indices of bone formation, osteoblast proliferation and differentiation were measured through mitochondrial enzyme activity [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay] and bone marker alkaline phosphatase (ALP) activity. The aqueous extract of H. fusiforme stimulated the proliferation of the human osteoblast-like cell line MG63 and the ALP activity of the mouse osteoblast-like cell line MC3T3-E1. Moreover, extracellular matrix mineralization was accelerated by the addition of H. fusiforme. As the indices of bone resorption, differentiation of the murine macrophage/osteoclast precursor cell line RAW 264.7 by receptor activator of nuclear factor-κB ligand (RANKL) was measured as tartrate-resistant acid phosphatase-positive multinucleated cells, which were suppressed by H. fusiforme. Additionally, H. fusiforme lowered the secreted amount of RANKL that is required for the osteoclastic differentiation and activation, but the amount of osteoprotegerin as a decoy receptor for RANKL was not affected. The bone-protective effects of H. fusiforme in estrogen-deficient ovariectomized rats were also investigated. Osteoporosis was induced in female Sprague-Dawley rats by ovariectomy for 15 weeks, and then H. fusiforme was orally administered at a dose of 100  mg/kg of body weight every day for 6 weeks. Bone mineral density in the group orally administered H. fusiforme was increased, compared with ovariectomized rats, but not significantly (P>.05). Oral administration of H. fusiforme improved microarchitecture of bone in terms of bone volume (bone volume/total volume ratio) and trabecular separation (P<.05). The amounts of osteocalcin and C-telopeptide type I collagen in serum were measured as the biomarkers for bone formation and resorption. The level of osteocalcin in serum was increased, but not significantly. However, the level of C-telopeptide type I collagen in serum was significantly decreased (P<.05). When the results are taken together, the present study indicates that H. fusiforme might be useful in the treatment of osteoporosis.

Topics: Acid Phosphatase; Administration, Oral; Alkaline Phosphatase; Animals; Biomarkers; Bone Density; Bone Resorption; Cell Differentiation; Cell Line; Cell Proliferation; Collagen Type I; Female; Humans; Isoenzymes; Mice; Osteocalcin; Osteoclasts; Osteogenesis; Osteoporosis; Ovariectomy; Peptides; Phaeophyceae; RANK Ligand; Rats; Rats, Sprague-Dawley; Tartrate-Resistant Acid Phosphatase; Tetrazolium Salts; Thiazoles

Hachimi-jio-gan is one of the most common recipes in traditional Chinese, Japanese and Korean medicines and has been used for preventing and treating various diseases associated with aging, including osteoporosis.. The present study was performed to examine the combined effects of a traditional Chinese medicine, Hachimi-jio-gan (HJG) and antiresorptive agent, alendronate (ALN) on ovariectomy-induced bone loss in rats.. Six-month-old female Sprague-Dawley rats were underwent ovariectomy (OVX) or sham operation. Eight weeks later, the OVX rats were treated either with HJG or ALN alone or in combination of both. The skeletal response was evaluated using micro-computed tomography (micro-CT), image analysis software, and biochemical markers.. This study demonstrated that treatment with HJG or ALN alone increased trabecular bone volume and bone mineral density (BMD), and partially improved bone microstructure of the proximal tibia and vertebra in OVX rats. Treatment with ALN to OVX rats resulted in significant reduction in both bone resorption and bone formation. Treatment with HJG to OVX rats inhibited bone resorption, with no marked effects on bone formation. Combined treatment of HJG and ALN significantly improved trabecular bone mass and bone microstructure, compared with either agent alone.. We conclude that the combined treatment with HJG and ALN has beneficial effects on trabecular bone mass, improving the structural properties of both tibia and vertebra in OVX rats.

Topics: Acid Phosphatase; Alendronate; Animals; Bone Density Conservation Agents; Drug Therapy, Combination; Drugs, Chinese Herbal; Female; Isoenzymes; Lumbar Vertebrae; Medicine, Chinese Traditional; Osteocalcin; Osteogenesis; Osteoporosis; Ovariectomy; Rats; Rats, Sprague-Dawley; Tartrate-Resistant Acid Phosphatase; Tibia

Various markers of bone turnover are already under clinical use in Japan, and mostly for clinical investigation in some countries. Standard values including ranges and variations are summarized in the previous edition of the guideline. The information of additional new markers adapted by government is summarized including clinical features in the new edition 2012. Among the new markers, the methods for measurement for TRACP-5b and ucOC are developed in Japan. As P1NP and TRACP-5b levels are not affected by meals, biological variations are smaller compared with other markers. ucOC is unique because it is to evaluate vitamin K insufficiency for bone. New bone markers adapted in the Japanese guideline 2012 will facilitate clinicians to utilize of metabolic markers of bone for osteoporosis treatment.

Topics: Acid Phosphatase; Biomarkers; Bone and Bones; Humans; Isoenzymes; Japan; Osteocalcin; Osteoporosis; Practice Guidelines as Topic; Tartrate-Resistant Acid Phosphatase

In osteoprotegerin-deficient (OPG-/-) mice, osteoclast activity causes bone resorption to outpace bone formation, leading to the development of severe osteoporosis. Such mice are therefore useful for investigating the alveolar bone of patients with osteoporosis. Reveromycin A (RM-A) was recently identified as the unique agent acting on osteoclast activation. This study aimed to analyze the effect of RM-A on the orthodontic treatment of OPG-/- mice (a model of osteoporosis patients with high levels of bone turnover). We examined alveolar bone remodeling in OPG-/- and wild-type (WT) mice during continuous tooth movement. The orthodontic force was induced by means of a Ni-Ti closed-coil spring to move the maxillary first molar for 14 days. RM-A sodium salt (1 mg/kg) was administered intraperitoneally twice daily. In OPG-/- mice, the tooth movement distance was longer, alveolar bone resorption was enhanced, the osteoclast count was greater, and serum alkaline phosphatase and tartrate-resistant acid phosphatase levels were higher relative to those in WT mice. However, the administration of RM-A in OPG-/- mice reduced these parameters. We conclude that RM-A normalizes bone metabolism and loss of alveolar bone during continuous tooth movement in OPG-/- mice.

Topics: Acid Phosphatase; Alkaline Phosphatase; Alveolar Process; Animals; Biomarkers; Bone Density Conservation Agents; Bone Remodeling; Bone Resorption; Cell Count; Dental Alloys; Disease Models, Animal; Injections, Intraperitoneal; Isoenzymes; Male; Maxilla; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Mice, Knockout; Mutation; Nickel; Orthodontic Wires; Osteitis Deformans; Osteoclasts; Osteoporosis; Osteoprotegerin; Pyrans; Spiro Compounds; Tartrate-Resistant Acid Phosphatase; Titanium; Tooth Movement Techniques; X-Ray Microtomography

Puerarin, a daidzein-8-C glucoside, is the major isoflavonoid in Kudzu (Pueraria lobata), and is unique in that it contains C-C conjugated glucose at position 8 of the isoflavonoid structure. A puerarin diet at a dose of 5 mg/kg b.w./d to fed ovariectomized mice for 2 mo diminished the urinary deoxypyridinoline, a typical bone-degradation product. Since the bone absorption marker, serum tartarate-resistant acid phosphatase (TRAP) activity of puerarin-fed mice decreased but the bone formation marker, osteocalcin level, did not alter, the puerarin diet was proved to specifically depress the bone absorption, but not the overall bone metabolism. In accordance with that results, the femur structure of puerarin-fed mice was restored compared with that of puerarin-free diet mice. The atrophied uterine due to low estrogen (E2) level after ovariectomy was not restored by the puerarin diet, suggesting that puerarin exerted the anti-osteoporotic action through a non estrogen receptor (ER) mediated-pathway, in vivo. The growth of an ER-positive human breast cancer cell, MCF-70, was not enhanced by puerarin, suggesting that puerarin did not show estrogen-like action on MCF-7 cells, even at a ten thousand times higher concentration than that of E2. Furthermore, ICI182,780 (ICI), an estrogen antagonist, suppressed the enhanced growth of MCF-7 cells by E2, but not that by puerarin. In an ER-binding assay, puerarin was proved not to bind to ERα or β, or if all, extremely weakly, although daidzein, an aglycon of puerarin, showed a little stronger binding compared with puerarin. All these results strongly indicate that puerarin exerts its anti-osteoprotic action independently of the ER-mediated pathway.

Topics: Acid Phosphatase; Amino Acids; Animals; Breast Neoplasms; Cell Proliferation; Diet; Estradiol; Female; Fulvestrant; Humans; Isoflavones; MCF-7 Cells; Mice; Osteocalcin; Osteoporosis; Ovariectomy; Pueraria; Receptors, Estrogen

Purple acid phosphatases are metalloenzymes found in animals, plants and fungi. They possess a binuclear metal centre to catalyse the hydrolysis of phosphate esters and anhydrides under acidic conditions. In humans, elevated purple acid phosphatases levels in sera are correlated with the progression of osteoporosis and metabolic bone malignancies, making this enzyme a target for the development of new chemotherapeutics to treat bone-related illnesses. To date, little progress has been achieved towards the design of specific and potent inhibitors of this enzyme that have drug-like properties. Here, we have undertaken a fragment-based screening approach using a 500-compound library identifying three inhibitors of purple acid phosphatases with K(i) values in the 30-60 μm range. Ligand efficiency values are 0.39-0.44 kcal/mol per heavy atom. X-ray crystal structures of these compounds in complex with a plant purple acid phosphatases (2.3-2.7 Å resolution) have been determined and show that all bind in the active site within contact of the binuclear centre. For one of these compounds, the phenyl ring is positioned within 3.5 Å of the binuclear centre. Docking simulations indicate that the three compounds fit into the active site of human purple acid phosphatases. These studies open the way to the design of more potent and selective inhibitors of purple acid phosphatases that can be tested as anti-osteoporotic drug leads.

Topics: Acid Phosphatase; Amino Acid Sequence; Animals; Catalytic Domain; Crystallography, X-Ray; Drug Design; Enzyme Inhibitors; Glycoproteins; Humans; Molecular Docking Simulation; Molecular Sequence Data; Osteoporosis; Phaseolus; Swine

Insufficient sleep over long durations of the lifespan is believed to adversely affect proper development and healthful aging, although how this might become manifested is unknown. In the present study, rats were repeatedly sleep-restricted during 72 days to permit maladaptations to evolve, thereby permitting study. Densitometric and histomorphometric analyses were performed on harvested bone. In sleep-restricted rats, bone lined by osteoid was reduced 45-fold and osteoid thickness was decreased, compared with controls. This corresponded to a decrease in osteoblast number and activity. The percentage of bone lined by osteoclasts did not differ from that of controls. Plasma concentrations of an osteoclast marker (TRACP 5b) were increased in sleep-restricted rats, indicating increased bone resorption. The low amount of new bone formation without a reduction in bone resorption is diagnostic of osteopenia. Bone mineral density was decreased in femurs from sleep-restricted rats compared with controls, indicating osteoporosis. Red marrow in sleep-restricted rats contained only 37% of the fat and more than twice the number of megakaryocytes compared with that of the control rats. These findings in marrow suggest changed plasticity and increased hematopoiesis. Plasma concentrations of insulin-like growth factor-1, a known, major mediator of osteoblast differentiation and the proliferation of progenitor cells, was decreased by 30% in sleep-restricted rats. Taken together, these findings suggest that chronically inadequate sleep affects bone metabolism and bone marrow composition in ways that have implications for development, aging, bone healing and repair, and blood cell differentiation.

Topics: Acid Phosphatase; Animals; Bone and Bones; Bone Density; Bone Development; Bone Diseases, Metabolic; Bone Marrow; Bone Marrow Cells; Bone Resorption; Cell Proliferation; Hematopoiesis; Insulin-Like Growth Factor I; Isoenzymes; Megakaryocytes; Osteoblasts; Osteoclasts; Osteoporosis; Rats; Rats, Sprague-Dawley; Sleep Deprivation; Tartrate-Resistant Acid Phosphatase

The goal was to find out the clinical significances of tartrate-resistant acid phosphatase isoform 5b (TRACP 5b), a biomarker of bone resorption, and bone alkaline phosphatase (BAP) and osteocalcin, two markers of bone formation, in evaluating the osteoporotic fracture risk in Chinese patients.. Thirty six Chinese osteoporotic fracture patients and 32 Chinese healthy subjects were included in the study. Bone mineral density (BMD) of lumbar spine and total body were determined by dual-energy X-ray absorptiometry in all subjects. Fasting blood samples were collected from all subjects and the serum concentrations of TRACP 5b, BAP, and osteocalcin were analyzed with enzyme-linked immunosorbent assay or immunoradiometric assay.. With lower BMD, the osteoporotic fracture patients had elevated levels of TRACP 5b and BAP, compared with the healthy controls. No difference in serum osteocalcin level was observed between the fracture patients and the control.. Elevated serum TRACP 5b and BAP, combined with or without increased osteocalcin, are valuable tools for the assessment of osteoporotic fracture risk in Chinese patients.

Topics: Absorptiometry, Photon; Acid Phosphatase; Aged; Aged, 80 and over; Alkaline Phosphatase; Bone and Bones; Bone Density; China; Female; Fractures, Bone; Humans; Isoenzymes; Male; Middle Aged; Osteocalcin; Osteoporosis; Tartrate-Resistant Acid Phosphatase

Soy with its isoflavones has been shown to positively influence bone mineral density in female ovariectomized rats; hence, we hypothesized a similar effect in orchidectomized (ORX) male rats. Forty male Sprague-Dawley rats, aged 95 days, were divided into 4 groups and were either sham operated (Sham) or ORX. The ORX groups were fed a soy protein-based diet (SOY), an isoflavone-depleted soy protein diet (SOY-), or a casein based diet for 65 days after surgery. Orchidectomy increased the rate of bone turnover, resulting in reduced bone mineral density and bone mineral content by 3.5% and 14%, respectively, and compromised biomechanical properties. The mean femoral length of ORX animals was also significantly shorter than Sham animals, but ORX rats that were fed SOY diet did not experience this reduction in bone length, implicating a role for soy protein in bone growth (4.02 ± 0.02, 3.93 ± 0.01, 3.99 ± 0.02, 3.91 ± 0.01 for Sham, ORX, SOY, SOY-, respectively). The SOY and SOY- positively influenced the biomechanical properties of bone such as yield and ultimate force, the measures of bone elasticity, and plasticity. In terms of bone histomorphometry, the data indicate that SOY- tends to reduce ORX-induced increase in bone turnover as evidenced by suppressed bone formation rate/mineralized surface by about 9%. Overall, our results indicated that soy protein, regardless of its isoflavone content, was unable to prevent the ORX-induced femoral decrease in bone density and mineral content. However, soy may enhance the quality of bone as indicated by increased yield force.

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Bone Density; Caseins; Disease Models, Animal; Energy Intake; Glycine max; Gonadal Hormones; Isoenzymes; Isoflavones; Male; Orchiectomy; Osteoporosis; Rats; Rats, Sprague-Dawley; Soybean Proteins; Tartrate-Resistant Acid Phosphatase

Our cross-sectional analysis of 1,576 men aged ≥65 years examined smoking effects on bone status. Number of smoking years was associated with decreased bone mineral density (BMD), after adjusting for age, height, weight, and number of cigarettes smoked daily. Smoking did not affect biochemical marker serum values for bone turnover.. The impact of smoking on bone status in men has not been conclusively established. We examined how smoking and its cessation influence bone status and metabolism in men.. We analyzed 1,576 men among a baseline survey of Japanese men aged ≥65 years, the Fujiwara-kyo Osteoporosis Risk in Men study, conducted during 2007-2008.. Lumbar spine (LS) BMD values among never, former, and current smokers were 1.045 ± 0.194, 1.030 ± 0.189, and 1.001 ± 0.182 g/cm(2) (P = 0.005), respectively, while total hip (TH) BMD values were 0.888 ± 0.120, 0.885 ± 0.127, and 0.870 ± 0.124 (P = 0.078), respectively. The significant trend for LS BMD remained after adjusting for the covariates; age, height, weight, physical activity, milk consumption, and drinking habit (P = 0.036). Among never and ever (current and former) smokers, LS and TH BMD decreased with the number of pack years or the number of smoking years, respectively, adjusted for those covariates. Among ever smokers, LS and TH BMD decreased with the number of smoking years after adjusting for age, height, weight, and number of cigarettes smoked daily. Smoking did not reveal significant effect for serum osteocalcin or tartrate resistant acid phosphatase isoenzyme 5b.. The impact of smoking on bone status is mainly associated with the number of smoking years in elderly men.

Topics: Acid Phosphatase; Aged; Biomarkers; Bone and Bones; Bone Density; Cross-Sectional Studies; Hip Joint; Humans; Isoenzymes; Lumbar Vertebrae; Male; Osteocalcin; Osteoporosis; Smoking; Smoking Cessation; Tartrate-Resistant Acid Phosphatase

The purpose of this study is to investigate the dose-dependent effects of SWH on bone properties and the mechanism involved in mediating the osteoprotective actions of SWH. The results indicated that SWH could improve bone properties by inhibiting the process of bone resorption and stimulating the process of bone formation.. Our previous study showed that Sambucus williamsii HANCE (SWH) improved trabecular bone mass and cortical bone strength in ovariectomized (OVX) rats. The purpose of this study is to investigate the dose-dependent effects of SWH on bone properties and the mechanism involved in mediating the osteoprotective actions of SWH.. Three-month-old C57BL/6J mice were fed a phytoestrogen-free diet and subjected to either ovariectomy or sham operation. OVX mice were treated with genistein (50 mg/kg), or a low (200 mg/kg), medium (500 mg/kg), or high (1,000 mg/kg) dose of SWH extract.. SWH could dose-dependently decrease urinary Ca excretion and increase serum Ca level in OVX mice. It could increase tibial bone mineral density and exert beneficial effects on the microarchitecture of trabecular bone in the OVX mice. SWH suppressed the ovariectomy-induced expression of Cbfa1 mRNA and cathepsin K mRNA and enhanced the ratio of OPG/RANKL mRNA expression in the tibia. In vitro study showed that SWH dramatically reduced the number of TRAP-positive cells in RANKL-induced RAW 264.7 cells.. The present study indicated that SWH could improve bone properties by inhibiting the process of bone resorption and stimulating the process of bone formation.

Topics: Acid Phosphatase; Animals; Bone Density; Bone Resorption; Calcium; Case-Control Studies; Cathepsin K; Cell Line; Core Binding Factor Alpha 1 Subunit; Eye Proteins; Female; Hindlimb; Homeodomain Proteins; Isoenzymes; Mice; Mice, Inbred C57BL; Osteoporosis; Osteoprotegerin; Ovariectomy; Plant Extracts; RANK Ligand; Sambucus; Tartrate-Resistant Acid Phosphatase; Tibia; Transcription Factors; Treatment Outcome

Despite the clinical adoption of distraction osteogenesis (DO), studies examining the bone healing process at the distraction gap in osteoporotic bone are limited. We examined the effect of osteoporosis in the ovariectomized rat on DO.. Mid-diaphyseal osteotomies were performed on the femurs of ovariectomized (OVX) rats. External distractors were placed on these rats and also on sham-ovariectomized rats. After a 7-day latency period, distraction was carried out at a rate of 0.5mm/day for 10 days. The bone volume (BV) of the distraction gap was measured by Micro-focused X-ray computed tomography (micro-CT) at 0, 2, and 4 weeks after completion of the distraction, and the distraction gap was examined histologically.. The BV of the distraction gap in the OVX group was significantly lower than that in the sham group at 2 and 4 weeks after completion of distraction (p<0.01). On histological examination, the distraction gap in the OVX group was filled with scattered smaller bone trabeculae than those seen in the sham group at 4 weeks after completion of distraction. Osteoclast numbers at the distraction gap in the OVX group were significantly increased when compared to the sham group (p<0.01).. Bone turnover with osteoclast predominance in ovariectomized rats is likely to be the cause of a reduction in new bone formation at the distraction gap.

Topics: Acid Phosphatase; Animals; Biomarkers; Body Weight; Bone Density; Bone Marrow; Bone Matrix; Cartilage; Connective Tissue; Diaphyses; Disease Models, Animal; External Fixators; Female; Femur; Isoenzymes; Osteoclasts; Osteogenesis; Osteogenesis, Distraction; Osteoporosis; Ovariectomy; Rats; Rats, Wistar; Tartrate-Resistant Acid Phosphatase; Time Factors; Wound Healing; X-Ray Microtomography

The effects of Cordyceps sinensis (Caterpillar fungus) and strontium ranelate on ovariectomized osteopenic rats was studied in this paper. After the rats were treated orally with C. sinensis, strontium, and C. sinensis rich in strontium ranelate (CSS) respectively, serum alkaline phosphatase (ALP), tartarate-resistant acid phosphatase (TRAP), serum osteocalcin (OC), homocysteine, C-terminal crosslinked telopeptides of collagen type I (CTX), estradiol, and interferon-gamma (IFN-γ) level were examined. The beneficial effects of CSS on improvement of osteoporosis in rats were attributable mainly to decrease ALP activity, TRAP activity, CTX level, and IFN-γ level. At the same time, CSS also increase the OC and estradiol level in ovariectomized osteopenic rats. This study demonstrates the value of C. sinensis rich in strontium ranelate in the management of postmenopausal osteoporosis in humans.

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Collagen Type I; Cordyceps; Interferon-gamma; Isoenzymes; Organometallic Compounds; Osteoporosis; Rats; Strontium; Tartrate-Resistant Acid Phosphatase; Thiophenes

Human osteoclasts express functional TRPV1 channels, CB1/CB2 cannabinoid receptors and endocannabinoid/endovanilloid synthetic/catabolic enzymes. Pharmacologic manipulation of this system can modulate osteoclast activity. Here, through multidisciplinary approaches, we demonstrate that enzymes and receptors of the endocannabinoid/endovanilloid system are differently expressed in osteoclasts from menopausal women without or with osteoporosis. We report that in osteoclasts from osteoporotic patients, TRPV1 channels are upregulated and, if persistently stimulated with resiniferatoxin, become clustered to the plasma membrane while inducing a massive over-expression of CB2 receptors. By providing new evidence for a critical functional cross-talk between CB2 and TRPV1 receptors in osteoporosis, we speculate that TRPV1 desensitization, or its enhanced trafficking, together with TRPV1 agonist-induced CB2 receptor overexpression, might be critical to minimize calcium entry in osteoclasts, which could be in turn responsible of cell over-activation and higher bone resorption. Our data pave the way to the use of TRPV1 agonist together with CB2 agonists or CB1 antagonists in osteoporosis.

Topics: Acid Phosphatase; Amidohydrolases; Bone and Bones; Calcium; Cannabinoid Receptor Modulators; Cell Count; Cells, Cultured; Endocannabinoids; Female; Gene Expression Regulation; Gene Silencing; Humans; Immunohistochemistry; Intracellular Space; Isoenzymes; Ligands; Lipase; NF-kappa B; Osteoclasts; Osteoporosis; Phospholipase D; Polymorphism, Single Nucleotide; Postmenopause; Receptor, Cannabinoid, CB1; Receptor, Cannabinoid, CB2; RNA, Messenger; Tartrate-Resistant Acid Phosphatase; TRPV Cation Channels

There are no data concerning a relationship between alcohol and bone status from a large-scale community-based study of elderly Japanese men. The baseline survey for the Fujiwara-kyo Osteoporosis Risk in Men Study was performed in 2174 male participants during the period from 2007 to 2008 in Nara Prefecture, Japan. Among them 1665 fitted the following inclusion criteria: (a) age ≥65years, (b) no diseases or drug therapy that could affect bone mineral density (BMD). We analyzed 1421 men with complete information about alcohol intake. We found that alcohol intake and BMD were positively correlated after adjustment for age, body mass index, natto intake, milk intake, smoking, physical activity, education, marital status, and hypertension. Adjusted total hip BMD of men with alcohol intake >39g/day was 0.90g/cm(2) and that of abstainers was 0.85g/cm(2). With regard to bone turnover markers, alcohol intake was inversely associated with serum levels of osteocalcin and tartrate-resistant acid phosphatase isoenzyme 5b. A two-piece linear regression model revealed a positive relationship between alcohol intake and crude mean BMD for the total hip in those with alcohol intake of less than 55g/day. In contrast, alcohol intake and BMD in those with an alcohol intake of 55g/day or more was inversely correlated. The present large-scale study of elderly Japanese men revealed that although an alcohol intake of <55g/day was positively correlated to BMD, alcohol intake of ≥55g/day was inversely correlated to BMD.

Topics: Acid Phosphatase; Aged; Alcohol Drinking; Body Mass Index; Bone Density; Humans; Isoenzymes; Japan; Male; Osteocalcin; Osteoporosis; Tartrate-Resistant Acid Phosphatase

Osteoporosis is a common disorder in aging populations that imposes considerable health problems. Tartrate-resistant acid phosphatase type 5b (TRAP-5b) is derived from osteoclasts, and is involved in normal bone homeostasis. Recently, a novel assay system for TRAP-5b, the fragments absorbed immunocapture enzymatic assay method, has been developed. To evaluate the suitability of TRAP-5b as a screening marker for bone mineral density (BMD), we explored the correlations between serum TRAP-5b concentrations and laboratory findings, body mass index, or BMD in 462 community-dwelling elderly individuals (249 men and 213 women, age 73.4±6.5 years) who participated in a regular medical screening program. By multivariate linear regression analysis adjusted for confounding factors, TRAP-5b was significantly correlated with body mass index (β=-0.005, p=0.043), alkaline phosphatase, a marker for osteoid formation and calcification (β=0.001, p<0.001), and triglyceride (β=-0.097, p=0.016) in men, and with body mass index (β=-0.009, p=0.025), alkaline phosphatase (β=0.001, p<0.001), calcium (β=-0.059, p=0.039), and bone trabecular area ratio (β=-0.47, p=0.025) in women. In conclusion, the elevated serum level of TRAP-5b is independently correlated with the decreased BMD in women, but not in men. Because measurement of TRAP-5b is not affected by food intake, and blood samples can be collected at any time of the day, we suggest the suitability of serum TRAP-5b as a simple marker for the evaluation of BMD in women.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Biomarkers; Bone Density; Female; Homes for the Aged; Humans; Isoenzymes; Male; Mass Screening; Osteoporosis; Tartrate-Resistant Acid Phosphatase

Regulation of RANKL (receptor activator of nuclear factor κB ligand)-induced osteoclast differentiation is of current interest in the development of antiresorptive agents. Osteoclasts are multinucleated cells that play a crucial role in bone resorption. In this study, we investigated the effects of N-methylpyrrolidone (NMP) on the regulation of RANKL-induced osteoclastogenesis. NMP inhibited RANKL-induced tartrate-resistant acid phosphatase activity and the formation of tartrate-resistant acid phosphatase-positive multinucleated cells. The RANKL-induced expression of NFATc1 (nuclear factor of activated T cells, cytoplasmic 1) and c-Fos, which are key transcription factors for osteoclastogenesis, was also reduced by treatment with NMP. Furthermore, NMP induced disruption of the actin rings and decreased the mRNAs of cathepsin K and MMP-9 (matrix metalloproteinase-9), both involved in bone resorption. Taken together, these results suggest that NMP inhibits osteoclast differentiation and attenuates bone resorption. Therefore, NMP could prove useful for the treatment of osteoporosis or other bone diseases associated with excessive bone resorption.

Topics: Acid Phosphatase; Animals; Bone Resorption; Cathepsin K; Cell Differentiation; Enzyme Activation; Isoenzymes; Matrix Metalloproteinase 9; Mice; NFATC Transcription Factors; Osteoclasts; Osteoporosis; Proto-Oncogene Proteins c-fos; Pyrrolidines; RANK Ligand; RNA, Messenger; Tartrate-Resistant Acid Phosphatase

Many studies have identified smoking as a risk factor for osteoporosis, but it is unclear whether passive smoking has an effect on bone mineral density and bone turnover and if such an effect could cause osteoporosis.The purpose of the study was to investigate the effect of passive smoking on bone mineral density (BMD) and bone turnover and the relationship between BMD and bone turnover in female rat.. Forty-eight female Wistar rats were randomized into six groups: 2-month, 3-month,4-month smoke-exposed rats and their controls. A rat model of passive cigarette smoking was prepared by breeding female rats in a cigarette-smoking box for 2, 3 or 4 months. Serums were analyzed for levels of osteocalcin, bone-specific alkaline phosphatase (b-ALP) and Tartrate-resistant acid phosphatase 5b (TRACP 5b). BMD was assessed at lumbar vertebrae and femur by dual energy X-ray absorptiometry in passive smoking rats and in control rats.. BMD of lumbar spine and femur was lower in 4-month smoke-exposed female rats than that in controls. However, there was no significant difference in serum osteocalcin levels between smoke-exposed rats and controls. Significantly lower b-ALP and higher TRACP 5b were found in the 3-month or 4-month smoke-exposed rats compared to controls. Subsequent analysis showed that b-ALP positively correlated with BMD of the lumbar vertebrae(r = 0.764, P = 0.027) and femur(r = 0.899, P = 0.002) in 4-month smoke-exposed female rats. Furthermore, TRACP 5b levels negatively correlated with BMD of lumbar vertebrae (r = -0.871, P = 0.005) and femur (r = -0.715, P = 0.046) in 4-month smoke-exposed female rats.. Our data suggest that smoke exposure can inhibit bone formation and increase bone resorption. The hazardous effects of passive smoking on bone status are associated with increased bone turnover in female rat.

Topics: Absorptiometry, Photon; Acid Phosphatase; Alkaline Phosphatase; Analysis of Variance; Animals; Biomarkers; Bone Density; Bone Remodeling; Bone Resorption; Female; Femur; Isoenzymes; Lumbar Vertebrae; Nicotine; Osteocalcin; Osteoporosis; Random Allocation; Rats; Rats, Wistar; Smoking; Tartrate-Resistant Acid Phosphatase; Time Factors; Tobacco Smoke Pollution

Omentin-1 (also known as intelectin-1) is a recently identified visceral adipose tissue-derived cytokine that is inversely related to obesity. Our previous study showed that omentin-1 inhibits osteoblastic differentiation of calcifying vascular smooth muscle cells (CVSMCs) in vitro. This study was undertaken to investigate the effects of omentin-1 on arterial calcification and bone metabolism in vivo.. In vitro, omentin-1 stimulated production of osteoprotegerin (OPG) and inhibited production of receptor activator for nuclear factor κB ligand (RANKL) in both CVSMCs and osteoblasts. In vivo, adenovirus-mediated over-expression of omentin-1 attenuated arterial calcification and bone loss in OPG(-/-) mice. All these in vitro and in vivo actions were abrogated by blockade of the PI3K-Akt signalling pathway. Furthermore, omentin-1 reduced serum levels of RANKL, tartarate-resistant acid phosphatase-5b and osteocalcin, all of which are increased dramatically in OPG(-/-) mice.. These data suggest that omentin-1 ameliorates arterial calcification and bone loss in vivo through the regulation of the RANK signalling pathway.

Topics: Acid Phosphatase; Adiponectin; Animals; Bone Density; Cell Differentiation; Cell Proliferation; Cells, Cultured; Cytokines; Disease Models, Animal; Down-Regulation; Female; Genetic Therapy; GPI-Linked Proteins; Humans; Isoenzymes; Lectins; Mice; Mice, Inbred C57BL; Mice, Knockout; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Osteoblasts; Osteocalcin; Osteoporosis; Osteoprotegerin; Phosphatidylinositol 3-Kinase; Proto-Oncogene Proteins c-akt; RANK Ligand; Recombinant Proteins; Signal Transduction; Tartrate-Resistant Acid Phosphatase; Time Factors; Vascular Calcification

The possible biochemical mechanism of gallium was studied in this paper. One-day-old hens were fed to up to 68 weeks on a control diet and diets containing gallium. Serum calcium and phosphorus, serum alkaline phosphatase, tartrate resistant acid phosphatase (TRAP), serum osteocalcin, homocysteine, C-terminal crosslinked telopeptides of collagen type I, and bone mineral content were measured, respectively. The beneficial effects of gallium supplementation on improvement of cage layer osteoporosis were attributable mainly to decrease TRAP activity, C-terminal crosslinked telopeptides of collagen type I level, plasma calcium and phosphate concentrations, and increase the mineral content in the bones and osteocalcin level in plasma.

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Bone Density; Calcium; Chickens; Gallium; Isoenzymes; Osteocalcin; Osteoporosis; Phosphorus; Poultry Diseases; Tartrate-Resistant Acid Phosphatase

Two side effects of irradiation are premature ovarian failure (POF) and osteoporosis, both of which are concerns not only clinically, for patients, but also experimentally, for animals. We examine whether bone marrow transplantation (BMT) can correct the POF induced by radiation and also address whether allogeneic ovarian transplantation (OT) can modulate the adverse effects of radiotherapy.. Eight-week-old female C57BL/6 mice were lethally irradiated with 6 Gy x2, and then injected with allogeneic bone marrow cells into their bone marrow cavity using our previously described intrabone marrow (IBM)-BMT technique. Allogeneic ovaries were simultaneously transplanted under the renal capsules of the mice.. Three months after the transplantation, we noted that hematopoietic and lymphoid cells had been successfully reconstituted. The ovaries transplanted under the renal capsules demonstrated signs of development with a large number of differentiating follicles at different stages of development. Importantly, the total bone mineral density of the tibia in the "IBM-BMT+OT" (BMT/OT) group remained normal. However, the reproductive function of the recipient mice was not restored, despite the presence of many immature oocytes in the host ovaries in the BMT/OT group. In the BMT group, no oocytes were found in the host ovaries.. These findings suggest that IBM-BMT with ovarian allografts can be advantageous for young women with POF and osteopenia or osteoporosis that is due to chemotherapy and radiotherapy for malignant diseases.

Topics: Acid Phosphatase; Animals; Bone Marrow Cells; Bone Marrow Transplantation; Estradiol; Female; Isoenzymes; Mice; Mice, Inbred C57BL; Osteoporosis; Ovary; Primary Ovarian Insufficiency; Radiotherapy; Tartrate-Resistant Acid Phosphatase; Transplantation, Homologous

Despite the important physiological role of periosteum in the pathogenesis and treatment of osteoporosis, little is known about the structural and cellular characteristics of periosteum in osteoporosis. To study the structural and cellular differences in both diaphyseal and metaphyseal periosteum of osteoporotic rats, samples from the right femur of osteoporotic and normal female Lewis rats were collected and tissue sections were stained with hematoxylin and eosin, antibodies or staining kit against tartrate resistant acid phosphatase (TRAP), alkaline phosphatase (ALP), vascular endothelial growth factor (VEGF), von Willebrand (vWF), tyrosine hydroxylase (TH) and calcitonin gene-related peptide (CGRP). The results showed that the osteoporotic rats had much thicker and more cellular cambial layer of metaphyseal periosteum compared with other periosteal areas and normal rats (P < 0.001). The number of TRAP(+) osteoclasts in bone resorption pits, VEGF(+) cells and the degree of vascularization were found to be greater in the cambial layer of metaphyseal periosteum of osteoporotic rats (P < 0.05), while no significant difference was detected in the number of ALP(+) cells between the two groups. Sympathetic nerve fibers identified by TH staining were predominantly located in the cambial layer of metaphyseal periosteum of osteoporotic rats. No obvious difference in the expression of CGRP between the two groups was found. In conclusion, periosteum may play an important role in the cortical bone resorption in osteoporotic rats and this pathological process may be regulated by the sympathetic nervous system.

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Blood Vessels; Calcitonin Gene-Related Peptide; Diaphyses; Female; Immunohistochemistry; Isoenzymes; Osteoclasts; Osteoporosis; Periosteum; Rats; Rats, Inbred Lew; Staining and Labeling; Tartrate-Resistant Acid Phosphatase; Tyrosine 3-Monooxygenase; Vascular Endothelial Growth Factor A; von Willebrand Factor

Our previous study showed that Erythrina variegata L. (EV) inhibited bone loss and improved bone properties in ovariectomised rats. The purpose of the present study is to investigate the potential mechanism involved in mediating the osteoprotective actions of EV. Female Sprague-Dawley rats were fed a phyto-oestrogen-free diet and subjected to either ovariectomy or a sham operation. Ovariectomised rats were treated with genistein (40 mg/kg) as well as low (200 mg/kg), medium (500 mg/kg) or high (1000 mg/kg) doses of EV extract. Bone properties and mRNA expressions were evaluated by micro-computed tomography and quantitative RT-PCR, respectively. Osteoclast differentiation in RAW 264.7 cells was studied by tartrate-resistant acid phosphatase (TRAP) staining. High doses of EV could decrease urinary Ca and P excretion, maintain serum Ca and P level, and exert beneficial effects on the micro-structure and morphology of trabecular bone and cortical bone in ovariectomised rats. EV suppressed the up-regulation of cathepsin K mRNA and the down-regulation of osteoprotegrin mRNA in the tibia of ovariectomised rats. TRAP-positive cell numbers were significantly decreased in receptor activator of nuclear factor-κB ligand (RANKL)-induced RAW 264.7 cells when co-cultured with EV extracts. The present study indicated that the protective effects of EV on bone properties in ovariectomised rats are likely to be mediated by its inhibitory actions on the process of bone resorption via the suppression of osteoclast differentiation and maturation.

Topics: Acid Phosphatase; Animals; Bone Density Conservation Agents; Bone Resorption; Calcium; Cathepsin K; Cell Differentiation; Erythrina; Female; Genistein; Isoenzymes; Macrophages; Mice; Osteoclasts; Osteoporosis; Osteoprotegerin; Ovariectomy; Phosphorus; Phytotherapy; Plant Extracts; RANK Ligand; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Tartrate-Resistant Acid Phosphatase

An experimental rat model was used to test the hypothesis that in osteoporosis (OP) the molecular composition of the extracellular matrix in the fracture callus is disturbed. OP was induced at 10 weeks of age by ovariectomy and a vitamin D(3)-deficient diet, and sham-operated animals fed normal diet served as controls. Three months later a closed tibial fracture was made and stabilized with an intramedullary nail. After 3 and 6 weeks of healing, the animals were killed and the fracture calluses examined with global gene expression, in situ mRNA expression, and ultrastructural protein distribution of four bone turnover markers: osteopontin, bone sialoprotein, tartrate-resistant acid phosphatase, and cathepsin K. Global gene expression showed a relatively small number of differently regulated genes, mostly upregulated and at 3 weeks. The four chosen markers were not differently regulated, and only minor differences in the in situ mRNA expression and ultrastructural protein distribution were detected. Gene expression and composition of fracture calluses are not generally disturbed in experimental OP.

Topics: Acid Phosphatase; Animals; Biomarkers; Bony Callus; Cathepsin K; Estrogens; Female; Fractures, Bone; Gene Expression; Isoenzymes; Osteoporosis; Ovariectomy; Rats; Rats, Wistar; Tartrate-Resistant Acid Phosphatase; Tibia; Tibial Fractures; Vitamin D; Vitamin D Deficiency

Purple acid phosphatases (PAPs) are binuclear hydrolases that catalyse the hydrolysis of a range of phosphorylated substrates. Human PAP is a major histochemical marker for the diagnosis of osteoporosis. In patients suffering from this disorder, PAP activity contributes to increased bone resorption and, therefore, human PAP is a key target for the development of anti-osteoporotic drugs. This manuscript describes the design and synthesis of derivatives of 1-naphthylmethylphosphonic acids as inhibitors of PAP. The K(i) values of these compounds are as low as 4 microM, the lowest reported to date for a PAP inhibitor.

Topics: Acid Phosphatase; Bone Resorption; Enzyme Inhibitors; Glycoproteins; Humans; Naphthalenes; Organophosphonates; Osteoporosis

Patients with neurofibromatosis 1 (NF1) are shorter than expected and often have low bone mineral density (BMD), but the pathogenesis of these bony problems is poorly understood.. We performed an exploratory study of BMD, 18 laboratory measures of bone metabolism, and fracture history in 72 adult NF1 patients.. Eight of the 18 clinical biochemical measures of bone health had at least 10% of NF1 patients outside the standard reference range. Serum 25-hydroxy-vitamin D concentrations were low in 56% of the NF1 patients, serum parathyroid hormone (PTH) concentrations were high in 34%, and urine deoxypyridinoline cross-link concentrations were high in 50%. Mean serum 25-hydroxy-vitamin D concentrations were significantly lower in people with NF1 than in season matched controls in both summer (p = 0.008) and winter (p<0.001). 36 (50%) of the 72 people with NF1 studied had BMD consistent with osteopenia, and 14 (19%) had BMD consistent with osteoporosis. High serum PTH concentration, high serum bone tartrate resistant acid phosphatase concentration, and high serum calcium concentration were associated with lower BMD among the NF1 patients. Males were more likely than females to have low BMD. The reported frequency of fractures in individuals with NF1 was much higher than in their unaffected siblings and spouses (p<0.001), and pathological fractures were reported only in NF1 patients.. People with NF1 often have a generalised abnormality of bone metabolism. Further studies are needed to determine the biochemical and molecular basis of this abnormality.

Topics: Acid Phosphatase; Adult; Aged; Amino Acids; Animals; Bone Density; Bone Diseases, Metabolic; Calcium; Female; Fractures, Bone; Humans; Isoenzymes; Logistic Models; Male; Middle Aged; Multivariate Analysis; Neurofibromatosis 1; Osteoporosis; Parathyroid Hormone; Phosphates; Tartrate-Resistant Acid Phosphatase; Vitamin D; Young Adult

To investigate the relationship of serum 25- Hydroxy D with bone mass density and other indicators in male patients with diabetes.. Bone mass density (BMD), serum 25- HydroxyD (25 (OH)VD) and several other biochemical indicators were measured in 82 male patients with diabetes, among whom 49 had osteoporosis.. The diabetic patients with osteoporosis had higher tartrate-resistant acid phosphatase-5b (TRCAP-5b) and lower 25(OH)VD, testosterone (T), Dehydroepiandrosterone sulfate (DHEA-S), and bone-specific alkaline phosphatase (B-ALP) than those without osteoporosis (P < 0.05). The Parathormone (PTH) and albumin-creatinine ratio (UAlb/Cr) also increased in the diabetic patients with osteoporosis, but with no statistical significance. No difference was observed in glycosylated hemoglobin (HBA1c) between the diabetic patients with and without osteoporosis. The serum 25(OH)VD was negatively correlated with the duration of diabetes in both groups (P < 0.05), which was independent from the increase of age. The serum 25(OH)VD was positively correlated with T score of neck, ward, greater trochanter of femur and vertebrae lumbales, and T and DHEA-S in both patients with and without osteoporosis (P < 0.05). The 25(OH)VD was also positively correlated with PTH in the patients with osteoporosis. Negative correlation was noted between 25(OH)VD and B-ALP. There were no correlations between 25(OH)VD and TRCAP-5b, HBA1c and UAlb/Cr.. Serum 25(OH)VD, T and DHEA-S may play an important role in the development of osteoporosis in male patients with diabetes mellitus.

Topics: Acid Phosphatase; Adult; Aged; Bone Density; Dehydroepiandrosterone Sulfate; Diabetes Mellitus, Type 2; Humans; Isoenzymes; Male; Middle Aged; Osteoporosis; Tartrate-Resistant Acid Phosphatase; Testosterone; Vitamin D

Six phenolic compounds isolated from Curculigo orchioides, including 2,6-dimethoxy benzoic acid (1), curculigoside A (2), curculigoside B (3), curculigine A (4), curculigine D (5) and 3,3',5,5'-tetramethoxy-7,9':7',9-diepoxylignan-4,4'-di-O-beta-D-glucopyranoside (6), together with the ethanol extract of Curculigo orchioides were evaluated for their activity on osteoblasts in neonatal rat calvaria cultures and multinucleated osteoclasts derived from rat marrow cells so as to characterize the antiosteoporotic components of this plant and explore the relationship of chemical structure with antiosteoporotic activity. The proliferation of osteoblast was assayed by MTT methods. The activity of ALP (alkaline phosphatase) and TRAP (tartrate-resistant acid phosphatase) was measured by p-nitrophenyl sodium phosphate assay. The TRAP stain was used to identify osteoclast in morphology. The resorption pit area on the bone slices formed by osteoclast was measured by computer image processing. The ethanol extract exhibited stimulatory effect on both the osteoblast proliferation and the ALP activity. Six compounds all increased the osteoblast proliferation, and compounds (1), (2) and (4) also slightly increased the osteoblastic ALP activity. Compounds (1), (2), (3), (6) and the ethanol extract decreased area of bone resorption pit, osteoclastic formation and TRAP activity. These results indicated that phenolic compounds are antiosteoporotic chemical constituents from Curculigo orchioides, and their activities are related with chemical structures.

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Animals, Newborn; Bone and Bones; Bone Density Conservation Agents; Cell Proliferation; Cells, Cultured; Curculigo; Isoenzymes; Osteoblasts; Osteoclasts; Osteoporosis; Phenols; Plant Extracts; Rats; Rats, Wistar; Rhizome; Tartrate-Resistant Acid Phosphatase

RANKL has been implicated in the pathogenesis of glucocorticoid-induced osteoporosis. This study was undertaken to evaluate the efficacy of denosumab, a neutralizing monoclonal antibody against human RANKL (hRANKL), in a murine model of glucocorticoid-induced osteoporosis.. Eight-month-old male homozygous hRANKL-knockin mice expressing a chimeric RANKL protein with a humanized exon 5 received 2.1 mg/kg of prednisolone or placebo daily over 4 weeks via subcutaneous slow-release pellets and were additionally treated with phosphate buffered saline or denosumab (10 mg/kg subcutaneously twice weekly). Two groups of wild-type mice were also treated with either prednisolone or vehicle.. The 4-week prednisolone treatment induced loss of vertebral and femoral volumetric bone mineral density in the hRANKL-knockin mice. Glucocorticoid-induced bone loss was associated with suppressed vertebral bone formation and increased bone resorption, as evidenced by increases in the number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts, TRAP-5b protein in bone extracts, serum levels of TRAP-5b, and urinary excretion of deoxypyridinoline. Denosumab prevented prednisolone-induced bone loss by a pronounced antiresorptive effect. Biomechanical compression tests of lumbar vertebrae revealed a detrimental effect of prednisolone on bone strength that was prevented by denosumab.. Our findings indicate that RANKL inhibition by denosumab prevents glucocorticoid-induced loss of bone mass and strength in hRANKL-knockin mice.

Topics: Acid Phosphatase; Amino Acids; Animals; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Bone Density; Bone Resorption; Denosumab; Gene Knock-In Techniques; Glucocorticoids; Male; Mice; Osteoporosis; Prednisolone; RANK Ligand

Dickkopf-1 is an inhibitor of Wnt signaling, which is crucial for osteoblast differentiation. We evaluated serum levels of Dickkopf-1 in 66 patients with thalassemia-induced osteoporosis who received therapy with zoledronic acid in a placebo-controlled, randomized trial. At baseline, thalassemia patients had increased serum levels of Dickkopf-1 that correlated with reduced bone mineral density of the lumbar spine and the distal radius. High Dickkopf-1 also correlated with increased bone resorption and reduced bone formation markers. Zoledronic acid produced a reduction in serum Dickkopf-1, which was associated with bone mineral density increase after 12 months of therapy. On the contrary, placebo group showed a borderline increase of Dickkopf-1, which was higher in patients who showed deterioration in pain scores. These results suggest that Dickkopf-1 is implicated in the pathogenesis of osteoporosis in thalassemia and reveal Dickkopf-1 as a possible target for the development of novel agents for the management of thalassemia-induced osteoporosis.

Topics: Absorptiometry, Photon; Acid Phosphatase; Adult; Alkaline Phosphatase; Bone Density; Bone Density Conservation Agents; Collagen Type I; Diphosphonates; Enzyme-Linked Immunosorbent Assay; Female; Follow-Up Studies; Humans; Imidazoles; Intercellular Signaling Peptides and Proteins; Isoenzymes; Male; Middle Aged; Osteocalcin; Osteopontin; Osteoporosis; Osteoprotegerin; Peptides; Randomized Controlled Trials as Topic; Tartrate-Resistant Acid Phosphatase; Thalassemia; Treatment Outcome; Young Adult; Zoledronic Acid

A recent analysis of clinical studies suggests that angiotensin-converting enzyme (ACE) inhibitors might reduce bone fractures. In this study, we examined whether an ACE inhibitor might attenuate osteoporosis in a hypertensive rat model. In spontaneous hypertensive rats (SHRs), estrogen deficiency induced by ovariectomy (OVX) resulted in a significant increase in osteoclast activation as assessed by the tartrate-resistant acid phosphatase (TRAP) activity in the tibia, accompanied by a significant decrease in bone density evaluated by dual-energy X-ray absorptiometry and an increase in urinary deoxypyridinoline. Treatment with an ACE inhibitor, imidapril, attenuated OVX-induced decrease in bone density and increase in TRAP activity and urinary deoxypyridinoline. As ACE inhibitors possess the effects of blockade of the renin-angiotensin system (RAS) and activation of the bradykinin-nitric oxide pathway, we examined the contribution of both pathways in an OVX-induced osteoporosis model. Administration of nitro-L-arginine methylester (L-NAME) did not alter TRAP activity, urinary deoxypyridinoline or bone density, whereas the administration of a subpressor dose of angiotensin II accelerated the increase in TRAP activity in the tibia, accompanied by a significant decrease in bone density and an increase in urinary deoxypyridinoline. Thus, ACE inhibitors prevented osteoporosis, probably because of the inhibition of RAS, but not of nitric oxide. Overall, ACE inhibitors attenuated osteoporosis in a hypertensive rat model through the blockade of RAS.

Topics: Absorptiometry, Photon; Acid Phosphatase; Alkaline Phosphatase; Angiotensin-Converting Enzyme Inhibitors; Animals; Biomarkers; Blood Pressure; Bone and Bones; Bone Density Conservation Agents; Enzyme Inhibitors; Female; Heart Rate; Imidazolidines; Isoenzymes; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase; Osteoclasts; Osteoporosis; Ovariectomy; Rats; Rats, Inbred SHR; Rats, Wistar; Regional Blood Flow; Renin-Angiotensin System; Tartrate-Resistant Acid Phosphatase

We evaluated the protective effects of soy isoflavones (SIF) against osteoporosis in middle-aged ovariectomized (OVX) mice. SIF (30 mg/kg or 60 mg/kg) or 17beta-estradiol (E(2)) was administered to OVX mice for 4 months after bilateral ovariectomy. We observed the biochemical markers of bone turnover, e.g., alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP), in serum. We also observed the bone mineral density (BMD) in femurs and lumbar vertebrae. In addition, we examined trabecular bone and interstitial cells in the femur using hematoxylin and eosin staining. The decrease in ALP levels and the increase in TRAP levels normally resulting from ovariectomy were suppressed by administration of 60 mg/kg SIF or E(2). Administration of 60 mg/kg SIF or E(2) also maintained the BMD, trabecular bone, and interstitial cells in OVX mice compared to those in pre-OVX mice. These results suggest that 60 mg/kg SIF effectively mitigates ovariectomy-induced osteoporosis in middle-aged mice.

Topics: Acid Phosphatase; Aging; Alkaline Phosphatase; Animals; Bone Density; Bone Density Conservation Agents; Estradiol; Female; Femur; Glycine max; Isoflavones; Lumbar Vertebrae; Mice; Mice, Inbred ICR; Osteoporosis; Ovariectomy; Phytotherapy; Plant Extracts

Extract of the whole plant, Ajuga decumbens (KE) has long been used in China as a medication for the relief of joint pain. Previously, we proved that KE up-regulated the synthesis of collagen in false aged model rats. In this paper we examined the effects of KE on nitric oxide (NO) production, expression of inducible nitric oxide synthase (iNOS), osteoblast and osteoclast activity. We also investigated whether KE had any anti-osteoporosis or anti-arthritic activity by using ovariectmized mice and adjuvant induced arthritic rats. KE exhibited down-regulation of differentiation into osteoclast and up-regulation of mineralization in osteoblast-like MC3T3-E1 cells in a concentration-dependent manner. NO synthesized by iNOS plays important roles in inflammatory disease and imbalance between bone resorption and bone formation caused by estrogen depletion. KE inhibited expression of iNOS which caused concentration dependent inhibition of NO production. Furthermore, KE prevented brittle bones in ovariectomized mice and swelling of the left hind ankle in adjuvant induced arthritic rats. Therefore, KE improved the balance of bone resorption and bone formation, showing anti-inflammatory effects. Consequently, KE is beneficial for sufferers of bone and joint disease.

Topics: 3T3 Cells; Acid Phosphatase; Ajuga; Animals; Anthraquinones; Arthritis; Arthritis, Experimental; Bone Resorption; Calcium; Coculture Techniques; Collagen; Coloring Agents; Female; Freund's Adjuvant; Isoenzymes; Male; Mice; Nitric Oxide; Nitric Oxide Synthase Type II; Osteoclasts; Osteoporosis; Ovariectomy; Phytotherapy; Plant Extracts; Rats; Rats, Inbred Lew; Tartrate-Resistant Acid Phosphatase

Postmenopausal bone loss is a major public health concern. Although drug therapies are available, women are interested in alternative/adjunct therapies to slow down the bone loss associated with ovarian hormone deficiency. The purpose of this study was to determine whether dietary supplementation of l-carnitine can influence bone density and slow the rate of bone turnover in an aging ovariectomized rat model. Eighteen-month-old Fisher-344 female rats were ovariectomized and assigned to two groups: (1) a control group in which rats were fed ad libitum a carnitine-free (-CN) diet (AIN-93M) and (2) another fed the same diet but supplemented with l-carnitine (+CN). At the end of 8 weeks of feeding, animals were sacrificed and bone specimens were collected for measuring bone mineral content (BMC) and density (BMD) using dual energy X-ray absorptiometry. Femoral microarchitectural properties were assessed by microcomputed tomography. Femoral mRNA levels of selected bone matrix proteins were determined by northern blot analysis. Data showed that tibial BMD was significantly higher in the rat fed the +CN diet than those fed the -CN (control) diet. Dietary carnitine significantly decreased the mRNA level of tartrate-resistant acid phosphatase (TRAP), an indicator of bone resorption by 72.8%, and decreased the mRNA abundance of alkaline phosphatase (ALP) and collagen type-1 (COL), measures of bone formation by 63.6% and 61.2%, respectively. The findings suggest that carnitine supplementation slows bone loss and improves bone microstructural properties by decreasing bone turnover.

Topics: Acid Phosphatase; Aging; Alkaline Phosphatase; Animals; Bone Density; Carnitine; Collagen Type I; Dietary Supplements; Eating; Female; Femur; Isoenzymes; Lumbar Vertebrae; Osteoporosis; Ovariectomy; Phytotherapy; Rats; Rats, Inbred F344; RNA, Messenger; Tartrate-Resistant Acid Phosphatase; Tibia; Vitamin B Complex; Weight Gain

We determined the effects of yolk water-soluble protein (YSP) on bone resorption. YSP potently suppressed osteoclastogenesis from bone marrow-derived precursor cells driven by tumor necrosis factor-alpha (TNF-alpha). YSP (200 microg/ml) abolished the formation of tartarate-resistant acid phosphatase (TRAP)-positive osteoclasts. Furthermore, TNF-alpha induced TRAP activity was greatly inhibited by YSP (100 microg/ml) treatment. Our results suggest that YSP has therapeutic potential for bone-erosive diseases.

Topics: Acid Phosphatase; Animals; Bone Resorption; Cell Differentiation; Cells, Cultured; Egg Proteins; Isoenzymes; Male; Mice; Osteoclasts; Osteoporosis; Tartrate-Resistant Acid Phosphatase

This study sought to assess the effects of serum containing Guilu-Erxian (GLEX) on treating osteoporosis at the cellular level. First, Enzyme-digestion was used to obtain osteoblasts from newborn SD rats. Alkaline phosphatase staining was used to identify osteoblasts. The proliferation and the secretion of Insulin Like Growth Factor-1 (IGF-1) of osteoblasts were examined. Second, osteoclasts were generated by inducing bone marrow cells of SD male rat (6-9 weeks) with 1,25(OH)2D3. The osteoclasts were identified through tartrate-resistant acid phosphatase (TRAP) staining. Bone pits of osteoclasts were observed through Electron Scanning Microscope. At the same time, TRAP(+) cells with more than two nuclei and TRAP activity of osteoclasts were examined. Last, serum containing Guilu-Erxian was made through serum pharmacology. And we observed the effects of serum containing Guilu-Erxian on the function of osteoblasts and osteoclasts. We found that high doses of serum containing Guilu-Erxian had obvious effects on stimulating the multiplication and capability of secreting IGF-1 of osteoblasts cultured in vitro. Middle doses obviously inhibited the formation of osteoclasts and bone pits; TRAP activity of osteoclasts was also lowered clearly. This study indicated that Guilu-Erxian has positive effects on treating osteoporosis.

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Animals, Newborn; Cell Proliferation; Cells, Cultured; Drugs, Chinese Herbal; Insulin-Like Growth Factor I; Male; Osteoblasts; Osteoclasts; Osteoporosis; Phytotherapy; Rats; Rats, Sprague-Dawley; Serum

To observe the effect of acupuncture (Acu) on bone metabolism and serum estradiol (E2) in ovariectomized (OVX) rats for studying its underlying mechanism in treating osteoporosis.. Forty female SD rats of six months were randomized into sham operation (sham), model, Acu and Diethylstibestrol (DES) groups, with 10 cases in each. Postmenopausal osteoporosis model was established by removing ovaries under anesthesia. In Acu group, bilateral "Dazhu" (BL 11), "Shenshu" (BL 23) and "Pishu" (BL 20) were punctured and stimulated for 30 minutes, once daily for 60 days. Rats of DES group were drenched with saline+DES (22.5 microg/ml) 1 ml/100 g, once daily for 60 days. At the end of experiments, blood samples were collected from femoral artery for assaying serum alkaline phosphatase (ALP), tartrate-resistant acid phosphatase (TRAP) contents by using biochemistry, and serum bone gla protein (BGP) and E2 levels by immunoradioassay.. Compared with sham group, uterus wet weight, serum E2 content in model group decreased significantly (P < 0.01) while body weight, serum ALP, BGP and TRAP levels in model group increased significantly (P < 0.01, 0.05). Compared with model group, uterus wet weight and serum Ez content in Acu and DES groups increased significantly (P < 0.01); while body weight, serum ALP, BGP and TRAP levels decreased considerably (P < 0.01). No significant differences were found between Acu and DES groups in serum E2, ALP, BGP and TRAP levels (P > 0.05).. Acupuncture can suppress abnormal increase of body weight and decrease of serum E2 level, and significantly downregulate serum ALP, BGP and TRAP levels in OVX rats, which may contribute to its effect in relieving osteoporosis.

Topics: Acid Phosphatase; Acupuncture Therapy; Alkaline Phosphatase; Animals; Body Weight; Bone and Bones; Estradiol; Female; Humans; Isoenzymes; Osteocalcin; Osteoporosis; Ovariectomy; Random Allocation; Rats; Rats, Sprague-Dawley; Tartrate-Resistant Acid Phosphatase

To observe effects of the drug-containing serum of Bu Shen Zhuang Gu Capsule (BSZGC Capsule for Tonifying the Kidney to Strengthen the Bones) on proliferation of the rat's osteoclasts and tartrate-resistant acid phosphatase (TRACP) activity in vitro so as to delve into the mechanisms of its preventive and therapeutic actions on osteoporosis.. Forty female Sprague-Dawley rats aged three months were randomly divided into high dosage BSZGC group, medium dosage BSZGC group, low dosage BSZGC group, and the control group. BSZGC was orally administered into the rats of high, medium, and low dosage groups at different dosages for 12 days, and isometric normal saline was orally administered to the rats of the control group. The drug-containing serum and control serum were prepared. Osteoclasts isolated mechanically from the femur and tibia of Sprague-Dawley rats aged one week were cultured with medium added with different drug-containing sera and control serum. The growth of osteoclasts was observed under an inverted phase-contrast microscope, and optic density (OD) value of osteoclasts was determined by MTT colorimetric assay. TRACP activity was measured by the diazol method.. OD value of osteoclasts in the high dosage drug-containing serum group, medium dosage drug-containing serum group, and low dosage drug-containing serum group was significantly lower than that in the control serum group (P < 0.05) with a dose-effect correlation. TRACP activity in high dosage drug-containing serum group, medium dosage drug-containing serum group, low dosage drug-containing serum group was significantly lower than that of the control serum group (P < 0.01), and no significant differences in TRACP activity were not found among the different dosages drug-containing serum groups.. BSZGC can inhibit the proliferation of the osteoclasts and reduce TRACP activity, which may be one of the mechanisms of its preventive and therapeutic actions on osteoporosis.

Topics: Acid Phosphatase; Animals; Cell Proliferation; Cells, Cultured; Drugs, Chinese Herbal; Female; Humans; Isoenzymes; Osteoclasts; Osteoporosis; Random Allocation; Rats; Rats, Sprague-Dawley; Serum; Tartrate-Resistant Acid Phosphatase

To observe anti-osteoporotic effect of Plants of Camelia genus induced by retinoic acid in rats, in adqulis crude drug dosage, and to compare activities of them.. Extracts of Camellia japonica and Camellia oleifera were given to rats with osteoporosis induced by retinoic acid, some indexes of rats were measured and compared with those of modle group, control group and positive control group, including weight/length (G/L), bone density, earth and calcium content of bone, morphology change and serum calcium, tartrate-resistant acid phosphatase and alkaline phosphatase. We also compared effective intensity between different groups in adqulis crude drug dosage.. Ethanol extracts of seed from Camellia japonica 0.51 g/kg could markedly enhance weight/length (G/L), bone density of femur, serum calcium and alkaline phosphatase level, with the decreasing of anti-tartaric acid tartrate-resistant acid phosphatase level. Meanwhile, they were accompanied by a significant increase of morphologic observed sclerotomal cell and by a significant decrease of osteoclast. Moreover, it was observed greatly that bone trabecula transformateed to normal morphous. The results of this study indicated that effects of ethanol extracts of seed from Camellia japonica on anti-osteoporosis with retinoic acid were the strongest. Ethanol extracts of seed from Camellia japonica , ethanol extracts of leaves from Camellia Oleifera, and aqueous extracts of leaves from Camellia Oleifera were stronger than positive control drug. The other extracts didnt show obvious anti-osteoporotic effects. Eventually the strength order of each group on anti-osteoporosis was as following: ethanol extracts of seed from Camellia japonica > ethanol extracts of leaves from Camellia Oleifera > aqueous extracts of leaves from Camellia Oleifera > aqueous extracts of seed from Camellia Oleifera > positive control drug > aqueous extracts of seed from Camellia Japonica.. Plants of Camellia genus have different degree anti-osteoporosis effect, which can offer significant theory basis for progressive investigation and exploitation of them.

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Bone and Bones; Bone Density; Calcium; Camellia; Camellia sinensis; Drugs, Chinese Herbal; Female; Femur; Isoenzymes; Male; Osteoporosis; Phytotherapy; Random Allocation; Rats; Rats, Sprague-Dawley; Tartrate-Resistant Acid Phosphatase; Tea; Tretinoin

Recent clinical studies suggest that several antihypertensive drugs, especially angiotensin-converting enzyme inhibitors, reduced bone fractures. To clarify the relationship between hypertension and osteoporosis, we focused on the role of angiotensin II (Ang II) on bone metabolism. In bone marrow-derived mononuclear cells, Ang II (1x10(-6) M) significantly increased tartrate-resistant acid phosphatase (TRAP) -positive multinuclear osteoclasts. Of importance, Ang II significantly induced the expression of receptor activator of NF-kappaB ligand (RANKL) in osteoblasts, leading to the activation of osteoclasts, whereas these effects were completely blocked by an Ang II type 1 receptor blockade (olmesartan) and mitogen-activated protein kinase kinase inhibitors. In a rat ovariectomy model of estrogen deficiency, administration of Ang II (200 ng/kg/min) accelerated the increase in TRAP activity, accompanied by a significant decrease in bone density and an increase in urinary deoxypyridinoline. In hypertensive rats, treatment with olmesartan attenuated the ovariectomy-induced decrease in bone density and increase in TRAP activity and urinary deoxypyridinoline. Furthermore, in wild-type mice ovariectomy with five-sixths nephrectomy decreased bone volume by microcomputed tomography, whereas these change was not detect in Ang II type 1a receptor-deficient mice. Overall, Ang II accelerates osteoporosis by activating osteoclasts via RANKL induction. Blockade of Ang II might become a novel therapeutic approach to prevent osteoporosis in hypertensive patients.

Topics: Acid Phosphatase; Angiotensin II; Animals; Bone Marrow Cells; Cell Differentiation; Humans; Osteoclasts; Osteoporosis; Osteoprotegerin; Rabbits; RANK Ligand; Reverse Transcriptase Polymerase Chain Reaction

A severely osteopenic rat model was obtained by combining orchidectomy (ORX) and disuse (due to local paralysis induced by botulinum toxin [BTX] in the quadriceps muscle).. Forty-two aged male rats (5-6 months old) were randomized into three groups: 18 were SHAM operated; 6 were ORX; and 18 were ORX and BTX injected in the right hindlimb. One, two, and three months after surgery, bone mass (BV/TV) and microarchitectural parameters (Tb.Th, Tb.N, Tb.Sp, Tb.Pf, and structure model index [SMI]) were measured by microcomputed tomography (microCT) on the primary and secondary spongiosa of the femur. Osteoid parameters (OS/BS, O.Th), the number of osteoclasts (Nb.Oc), and the mineral apposition rate (Ct.MAR, Cn.MAR) were measured by histology. The serum tartrate-resistant acid phosphatase (TRAcP) 5b activity was measured by immunoassay.. ORX induced a decrease of BV/TV, Tb.N and an increase of Tb.Sp, Tb.Pf, and SMI on both primary and secondary spongiosa. ORX and BTX had cumulative effects on bone loss, since differences were maximized on the right femur. The decrease in BV/TV reached -65%. Osteoid parameters and mineral apposition rate increased during the time course of the study. A peak of serum TRAcP was found at 7 days post-ORX. TRAcP levels reached the highest values in the ORX-BTX groups and the effect lasted longer than in the group with ORX alone. The association of ORX-BTX induced a greater bone resorption, due to the removal of complete trabeculae, compared to ORX alone.. This model induced a severe and rapid bone loss and can be used to explore pharmacological- and biomaterial-based countermeasures.

Topics: Acid Phosphatase; Animals; Botulinum Toxins; Disease Models, Animal; Imaging, Three-Dimensional; Isoenzymes; Male; Orchiectomy; Osteoclasts; Osteoporosis; Paralysis; Rats; Rats, Wistar; Tartrate-Resistant Acid Phosphatase; Tomography, X-Ray Computed

Cathepsin K and MMP-9 are considered to be the most abundant proteases in osteoclasts. TRAP is a marker for osteoclasts, and there is increasing evidence of its proteolytic role in bone resorption. RANKL is a recently discovered regulator of osteoclast maturation and activity and induces expression of many genes. This study compared cathepsin K, MMP-9, TRAP, RANKL, OPG, and osteocalcin gene expression in the proximal femur of patients with osteoarthritis with that of patients with femoral neck fracture. Fifty-six patients undergoing arthroplasty because of osteoarthritis or femoral neck fracture were included in the study. Total mRNA was extracted from the bone samples obtained from the intertrochanteric region of the proximal femur. Real-time RT-PCR was used to quantify CTSK (cathepsin K), MMP-9 (matrix metalloproteinase 9), ACP5 (TRAP), TNFSF11 (RANKL), TNFRSF11B (OPG), and BGLAP (osteocalcin) mRNAs. The levels of mRNAs coding for MMP-9 and osteocalcin indicated higher expression in the osteoarthritic group (P = 0.011, P = 0.001, respectively), whereas RANKL expression and the ratio RANKL/OPG were both significantly lower in the osteoarthritic group than in the fracture group. Expression of cathepsin K, MMP-9, and TRAP relative to RANKL was significantly higher in the osteoarthritic group. Ratios of all three proteolytic enzymes relative to formation marker osteocalcin were higher in the fracture group. Gene expression of cathepsin K, MMP-9, TRAP, RANKL, OPG, and osteocalcin and the association between their mRNA levels pointed to higher bone resorption and bone formation in osteoarthritis, differences in balance between them, and differences in regulation of bone resorption in osteoarthritic and osteoporotic bone.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Bone Resorption; Cathepsin K; Cathepsins; Female; Gene Expression Regulation; Humans; Isoenzymes; Male; Matrix Metalloproteinase 9; Osteoarthritis; Osteocalcin; Osteoporosis; Osteoprotegerin; RANK Ligand; Tartrate-Resistant Acid Phosphatase

This study was to examine whether skeletal health deterioration in the hypogonadal situation is a consequence of an alteration in the functional status of peripheral mononuclear cells and its amelioration, if any, by an oil extract of garlic. The results suggest that hypogonadism-induced oxidative stress of peritoneal macrophages and lymphocytes could be reduced by supplementation with an oil extract of garlic. However, estrogen deficiency did not cause any significant change in DNA fragmentation of peritoneal macrophages. The hypogonadism-induced increase in the serum levels of IL-6 and TNF-alpha were significantly reduced by an oil extract of garlic. Further, such supplementation could revive the hypogonadism-induced decrease in serum estrogen titer and counter-balance the increase in bone turnover as determined by low bone tensile strength and alterations in bone related biochemical variables such as urinary calcium, hydroxyproline, calcium to creatinine ratio and serum tartrate resistant acid phosphatase activity (TRAP). The garlic oil supplemented partial recovery of the serum estrogen titer in hypogonadal rats was found to be persistently associated with reduced oxidative stress of peritoneal macrophages and lymphocytes, reduced serum interleukins and better preservation of bone mass. This study proposes that the hypogonadism-induced bone loss has a direct correlation with the functional status of lymphocytes and peritoneal macrophages, and garlic can prevent this.

Topics: Acid Phosphatase; Allyl Compounds; Animals; Catalase; Disulfides; DNA Fragmentation; Estradiol; Female; Femur; Garlic; Interleukin-6; Lipid Peroxidation; Lymphocytes; Macrophages, Peritoneal; Nitrites; Osteoporosis; Ovariectomy; Phytoestrogens; Phytotherapy; Plant Extracts; Rats; Rats, Wistar; Superoxide Dismutase; Tensile Strength; Tumor Necrosis Factor-alpha

To study the curative effects of Xianling Qianggu koufuye (XLQG) on postmenopausal osteoporosis in ovariectomized female rats.. Sixty female Sprague-dawley rats aged 12-months were used, 50 of them were ovariectomized and randomly divided into 5 groups: ovariectomized (OVX), OVX + Nylestriol, OVX + XLQG (high dose, middle dose, low dose), and the others were sham-operated group. Rats were treated with drugs starting at the 45 day after the operation for 90 days. Double in vivo fluorochrome labeling was administered to all rats. At the end-point of study, the blood was collected to detecte the contents of ALP and StrACP in serum, and the fourth lumar vertebra (LV4) and femur bone sections were cut and stained for bone histomorphometric analyses, biomechanical analyses and BMP analyses.. XLQGKFY decreased greatly the StrACP content, increased BMP and bone stiffness, and improved the bone biomechanical property.. Xianling Qianggu koufuye has a curative effect on postmenopausal osteoporosis, which provides for clinical use.

Topics: Acid Phosphatase; Administration, Oral; Alkaline Phosphatase; Animals; Bone Density; Cockroaches; Drug Combinations; Drugs, Chinese Herbal; Female; Humans; Isoenzymes; Materia Medica; Medicine, Chinese Traditional; Osteoporosis; Osteoporosis, Postmenopausal; Ovariectomy; Plants, Medicinal; Random Allocation; Rats; Rats, Sprague-Dawley; Tartrate-Resistant Acid Phosphatase

Estrogen deficiency results in trabecular bone loss, associated with T-cell proliferation in the bone marrow. Insulin-like growth factor I (IGF-I) is involved in the regulation of both bone metabolism and lymphopoiesis. A major part of serum IGF-I is derived from the liver. The aim of the present study was to investigate the role of liver-derived IGF-I for ovariectomy (ovx)-induced trabecular bone loss.. Mice with adult liver-specific IGF-I inactivation (LI-IGF-I-/-) and wild type mice (WT) were either ovx or sham operated. After 5 weeks, the skeletal phenotype was analyzed by pQCT and microCT. The bone marrow cellularity was analyzed using FACS technique, and mRNA levels were quantified using real-time PCR.. Ovx resulted in a pronounced reduction in trabecular bone mineral density (-52%, P < 0.001), number (-45%, P < 0.01) and thickness (-13%, P < 0.01) in WT mice while these bone parameters were unaffected by ovx in LI-IGF-I-/- mice. Furthermore, ovx increased the number of T-cells in the bone marrow of the femur in WT but not in LI-IGF-I-/- mice. Interleukin 7 (IL-7) has been reported to stimulate the formation and function of osteoclasts by inducing the expression of receptor activator of NF-kappaB ligand (RANKL) on T-cells. IL-7 mRNA levels and the RANKL/osteoprotegerin ratio in bone were increased by ovx in WT but not in LI-IGF-I-/- mice.. Liver-derived IGF-I is permissive for ovx-induced trabecular bone loss. Our studies indicate that IGF-I might exert this permissive action by modulation of the number of T-cells and the expression of IL-7, which in turn is of importance for the RANKL/OPG ratio and consequently osteoclastogenesis in the bone marrow.

Topics: Acid Phosphatase; Animals; B-Lymphocytes; Bone Density; Carrier Proteins; Female; Femur; Flow Cytometry; Insulin-Like Growth Factor I; Isoenzymes; Liver; Membrane Glycoproteins; Mice; Mice, Knockout; Osteoporosis; Ovariectomy; Polymerase Chain Reaction; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; RNA, Messenger; T-Lymphocytes; Tartrate-Resistant Acid Phosphatase; Tomography, X-Ray Computed

We developed a cyclic PTH regimen with repeated cycles of 1-week on and off daily PTH injection and explored its effects on bone strength, BMD, bone markers, and bone structure in mice. Cyclic protocols produced 60-85% of the effects achieved by daily protocols with 57% of the total PTH given, indicating more economic use of PTH. The study supports further exploration of cyclic PTH regimens for the treatment of osteoporosis.. To minimize the cost and the catabolic action of hPTH(1-34), a cyclic PTH regimen with repeated 3-month cycles of on-and-off daily injection of hPTH(1-34) was developed in humans and shown to be as effective as a daily regimen in increasing vertebral BMD. However, changes in BMD may not adequately predict changes in bone strength. A murine model was developed to explore the efficacy of a cyclic PTH regimen on bone strength in association with other bone variables.. Twenty-week-old, intact, female C57BL/J6 mice (n = 7/group) were treated with (1) daily injection with vehicle for 7 weeks (control); (2) daily injection with hPTH(1-34) (40 microg/kg/day) for 7 weeks (daily PTH); and (3) daily injection with hPTH(1-34) and vehicle alternating weekly for 7 weeks (cyclic PTH). BMD was measured weekly by DXA, and serum bone markers, bone structure, and strength were measured at 7 weeks.. Daily and cyclic PTH regimens increased BMD at all sites by 16-17% and 9-12%, respectively (all p < 0.01). The most dramatic effect of cyclic PTH occurred during the second week of treatment when PTH was off, with femoral and tibial BMD continuing to increase to the same extent as that produced by daily PTH. Both daily and cyclic PTH regimens significantly increased osteocalcin (daily, 330%; cyclic, 260%), mTRACP (daily, 145%; cyclic, 70%), femoral cortical width (daily, 23%; cyclic, 13%), periosteal circumference (daily, 5%; cyclic, 3.5%), and bone strength (max load: daily, 48%; cyclic, 28%; energy absorbed: daily, 103%; cyclic, 61%), respectively. Femoral bone strength was positively correlated with BMD, bone markers, and cortical structure. Neither regimen had an effect on vertebral bone strength. Although actual effects of cyclic PTH were 60-85% of those produced by daily PTH, the effects of cyclic PTH per unit amount administered were slightly greater than those of daily PTH for most measures.. PTH-enhanced femoral bone strength is positively correlated with its effects on femoral BMD, bone markers, and bone structure. Cyclic PTH regimens represent a potential economic use of PTH and warrant further study.

Topics: Acid Phosphatase; Animals; Biomarkers; Bone Density; Calcium; Drug Administration Schedule; Female; Femur; Isoenzymes; Mice; Mice, Inbred C57BL; Osteocalcin; Osteoporosis; Peptide Fragments; Radiography; Spine; Tartrate-Resistant Acid Phosphatase; Teriparatide; Weight-Bearing

An experiment evaluated the effect of citrus juice on enhancing serum antioxidant status and on osteoporosis prevention in orchidectomized rats.. Thirty-six 1-y-old male rats were randomized to two groups: a sham-control group (n = 9) and an orchidectomized group (n = 27). The orchidectomized group was divided into three groups of nine and assigned to one of the following treatments: orchidectomy, orchidectomy plus orange juice, and orchidectomy plus grapefruit juice. Sixty days after initiation of the study, all rats were killed, blood was collected, and serum was harvested for total antioxidant status and indices of bone formation and resorption. Femoral density and biomechanical properties were monitored.. Orchidectomy decreased (P < 0.05) total antioxidant capacity, femoral density, and biomechanical properties and increased (P < 0.05) alkaline phosphatase, acid phosphatase, and urinary excretion of hydroxyproline compared with the sham-control group. In contrast to orchidectomy, orchidectomy plus orange juice and orchidectomy plus grapefruit juice reversed (P < 0.05) orchidectomy-induced antioxidant suppression, decreased (P < 0.05) alkaline phosphatase and acid phosphatase activities, moderately restored (P = 0.07) femoral density, increased (P < 0.05) femoral strength, significantly delayed time-induced femoral fracture, and decreased (P < 0.05) urinary excretion of hydroxyproline.. The present study supports the supposition in that drinking citrus juice positively affects serum antioxidant status and bone strength.

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Antioxidants; Beverages; Bone and Bones; Bone Density; Citrus; Disease Models, Animal; Hydroxyproline; Male; Orchiectomy; Osteoporosis; Random Allocation; Rats; Rats, Sprague-Dawley

The transcription factor, nuclear factor-kappa B (NFkappaB), is believed to play a pivotal role in osteoclast formation. In this study, we focused on NFkappaB decoy oligodeoxynucleotides (ODN) as a new therapeutic strategy to attenuate osteoporosis. Tartrate-resistant acid phosphatase (TRAP)-positive multinuclear osteoclasts formed in mononuclear cells including osteoclast precursors from neonatal rabbit bone marrow were increased in the presence of 1,25-dihydroxyvitamin D3, whereas transfection of NFkappaB decoy ODN decreased the number of TRAP-positive cells and attenuated RANKL and M-CSF-induced osteoclast formation. NFkappaB decoy ODN also inhibited the activity of osteoclasts, as assessed by pit formation. In rat ovariectomized model of estrogen deficiency, continuous administration of NFkappaB decoy ODN attenuated the increase of TRAP activity, accompanied by a significant increase in calcium concentration in tibia and femur and decrease in urinary deoxypyridinoline. In additional osteoporosis model using vitamin C-deficient rat, inhibition of NFkappaB by decoy ODN dramatically improved the bone length, weight, density as assessed by dual-energy X-ray absorptiometry. Overall, inhibition of NFkappaB by decoy strategy prevented osteoporosis through the inhibition of bone resorption. Targeting of NFkappaB might be potential therapy in various bone metabolic diseases.

Topics: Absorptiometry, Photon; Acid Phosphatase; Animals; Ascorbic Acid Deficiency; Cell Differentiation; Female; Femur; Genetic Therapy; Isoenzymes; Models, Animal; NF-kappa B; Oligodeoxyribonucleotides; Osteoclasts; Osteoporosis; Ovariectomy; Rabbits; Rats; Rats, Wistar; Tartrate-Resistant Acid Phosphatase; Transfection

To investigate the effect of gallium salts on bone metabolism in osteoporosis rats caused by tretinoin.. After duplicating osteoporotic model of rats by using tretinoin, we observed the metabolism of blood, urine and bone in vivo. The rats were divided into control group, osteoporosis group, estrogen treated and gallium chloride treated group. The indexes of bone metabolism and related indexes in serum and urine were observed after 60 days of treatment. In the same time, we observed the dynamic effect of 30 days and 60 days of treatment.. After duplicating osteoporotic model, rats' bone structures were injured, the bone mineral density and the organic matrix decreased, the contents of tartrate-resistant acid phosphatase (TRAP) in serum were higher. After gallium salt treating, the above damages were inhibited or retarded. Trabecular width and thickness of bone cortex were significantly increased. AKP and TRAP activities were decreased to the level close to that of the control group.. Gallium salt is effective in treating osteoporosis.

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Bone Density; Disease Models, Animal; Female; Gallium; Isoenzymes; Osteoporosis; Random Allocation; Rats; Rats, Sprague-Dawley; Tartrate-Resistant Acid Phosphatase; Tretinoin

Hyperhomocystinemia is a modifiable risk factor for osteoporosis and fracture. Physiologic concentrations of Hcy directly activate osteoclast formation and activity through stimulation of p38 MAPK and integrin beta3. The effects of Hcy were mediated by generation of intracellular ROS.. Hyperhomocysteinemia is a modifiable risk factor for osteoporosis and its related bone fractures. It has been reported that bone resorption and turnover rate were increased in hyperhomocystinemia. Using mouse bone marrow cells, we examined the direct effects of homocysteine (Hcy) on osteoclast formation and activity.. Osteoclast formation was determined by TRACP staining and TRACP activity. Intracellular reactive oxygen species (ROS) generation was measured using a fluorescent probe, dichlorodihydrofluorescein diacetate. Intracellular signaling cascades of p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and NF-kappaB were measured by Western blotting. Integrin beta3 mRNA levels were measured by RT-PCR. Actin ring formation and bone resorption assays were also performed.. Physiologic concentrations of Hcy upregulated TRACP+ multinucleated cells and TRACP activity, stimulated actin ring formation, and increased the number of nuclei per cell and the level of expression of integrin beta3 mRNA. In addition, Hcy increased bone resorption and stimulated p38 MAPK activity and intracellular reactive oxygen species (ROS) generation. All of these Hcy-induced changes were blocked by pretreatment with the antioxidant, N-acetyl cysteine.. Hcy directly activates osteoclast formation and activity through increased generation of intracellular ROS. These findings suggest that, in individuals with mild to moderate hyperhomocystinemia, increased bone resorption by osteoclasts may contribute to osteoporosis and that an antioxidant may attenuate bone loss in these individuals.

Topics: Acid Phosphatase; Animals; Bone Marrow Cells; Bone Resorption; Cell Differentiation; Cells, Cultured; Fractures, Bone; Homocysteine; Hyperhomocysteinemia; Isoenzymes; MAP Kinase Signaling System; Mice; Mice, Inbred ICR; Osteoclasts; Osteoporosis; Protein Kinases; Reactive Oxygen Species; Risk Factors; Tartrate-Resistant Acid Phosphatase

Patients with rheumatoid arthritis commonly suffer both systemic and periarticular osteoporosis. Bisphosphonates (BPs) are inhibitors of bone resorption, and several derivatives have been developed for treatment of enhanced bone resorption. We aimed to characterize osteoclast formation in two different sites, the proximal tibial and distal tibial areas, in rats with adjuvant arthritis, and to investigate the impact of amino or non-amino types of bisphosphonate. Adjuvant arthritis was initiated in rats while administering daily injections of either etidronate, a non-amino BP, or alendronate, an amino BP, for 3 weeks. On the day following the last injection, bone mineral density (BMD) was measured in the proximal tibia to assess systemic osteoporosis and in the distal tibia for periarticular osteoporosis using dual-energy X-ray absorptiometry. Subsequently, bone marrow cells from either end of the tibia were collected and incubated for 7 days before staining and counting tartrate-resistant acid phosphatase positive cells. In the rats with adjuvant arthritis, BMD of either end of the tibia was lower than in normal rats. Although etidronate prevented bone mineral loss at both ends, distal loss was significantly less than proximal. In contrast, alendronate significantly inhibited mineral loss primarily in the proximal area. Large osteoclasts, defined as having five or more nuclei, formed preferentially in the proximal tibia, while small osteoclasts with fewer than four nuclei were found mainly distally. The suppressive effect of alendronate was greater on the large osteoclasts, while etidronate had a greater effect on the small osteoclasts. These results show that the size and multinuclearity of osteoclasts and the number of osteoclasts formed are different in the distal and proximal areas of the tibia, and that alendronate and etidronate may suppress different types of osteoclasts as discriminated by the number of nuclei.

Topics: Absorptiometry, Photon; Acid Phosphatase; Alendronate; Animals; Arthritis, Experimental; Bone Density; Bone Density Conservation Agents; Bone Marrow Cells; Cells, Cultured; Dose-Response Relationship, Drug; Etidronic Acid; Giant Cells; Isoenzymes; Male; Osteoclasts; Osteoporosis; Rats; Rats, Inbred Lew; Tartrate-Resistant Acid Phosphatase; Tibia

To observe the therapeutic efficacy of dietary boron supplement on retinoic acid-induced osteoporosis in rats, so as to provide experimental evidence for clinical management of osteoporosis with boron.. Thirty-two SD rats were randomized into normal control group (8 rats) and osteoporotic group (24 rats), and osteoporosis was induced in rats of the latter group by intragastric retinoic acid administration at the daily dose of 80 mg/kg for 15 consecutive days. The osteoporotic rats were subdivided into control group (8 rats) without treatment, boron treatment group (8 rats) and estradiol treatment group (8 rats). After 30 days of treatment, the serum contents of Ca, P, boron and the activities of alkaline phosphatase (AKP) and tartrate-resistant acid phosphatase (TRAP) in the rats were assayed, the bone mineral density (BMD) of the whole body, lumbar vertebrae and tibia were determined, and the morphological changes of the femurs were observed.. The serum contents of Ca and P in the rats of the 4 groups differed scarcely, but the content of boron in boron treatment group was markedly higher than that in the other three groups. In the osteoporotic control group, the activities of serum AKP and TRAP, the masses of spongy bone and cortical bone of the femurs, and the quantity of the osteoclasts were increased, with the BMD of the lumbar vertebrae and tibia decreased, suggesting osteoporotic conditions. The mean trabecular plate density and thickness, trabecular bone volume and cortical bone volume of the femurs in the osteoporotic rats treated with boron or estradiol were significantly increased, but the active osteoclast quantity in the spongy bone and serum TRAP activities were obviously decreased, and the bone quality was comparable with that of the normal group. In addition, the serum AKP activity and the active osteoblast quantity in the spongy bone were obviously increased in boron treatment group.. The dietary boron supplement can increase the serum content of boron of osteoporotic rats to stimulate bone formation and inhibit bone resorption, producing therefore obvious therapeutical effect against osteoporosis.

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Bone Density; Boron; Dietary Supplements; Female; Femur; Isoenzymes; Osteoporosis; Random Allocation; Rats; Rats, Sprague-Dawley; Tartrate-Resistant Acid Phosphatase; Time Factors; Tretinoin

Recent studies suggest that vitamin D signaling regulates bone formation. However, the overall effect of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] on bone turnover in vivo is still unclear. In this study, our aim was to examine the effect of 1,25(OH)2D3 on bone turnover in SAM-P/6, a hormone-independent mouse model of senile osteoporosis characterized by a decrease in bone formation. Male and female 4-mo-old SAM-P/6 mice were treated with 1,25(OH)2D3 (18 pmol/24 h) or vehicle for a period of 6 wk, and a group of age- and sex-matched nonosteoporotic animals was used as control. Bone mineral density (BMD) at the lumbar spine increased rapidly by >30 +/- 5% (P < 0.001) in 1,25(OH)2D3-treated SAM-P/6 animals, whereas BMD decreased significantly by 18 +/- 2% (P < 0.01) in vehicle-treated SAM-P/6 animals and remained stable in control animals during the same period. Static and dynamic bone histomorphometry indicated that 1,25(OH)2D3 significantly increased bone volume and other parameters of bone quality as well as subperiosteal bone formation rate compared with vehicle-treated SAM-P/6 mice. However, no effect on trabecular bone formation was observed. This was accompanied by a marked decrease in the number of osteoclasts and eroded surfaces. A significant increase in circulating bone formation markers and a decrease in bone resorption markers was also observed. Finally, bone marrow cells, obtained from 1,25(OH)2D3-treated animals and cultured in the absence of 1,25(OH)2D3, differentiated more intensely into osteoblasts compared with those derived from vehicle-treated mice cultured in the same conditions. Taken together, these findings demonstrate that 1,25(OH)2D3 acts simultaneously on bone formation and resorption to prevent the development of senile osteoporosis.

Topics: Absorptiometry, Photon; Acid Phosphatase; Alkaline Phosphatase; Animals; Bone and Bones; Bone Density; Bone Marrow Cells; Bone Remodeling; Calcitriol; Cell Differentiation; Collagen; Collagen Type I; Female; Femur; Histocytochemistry; Isoenzymes; Male; Mice; Osteocalcin; Osteoporosis; Parathyroid Hormone; Peptides; Tartrate-Resistant Acid Phosphatase

To observe the effects of Icariin on ovariectomized osteoporotic rats.. Female Wistar rats were ovariectomized and administered different dosage of Icariin and 17beta-estradiol for eight weeks. Bone mineral density (BMD), indexes of biomechanics and bone metabolism-associated biochemical markers were measured.. Icariin increased the BMD, maximum load and flexural rigidity in the osteoporotic rats. The activities of serum tartrate-resistant acid phosphatase (TRACP) and bone alkaline phosphatase (BALP) were decreased in the Icraiin-fed ovariectomized rats.. Icariin 225mg/kg per day could increase the BMD and improve indexes of bone biomechanics in ovariectomized osteoporotic rats. It was effective in preventing bone loss induced by ovariectomy.

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Biomechanical Phenomena; Bone Density; Dose-Response Relationship, Drug; Drugs, Chinese Herbal; Female; Flavonoids; Isoenzymes; Osteoporosis; Ovariectomy; Rats; Rats, Wistar; Tartrate-Resistant Acid Phosphatase

Stromal/osteoblastic cell expression of RANKL and M-CSF regulates osteoclastogenesis. We show that aging is accompanied by increased RANKL and M-CSF expression, increased stromal/osteoblastic cell-induced osteoclastogenesis, and expansion of the osteoclast precursor pool. These changes correlate with age-related alterations in the relationship between osteoblasts and osteoclasts in cancellous bone.. Bone mass is maintained through a balance between osteoblast and osteoclast activity. Osteoblasts regulate the number and activity of osteoclasts through expression of RANKL, osteoprotegerin (OPG), and macrophage-colony stimulation factor (M-CSF). To determine whether age-related changes in stromal/osteoblastic cell expression of RANKL, OPG, and M-CSF are associated with stimulation of osteoclastogenesis and whether the osteoclast precursor pool changes with age, we studied cultures of stromal/osteoblastic cells and osteoclast precursor cells from animals of different ages and examined how aging influences bone cell populations in vivo.. Osteoclast precursors from male C57BL/6 mice of 6 weeks (young), 6 months (adult), and 24 months (old) of age were either co-cultured with stromal/osteoblastic cells from young, adult, or old mice or treated with M-CSF, RANKL, and/or OPG. Osteoclast precursor pool size was determined by fluorescence-activated cell sorting (FACS), and osteoclast formation was assessed by measuring the number of multinucleated TRACP(+) cells and pit formation. The levels of mRNA for RANKL, M-CSF, and OPG were determined by quantitative RT-PCR, and transcription was measured by PCR-based run-on assays. Osteoblast and osteoclast numbers in bone were measured by histomorphometry.. Osteoclast formation increased dramatically when stromal/osteoblastic cells from old compared with young donors were used to induce osteoclastogenesis. Regardless of the origin of the stromal/osteoblastic cells, the number of osteoclasts formed from the nonadherent population of cells increased with increasing age. Stromal/osteoblastic cell expression of RANKL and M-CSF increased, whereas OPG decreased with aging. Exogenously administered RANKL and M-CSF increased, dose-dependently, osteoclast formation from all donors, but the response was greater in cells from old donors. Osteoclast formation in vitro positively, and the ratio of osteoblasts to osteoclasts in vivo negatively, correlated with the ratio of RANKL to OPG expression in stromal/osteoblastic cells for all ages. The effects of RANKL-induced osteoclastogenesis in vitro were blocked by OPG, suggesting a causal relationship between RANKL expression and osteoclast-inducing potential. The osteoclast precursor pool and expression of RANK and c-fms increased with age.. Our results show that aging significantly increases stromal/osteoblastic cell-induced osteoclastogenesis, promotes expansion of the osteoclast precursor pool and alters the relationship between osteoblasts and osteoclasts in cancellous bone.

Topics: Acid Phosphatase; Age Factors; Aging; Animals; Bone and Bones; Bone Resorption; Carrier Proteins; Cell Nucleus; Cell Separation; Coculture Techniques; Dose-Response Relationship, Drug; Flow Cytometry; Gene Expression Regulation; Glycoproteins; Immunomagnetic Separation; Isoenzymes; Macrophage Colony-Stimulating Factor; Macrophages; Male; Membrane Glycoproteins; Mice; Mice, Inbred C57BL; Osteoblasts; Osteoclasts; Osteoporosis; Osteoprotegerin; Polymerase Chain Reaction; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Stromal Cells; Tartrate-Resistant Acid Phosphatase; Time Factors

A number of alternative medicines (AMs) have often been used as traditional therapies for various diseases without scientific or clinical evidence supporting their use. The present study examined the pharmaceutical effects of an AM extract with a long history of use as a traditional medicine for various bone diseases. To evaluate it as a potential candidate for use as an anti-osteoporotic drug, we investigated the effects of the AM extract on the progression of bone loss in ovariectomized (OVX) rats fed a calcium (Ca)-deficient diet for 4 or 12 weeks. We also compared the AM extract with alendronate, an anti-resorptive drug. The AM extract did not influence bone turnover as indicated by biochemical markers [i.e., deoxypyridinoline (DPD)]. In contrast, alendronate treatment seemed to reduce bone turnover via inhibition of bone resorption as evidenced by reduced urinary DPD concentrations accompanied by a tendency for decreased serum tartrate-resistant acid phosphatase. Administration of alendronate or AM extracts did not significantly affect bone density, although both tended to increase bone mineral density (BMD) and bone strength of the femur. Although both treatments did not affect vertebral BMD and bone strength, histological analysis of vertebrae showed well-developed trabecular networking in OVX rats treated with alendronate or AM extract, in contrast to the thin and disconnected trabecule in OVX rats. In conclusion, the AM extract produced a very weak effect on the prevention of bone loss induced by OVX and Ca deficiency in rats, but was similar to the results observed with alendronate. Further verification is necessary to justify the use of the AM extract as a treatment for osteoporosis.

Topics: Acid Phosphatase; Alendronate; Amino Acids; Animals; Biomechanical Phenomena; Bone Density; Bone Remodeling; Bone Resorption; Calcium; Complementary Therapies; Female; Korea; Medicine, Traditional; Osteoporosis; Ovariectomy; Rats; Rats, Sprague-Dawley; Spine

Etodolac, a cyclooxygenase-2 inhibitor, may alleviate nociceptive pain and inhibit the activation of osteoclasts. The aim of the present study was to determine whether etodolac can alleviate heat-evoked hyperalgesia and investigate its possible protective effects on osteoporosis induced by chronic constriction injury (CCI) in rats. A CCI to the sciatic nerve was performed, after which the rats received etodolac orally in a volume of 2 ml at 0, 1, and 10 mg/kg/day for 1 to 5 weeks following surgery (experiment 1); at 0 and 10 mg/kg/day for 1 day to 5 weeks following surgery (experiment 2); and at 0 mg/kg/day for 1 to 5 weeks, 10 mg/kg/day for 1 to 2 weeks after surgery, or 10 mg/kg/day for 1 to 3 weeks after surgery (experiment 3). Paw withdrawal latency after exposure to heat, bone mineral content (BMC) and bone mineral density (BMD) in the whole tibial bone, and the number of tartrate resistant acid phosphate (TRAP)-positive multinucleated osteoclasts were measured. Etodolac alleviated heat-evoked hyperalgesia in the CCI rats and the increase in number of TRAP-positive multinucleated osteoclasts on the CCI-side was abrogated, however, it did not inhibit the decrease of BMC and BMD on the CCI-side. Our results suggest that etodolac is useful for treatment of neuropathic pain.

Topics: Acid Phosphatase; Animals; Bone Density; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Disease Models, Animal; Etodolac; Hyperalgesia; Isoenzymes; Ligation; Neuralgia; Osteoclasts; Osteoporosis; Pain Measurement; Peripheral Nerves; Peripheral Nervous System Diseases; Prostaglandin-Endoperoxide Synthases; Rats; Rats, Sprague-Dawley; Reaction Time; Sciatic Neuropathy; Tartrate-Resistant Acid Phosphatase; Up-Regulation

To examine a potential role for soybean phytoestrogens in postmenopausal bone loss, twenty-four 12-week-old Sprague-Dawley rats were divided randomly into 4 groups and given controlled diets for 16 weeks. The treatment groups were as followed: sham operated, ovariectomized (OVX) control, OVX + isoflavone extract (6.25 g/kg), and OVX + 17beta-estradiol (4 mg/kg). OVX treatments reduced femoral and fourth lumbar vertebral bone density and mineral content (p<0.01), decreased uterine weight (p<0.01), accelerated body weight increases (p<0.05), and increased the activities (p<0.01) of both serum alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP). Supplementation with isoflavone prevented the losses of bone density and mineral content caused by OVX (p<0.01). Although both isoflavone and 17beta-estradiol exhibited similar bone-sparing ability on the OVX-induced bone loss, the effect of isoflavone was not the same as that of 17beta-estradiol on the serum ALP and TRAP, body weight increase, and uterine weight change. We concluded that dietary supplementation with soybean isoflavone can prevent postmenopausal bone loss via a different mechanism of estrogen in OVX rats.

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Bone Density; Calcium; Eating; Estradiol; Female; Genistein; Glycine max; Humans; Isoenzymes; Isoflavones; Organ Size; Osteoporosis; Osteoporosis, Postmenopausal; Ovariectomy; Plant Extracts; Rats; Rats, Sprague-Dawley; Tartrate-Resistant Acid Phosphatase

Bone loss was previously shown to be induced in the femoral tissue of regucalcin transgenic (TG) rats. Regucalcin is expressed in rat bone marrow cells and its expression is enhanced in regucalcin TG rats. This study was undertaken to determine the change in osteoclastic bone resorption in regucalcin TG rats with increasing age. Femoral-diaphyseal and -metaphyseal tissues were obtained from normal (wild-type) and regucalcin TG rats aged 5, 14, 25 or 50 weeks. Calcium content in the femoral-diaphyseal and -metaphyseal tissues was significantly decreased in regucalcin TG male and female rats aged 5, 14, 25 or 50 weeks as compared with the value obtained from normal rats with each age. When the marrow cells obtained from normal or regucalcin TG rats were cultured for 7 days, the number of tartrate-resistant acid phosphatase (TRACP), a marker of osteoclasts, positive multinucleated cells (MNCs) were significantly increased in the marrow culture of regucalcin TG male and female rats aged 5, 14, 25 or 50 weeks. The effect of parathyroid hormone [human PTH (1-34); 10(-7) M] or 1,25-dihydroxyvitamin D3 [1,25(OH)2D3; 10(-7) M] in stimulating TRACP-positive MNC formation was significantly enhanced in regucalcin TG male and female rats aged 14 or 25 weeks. This study demonstrates that osteoclastic bone resorption is stimulated in regucalcin TG male and female rats with increasing age.

Topics: Acid Phosphatase; Aging; Animals; Animals, Genetically Modified; Biomarkers; Bone Marrow Cells; Calcium; Calcium-Binding Proteins; Carboxylic Ester Hydrolases; Cell Lineage; Cells, Cultured; Disease Models, Animal; Female; Gene Expression Regulation; Humans; Intracellular Signaling Peptides and Proteins; Isoenzymes; Male; Osteoclasts; Osteoporosis; Parathyroid Hormone; Rats; Rats, Sprague-Dawley; Sulfotransferases; Tartrate-Resistant Acid Phosphatase; Time Factors; Vitamin D

High and low bone turnover situations, both of which are typically observed as postmenopausal and senile osteoporosis, were created by ovariectomy (OVX), and then an investigation of whether or not the difference of bone turnover affected peri-titanium (Ti) implant osteogenesis in rats was conducted. Female rats were divided into four groups. The experimental and control groups underwent OVX or sham operations at 15 or 27 weeks of age, as high or low bone turnover groups, respectively. Ti implants were inserted into the tibiae at 30 weeks, then fluorochromes were injected 10 or 20 days after the implantation for histometry. The implants were retained for 30 days and then ground sections were prepared. Afterward, the cortical bone growth rate, bone contact ratio (BCR) of the implant in both the cortical bone area and medullary canal area, and the average trabecular bone thickness around the implant were evaluated. Biochemical markers of bone turnover were also measured. Biochemical measurements indicated both increasing osteocalcin production in OVX rats and decreasing tartrate-resistant acid phosphatase activity in the low-turnover group. Histometrical measurements showed decreasing cortical growth and low BCR in the medullary canal of the low-turnover group. The high-turnover group demonstrated BCR as high as that of the control group. There was no significant difference in the average trabecular bone thickness around the implant among the groups. As a result, two types of osteoporotic situations were confirmed and it was shown that the difference of bone turnover was clearly due to the diverse osteogenesis around the Ti implant.

Topics: Acid Phosphatase; Animals; Biocompatible Materials; Female; Isoenzymes; Materials Testing; Osteocalcin; Osteogenesis; Osteoporosis; Ovariectomy; Prostheses and Implants; Rats; Rats, Wistar; Tartrate-Resistant Acid Phosphatase; Tibia; Titanium

We investigated time-course changes in the expression of receptor activator of nuclear factor-kappaB (RANK), its ligand (RANKL), osteoprotegerin (OPG), bone-type alkaline phosphatase (BAP), and tartrate-resistant acid phosphatase (TRAP) in ovariectomized (OVX) rats. Samples of sera and coccyges were used for analysis of the enzyme activities and expression levels of proteins and mRNAs, and an immunohistochemical analysis was also performed. Serum BAP activity increased to 158.6% of the pre-operation value at 1 week after OVX, and then decreased to 38.7% at 8 weeks after OVX. On the other hand, the serum TRAP activity increased to 130.9% of the pre-operation level at 1 week after OVX, and was maintained at a high level, compared with the pre-operation level. The patterns of BAP and TRAP activity in the coccyges specimens were similar to those seen in the sera. The expression profiles of TRAP, RANK, and RANKL proteins in the coccyx specimens were similar to the pattern of serum TRAP activity, while the profiles of the BAP and OPG proteins were similar to the pattern of serum BAP activity in OVX rats. The changes in the mRNA expression levels of the osteogenic proteins were similar to those for protein expression. These biochemical changes in OVX rats were confirmed by immunohistochemical studies. Our results suggest that not only osteoclastogenesis accelerated but also osteoblastogenesis transiently increased during the early phase of osteoporosis.

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Carrier Proteins; Coccyx; Female; Glycoproteins; Immunohistochemistry; Isoenzymes; Membrane Glycoproteins; Osteoporosis; Osteoprotegerin; Ovariectomy; RANK Ligand; Rats; Rats, Wistar; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor; Tartrate-Resistant Acid Phosphatase

Osteoclasts secrete tartrate-resistant acid phosphatase 5b (TRACP 5b) into the circulation. We have developed an immunoassay for the determination of rat TRACP 5b activity. Intra-assay variation of the immunoassay was 4.5%, interassay variation was 3.8%, dilution linearity was 104.6 +/- 7.6%, and recovery of recombinant rat TRACP was 99.1 +/- 5.8%. We studied serum TRACP 5b as a marker of bone resorption using orchidectomized (ORC) rats as a model for osteoporosis and age-matched sham-operated rats as controls in a 6-month study. After the operation, trabecular bone mineral density decreased significantly more in the ORC group than in the sham group, whereas cortical bone mineral density increased similarly in both groups. Serum TRACP 5b activity was significantly elevated within the first week after ORC, returned to the control level in the third week, and was not increased above the sham level at any of the later time points. At 6 months, trabecular bone volume was 80% lower in ORC rats than in controls. Osteoclast number per trabecular bone perimeter was slightly increased, but the absolute number of osteoclasts in trabecular bone was significantly decreased. These results suggest that absolute bone resorption is increased within the first week after ORC. Later, it is decreased because there is less bone to be resorbed. However, relative bone resorption (compared with the amount of remaining bone) is still increased, leading to further bone loss. We conclude that serum TRACP 5b is a useful marker for monitoring changes in the bone resorption rate in rat ORC model.

Topics: Acid Phosphatase; Animals; Blood Chemical Analysis; Bone Density; Bone Resorption; Disease Models, Animal; Immunoassay; Isoenzymes; Male; Orchiectomy; Osteoporosis; Rats; Rats, Sprague-Dawley; Tartrate-Resistant Acid Phosphatase; Time Factors

The mechanisms of action of dietary fish oil (FO) on osteoporosis are not fully understood. This study showed FO decreased bone loss in ovariectomized mice because of inhibition of osteoclastogenesis. This finding supports a beneficial effect of FO on the attenuation of osteoporosis.. Consumption of fish or n-3 fatty acids protects against cardiovascular and autoimmune disorders. Beneficial effects on bone mineral density have also been reported in rats and humans, but the precise mechanisms involved have not been described.. Sham and ovariectomized (OVX) mice were fed diets containing either 5% corn oil (CO) or 5% fish oil (FO). Bone mineral density was analyzed by DXA. The serum lipid profile was analyzed by gas chromatography. Receptor activator of NF-kappaB ligand (RANKL) expression and cytokine production in activated T-cells were analyzed by flow cytometry and ELISA, respectively. Osteoclasts were generated by culturing bone marrow (BM) cells with 1,25(OH)2D3. NF-kappaB activation in BM macrophages was measured by an electrophoretic mobility shift assay.. Plasma lipid C16:1n6, C20:5n3, and C22:6n3 were significantly increased and C20:4n6 and C18:2n6 decreased in FO-fed mice. Significantly increased bone mineral density loss (20% in distal left femur and 22.6% in lumbar vertebrae) was observed in OVX mice fed CO, whereas FO-fed mice showed only 10% and no change, respectively. Bone mineral density loss was correlated with increased RANKL expression in activated CD4+ T-cells from CO-fed OVX mice, but there was no change in FO-fed mice. Selected n-3 fatty acids (docosahexaenoic acid [DHA] and eicosapentaenoic acid [EPA]) added in vitro caused a significant decrease in TRACP activity and TRACP+ multinuclear cell formation from BM cells compared with selected n-6 fatty acids (linoleic acid [LA] and arachidonic acid [AA]). DHA and EPA also inhibited BM macrophage NF-kappaB activation induced by RANKL in vitro. TNF-alpha, interleukin (IL)-2, and interferon (IFN)-gamma concentrations from both sham and OVX FO-fed mice were decreased in the culture medium of splenocytes, and interleukin-6 was decreased in sham-operated FO-fed mice. In conclusion, inhibition of osteoclast generation and activation may be one of the mechanisms by which dietary n-3 fatty acids reduce bone loss in OVX mice.

Topics: Acid Phosphatase; Animals; Carrier Proteins; Corn Oil; Cytokines; Dietary Fats; Fatty Acids; Fatty Acids, Omega-3; Female; Fish Oils; Isoenzymes; Macrophages; Membrane Glycoproteins; Mice; Mice, Inbred BALB C; NF-kappa B; Organ Size; Osteoclasts; Osteogenesis; Osteoporosis; Ovariectomy; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Spine; Spleen; Tartrate-Resistant Acid Phosphatase; Uterus

Long-term administration of glucocorticoids (GCs) causes osteoporosis with a rapid and severe bone loss and with a slow and prolonged bone disruption. Although the involvement of GCs in osteoblastic proliferation and differentiation has been studied extensively, their direct action on osteoclasts is still controversial and not conclusive. In this study, we investigated the direct participation of GCs in osteoclastogenesis. Dexamethasone (Dex) at <10(-8) M stimulated, but at >10(-7) M depressed, receptor activator of NF-kappaB ligand (RANKL)-induced osteoclast formation synergistically with transforming growth factor-beta. The stimulatory action of Dex was restricted to the early phase of osteoclast differentiation and enhanced the priming of osteoclast progenitors (bone marrow-derived monocytes/macrophages) toward differentiation into cells of the osteoclast lineage. The osteoclast differentiation depending on RANKL requires the activation of NF-kappaB and AP-1, and the DNA binding of these transcription factors to their respective consensus cis-elements was enhanced by Dex, consistent with the stimulation of osteoclastogenesis. However, Dex did not affect the RANKL-induced signaling pathways such as the activation of IkappaB kinase followed by NF-kappaB nuclear translocation or the activation of JNK. On the other hand, Dex significantly decreased the endogenous production of interferon-beta, and this cytokine depressed the RANKL-elicited DNA binding of NF-kappaB and AP-1, as well as osteoclast formation. Thus, the down-regulation of inhibitory cytokines such as interferon-beta by Dex may allow the osteoclast progenitors to be freed from the suppression of osteoclastogenesis, resulting in an increased number of osteoclasts, as is observed in the early phase of GC-induced osteoporosis.

Topics: Acid Phosphatase; Animals; Bone Marrow Cells; Carrier Proteins; Cell Differentiation; Dexamethasone; DNA; Drug Synergism; Glucocorticoids; Humans; Interferon-beta; Macrophage Colony-Stimulating Factor; Membrane Glycoproteins; Mice; Mice, Inbred ICR; NF-kappa B; Osteoclasts; Osteoporosis; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Recombinant Proteins; RNA, Messenger; Signal Transduction; Spectrometry, Fluorescence; Stem Cells; Transcription Factor AP-1; Transforming Growth Factor beta

Osteoporosis in beta-thalassaemia is multifactorial; increased osteoclast function seems to play an important role in its pathogenesis. The aim of this study was to evaluate the effect of pamidronate on the osteoporosis of thalassaemia. To this effect we studied 26 patients who received this drug in doses of 30 or 60 mg i.v. once a month over 12 months. The effects were monitored by measuring bone mineral density (BMD) in association with markers of osteoclast function [soluble receptor activator of nuclear factor-kappa B ligand (sRANKL), osteoprotegerin (OPG)] and of bone remodelling [N-telopeptide of collagen type-I (NTX), tartrate-resistant acid phosphatase isoform-5b (TRACP-5b), bone-alkaline phosphatase (bALP), and osteocalcin (OC)]. Thirty healthy individuals were also studied, as controls. NTX, TRACP-5b, bALP and OC levels were significantly higher in thalassaemic patients compared with controls; in contrast, OPG levels were significantly lower, while the levels of sRANKL varied within normal limits. Administration of pamidronate was followed by a clear decrease of NTX, TRACP-5b, OPG, and OC, and by a significant increase in the BMD of the lumbar spine, which was similar in patients of both treatment groups. These data suggest that pamidronate, at a monthly dose of 30 mg, is an effective treatment for thalassaemic osteoporosis.

Topics: Acid Phosphatase; Adult; Alkaline Phosphatase; Anti-Inflammatory Agents; beta-Thalassemia; Biomarkers; Blood Transfusion; Bone Density; Carrier Proteins; Case-Control Studies; Collagen; Collagen Type I; Diphosphonates; Drug Administration Schedule; Female; Glycoproteins; Humans; Isoenzymes; Lumbar Vertebrae; Male; Membrane Glycoproteins; Middle Aged; Osteocalcin; Osteoporosis; Osteoprotegerin; Pamidronate; Peptides; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor; Statistics, Nonparametric; Tartrate-Resistant Acid Phosphatase

To study the changes of serum sex hormone levels and tartrate-resistant acid phosphatase (TRACP) activity in healthy women of different ages, and to provide parameters for basic and clinical research of osteoporosis.. Serum sex hormone (FSH, LH, E2, P) levels and TRACP activity were measured in 236 premenopausal healthy women aged 23-53 years and divided into 3 groups, and in 91 postmenopausal healthy women aged 48-71 years.. Except serum FSH levels which were significantly higher in the third group than those of the other groups in premenopausal healthy women (P < 0.05), no significant difference in sex hormone levels and TRACP activity was found among the 3 groups; the postmenopausal group showed a significant increase in serum FSH, LH levels and TRACP activity and a significant decrease in serum E2, P levels, compared with the premenopausal groups (P < 0.01). There was a negative correlation between E2, P levels and TRACP activity in the postmenopausal women (r = -0.41 and -0.37, respectively, P < 0.01).. Postmenopausal diminution of E2, P results in an increase of serum FSH and LH levels, and may bring about an increase of bone resorption, which results in the increase of TRACP activity.

Topics: Acid Phosphatase; Adult; Female; Follicle Stimulating Hormone; Humans; Isoenzymes; Luteinizing Hormone; Middle Aged; Osteoporosis; Tartrate-Resistant Acid Phosphatase

The aim of this study was to evaluate the activity of alkaline (ALP) and acid (ACP) phosphatase in the blood serum of rats after ovariectomy and with estrogen replacement therapy. The relationship between mandible and spine bone mineral density (BMD) and parameters of bone remodeling was also estimated. The concentration of serum total alkaline and acid phosphatase was higher in the rats with estrogen deficiency, and statistically lower in rats administering 17 beta-estradiol. ALP and ACP levels were correlated significantly negative with mandible and spine BMD. Carried out examinations confirmed increasing bone resorption during experimental postmenopausal osteoporosis.

Topics: Acid Phosphatase; Alkaline Phosphatase; Analysis of Variance; Animals; Biomarkers; Bone Density; Bone Remodeling; Estradiol; Female; Models, Animal; Osteoporosis; Ovariectomy; Postmenopause; Rats; Rats, Wistar

This article deals with an osteoporosis model using New Zealand rabbits in order to study the function of inorganic elements for women patients with osteoporosis. Thirty cases of iliac crests were collected and determined using the neutron activation analysis technique. The results show that the fluorine concentrations in the experimental group are higher than those in the control group and that the magnesium concentrations are significantly lower (p < 0.001), but the concentrations of potassium, sodium, calcium, barium, manganese, and strontium show no significant differences. Combined with the serum biochemical markers of bone formation and resorption, the physiological functions of some metal elements in bone are also discussed.

Topics: Acid Phosphatase; Animals; Female; Fluorine; Ilium; Magnesium; Metals; Neutron Activation Analysis; Osteoporosis; Potassium; Rabbits; Trace Elements; Zinc

Our previous studies demonstrated that estrogen (E2) prevents the development of disuse atrophy of the femur in tail-suspended rats. To elucidate the mechanisms of this E2 action, we investigated the effects of E2 on the expression of alkaline phosphatase (ALP, a marker for bone formation) and tartrate-resistant acid phosphatase (TRAP, a marker for bone resorption) in the femur of ovariectomized and tail-suspended rats. One group of ovariectomized rats received estradiol dipropionate (OVX-E2), and the other the vehicle alone (OVX). Each group was subjected to tail-suspension. After 1, 3, 5 or 7 days of suspension, ALP and TRAP mRNA levels were determined by Northern blot analysis. The ALP mRNA level was not altered by suspension in the OVX group, but it gradually increased in the OVX-E2 group, the highest level being observed at day 5 of suspension. In contrast, TRAP mRNA significantly increased at days 5 and 7 in the OVX group, while it is decreased significantly from day 3 to 7 in the OVX-E2 group. These results indicate that E2 prevents disuse atrophy of the femur in an ovariectomized and tail-suspended rat model by stimulating bone formation and by inhibiting bone resorption.

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Biomarkers; Estradiol; Female; Femur; Hindlimb Suspension; Isoenzymes; Osteoporosis; Ovariectomy; Rats; Rats, Wistar; RNA, Messenger; Tartrate-Resistant Acid Phosphatase; Time Factors

Topics: Acid Phosphatase; Aged; Biomarkers; Bone and Bones; Bone Diseases, Metabolic; Female; Humans; Isoenzymes; Male; Middle Aged; Osteoporosis; Tartrate-Resistant Acid Phosphatase

Topics: Acid Phosphatase; Adult; Aged; Alkaline Phosphatase; Biomarkers; Bone Resorption; Collagen; Collagen Type I; Enzyme-Linked Immunosorbent Assay; Glucocorticoids; Humans; Isoenzymes; Male; Middle Aged; Osteocalcin; Osteoporosis; Peptides; Spectrophotometry; Tartrate-Resistant Acid Phosphatase

The aim of this study was to assess the skeletal metabolism in a murine model of systemic lupus erythematosus (SLE). MRL/n and MRL/l mice (respectively representing a benign and a malignant form of the disease) were observed from 1.5 to 6.5 months of life. The monthly follow-up included: biochemical and histomorphometrical studies of the femoral bone, serum biochemistry, immunoglobulins and osteocalcin, and histological evaluation of the kidney tissue. The results showed a higher femoral weight (+11.5%), calcium (+4.4%) and protein bone content (+11.4%) and a significantly higher (+77%) phosphorus bone content in the MRL/n group; significantly lower (-48.9%) bone alkaline phosphatase enzymatic activity, lower bone alkaline/acid phosphatase enzymatic activities ratio (-40.8%) and lower (-38.4%) serum osteocalcin values in the MRL/l group (which might suggest reduced bone formation in these animals); markedly smaller trabecular bone volume (BV/TV) in the femoral head (-36.2%) and femoral neck (-39.8%), and smaller cortical and femoral areas in the mid-femoral shaft (-38.8% and -38.1% respectively) in the MRL/l group; higher serum immunoglobulins, increased serum blood urea nitrogen (BUN) and creatinine and a higher index of activity in the kidney histology in the MRL/l group, indicating increased activity of the disease in this substrain. The MRL mice, through their two substrains, may serve as a valuable laboratory animal model for study of the skeletal changes in SLE and of the influence of the disease activity on the skeletal metabolism.

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Calcium; Disease Models, Animal; Femur; Lupus Erythematosus, Systemic; Magnesium; Mice; Mice, Inbred MRL lpr; Organ Size; Osteocalcin; Osteoporosis; Phosphorus

At the level of prevention of bone mineral loss produced by ovariectomy, the aim of the present study was to determine the effect produced by supplementation of Ca in the diet and a moderate exercise programme (treadmill), simultaneously or separately, in ovariectomized rats, an experimental model of postmenopausal bone loss. Female Wistar rats (n 110, 15 weeks old) were divided into five groups: (1) OVX, rats ovariectomized at 15 weeks of age, fed a standard diet; (2) SHAM, rats sham operated at 15 weeks of age, fed a standard diet; (3) OVX-EX, ovariectomized rats, fed a standard diet and performing the established exercise programme; (4) OVX-Ca, ovariectomized rats fed a diet supplemented with Ca; (5) OVX-EXCa, ovariectomized rats with the exercise programme and diet supplemented with Ca. The different treatments were initiated 1 week after ovariectomy and were continued for 13 weeks for subgroup 1 and 28 weeks for subgroup 2, to look at the interaction of age and time passed from ovariectomy on the treatments. Bone mineral density (BMD) was determined, at the end of the study, in the lumbar spine (L2, L3 and L4) and in the left femur using a densitometer. Bone turnover was also estimated at the end of the study, measuring the serum formation marker total alkaline phosphatase (AP) and the resorption marker serum tartrate-resistant acid phosphatase (TRAP). As expected, OVX rats showed a significant decrease (P<0.05) in BMD, more pronounced in subgroup 2, and a significant increase in AP and TRAP with regard to their respective SHAM group. The simultaneous treatment with Ca and exercise produced the best effects on lumbar and femoral BMD of ovariectomized rats, partially avoiding bone loss produced by ovariectomy, although it was not able to fully maintain BMD levels of intact animals. This combined treatment produced a significant increase in AP, both in subgroups 1 and 2, and a decrease in TRAP in subgroup 1, with regard to OVX group. The exercise treatment alone was able to produce an increase in BMD with regard to OVX group only in subgroup 1 of rats (younger animals and less time from ovariectomy), but not in subgroup 2. In agreement with this, there was an increase of AP in both subgroups, lower than that observed in animals submitted to exercise plus Ca supplement, and a decrease of TRAP in subgroup 1, without significant changes in this marker in the older rats. Ca treatment did not produce any significant effect on BMD in OVX rats in both subgrou

Topics: Acid Phosphatase; Aging; Alkaline Phosphatase; Animals; Biomarkers; Bone Density; Calcium, Dietary; Female; Femur; Isoenzymes; Lumbar Vertebrae; Models, Animal; Osteoporosis; Ovariectomy; Physical Conditioning, Animal; Rats; Rats, Wistar; Tartrate-Resistant Acid Phosphatase; Time Factors

High systemic levels of osteoprotegerin (OPG) in OPG transgenic mice cause osteopetrosis with normal tooth eruption and bone elongation and inhibit the development and activity of endosteal, but not periosteal, osteoclasts. We demonstrate that both intravenous injection of recombinant OPG protein and transgenic overexpression of OPG in OPG(-/-) mice effectively rescue the osteoporotic bone phenotype observed in OPG-deficient mice. However, intravenous injection of recombinant OPG over a 4-wk period could not reverse the arterial calcification observed in OPG(-/-) mice. In contrast, transgenic OPG delivered from mid-gestation through adulthood does prevent the formation of arterial calcification in OPG(-/-) mice. Although OPG is normally expressed in arteries, OPG ligand (OPGL) and receptor activator of NF-kappaB (RANK) are not detected in the arterial walls of wild-type adult mice. Interestingly, OPGL and RANK transcripts are detected in the calcified arteries of OPG(-/-) mice. Furthermore, RANK transcript expression coincides with the presence of multinuclear osteoclast-like cells. These findings indicate that the OPG/OPGL/RANK signaling pathway may play an important role in both pathological and physiological calcification processes. Such findings may also explain the observed high clinical incidence of vascular calcification in the osteoporotic patient population.

Topics: Acid Phosphatase; Animals; Aorta; Blotting, Western; Bone Density; Calcinosis; Cathepsin K; Cathepsins; CHO Cells; Cricetinae; Femur; Glycoproteins; Humans; Immunohistochemistry; In Situ Hybridization; Isoenzymes; Mice; Mice, Knockout; Mice, Transgenic; NF-kappa B; Osteoclasts; Osteopetrosis; Osteoporosis; Osteoprotegerin; Radiography; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor; Recombinant Fusion Proteins; Tartrate-Resistant Acid Phosphatase

The report discusses a study of pyridinoline (Pyd) and deoxypyridinoline (Dpyd) as biochemical markers of bone resorption as well as total bone alkaline phosphatase level (APh) and that of its bone fraction as criteria of osteogenesis in skeletal lesions in breast, prostate and lung cancer and multiple myeloma. The investigation established a significantly enhanced Pyd and Dpyd excretion with urine and increased blood-serum APh levels in skeletal cancers (n = 271) as compared with healthy subjects (n = 173) and patients without bone metastases (n = 94). A case has been made for determination of total excretion of Pyd crosslinks of collagen to diagnose bone metastases. Most pronounced hyperenzymemia was found in prostate cancer which points to the leading role of APh as a bone metastasis marker. Pyd and Dpyd excretion and APh levels were significantly higher among patients multiple metastases with than in those with single bone metastases. The universality of pyridinoline crosslinks as skeletal damage markers has been confirmed by establishing a significant correlation between drug and therapeutic effect for Pyd and Dpyd only, in patients receiving ibandronate.

Topics: Acid Phosphatase; Amino Acids; Biomarkers, Tumor; Bone and Bones; Bone Neoplasms; Bone Remodeling; Clinical Enzyme Tests; Female; Humans; Male; Neoplasms; Osteoporosis; Reference Values

This study was carried out to evaluate the clinical validity and usefulness of serum tartrate-resistant fluoride-sensitive acid phosphatase (TrFsACP) activity using 2,6-dichloro-4-acetylphenyl phosphate as substrate at pH 6.2 in metabolic bone diseases. The mean Z-scores of TrFsACP activity in patients on hemodialysis were higher than in healthy subjects (male: 2.04+/-1.98, n = 49, P < .05; female: 1.49+/-2.43, n = 39, P < .05) and increased with duration of hemodialysis (r = .516, P < .01). Bone alkaline phosphatase also was found to be significantly higher in hemodialysis patients (male: 0.93+/-1.49, P < .05; female: 1.66+/-2.42, P < .05) compared with normal subjects: but had lower correlation with duration of hemodialysis than TrFsACP (r = .277, P < .05). Ulcerative colitis (1.37+/-2.21, n = 15) in males showed a significantly higher Z-score of TrFsACP compared with control subjects (P < .05). The relationship of TrFsACP activity and ultrasound findings (stiffness; speed of sound [SOS]; broadband ultra sound attenuation [BUA]) in healthy women aged 30-75 years (n = 95) were inversely and significantly correlated with stiffness (r = -.465, P < .01 ), SOS (r = -.484, P < .01), and BUA (r = -.366, P < .01), but were age dependent. TrFsACP activity significantly correlated with stiffness (r = -.521, P < .05) and SOS (r = -.527, P < .05) only in the age group of 46-55 years. BUA (r = -.313, P > .05) did not correlate significantly in any subject in the present study. We conclude that serum TrFsACP activity is useful in the diagnosis and monitoring of bone turnover.

Topics: Acid Phosphatase; Adult; Aged; Arthritis, Rheumatoid; Biomarkers; Bone and Bones; Bone Remodeling; Case-Control Studies; Colitis, Ulcerative; Female; Fluorides; Humans; Male; Middle Aged; Osteogenesis Imperfecta; Osteoporosis; Predictive Value of Tests; Reference Values; Renal Dialysis; Tartrates; Ultrasonography

A potential negative side effect of intermittent parathyroid hormone (PTH) therapy to treat osteoporosis is the loss of cortical bone concomitant with increased cancellous bone mass. We addressed this issue by studying the effects of PTH on whole-body, axial, and appendicular bone mass in an animal model with haversian cortical bone remodeling. Ovariectomized, young adult female cynomolgus monkeys were assigned to placebo (n = 9) or PTH groups (n = 10). The PTH group received 10 microg/kg synthetic human PTH(1-34) peptide by subcutaneous injection, 3 days/week for 6 months, and the placebo group received vehicle. Multiple endpoints of bone mass, strength, and turnover in the axial and appendicular skeleton were assessed, including dual-energy X-ray absorptiometry (DEXA), quantitative computed tomography (qCT), analysis of serum (calcium, phosphorus, alkaline phosphatase, osteocalcin, and tartrate-resistant acid phosphatase) and urinary (calcium and creatinine) biomarkers, histomorphometry, and biomechanical testing. Compared with placebo-treated animals, PTH-treated monkeys had no change in whole-body bone mass, but a 6.7% increase in spinal areal bone mineral density (aBMD) was observed. Cortical bone mass measured by qCT at appendicular sites was not affected by PTH treatment, but there were significant increases in cancellous bone mass in the proximal tibia, and a similar trend in the distal radius. Small, transient increases in serum and urinary calcium were observed, but there were no treatment-related effects on other biochemical endpoints. Increased bone formation rate (BFR/BV) in the midradius and midfemur was accompanied by a nonsignificant increase in midfemur porosity. Increased vertebral cancellous bone volume (BV/TV) was associated with greater trabecular and interstitial thickness with no effect on wall thickness. Increases in bone strength were observed in both axial (vertebral maximum stress and load at fracture) and appendicular (femoral neck fracture load) skeleton. Together, these results indicate that PTH therapy in the cynomolgus monkey results in a net gain of spinal and appendicular cancellous bone mass with no adverse effect on cortical bone.

Topics: Absorptiometry, Photon; Acid Phosphatase; Alkaline Phosphatase; Animals; Bone and Bones; Bone Density; Calcium; Creatinine; Female; Injections, Subcutaneous; Isoenzymes; Macaca fascicularis; Osteocalcin; Osteoporosis; Ovariectomy; Parathyroid Hormone; Peptide Fragments; Phosphorus; Tartrate-Resistant Acid Phosphatase; Tomography, Emission-Computed, Single-Photon; Weight-Bearing

Bone loss occurs close to a fracture and is associated with increased bone turnover. Fracture healing itself results in increased markers of bone turnover. But the exact patterns of these changes after different fractures are unclear. We aimed to investigate the changes in bone density and biochemical markers following distal forearm fracture. Twenty women (mean age 63 years) were recruited following fracture of the distal radius and ulna. Bone mineral density (BMD) of the hand and forearm were measured by dual-energy X-ray absorptiometry (DXA) and quantitative ultrasound (QUS) of the fingers was measured at 0, 6, 12, 26 and 52 weeks after fracture. Serum and urine samples were collected at 0, 3 and 7 days and at 2, 4, 6, 12, 26 and 52 weeks after fracture to measure markers of bone turnover. For bone formation we measured: bone alkaline phosphatase (iBAP), osteocalcin (Oc), procollagen type I N-terminal propeptide (PINP); and for bone resorption: tartrate-resistant acid phosphatase (TRAcP), free deoxypyridinoline (iFDpd), N-telopeptides of type I collagen (NTx). We used the nonfractured limb to calculate values for baseline BMD and amplitude-dependent speed of sound (AD-SoS). There was a decrease in BMD at the hand and in AD-SoS of the fingers after forearm fracture (p<0.001). This bone loss was maximal for BMD by 6 weeks at 9% (p<0. 001) and remained decreased at 52 weeks. AD-SoS decreased at 12 weeks by 3% (p<0.01) and recovered completely by 52 weeks. Bone formation markers increased between 2 and 4 weeks by 13-52% (p<0. 001), and were still elevated at 52 weeks. Bone resorption markers increased between 2 and 6 weeks by 18-35% and returned to baseline at 52 weeks (TRAcP remained elevated). We conclude that BMD decreased distal and immediately proximal to the fracture line when measured with DXA and QUS. Bone loss after distal forearm fracture did not recover by 52 weeks and most bone turnover markers did not return to baseline.

Topics: Acid Phosphatase; Aged; Alkaline Phosphatase; Amino Acids; Analysis of Variance; Area Under Curve; Biomarkers; Bone Density; Colles' Fracture; Female; Fingers; Humans; Isoenzymes; Middle Aged; Osteocalcin; Osteoporosis; Peptide Fragments; Procollagen; Reflex Sympathetic Dystrophy; Tartrate-Resistant Acid Phosphatase; Ultrasonography

Since bone markers may reflect different aspects of bone disorders and cell function, and osteolytic and osteoblastic activities may be individually or concomitantly altered, determination of more than one marker type is generally appropriate. Also, the individual markers of a particular type do not necessarily show parallelism. For example, in osteomalacia from vitamin D deficiency, bone-specific alkaline phosphatase may be grossly elevated because of enhanced osteoblastic activity, whereas the vitamin D dependent osteocalcin may be decreased. With the exception of measurement of the bone enzymes, bone-specific alkaline phosphatase and tartrate-resistant acid phosphatase, bone marker measurements require complex and expensive immunoassays. As a general rule, the simple enzyme measurements can precede other investigation in most bone disorder> Bone-specific alkaline phosphatase measurement alone is generally adequate for the investigation of osteomalacia, Paget's disease and hyperparathyroidism but should be combined with measurement of tartrate-resistant acid phosphatase in suspected metastatic disease, and in multiple myeloma. Determination of both enzymes together may also be of value in the investigation of osteoporosis but in this disorder added benefit may be obtained by the addition of other bone markers, particularly urine deoxypyridinoline and possibly serum collagen telopeptide.

Topics: Acid Phosphatase; Alkaline Phosphatase; Biomarkers; Bone and Bones; Bone Resorption; Humans; Osteocalcin; Osteogenesis; Osteoporosis; Procollagen

This study was conducted to examine, in detail, the histological changes in the femurs of suspended ovariectomized (OVX) mice to assess the role of mechanical stress on bone remodeling. Suspended-OVX, suspended-sham-ope, nonsuspended-OVX, and nonsuspended-sham-operated mice underwent operations 8 weeks after birth. Immediately after operation, hypokinesia/hypodynamia was created by a suspension harness for one week. Five specimens in each group were sacrificed 9 weeks after birth. The trabecular bone of the femurs in the suspended-OVX mice was removed and replaced extensively by bone marrow. The number of tartrate-resistant acid phosphatase (TRAP)-positive cells was larger in the suspended-OVX mice than in the remaining three groups. No significant differences in the number of TRAP positive cells were found between the suspended-sham-ope, nonsuspended-OVX and nonsuspended-sham-ope mice. The femurs of the OVX mouse with suspension "hypokinesia/hypodynamia" thus exhibits extensive trabecular bone loss in association with an increase of osteoclasts.

Topics: Acid Phosphatase; Animals; Bone Density; Bone Remodeling; Female; Femur; Hypokinesia; Immobilization; Isoenzymes; Male; Mice; Mice, Inbred C57BL; Osteoclasts; Osteoporosis; Ovariectomy; Stress, Mechanical; Tartrate-Resistant Acid Phosphatase

Collagen type 1 represents more than 90% of bone matrix. Therefore, quantitation of collagen crosslinks, such as deoxypyridinoline, can provide information on bone resorption degree. An evaluation was made of deoxypyridinoline as well as other bone markets, such as alkaline phosphatase, tartrate resistant acid phosphatase, and hydroxyproline in patients with the diagnosis of osteoporosis. Paget's disease, hyperthyroidism, and chronic renal failure on haemodialysis or not. Deoxypyridinoline levels were significantly increased in patients with osteoporosis, Paget's disease, and hyperthyroidism. Hydroxyproline levels were increased in patients with Paget's disease, and tartrate resistant acid phosphatase was increased in all the entities studied. Deoxypyridinoline can be a more sensitive marker than hydroxyproline, with some advantages, such as its quantitation in a urine specimen and its high bone specificity. In patients with renal failure, tartrate resistant acid phosphatase was the only biochemical marker of bone resorption with increased levels.

Topics: Acid Phosphatase; Adult; Alkaline Phosphatase; Amino Acids; Biomarkers; Bone Resorption; Female; Humans; Hydroxyproline; Hyperthyroidism; Kidney Failure, Chronic; Male; Middle Aged; Osteitis Deformans; Osteoporosis; Sensitivity and Specificity

Active hyperthyroidism is associated with reduced bone mass. Nevertheless, not all patients show the same risk for developing osteoporosis. Our aim was to analyze some clinical and biochemical potential predictors of low bone mass in hyperthyroid patients. We studied 127 consecutive hyperthyroid patients (110 females, 17 males; aged 42 +/- 16 years). Bone mineral density (BMD) was measured by dual X-ray absorptiometry (DXA) at lumbar spine (LS; L2-L4) and femoral neck (FN). Data were expressed as g/cm2 and T-score. Patients were placed into two groups based on recent WHO criteria: Group A, no osteoporosis (n = 98); and group B, lumbar or femoral osteoporosis (n = 29). Study protocol included evaluation of osteoporosis risk factors, anthropometrical variables, thyroid function, and bone turnover markers. Receiver-operating characteristic (ROC) plots for the precision of bone markers and multivariate analysis for the prediction of BMD and osteoporosis were performed. Group B showed greater age and proportion of menopausal females; lower weight, height, and calcium intake; longer duration of menopause; and greater levels of total and bone alkaline phosphatase and of urine hydroxyproline. No differences in thyroid function, osteocalcin, tartrate-resistant acid phosphatase, and type I collagen C-telopeptide (ICTP) were found. The best predictive model accounted for 46% and 62% of the variability of lumbar and femoral BMD respectively and correctly classified 89% of the osteoporotic hyperthyroid patients. No significant difference in ROC plots was observed. It is concluded that hyperthyroid patients with lumbar or femoral osteoporosis show a typical clinical and biochemical profile illustrating that the relationship between BMD and bone markers is better in high turnover states. Classical bone turnover markers show high performance in the evaluation of hyperthyroid bone disease.

Topics: Absorptiometry, Photon; Acid Phosphatase; Adult; Alkaline Phosphatase; Biomarkers; Bone Density; Bone Diseases, Metabolic; Bone Remodeling; Female; Femur Neck; Humans; Hydroxyproline; Hyperthyroidism; Isoenzymes; Lumbar Vertebrae; Male; Middle Aged; Osteoporosis; Peptide Fragments; Procollagen; Tartrate-Resistant Acid Phosphatase; Thyrotropin

To determine how bone recovers from immobilization-induced bone loss and to specify whether its recovering capacity is improved by physical exercise, 5-week-old male Wistar rats (287.07 g +/- 10.65 SD) were tail suspended for 14 days, then returned to either normal weight-bearing (R) or controlled physical exercise for 28 days (R + E). Bone mineral density (BMD) was measured in three parts of the femur. Using histomorphometric analysis, bone mass and architecture were estimated in the primary (1 degree sp) and secondary spongiosa (2 degrees sp) of the proximal tibial metaphysis. Bone cellular parameters were measured in the 2 degrees sp of the tibia. Tail suspension induced a significant decrease in BMD, 2 degrees sp bone mass, mineral apposition rate, and bone formation rate and marked alterations of the trabecular network. In R rats, BMD was still significantly decreased, except in the distal part of the femur. Long-bone lengthening was significantly altered. The 2 degrees sp bone mass returned to the age-matched control values; however, the trabeculae were still significantly thinner and bone resorption was significantly higher. R + E rats had a normal long bone lengthening and a significant increase in 2 degrees sp bone mass and trabecular thickness when compared with R rats. Bone resorption was significantly depressed, and osteoid surfaces and thickness were significantly increased. Thus, although bone mass returns to normal values in the R group, trabecular alterations persist.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acid Phosphatase; Animals; Body Weight; Bone Density; Bone Development; Bone Resorption; Femur; Fluorescent Dyes; Immobilization; Male; Osteoclasts; Osteoporosis; Physical Conditioning, Animal; Rats; Rats, Wistar; Tail; Tissue Fixation; Weight-Bearing

Bisphosphonates are known to be potent inhibitors of osteoclast activity and their only clinically relevant effect in the short-term is the selective inhibition of bone resorption. The purpose of this study was to compare the response to the intravenous administration of two bisphosphonates, clodronate and alendronate, of several biochemical markers of bone resorption, including tartrate-resistant acid phosphatase (TRAP) and cross-linked carboxyterminal telopeptide of collagen I (ICTP) in serum and hydroxyproline (OHP), free pyridinium cross-links (Pyr), and cross-linked N-telopeptides of collagen I (NTx) in urine. The study was carried out on 11 osteoporotic and 12 Pagetic subjects of both sexes, treated with clodronate (600 mg/day for 2 days) or alendronate (5 mg/day for 2 days), and monitored for 28 days after bisphosphonate administration. All the urinary markers of bone resorption showed a prompt decline after bisphosphonates, with maximum reductions after 7-14 days: Pyr decreased by 43% +/- 9% and 42% +/- 22% (mean +/- SD), respectively in osteoporotic and pagetic subjects, OHP by 51% +/- 14% and 51% +/- 20%, and NTx by 55% +/- 15% and 65% +/- 26%. In the osteoporotic group, the urinary markers began to increase again at 30 days, though still remaining well below the basal level, whereas in the pagetic group, the excretion of all markers remained depressed until the end of the observation period. The reduction of NTx was significantly greater than that of Pyr and OHP in pagetic patients (P < 0.05) and tended to be greater than that of Pyr in osteoporotic patients (p = 0.07).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Alendronate; Amino Acids; Biomarkers; Bone and Bones; Bone Resorption; Clodronic Acid; Collagen; Collagen Type I; Diphosphonates; Female; Humans; Hydroxyproline; Injections, Intravenous; Male; Middle Aged; Osteitis Deformans; Osteoporosis; Peptides; Time Factors

In our previous study, globin was found to be an effective dietary source for increasing bone mineral density (BMD) and mechanical strength. In this study, the bioavailability of the globin preparation was examined to clarify the mechanism of increase in bone density and strength. Six-week-old Sprague-Dawley female rats were ovariectomized and were fed on a low Ca diet for 30 days to produce the experimental osteoporotic rats. Thereafter they were divided into two groups. The BMD and the mechanical strength of bone of the rat group, whose diet was supplemented with globin, were significantly higher than those of the control group. The levels of the serum calcitonin and the bone-type alkaline phosphatase (Alp) activity in serum and bone were also higher, and the tartrate-resistant acid phosphatase (Tr-Acp) activity in serum and bone was lower in the globin group. Moreover, the bone morphogenetic protein activity in bone in the globin group was found to be greater. From these results, it is concluded that alimentary globin is effective for the acceleration of bone formation and the prevention of bone resorption.

Topics: Acid Phosphatase; Alkaline Phosphatase; Animal Nutritional Physiological Phenomena; Animals; Bone and Bones; Bone Density; Calcitonin; Calcium; Diet; Female; Globins; Osteoporosis; Ovariectomy; Phosphorus; Rats; Rats, Sprague-Dawley; Tensile Strength

To evaluate the effect of 17 beta-estradiol replacement (10 micrograms, twice a week) (E2) and treadmill exercise (18 m/min, 45 min/day) (EX) on long bone and vertebral bone mass and density, 10-month-old rats were ovariectomized (OV) and divided into four groups: OV, OV + E2, OV + EX, OV + EX + E2 2 months after surgery. After 7 weeks intervention, the calcium content and the density of lumbar-5 were higher in both OV + E2 and OV + EX + E2 groups than in the OV group, but, only the OV + EX + E2 group had a significantly higher femoral bone weight and density than the OV group. After 16 weeks intervention, the bone-conserving effects of E2 and EX were significant on lumbar-5 and femoral dry weight and density. The effect of E2 on both two sides of bones was due to the suppression of the bone turnover rate, while EX suppressed bone turnover rate primarily on the femur. We conclude that the effect of the two interventions on lumbar-5 and femoral bone mass were additive and independent.

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Bone and Bones; Bone Density; Bone Remodeling; Calcium; Estradiol; Female; Femur; Lumbar Vertebrae; Organ Size; Osteocalcin; Osteoporosis; Ovariectomy; Physical Exertion; Rats; Rats, Sprague-Dawley; Tetracycline; Tritium

To test conditions under which thyroid hormone might be deleterious to bone, we studied a group of 58 patients who had undergone thyroidectomy because of thyroid cancer 1 to 21 years previously and were treated with steady doses of exogenous thyroid hormone. Vertebral bone density (BMD Z-score) was significantly reduced and biochemical indices of bone resorption (urinary hydroxyproline and plasma tartrate-resistant acid phosphatase activity) and of osteoblastic activity (plasma osteocalcin and bone isoenzyme of serum alkaline phosphatase) as well as the calculated prevalence of bone resorption relative to osteoblastic activity (HBP) were significantly increased in thyroid hormone-treated post-menopausal women but not in men and premenopausal women. The HBP as well as the biochemical indices of bone remodeling were significantly negatively correlated with serum TSH levels. In treated patients, BMD Z-score was significantly dependent on the HBP, menopausal state, duration of treatment and serum TSH levels. In conclusion, the further increase in bone resorption by thyroid hormone is predisposed by menopausal changes in bone turnover. The simultaneous evaluation of biochemical indices of bone resorption and formation improves the assessment of bone loss in patients treated with thyroid hormone in a suppressive dose.

Topics: Acid Phosphatase; Adult; Aged; Aged, 80 and over; Alkaline Phosphatase; Analysis of Variance; Bone Density; Bone Remodeling; Bone Resorption; Cross-Sectional Studies; Female; Humans; Hydroxyproline; Male; Menopause; Middle Aged; Osteocalcin; Osteoporosis; Regression Analysis; Thyroid Hormones; Thyrotropin

The study was carried out to evaluate the clinical validity and usefulness of serum tartrate-resistant acid phosphatase (TRAP) activity determined using an improved spectrophotometric assay. Enzyme activity was measured in 84 normal subjects and in 109 patients with common metabolic bone diseases. Mean values of serum TRAP activity in male subjects (n = 19; 10.4 +/- 2.15 U l-1) were not significantly different from those found in female subjects (n = 65; 10.8 +/- 1.8 U l-1). In the latter group mean values were significantly raised in post-menopausal subjects (10.5 +/- 2.0 U l-1; p less than 0.01) compared with mean values in pre-menopausal women (8.45 +/- 1.8 U l-1). We found a significant inverse correlation between serum TRAP activity values and bone mineral density (BMD) measured both at an ultradistal radial point (n = 33, r = -0.506; p less than 0.01), and at the lumbar spine (n = 57, r = -0.261; p less than 0.05). Mean serum TRAP activity values in patients with metabolic bone diseases were: primary hyperparathyroidism, n = 30: 14.2 +/- 4.89 U l-1, p less than 0.001 vs normal subjects; chronic maintenance haemodialysis, n = 19: 17.4 +/- 6.7, p less than 0.001; metastatic cancer, n = 13: 21.2 +/- 6.3, p less than 0.001; post-surgical hypoparathyroidism, n = 10: 9.9 +/- 1.8, NS; involutional osteoporosis, n = 20: 12.5 +/- 2.3 p less than 0.001; Paget's disease, n = 10: 16.8 +/- 3.5, p less than 0.001; osteomalacia, n = 7: 19.5 +/- 3.31, p less than 0.001.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acid Phosphatase; Adult; Aging; Bone Density; Bone Diseases, Metabolic; Bone Remodeling; Female; Humans; Hyperparathyroidism; Male; Menopause; Middle Aged; Osteitis Deformans; Osteomalacia; Osteoporosis; Osteoporosis, Postmenopausal; Spectrophotometry; Tartrates

The relationship between bone-resorbing cells, assessed by the presence of tartrate-resistant acid phosphatases (TRAP) and morphologic indices of bone resorption, was determined in 29 osteoporotic patients (14 postmenopausal females and 15 males) and 15 dialyzed patients. The number of TRAP-positive cells per unit of cancellous bone area (N.Oc/B.Ar) was higher in dialyzed patients than in those with osteoporosis (16.8 +/- 15.3 versus 4.95 +/- 2.86, p less than 0.05). The amount of bone resorbed at the basic multicellular unit level was estimated by calculating eroded area containing TRAP cells per bone area (E.Ar+/BA). This novel parameter was similar in dialyzed and in osteoporotic patients (41,700 +/- 28,400 versus 32,300 +/- 24,600). In contrast, trabecular spacing (Tb.Sp) was identical in both metabolic bone diseases. Trabecular width (169 +/- 38 versus 127 +/- 32 microns, p less than 0.05) and bone area were higher in dialyzed than in osteoporotic patients. N.Oc/B.Ar was significantly related to E.Ar+/BA in dialyzed (r = 0.76, p less than 0.05) but not in osteoporotic patients. Tb.Sp was significantly correlated to N.Oc/B.Ar and to the number of TRAP-positive cell nuclei per B.Ar (r = 0.44, p less than 0.05) in osteoporotic but not in dialyzed patients. This last result shows that in overt osteoporosis with thin trabeculae, trabecular spacing is related to the number of resorbing cells. In contrast, the spacing of thick trabeculae in dialysis osteodystrophy is not dependent on the number of osteoclasts.

Topics: Acid Phosphatase; Adult; Aged; Bone and Bones; Bone Resorption; Chronic Kidney Disease-Mineral and Bone Disorder; Female; Humans; Male; Middle Aged; Osteoblasts; Osteoclasts; Osteoporosis; Osteoporosis, Postmenopausal; Renal Dialysis

Topics: 25-Hydroxyvitamin D 2; Acid Phosphatase; Aging; Alkaline Phosphatase; Biomarkers; Calcitonin; Calcium; Humans; Osteocalcin; Osteoporosis; Parathyroid Hormone; Phosphorus

Tartrate-resistant serum acid phosphatase was measured in 123 subjects, 80 of which were normal and the rest pathologic, in order to define the profile and value of this parameter as a biological marker of osteoclastic activity. Normal subjects were divided into age groups based on the period where skeletal growth ends (under 20 years), at the age of menopause in women (50 years, between 20 and 50 years) and those over 50 years. There was an increase in tartrate-resistant serum acid phosphatase coinciding with puberty and no sex differences were observed after the 50 year mark, when women showed higher values than men (p less than 0.001). Such tartrate-resistant serum acid phosphatase increase, is reflected as higher values in the 50 year group than in the 20 to 50 year group (p less than 0.001), the only age limit where a negative significant correlation between tartrate-resistant serum acid phosphatase values and age could be observed (p less than 0.05). Values were higher up to the age of 20 years (p less than 0.001) than in any other older age group. Levels increased significantly (p less than 0.001 for both groups) in post-menopausal osteoporosis (n = 20) and in Paget's disease of bone (n = 15), and decreased significantly (p less than 0.05) in imperfect osteogenesis (n = 8), thus revealing its value as a biological marker of osteoclastic activity.

Topics: Acid Phosphatase; Adolescent; Adult; Aged; Aged, 80 and over; Aging; Biomarkers; Bone Resorption; Child; Child, Preschool; Female; Humans; Male; Middle Aged; Osteoporosis; Tartrates

The present study examined the effect of long-term, moderate physical exercise on trabecular bone volume (TBV), calcium content, 3H-proline uptake, and the activities of alkaline and acid phosphatases in lumbar vertebrae of aging and senescent mice. It became apparent that if physical activity starts at an early stage of life, i.e., prior to middle age and is extended until old age, it exerts beneficial effects on trabecular bone mass and mineralization. Such a positive effect is not obtained if the training program is initiated after middle age. The training-induced reduction in bone loss was accompanied by a significant decrease in acid phosphatase activity whereas no changes took place with regard to the activity of alkaline phosphatase. Long-term physical exercise also enhanced the uptake of 3H-proline by lining cells along the bone trabecules. In spite of its moderate nature, the endured training program served as a stress factor for the involved animals, a fact that was manifested by an increase in the serum levels of corticosterone. Thus, it seems that whereas young animals respond favorably to such a stimulatory stress, older animals lose this ability of adaptation.

Topics: Acid Phosphatase; Aging; Alkaline Phosphatase; Animals; Autoradiography; Bone Diseases, Metabolic; Calcium; Corticosterone; Female; Lumbar Vertebrae; Mice; Osteoporosis; Physical Conditioning, Animal; Proline; Time Factors; Tritium

Studies were carried out to examine whether parathyroid hormone (PTH) will prevent the age-related bone loss that results from ovarian hormone deficiency and to explore the mechanism of its action. Ovariectomy caused a significant decrease in bone density in the distal metaphysis and mid-diaphysis, but not in the vertebra and proximal metaphysis. The decrease was prevented by PTH injection and in all the bones examined PTH administration increased bone density and bone calcium content above the levels in sham-operated controls. Similar findings were made in bone hydroxyproline levels. PTH treated ovariectomized animals had lower serum 25(OH)vitamin D and higher 1,25(OH)2 vitamin D levels than ovariectomized and sham operated animals that received solvent vehicle. Compared to the sham operated controls, ovariectomy caused a 4.5-fold increase in the number of tartrate resistant acid phosphatase (TRAP) positive multinuclear cells. This increase did not occur in PTH-treated animals. We conclude that PTH is effective in preventing ovarian hormone deficiency bone loss in rats. PTH may mediate this effect partly by stimulating osteoblastic bone formation and partly by increasing 1,25(OH)2 vitamin D-mediated calcium absorption. The data from TRAP positive multinuclear cells indicate that an etiologic component of ovarian hormone deficiency bone loss is the expansion of a pool of osteoclast progenitors and that the bone anabolic action of PTH involves, in part, a decrease in bone resorption as a result of the suppression of the proliferation of osteoclast progenitors.

Topics: Acid Phosphatase; Aging; Animals; Bone Density; Calcium; Female; Osteoporosis; Ovariectomy; Parathyroid Hormone; Phosphates; Rats; Rats, Inbred Strains; Vitamin D

Serum tartrate-resistant acid phosphatase (sTr-AcP) and bone mineral content (BMC) were measured in 29 women with postmenopausal osteoporosis and in 12 control women. Serum Tr-AcP was higher in osteoporotic patients than in controls and a negative linear correlation was found between sTr-AcP and BMC in osteoporotic women. These results suggest that sTr-AcP could be a useful marker for bone loss and consequently, for the measure of bone resorption rate in postmenopausal women.

Topics: Acid Phosphatase; Adult; Aged; Aged, 80 and over; Bone and Bones; Drug Resistance; Female; Humans; Middle Aged; Minerals; Osteoporosis; Tartrates

The role of BGP (osteocalcin) as bone marker in the study and management control of involutional osteoporosis is emphasized and the different radioimmunoassays and their limitations are commented. Our results showed significantly lower sBGP levels in osteoporotic patients compared with control group and a positive linear correlation was found between sBGP and serum alkaline phosphatase but no correlation was obtained with urinary hydroxyproline/creatinine ratio, serum tartrate-resistant acid phosphatase or bone mineral content measured by dual photon absorptiometry.

Topics: Acid Phosphatase; Adult; Aged; Aged, 80 and over; Alkaline Phosphatase; Bone and Bones; Calcium-Binding Proteins; Densitometry; Female; Humans; Lumbar Vertebrae; Middle Aged; Minerals; Osteocalcin; Osteoporosis

Topics: Acid Phosphatase; Alkaline Phosphatase; Biomarkers; Bone and Bones; Calcium-Binding Proteins; Carrier Proteins; Diagnostic Tests, Routine; Humans; Osteocalcin; Osteonectin; Osteoporosis; Proteoglycans; Sialoglycoproteins

Changes in vertebral trabecular bone were quantified in female Wistar rats. This study utilized single photon absorptiometry for the measurement of bone mineral content (BMC), quantitative computed tomography (QCT) for the measurement of bone mineral density (BMD), and image analysis histomorphometry for the measurement of trabecular bone volume (TBV). The above measurements were accompanied by biochemical assays of protein and calcium concentrations in the tissues. Also, the activity of bone alkaline and acid phosphatases was measured. Lumbar vertebrae (L4, L5) in old rats 27 months old, compared with those of young rats 7 months old, showed significant decreases in BMC, BMD, TBV, protein and calcium, and enzyme activity. A high degree of correlation was recorded between the above changes. The various changes were accompanied by a marked reduction in the overall wet weight of the vertebrae. Hence, new noninvasive methods to quantitate bone mass can be applied in vivo to small laboratory animals such as the rat. These methods are much more accurate than standard radiographs in quantitating bone loss and are, therefore, recommended for experimental longitudinal studies related to aging of the skeleton.

Topics: Acid Phosphatase; Aging; Alkaline Phosphatase; Animals; Bone and Bones; Calcium; Female; Lumbar Vertebrae; Minerals; Osteoporosis; Proteins; Rats; Rats, Inbred Strains

In a cross-sectional study in 214 women who had undergone bilateral oophorectomy up to 12 years previously, the maximal rate of bone loss, as judged by radiogrammetry of the metacarpals and by dual-photon absorptiometry of the lumbar spine, coincided with the peak of the dissociation between urinary hydroxyproline excretion and/or plasma tartrate resistant acid phosphatase activity and the activity of bone isoenzyme of serum alkaline phosphatase. A significant negative correlation was found between the prevalence of the biochemical indices of bone resorption relative to bone formation and/or biochemical indices of bone resorption and the change in the metacarpal cortical area per year. The prevalence of bone resorption relative to bone formation was evident even 12 years after oophorectomy, indicating continuous imbalance of bone remodeling in the patients. Accordingly, the rates of 2.8% cortical and 8% trabecular bone loss per year on the first year after oophorectomy decreased exponentially but did not become asymptotic with the slow phase of bone loss in healthy women up to 12 years after oophorectomy.

Topics: Acid Phosphatase; Adult; Alkaline Phosphatase; Bone Resorption; Cross-Sectional Studies; Female; Humans; Hydroxyproline; Middle Aged; Osteoporosis; Ovariectomy

Chicks infected as 12-day-old embryos with an end-point purified derivative of avian myeloblastosis virus developed a rapidly progressive osteopetrosis that manifested within 1 week of hatching. A detailed comparison of osteopetrotic chicks and normal hatchmates revealed the following. (i) Osteopetrotic chicks exhibited a stunting syndrome, growing at a mean rate that was 26% of the control rats. (ii) At autopsy, the mass of the lymphoid organs was reduced, whereas the mass of the heart, pancreas, kidneys, lungs, brain, liver, and bones of osteopetrotic chicks was increased. Edema was likely responsible for most of the increase in organ weight. (iii) Infected chicks exhibited a normochromic, normocytic anemia that was virus dose dependent and was not required for the development of osteopetrosis. (iv) Bone collagen content was normal. (v) Osteopetrotic bone was initially hypomineralized, but later became more fully mineralized. (vi) The concentrations of alpha, beta, and gamma globulins in the plasma were elevated in osteopetrotic chicks, whereas albumin concentration was decreased. (vii) The level of plasma alkaline phosphatase was elevated in osteopetrotic chicks, yet the level of acid phosphatase was unchanged. (viii) Body and bone temperatures were unchanged.

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Avian Leukosis Virus; Avian Myeloblastosis Virus; Blood Proteins; Body Temperature; Bone and Bones; Chick Embryo; Chickens; Collagen; Organ Specificity; Osteopetrosis; Osteoporosis; Water

Under observation were 66 (50.3%) of 130 patients with an ossific form of hyperparathyroidism. Fourty five patients showed the classical picture of Recklinghausen disease, and 21-only diffuse osteoporosis. The correct diagnosis would be established 4-5 years following the onset of the disease. During the period of most distinct manifestations pains in bones were noted in 93 per cent of cases. Two thirds of patients showed marked atonia and fatigue. Pathological fractures were multiple and were observed in 45 of 66 patients (totally 125 fractures). Great importance in establishing the diagnosis of the form of hyperparathroidism is attached to roentgenological investigation of all bones and biochemical assay of blood and urine.

Topics: Acid Phosphatase; Adult; Aged; Calcium; Female; Haptoglobins; Humans; Hypercalcemia; Male; Middle Aged; Osteitis Fibrosa Cystica; Osteoporosis; Phosphorus

Topics: Acid Phosphatase; Alkaline Phosphatase; Breast Neoplasms; Humans; Hyperparathyroidism; Leucyl Aminopeptidase; Osteoblasts; Osteoclasts; Osteoporosis

Topics: Acid Phosphatase; Aging; Animals; Blood Chemical Analysis; Calcium; Citrates; Clinical Enzyme Tests; Humans; Osteoporosis; Poultry Diseases; Research; Sex

Topics: Acid Phosphatase; Bone and Bones; Formaldehyde; Head; Osteoporosis; Skull; Tissues