acid-phosphatase and Bone-Diseases--Metabolic

Disturbances in mineral metabolism and bone disease are common complications of chronic kidney disease (CKD) . There is increasing evidence suggesting that these disorders in mineral and bone metabolism are associated with increased risk for cardiovascular calcification, morbidity, and mortality, especially among those who undergo maintenance hemodialysis. It is very important for hemodialysis patients to assess the mineral and bone abnormalities. Although bone biopsy is necessary to diagnosis of renal osteodystrophy in CKD-mineral and bone disorder (CKD-MBD) classification system, this technique is not recommended of routine evaluation for this bone disease. Thus, the presumption of bone disorder in hemodialysis patients has been essentially based on the parathyroid hormone level. However, it is obvious that measurement of parathyroid hormone dose not provide sufficient information. The parathyroid hormone level basically reflects the degree of activity of parathyroid glands and the CKD state is often associated with resistance of bone to the action of parathyroid hormone. Therefore, measurement of bone metabolic markers, such as bone specific alkaline phosphatase and tartrate-resistant acid phosphatase isoform 5b, is increasingly recognized as a useful tool to assess bone metabolic states in hemodialysis patients. Bone metabolic markers may be useful for assessment in the rate of bone loss, the risk of fracture, and the effects of therapy as in osteoporotic patients without CKD.

Topics: Acid Phosphatase; Alkaline Phosphatase; Biomarkers; Bone and Bones; Bone Diseases, Metabolic; Chronic Disease; Chronic Kidney Disease-Mineral and Bone Disorder; Humans; Isoenzymes; Kidney Diseases; Minerals; Osteocalcin; Peptide Fragments; Procollagen; Renal Dialysis; Risk; Tartrate-Resistant Acid Phosphatase; Vascular Calcification

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

Changes of bone remodeling markers reflect bone growth and bone turnover. Information on bone metabolism can be attained by blood and urine laboratory tests. Recently developed bone specific markers are categorized by bone remodeling process, i.e. bone formation and resorption. The formation markers include bone-specific alkaline phosphatase (BAP), osteocalcin (OC), undercarboxylated osteocalcin (ucOC), procollagene type I C- and N-terminal peptides (P1CP and P1NP). Bone resorption markers include deoxypyridinoline, collagen I C- and N-terminal telopeptides (CTX and NTX) , and tartrate resistent acid phosphatase (TRACP) isoform 5b. These laboratory tests offer lots of advantages for the diagnosis of bone metabolic disorders and for the evaluation of clinical states of primary osteoporosis and other metabolic skeletal diseases.

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

Disturbances in mineral metabolism and bone disease are common complications of chronic kidney disease (CKD). There is increasing evidence suggesting that these disorders in mineral and bone metabolism are associated with increased risk for cardiovascular calcification, morbidity, and mortality, especially among those who undergo maintenance dialysis. It is very important for dialysis patients to assess the mineral and bone abnormalities. Although bone biopsy is necessary to diagnosis of renal osteodystrophy in CKD-mineral and bone disorder (CKD-MBD) classification system, this technique is not recommended of routine evaluation for this bone disease. Bone metabolic markers, such as bone specific alkaline phosphatase and tartrate-resistant acid phosphatase isoform 5b, may be useful clinical indicator of bone turnover in CKD-MBD.

Topics: Acid Phosphatase; Alkaline Phosphatase; Biomarkers; Bone and Bones; Bone Diseases, Metabolic; Cardiovascular Diseases; Chronic Disease; Dialysis; Humans; Isoenzymes; Kidney Diseases; Prognosis; Risk; 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; Biomarkers; Bone Diseases, Metabolic; Bone Remodeling; Bone Resorption; Humans; Isoenzymes; Osteoclasts; Tartrate-Resistant Acid Phosphatase

Topics: Acid Phosphatase; Biomarkers; Bone Diseases, Metabolic; Bone Neoplasms; Bone Remodeling; Bone Resorption; Electrophoresis, Polyacrylamide Gel; Humans; Immunoprecipitation; Isoenzymes; Osteoclasts; Reference Values; Specimen Handling; Spectrophotometry; Tartrate-Resistant Acid Phosphatase

Acid phosphatase (ACP) is a hydrolytic lysosomal enzyme secreted by a number of cells including blood cells as well as by the prostate, bones, liver and other tissues. Several isozymes of ACP have tissue specificity. The isozymes can be fractionated by electrophoresis into six bands. Prostatic ACP (bands 2-4) is frequently measured for the diagnosis of prostatic disease. Band 5, tartrate resistant ACP (TRACP) consists of two isoforms, bands 5a and 5b. TRACP 5b is considered to be a marker of the osteoclasts and 5a is found in Gaucher's cells, or in the leukocytes of patients with hairy cell leukemia.

Topics: Acid Phosphatase; Biomarkers; Bone Diseases, Metabolic; Clinical Enzyme Tests; Female; Hematologic Neoplasms; Humans; Isoenzymes; Male; Organ Specificity; Prostatic Neoplasms; Sphingolipidoses; Tartrates

Topics: Acid Phosphatase; Alkaline Phosphatase; Amino Acids; Biomarkers; Bone and Bones; Bone Diseases, Metabolic; Humans; Isoenzymes; Osteocalcin; Tartrate-Resistant Acid Phosphatase

Topics: Acid Phosphatase; Age Factors; Alkaline Phosphatase; Biomarkers; Bone Diseases, Metabolic; Bone Regeneration; Female; Humans; Hydroxyproline; Male; Osteocalcin; Peptide Fragments; Procollagen; Sex Factors

Menopause leads to an increased risk for osteoporosis in women. Although drug therapies exist, increasing numbers of people prefer alternative therapies such as dietary supplements, for example, calcium, vitamin D, and collagen hydrolysates for the prevention and treatment of osteoporosis. We have previously shown that a 3-month intervention using a calcium-collagen chelate (CC) dietary supplement was efficacious in improving bone mineral density (BMD) and blood biomarkers of bone turnover in osteopenic postmenopausal women. This study reports the long-term efficacy of CC in reducing bone loss in postmenopausal women with osteopenia. Thirty-nine women were randomly assigned to one of two groups: 5 g of CC containing 500 mg of elemental calcium and 200 IU vitamin D (1,25-dihydroxyvitamin D3) or control (500 mg of calcium and 200 IU vitamin D) daily for 12 months. Total body, lumbar, and hip BMD were evaluated at baseline, 6 and 12 months using dual-energy X-ray absorptiometry. Blood was collected at baseline, 6 and 12 months to assess levels of blood biomarkers of bone turnover. Intent-to-treat (ITT) analysis was performed using repeated measures analysis of variance pairwise comparisons and multivariate analysis to assess time and group interactions. The loss of whole body BMD in women taking CC was substantially lower than that of the control group at 12 months in those who completed the study and the ITT analysis, respectively (CC: -1.33% and -0.33% vs. control: -3.75% and -2.17%; P=.026, P=.035). The CC group had significantly reduced levels of sclerostin and tartrate-resistant acid phosphatase isoform 5b (TRAP5b) (P<.05), and higher bone-specific alkaline phosphatase/TRAP5b ratio (P<.05) than control at 6 months. These results support the use of CC in reducing bone loss in osteopenic postmenopausal women.

Topics: Acid Phosphatase; Adaptor Proteins, Signal Transducing; Alkaline Phosphatase; Biomarkers; Bone and Bones; Bone Density; Bone Diseases, Metabolic; Bone Morphogenetic Proteins; Calcium; Collagen; Dietary Supplements; Female; Genetic Markers; Humans; Intention to Treat Analysis; Middle Aged; Osteoporosis, Postmenopausal; Postmenopause

Aside from existing drug therapies, certain lifestyle and nutritional factors are known to reduce the risk of osteoporosis. Among the nutritional factors, dried plum or prunes (Prunus domestica L.) is the most effective fruit in both preventing and reversing bone loss. The objective of the present study was to examine the extent to which dried plum reverses bone loss in osteopenic postmenopausal women. We recruited 236 women, 1-10 years postmenopausal, not on hormone replacement therapy or any other prescribed medication known to influence bone metabolism. Qualified participants (n 160) were randomly assigned to one of the two treatment groups: dried plum (100 g/d) or dried apple (comparative control). Participants received 500 mg Ca plus 400 IU (10 μg) vitamin D daily. Bone mineral density (BMD) of lumbar spine, forearm, hip and whole body was assessed at baseline and at the end of the study using dual-energy X-ray absorptiometry. Blood samples were collected at baseline, 3, 6 and 12 months to assess bone biomarkers. Physical activity recall and 1-week FFQ were obtained at baseline, 3, 6 and 12 months to examine physical activity and dietary confounders as potential covariates. Dried plum significantly increased BMD of ulna and spine in comparison with dried apple. In comparison with corresponding baseline values, only dried plum significantly decreased serum levels of bone turnover markers including bone-specific alkaline phosphatase and tartrate-resistant acid phosphatase-5b. The findings of the present study confirmed the ability of dried plum in improving BMD in postmenopausal women in part due to suppressing the rate of bone turnover.

Topics: Acid Phosphatase; Aged; Alkaline Phosphatase; Anthropometry; Biomarkers; Bone and Bones; Bone Density; Bone Diseases, Metabolic; Calcium; Diet; Exercise; Female; Humans; Isoenzymes; Malus; Middle Aged; Osteoporosis, Postmenopausal; Postmenopause; Prunus; Spine; Tartrate-Resistant Acid Phosphatase; Ulna

Osteoclastic tartrate-resistant acid phosphatase activity in serum (S-TRACP 5b) was measured in postmenopausal women ( n =59, mean age 56.1 years) with vertebral osteopenia before and during 2-year treatment with an 800-mg daily dose of clodronate, with a non-amino bisphosphonate. Changes in TRACP 5b were compared with those in urinary excretion of type I collagen amino-terminal telopeptide (U-NTX), corrected for creatinine excretion, a well-established marker of bone resorption, and to serum type I procollagen amino-terminal propeptide (S-PINP), a marker of bone formation. Marker changes 1 year after start of treatment were correlated with changes in bone mineral density (BMD). The least significant change (LSC) for each marker and BMD was calculated from values for subjects receiving placebo. Responders to treatment were those exhibiting a change larger than LSC. In response to clodronate treatment S-TRACP 5b (mean change up to -18%) decreased less than did U-NTX (up to -51%) or S-PINP (up to -46%). Marker changes correlated with changes in lumbar spine and trochanter BMD. The most efficient marker for finding responders to treatment was S-PINP, which changed more than the LSC (32%) in 72% of the subjects at the 1-year time point and in 79% at the 2-year time point. S-TRACP 5b change exceeded the LSC (27%) in 40% and 34% of the subjects at each time point, while U-NTX change exceeded the LSC (55%) in 55% and 40%, respectively. We conclude that, in terms of the proportion of subjects exhibiting any change exceeding the LSC, S-TRACP 5b did not appear to be superior to U-NTX and S-PINP in the follow-up of clodronate treatment. The reason may lie in the mechanism of action of clodronate, which rather than reducing the number of TRACP 5b-secreting osteoclasts, reduces the activity of bone proteolytic enzymes and thus the rate of bone organic matrix degradation. This is seen in decreased amounts of type I collagen breakdown products (U-NTX), and through coupling of bone resorption with bone formation, in a decrease in circulating levels of the marker that reflects new collagen formation (S-PINP).

Topics: Acid Phosphatase; Biomarkers; Bone Density; Bone Density Conservation Agents; Bone Diseases, Metabolic; Clodronic Acid; Collagen; Collagen Type I; Double-Blind Method; Drug Monitoring; Female; Femur; Femur Neck; Follow-Up Studies; Humans; Isoenzymes; Lumbar Vertebrae; Middle Aged; Peptide Fragments; Peptides; Postmenopause; Procollagen; Tartrate-Resistant Acid Phosphatase; Treatment Outcome

Topics: Acid Phosphatase; Adult; Aged; Biomarkers; Bone Diseases, Metabolic; Bone Resorption; Breast Neoplasms; Female; Humans; Immunoassay; Isoenzymes; Middle Aged; Osteitis Deformans; Osteoporosis, Postmenopausal; Sensitivity and Specificity; Tartrate-Resistant Acid Phosphatase

Antioxidant lycopene supplementation has been shown to decrease oxidative stress and have beneficial effects on bone health. However, it remains unclear whether lycopene exerts its beneficial effect on bone metabolism through mitigation of oxidative stress in vivo. The aim of this study was to investigate whether lycopene intake protects against bone loss by reducing oxidative stress in ovariectomized rats. Female Sprague-Dawley 6-week-old rats were ovariectomized and randomly divided into four groups according to the lycopene content of their diet: 0, 50, 100, and 200 ppm. The tibial bone mineral density (BMD) in the 50, 100, and 200 ppm groups was significantly higher than that in the 0 ppm group. Serum and urinary bone resorption marker levels were significantly lower in the 50, 100, and 200 ppm groups than in the 0 ppm group. There was no significant difference in systemic oxidative stress markers among all groups. However, systemic oxidative stress levels were inversely correlated with the tibial BMD. Our findings suggest that lycopene intake significantly inhibits bone loss by suppressing bone resorption in ovariectomized rats. Further studies are necessary to clarify the effect of lycopene on oxidative stress in local tissues such as bone tissue.

Topics: Acid Phosphatase; Amino Acids; Animals; Antioxidants; Bone Density; Bone Diseases, Metabolic; Carotenoids; Deoxyguanosine; Female; Isoenzymes; Lycopene; Oxidative Stress; 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

Periodontitis is an inflammatory disease of tooth-supporting tissue leading to bone destruction and tooth loss. Periodontitis affects almost 50% of adults greater than 30 years of age.. This study evaluated the association between biomarkers linked to bone formation and resorption with the occurrence and progression of periodontal disease in older men (≥ 65 y).. The Osteoporotic Fractures in Men (MrOS) study is a prospective, observational study among men 65 years of age and older.. This ancillary study, Oral and Skeletal Bone Loss in Older Men, was conducted at two of the six MrOS study sites (Birmingham, AL and Portland, OR).. Patients underwent medical and dental evaluation. Diagnoses of periodontitis were based on clinical attachment loss, pocket depth, calculus, plaque, and bleeding on a random half-mouth. Bone metabolism biomarkers included serum levels of calcium, phosphate (Pi), alkaline phosphatase, albumin, carboxy-terminal collagen crosslinks (CTX), N-terminal propeptides of type I procollagen, isoform 5b of tartrate-resistant acid phosphatase, and urine alpha- carboxy-terminal collagen crosslinks (alpha-CTX) and beta-CTX and serum levels of calciotropic hormones vitamin D (25(OH)D) and PTH.. The aim of this study is to correlate bone metabolism biomarkers with prevalence and progression of periodontal disease in older men.. Patients with more severe periodontitis had significantly higher levels of PTH (P trend = .0004), whereas 25(OH)D was lower (P trend = .001). In a subset of men reevaluated at a second dental visit, improvement of periodontitis was associated with lower alpha-CTX, beta-CTX, and CTX levels at baseline after adjusting for age, site, and body mass index.. This study suggests that a distinct set of biomarkers of bone metabolism are associated with more severe periodontal disease (PTH, 25(OH)D) and periodontal progression (alpha-CTX, beta-CTX, and CTX) over time.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Biomarkers; Bone and Bones; Bone Diseases, Metabolic; Collagen Type I; Humans; Isoenzymes; Male; Osteoporotic Fractures; Peptides; Periodontal Diseases; Periodontitis; Tartrate-Resistant Acid Phosphatase; Vitamin D

There are contradictory results about the effect of angiotensin-converting enzyme inhibitors (ACEIs) on bone. This study was performed to address the skeletal renin-angiotensin system (RAS) activity and the effects of the ACEI, captopril, on the bone of streptozotocin-induced type 1 diabetic mice. Histochemical assessment on bone paraffin sections was conducted by Safranin O staining and tartrate-resistant acid phosphatase staining. Micro-computed tomography was performed to analyze bone biological parameters. Gene and protein expression were determined by real-time polymerase chain reaction and immunoblotting, respectively. Type 1 diabetic mice displayed osteopenia phenotype and captopril treatment showed no osteoprotective effects in diabetic mice as shown by the reduction of bone mineral density, trabecular thickness and bone volume/total volume. The mRNA expression of ACE and renin receptor, and the protein expression of renin and angiotensin II were markedly up-regulated in the bone of vehicle-treated diabetic mice compared to those of non-diabetic mice, and these molecular changes of skeletal RAS components were effectively inhibited by treatment with captopril. However, treatment with captopril significantly elevated serum tartrate-resistant acid phosphatase 5b levels, reduced the ratio of osteoprotegerin/receptor activator of nuclear factor-κB ligand expression, increased carbonic anhydrase II mRNA expression and the number of matured osteoclasts and decreased transforming growth factor-β and osteocalcin mRNA expression in the tibia compared to those of diabetic mice. The present study demonstrated that the use of the ACEI, captopril, has no beneficial effect on the skeletal biological properties of diabetic mice. However, this could be attributed, at least partially, to its suppression of osteogenesis and stimulation of osteoclastogenesis, even though it could effectively inhibit high activity of local RAS in the bone of diabetic mice.

Topics: Acid Phosphatase; Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Animals; Bone and Bones; Bone Density; Bone Diseases, Metabolic; Captopril; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Isoenzymes; Male; Mice; Mice, Inbred DBA; NF-kappa B; Osteocalcin; Osteoclasts; Random Allocation; Renin; Renin-Angiotensin System; RNA, Messenger; Streptozocin; Tartrate-Resistant Acid Phosphatase; Tibia; Transforming Growth Factor beta; Up-Regulation

Calcium ion (Ca(2+)) signals are required for osteoclast differentiation. Previous study showed that transient receptor potential vanilloid 5 (TRPV5) is an essential Ca(2+) transporter in osteoclastogenesis and bone resorption. TRPV5 and TRPV6 represent two highly homologous members within the transient receptor potential (TRP) superfamily. However, the role of TRPV6 in bone metabolism is still controversial and little is known about the involvement of TRPV6 in receptor activator of nuclear factor κ-B ligand (RANKL)-induced osteoclastogenesis.. In our study, gene knockout mice, RNA interference, western blot, quantitative real-time PCR, tartrate-resistant acid phosphatase (TRAP) staining, pit formation assay, histomorphometry and measurement of serum parameters were employed to investigate the role of TRPV6 in bone homeostasis, osteoclastogenesis and bone resorption.. We found that TRPV6 depletion results in noticeable destruction of bone microarchitecture in TRPV6 knockout mice (TRPV6(-/-)), suggesting that TRPV6 is a critical regulator in bone homeostasis. Inactivation of Trpv6 had no effect on osteoblastic bone formation. However, quantification of the TRAP staining showed a significantly increased osteoclast number and surface area in the metaphyseal area of femurs bone sections derived from TRPV6(-/-) mice. In agreement with our observations from TRPV6(-/-) mice, TRPV6 depletion in vitro significantly increased osteoclasts differentiation and bone resorption activity.. Based on these results above, we can draw conclusions that TRPV6 plays an essential role in bone metabolism and is a critical regulator in osteoclasts differentiation and bone resorption.

Topics: Acid Phosphatase; Animals; Bone Diseases, Metabolic; Calcium Channels; Calcium Signaling; Cell Differentiation; Femur; Isoenzymes; Mice; Mice, Knockout; Osteoclasts; RANK Ligand; Tartrate-Resistant Acid Phosphatase; TRPV Cation Channels

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

To date, intravenous drip infusion of zoledronic acid (ZA) has mainly been used for the treatment and prevention of skeletal-related events (SRE) in patients with multiple myeloma (MM). Recently, denosumab, a fully humanized monoclonal antibody against receptor activator of nuclear factor-κB ligand (RANKL), has also become available for the same purpose, but little is known about the impact of switching from ZA to denosumab. Herein, we present a retrospective study on bone metabolic markers in 10 MM patients initially treated with ZA and then switched to denosumab. Consequently, the levels of bone resorption markers, tartrate-resistant acid phosphatase 5b (TRACP-5b) and serum type-I collagen crosslinked N-telopeptide (sNTX), significantly decreased after denosumab treatment, while the levels of bone formation markers, osteocalcin (OC) and bone-specific alkaline phosphatase (BAP), showed no apparent changes. No patient developed severe hypocalcemia with denosumab treatment. In one patient not given chemotherapy, the M-protein level increased after switching from ZA to denosumab and plateaued when ZA was restarted. Based on this finding, we anticipate that switching from ZA to denosumab would exert a stronger suppressive effect on osteoclasts, but the anti-myeloma activity of ZA must be taken into consideration.

Topics: Acid Phosphatase; Adult; Aged; Aged, 80 and over; Alkaline Phosphatase; Antibodies, Monoclonal, Humanized; Biomarkers; Bone Density Conservation Agents; Bone Diseases, Metabolic; Bone Resorption; Calcium; Cell Differentiation; Collagen Type I; Denosumab; Diphosphonates; Drug Substitution; Female; Humans; Imidazoles; Isoenzymes; Male; Middle Aged; Multiple Myeloma; Myeloma Proteins; Osteoblasts; Osteocalcin; Osteogenesis; Peptides; RANK Ligand; Retrospective Studies; Tartrate-Resistant Acid Phosphatase; Zoledronic Acid

Gastrectomy (GX) is thought to result in osteomalacia due to deficiencies in Vitamin D and Ca. Using a GX rat model, we showed that GX induced high turnover of bone with hyperosteoidosis, prominent increase of mineralization and increased mRNA expression of both osteoclast-derived tartrate-resistant acid phosphatase 5b and osteocalcin. The increased 1, 25(OH)2D3 level and unchanged PTH and calcitonin levels suggested that conventional bone and Ca metabolic pathways were not involved or changed in compensation. Thus, GX-induced bone pathology was different from a typical osteomalacia. Gene expression profiles through microarray analysis and data mining using Ingenuity Pathway Analysis indicated that 612 genes were up-regulated and 1,097 genes were down-regulated in the GX bone. These genes were related functionally to connective tissue development, skeletal and muscular system development and function, Ca signaling and the role of osteoblasts, osteoclasts and chondrocytes. Network analysis indicated 9 genes (Aldehyde dehydrogenase 1 family, member A1; Aquaporin 9; Interleukin 1 receptor accessory protein; Very low density lipoprotein receptor; Periostin, osteoblast specific factor; Aggrecan; Gremlin 1; Angiopoietin-like 4; Wingless-type MMTV integration site family, member 10B) were hubs connected with tissue development and immunological diseases. These results suggest that chronic systemic inflammation might underlie the GX-induced pathological changes in bone.

Topics: Acid Phosphatase; Animals; Body Weight; Bone and Bones; Bone Diseases, Metabolic; Calcification, Physiologic; Chondrocytes; Gastrectomy; Isoenzymes; Male; Oligonucleotide Array Sequence Analysis; Osteoblasts; Osteocalcin; Osteomalacia; Rats; Rats, Wistar; Reverse Transcriptase Polymerase Chain Reaction; Tartrate-Resistant Acid Phosphatase; Tomography, X-Ray Computed; Vitamin D

To understand, in greater detail, the molecular mechanisms regulating the complex relationship between mechanical strain and alveolar bone metabolism during orthodontic treatment, passive cross-arch palatal springs were bonded to the maxillary molars of 6-wk-old rats, which were killed after 4 and 8 d. Outcome measures included serum assays for markers of bone formation and resorption and for the multifunctional hormone leptin, and histomorphometry of the inter-radicular bone. The concentration of the bone-formation marker alkaline phosphatase (ALP) was significantly reduced at both time points in the appliance group, accompanied by a 50% reduction in inter-radicular bone volume; however, osteocalcin (bone Gla protein) levels remained unaffected. Bone collagen deoxypyridinoline (DPD) crosslinks increased 2.3-fold at 4 d only, indicating a transient increase in bone resorption; in contrast, the level of the osteoclast-specific marker, tartrate-resistant acid phosphatase 5b (TRACP 5b), was unchanged. Leptin levels closely paralleled ALP reductions at both time points, suggesting an important role in the mechanostat negative-feedback loop required to normalize bone mass. These data suggest that an orthodontic appliance, in addition to remodeling the periodontal ligament (PDL)-bone interface, may exert unexpected side-effects on the tooth-supporting alveolar bone, and highlights the importance of recognizing that bone strains can have negative, as well as positive, effects on bone mass.

Topics: Acid Phosphatase; Alkaline Phosphatase; Alveolar Process; Amino Acids; Animals; Biomarkers; Bone Diseases, Metabolic; Bone Resorption; Enzyme-Linked Immunosorbent Assay; Isoenzymes; Leptin; Male; Orthodontic Appliances; Osteocalcin; Rats; Rats, Wistar; Tartrate-Resistant Acid Phosphatase

Increased levels of serum undercarboxylated osteocalcin, which were associated with bone metabolism markers, correlated inversely with indices of glucose metabolism (plasma glucose, hemoglobin A1C, and glycated albumin) in hemodialysis patients with abnormalities of bone metabolism.. Undercarboxylated osteocalcin (ucOC), a possible marker of bone metabolism and one of the osteoblast-specific secreted proteins, has recently been reported to be associated with glucose metabolism. We tested the hypothesis that ucOC levels are associated with indices of glucose metabolism in chronic hemodialysis patients with abnormalities of bone metabolism.. Serum ucOC, bone alkaline phosphatase (BAP, a bone formation marker), and tartrate-resistant acid phosphatase-5b (TRACP-5b, a bone resorption marker) were measured in 189 maintenance hemodialysis patients (96 diabetics and 93 non-diabetics), and their relationships with glucose metabolism were examined.. ucOC correlated positively with BAP (ρ = 0.489, p < 0.0001), TRACP-5b (ρ = 0.585, p < 0.0001) and intact parathyroid hormone (iPTH; ρ = 0.621, p < 0.0001). Serum ucOC levels in the diabetic patients were lower than those of non-diabetic patients (p < 0.001), although there were no significant differences in serum BAP or TRACP-5b between diabetic and non-diabetic patients. Serum ucOC correlated negatively with plasma glucose (ρ = -0.303, p < 0.0001), hemoglobin A1C (ρ = -0.214, p < 0.01), and glycated albumin (ρ = -0.271, p < 0.001), although serum BAP or TRACP-5b did not. In multiple linear regression analysis, log [plasma glucose], log [hemoglobin A1C], and log [glycated albumin] were associated significantly with log [ucOC] after adjustment for age, gender, hemodialysis duration, and body mass index but were not associated with log [BAP], log [TRACP-5b], or log [intact PTH].. Increased levels of serum ucOC, which were associated with bone metabolism markers, were inversely associated with indices of glucose metabolism in hemodialysis patients.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Alkaline Phosphatase; Biomarkers; Blood Glucose; Bone Diseases, Metabolic; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Female; Glycated Hemoglobin; Glycated Serum Albumin; Glycation End Products, Advanced; Humans; Isoenzymes; Kidney Failure, Chronic; Male; Middle Aged; Osteocalcin; Renal Dialysis; Serum Albumin; Tartrate-Resistant Acid Phosphatase

The transcription factor recombination signal binding protein-Jκ (RBP-J) is the critical transcription factor downstream to all four mammalian Notch receptors. Although it has been reported that Notch signaling pathway is involved in bone remodeling, the importance of RBP-J in osteoclastogenesis has not been fully explored. To investigate the role of RBP-J in osteoclastogenesis, we conditionally deleted RBP-J systemically in bone marrow (BM) or specifically in macrophages. We found that disruption of RBP-J in BM resulted in an obvious decrease in trabecular bone mass associated with an increase in osteoclasts, leading to osteopenia. Disruption of RBP-J in macrophages phenocopied the phenotypes of RBP-J deletion in BM with respect to osteoclastogenesis, suggesting that the osteopenia in RBP-J deficient mice is essentially resulted from increased osteoclastogenesis. Furthermore, we found that RBP-J deletion in osteoclasts resulted in a dramatic increase in tartrate-resistant acid phosphatase expression. These findings demonstrate a negatively role of RBP-J in the differentiation of osteoclasts and suggest that Notch pathway may be a new therapeutic target for bone diseases related to increased osteoclastogenesis.

Topics: Acid Phosphatase; Animals; Bone Diseases, Metabolic; Cell Differentiation; Gene Deletion; Gene Expression Regulation; Immunoglobulin J Recombination Signal Sequence-Binding Protein; Isoenzymes; Macrophages; Male; Mice; Mice, Knockout; Osteoclasts; Receptors, Notch; Signal Transduction; Tartrate-Resistant Acid Phosphatase

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

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

High consumption of alcohol is one of the risk factors for osteoporosis. Approximately 45% of Chinese and Japanese individuals have the inactive aldehyde dehydrogenase 2 (Aldh2) phenotype. The absence of the ALDH2*2 allele is found to adversely influence the risk of osteoporosis. The aim of this study is to clarify the effects of alcohol consumption on osteoblast differentiation in bone marrow and trabecular bone formation in Aldh2-disrupted mice.. Seven-week-old male Aldh2 knockout mice (Aldh2(-/-)) and wild-type (Aldh2(+/+)) mice were fed with water (groups Aldh2(-/-)/Wa and Aldh2(+/+)/Wa) or with 5% ethanol (groups Aldh2(-/-)/Al and Aldh2(+/+)/Al) for 4 weeks. At the age of 12 weeks, bone histomorphometry was performed at the secondary spongiosa of the tibias. Bone marrow cells from the bilateral femurs and tibias were used for mRNA expression analysis.. Histomorphometrical study revealed that trabecular bone was significantly reduced in the Aldh2(-/-)/Al group compared with that in the Aldh2(-/-)/Wa and Aldh2(+/+)/Wa groups. Bone formation rate was significantly decreased in Aldh2(-/-)/Al compared with the other three groups. Quantitative RT-PCR revealed a significant decrease in type I collagen, osterix, osteopontin, and osteocalcin mRNA expressions in Aldh2(-/-)/Al compared with Aldh2(-/-)/Wa. In bone marrow cell cultures, mineralized nodule formation in Aldh2(-/-)/Al was significantly decreased compared with that in Aldh2(+/+)/Wa and Aldh2(-/-)/Wa, while PAK18, a p21-activated kinase inhibitor, recovered the decreased mineralized nodule formation in Aldh2(-/-)/Al.. Alcohol consumption suppressed the differentiation and mineralization of osteoblasts and then reduced trabecular bone formation and bone volume in association with the elevated p21 expression in bone marrow cells, especially in aldehyde dehydrogenase 2-disrupted mice.

Topics: Acid Phosphatase; Alcohols; Aldehyde Dehydrogenase; Aldehyde Dehydrogenase, Mitochondrial; Alkaline Phosphatase; Animals; Biomarkers; Body Weight; Bone Density; Bone Diseases, Metabolic; Bone Marrow Cells; Bone Remodeling; Cell Adhesion; Cell Cycle; Colony-Forming Units Assay; Cyclin-Dependent Kinase Inhibitor p21; Gene Expression Regulation; Giant Cells; Isoenzymes; Liver Function Tests; Male; Mice; Organ Size; Osteocalcin; Osteoclasts; Osteogenesis; RNA, Messenger; Tartrate-Resistant Acid Phosphatase; Tibia

Bone loss in patients with osteoporosis may be predicted by the elevation of biochemical markers of bone turnover. Therefore, we studied the relationship between biochemical markers, including parathyroid hormone (PTH), and the 2-year change in radial cortical bone in patients under chronic hemodialysis.. Tartrate-resistant acid phosphatase-5b (TRACP-5b), bone-specific alkaline phosphatase, whole PTH, and total intact PTH were measured in 53 patients under maintenance hemodialysis. Additionally, radial cortical bone mineral density (BMD) and relative cortical area (RCA) were measured by peripheral quantitative computed tomography 2 years apart.. In all patients, BMD decreased by 2.5% and RCA decreased by 5.8% during 2 years. TRACP-5b levels significantly correlated with decreased RCA in all and female patients, but not with decreased BMD. Bone-specific alkaline phosphatase correlated with decreased BMD in all patients and with decreased RCA in all and female patients. Whole PTH did not correlate with decreased RCA or BMD. Total intact PTH significantly correlated with decreased BMD in all and male patients and with decreased RCA in all and female patients. In stepwise multiple regression analysis, TRACP-5b and total intact PTH were selected as explanatory variables for decreased RCA and decreased BMD, respectively.. These results suggest that TRACP-5b and total intact PTH are powerful markers to predict radial cortical bone loss in hemodialysis patients.

Topics: Acid Phosphatase; Aged; Biomarkers; Bone Density; Bone Diseases, Metabolic; Bone Remodeling; Bone Resorption; Female; Humans; Isoenzymes; Male; Middle Aged; Parathyroid Hormone; Radius; Renal Dialysis; Tartrate-Resistant Acid Phosphatase

Clinical studies have revealed a blunting of the bone anabolic effects of parathyroid hormone treatment in osteoporotic patients in the setting of pre- or cotreatment with the antiresorptive agent alendronate (ALN). Sclerostin monoclonal antibody (Scl-Ab) is currently under clinical investigation as a new potential anabolic therapy for postmenopausal osteoporosis. The purpose of these experiments was to examine the influence of pretreatment or cotreatment with ALN on the bone anabolic actions of Scl-Ab in ovariectomized (OVX) rats. Ten-month-old osteopenic OVX rats were treated with ALN or vehicle for 6 wk, before the start of Scl-Ab treatment. ALN-pretreated OVX rats were switched to Scl-Ab alone or to a combination of ALN and Scl-Ab for another 6 wk. Vehicle-pretreated OVX rats were switched to Scl-Ab or continued on vehicle to serve as controls. Scl-Ab treatment increased areal bone mineral density, volumetric bone mineral density, trabecular and cortical bone mass, and bone strength similarly in OVX rats pretreated with ALN or vehicle. Serum osteocalcin and bone formation rate on trabecular, endocortical, and periosteal surfaces responded similarly to Scl-Ab in ALN or vehicle-pretreated OVX rats. Furthermore, cotreatment with ALN did not have significant effects on the increased bone formation, bone mass, and bone strength induced by Scl-Ab in the OVX rats that were pretreated with ALN. These results indicate that the increases in bone formation, bone mass, and bone strength with Scl-Ab treatment were not affected by pre- or cotreatment with ALN in OVX rats with established osteopenia.

Topics: Acid Phosphatase; Alendronate; Animals; Antibodies, Monoclonal; Bone and Bones; Bone Density; Bone Density Conservation Agents; Bone Diseases, Metabolic; Bone Morphogenetic Proteins; Disease Models, Animal; Female; Genetic Markers; Isoenzymes; Osteocalcin; Osteogenesis; Ovariectomy; Rats; Rats, Sprague-Dawley; Tartrate-Resistant Acid Phosphatase

The study investigated the influence of 4-methylbenzylidene camphor (4-MBC), daidzein, and estradiol-17β-benzoate (E(2)) on either intact or osteotomized cancellous bone in ovariectomized (Ovx) rats. Three-month old Ovx rats were fed with soy-free (SF) diet over 8 weeks; thereafter, bilateral transverse metaphyseal osteotomy of tibia was performed and rats were divided into groups: rats fed with SF diet and SF diet supplemented with 4-MBC (200 mg), daidzein (50 mg), or E(2) (0.4 mg) per kilogram body weight. After 5 or 10 weeks, computed tomographical, biomechanical, histological, and ashing analyses were performed in lumbar spine and tibia of 12 rats from each group. 4-MBC and E(2) improved bone parameters in lumbar spine and tibia, were not favorable for osteotomy healing, and decreased serum osteocalcin level. However, daidzein improved bone parameters to a lesser extent and facilitated osteotomy healing. For lumbar spine, the bone mineral density was 338±9, 346±5, 361±6, and 360±5 mg/cm(3) in SF, daidzein, 4-MBC, and E(2), respectively, after 10 weeks. For tibia, the yield load was 98±5, 114±3, 90±2, and 52±4 N in SF, daidzein, 4-MBC, and E(2), respectively, after 10 weeks. Serum daidzein was 54±6 ng/ml in daidzein group and equol was not detected. Alp and Igf1 genes were down-regulated in callus after daidzein and E(2) compared with 4-MBC (week 5). The response of bone tissue and serum markers of bone metabolism could be ordered: daidzein<4-MBC

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Biomechanical Phenomena; Bone and Bones; Bone Density; Bone Diseases, Metabolic; Bony Callus; Camphor; Diet; Estrogens; Female; Gene Expression; Insulin-Like Growth Factor I; Isoenzymes; Isoflavones; Lumbar Vertebrae; Osteocalcin; Osteotomy; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; Tartrate-Resistant Acid Phosphatase; Tibia; Tomography, X-Ray Computed

The aim of our study was to see the efficacy of petroleum ether extract of Cissus quadrangularis (CQ) on development of osteopenia in ovariectomy induced Wistar rats.. The female Wistar rats were ovariectomized or Sham operated. The rats were anesthetized with pentobarbital sodium (40 mg/ kg b.w, i.p.), the ovaries were removed bilaterally. Sham-operation was performed in the same manner but only exposing the ovaries (sham operated (SHAM) group). A day later, the ovariectomized rats were randomly divided into four groups of eight animals each. The groups are 1. Sham operated (SHAM), 2. Ovariectomized (OVX), 3. Ovariectomized and treated with 25 mg/kg b.w of raloxifene (OVX+RAL), 4. Ovariectomized and treated with 500 mg/kg b.w of petroleum ether extract of CQ (OVX+CQ). The treatment continued for 30 days. At the end of the treatment, rats in all groups were sacrificed by cervical dislocation. Before sacrifice, blood was collected for the estimation of serum ALP, TRAP, Calcium and hydroxyproline; where as the left femur was used for histomorphometrical analysis.. The findings assessed on the basis of animal weight, morphology of femur, histomorphometry and biochemical analysis. As compared to SHAM group, OVX group animals showed a significant rise in serum ALP, TRAP and hydroxyproline levels at the end of 1 month following ovariectomy while no significant change was seen in the serum calcium levels. ALP and TRAP levels of OVX + RAL and OVX + CQ groups showed a further increase following administration of raloxifene and Cissus quadrangularis. The serum hydroxyproline content was found to be increased in the OVX + CQ compared to SHAM group. CQ significantly increased the thickness of both cortical (p <0.001) and trabecular bone (p <0.001).This action of CQ is comparable to action of Raloxifene. )These data suggest a strong anti-osteoporotic activity of CQ.. The results confirm, at least in part, for the use of Cissus quadrangularis in folk medicine to treat osteoporosis.

Topics: Acid Phosphatase; Alkaline Phosphatase; Alkanes; Animals; Biomarkers; Bone Diseases, Metabolic; Bone Resorption; Calcium; Cissus; Disease Models, Animal; Drug Evaluation, Preclinical; Female; Femur; Humans; Hydroxyproline; Isoenzymes; Osteoporosis, Postmenopausal; Ovariectomy; Phytotherapy; Plant Extracts; Raloxifene Hydrochloride; Random Allocation; Rats; Rats, Wistar; Tartrate-Resistant Acid Phosphatase

The objective of this study is to examine the effect of cyclosporine-A (CsA) on the rate of orthodontic tooth movement in rats.. This is a randomized controlled trial with a split-mouth design in Sprague-Dawley rats.. Eighteen rats, divided at random in two groups, were fed with 8 mg/kg CsA (experiment) or mineral oil (control) daily after initial healing of bilateral maxillary second molar removal. All rats received orthodontic coil springs (10 cN) secured to the maxillary incisors and first molars at the rights side, while no springs were placed at the left. Distances between first and third molars were measured on days 0, 3, 6, and 12. After sacrificing on day 12, the alveolar ridges of the maxillae were sectioned and blood samples were collected for serum tartrate-resistant acid phosphatase (TRAP)-5b level detection and for histology, respectively.. Significantly larger changes in intermolar distances were found after orthodontic force application in the CsA group at days 3 and 12 when compared with the control group. The inter-radicular dental alveolus of CSA-fed rats was osteopenic. Significantly increased TRAP-5b serum level was noted in the CsA group when compared with the control group.. We suggest that CsA enhanced the rate of orthodontic tooth movement. The osteopenia and the increased osteoclastic activity could be the underlying factors.

Topics: Acid Phosphatase; Alveolar Process; Animals; Biomarkers; Bone Diseases, Metabolic; Bone Remodeling; Cyclosporine; Immunosuppressive Agents; Isoenzymes; Male; Maxilla; Molar; Orthodontic Wires; Osteoclasts; Random Allocation; Rats; Rats, Sprague-Dawley; Stress, Mechanical; Tartrate-Resistant Acid Phosphatase; Time Factors; Tooth Movement Techniques

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

Increases in bone strains above a certain threshold have a positive effect on bone mass, whereas reductions in strain magnitude lead to bone loss and osteopenia; the term 'mechanostat' has been introduced to describe this tissue-level negative feedback mechanism. The mechanobiology of bone and particularly alveolar bone is poorly understood, and whether the mechanostat theory has any relevance to explaining the osseous changes that occur during orthodontic tooth movement remains unclear. To investigate the relationship further, an expansile force of 0.2 N was applied to the maxillary molars of 36, 6-week-old Wistar rats by helical coil springs. The animals were sacrificed at 1, 2, 4, and 8 days and the tissue response analyzed by histological, biochemical, and finite element (FE) methods. Differences between groups were determined by Student's t-test (two-tailed). The appliance produced an increase in the intermolar width averaging 0.5 mm after 8 days. Tetracycline uptake in the control rats suggested a rapid turnover of bone in both the interradicular domain and the bone-periodontal ligament interface. In the experimental group, however, incorporation of tetracycline into the interradicular domain was reduced and conventional histology revealed evidence of bone loss and osteopenia, in both the experimental and a group of sham-treated positive controls (with inactive, annealed springs). Serum alkaline phosphatase declined significantly in both experimental and sham-treated groups over the 8-day time course, indicating decreased bone formation. Serum acid phosphatase also declined, suggesting a concomitant decrease in bone resorption. Three-dimensional FE analysis of the stresses generated in the bone following occlusal (2 N) and orthodontic loading showed that the orthodontic force created a constant loading condition shielding some areas of bone from mechanical stress. Areas of low mechanical stimulation were coincident with sites of bone loss observed histologically, while bone mass was preserved in areas with higher levels of loading. These findings suggest that (1) the osteopenia resulted from stress shielding of the interradicular bone by the appliance, and a consequent reduction in occlusal loading below the critical threshold required for maintaining normal osseous architecture and (2) the mechanostat model can be employed to explain, at least in part, the response of the bone to orthodontic loading.

Topics: Acid Phosphatase; Alkaline Phosphatase; Alveolar Bone Loss; Alveolar Process; Animals; Biomechanical Phenomena; Bite Force; Bone Diseases, Metabolic; Bone Remodeling; Feedback; Finite Element Analysis; Fluorescent Dyes; Imaging, Three-Dimensional; Interleukin-1beta; Interleukin-6; Male; Models, Animal; Molar; Orthodontic Wires; Osteogenesis; Periodontal Ligament; Rats; Rats, Wistar; Stress, Mechanical; Tetracycline; Tooth Movement Techniques; Tooth Root; X-Ray Microtomography

In order to investigate the underlying mechanism of alterations in bone mineral metabolism in patients with type 2 diabetes, we determined circulating levels of bone functional markers along with urinary excretion of sorbitol (SOR) and bone mineral density (BMD), and also examined their mutual interrelationship. A total of 151 male type 2 diabetic patients were examined in this study. Forty-eight age-matched male healthy subjects were also studied as the controls. A significant reduction of serum intact osteocalcin (i-OC) was found in the diabetic groups (p<0.01). On the other hand, circulating levels of tartrate resistant acid phosphatase (TRAP) in the diabetic patients were significantly higher than those in the controls (p<0.01). Interestingly, a significantly negative relationship was observed between BMD and serum TRAP (p<0.01), although no significant relationship was noted between BMD and serum i-OC in diabetic patients. Urinary excretion of SOR was significantly elevated in the diabetic patients when compared with the controls (p<0.01). In addition, a significantly positive correlation was observed between serum TRAP and urinary SOR (p<0.01), but not between serum i-OC and urinary SOR. Elevated serum TRAP in diabetes was reduced after the administration of aldose reductase inhibitor (p<0.05). It seems most likely that the increase in osteoclastic function probably due to accelerated polyol pathway plays a crucial role in the pathogenesis of decreased bone mineral content in male patients with type 2 diabetes.

Topics: Acid Phosphatase; Bone Density; Bone Diseases, Metabolic; Bone Resorption; Diabetes Mellitus, Type 2; Humans; Isoenzymes; L-Iditol 2-Dehydrogenase; Male; Middle Aged; Osteocalcin; Polymers; Signal Transduction; Sorbitol; Tartrate-Resistant Acid Phosphatase

Osteoclastic activity is mainly assessed by measurement of urinary markers (eg C-terminal cross-linked telopeptides of type I collagen, N-terminal crosslinked telopeptides of type I collagen, etc), the levels of which could often be affected by renal clearance. Recently, serum tartrate-resistant acid phosphatase 5b (TRACP5b) has been used as an alternative serum marker to evaluate osteoclastic activity. We investigated the age-related changes of TRACP5b level and its association with bone mineral density (BMD) in Chinese women.. Seven-hundred and twenty-two Chinese mainland women aged 20-79 years were recruited in the study. Serum TRACP5b level was measured using immunoassay to evaluate the state of bone resorption. Bone mineral density (BMD) (g/cm2) at lumbar spine 1-4 and proximal femur were measured by duelenergy X-ray absorptiometry.. The serum TRACP5b level reached a bottom value in premenopausal women aged 30-39, gradually increased in women aged 40-49, rapidly rose in women aged 50-59, and culminated with a maximum value in women aged 60-69 before a slow drop in women aged 70- 79. The average level of TRACP5b was significantly higher in postmenopausal women [(3.29+/-1.07) U/L] than in premenopausal women ([1.70+/-0.59] U/L). The levels of TRACP5b were inversely correlated with BMD at all measured sites (P<0.001). Furthermore, the level of TRACP5b was obviously higher in women with osteoporosis and osteopenia than those with normal bone mass (P<0.001).. We have established the reference values of serum TRACP5b in Chinese mainland women, and found that postmenopausal women had higher TRACP5b concentration than younger women. The results showed that serum TRACP5b was a sensitive and useful parameter for the evaluation of age-related changes of bone absorption.

Topics: Absorptiometry, Photon; Acid Phosphatase; Adult; Aged; Aging; Biomarkers; Bone Density; Bone Diseases, Metabolic; Bone Resorption; China; Female; Humans; Isoenzymes; Middle Aged; Osteoporosis, Postmenopausal; Postmenopause; Tartrate-Resistant Acid Phosphatase; Young Adult

Although osteopenia has been associated with human diabetes mellitus, the pathogenesis of diabetic osteopenia is unclear. In the present study, we evaluated the effect of diabetes on histomorphometry, bone mineral density (BMD)-measured by dual-energy X-ray absorptiometry (DXA)-and biomarkers of bone metabolism in rats up to 120 days after the onset of experimental diabetes. Female Wistar rats with a regular estrous cycle were randomly divided into two groups: control rats (n = 15) and diabetic rats without insulin treatment (n = 25). Diabetes was induced by injection of alloxan and was confirmed by the determination of blood glucose concentration (>250 mg/dl). The results revealed an approximate threefold increase of femoral trabecular distance in diabetic rats compared to controls. Conversely, trabecular thickness and bone trabecular volume were reduced twofold and 77%, respectively. BMD in both the metadiaphyseal region and total area of the femur was found to be clearly reduced in diabetic animals, with no significant differences between the groups. Serum alkaline phosphatase (ALP) and tartarate-resistant acid phosphatase (TRAP) activities showed significant six- and twofold increases, respectively, in diabetic rats. There were significant decreases in serum calcium and albumin concentrations in diabetic rats, but no difference was observed in serum magnesium, phosphorus, or creatinine concentrations between the groups. Overall, our findings support the conclusion that the diabetic state is associated with alterations in bone turnover, resulting in the development of osteopenia, which is related to the time of evolution of the disorder.

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Biomarkers; Blood Glucose; Bone and Bones; Bone Density; Bone Diseases, Metabolic; Calcium; Creatine; Diabetes Mellitus, Experimental; Estrous Cycle; Female; Isoenzymes; Rats; Rats, Wistar; Serum Albumin; Tartrate-Resistant Acid Phosphatase

To evaluate bone and calcium-phosphorus metabolism, bone tissue density (BTD) in smokers and non-smokers with chronic obstructive pulmonary disease (COPD).. The study included 120 patients with COPD; smokers (n=68), smokers in the past (n=8) and non-smokers (n=44). Control 80 healthy subjects were matched by age and sex. Bone metabolism was estimated by concentration of osteocalcin (OC), markers of bone resorption (TRAP, betaCrossLaps-betaCL).. Smoking aggravates disturbance of calcium metabolism in COPD leading to hypocalcaemia and hypercalciuria. In smokers with COPD bone remodeling dysfunction is caused by suppression of osteogenesis and enhancement of resorption, in non-smokers--intensification of both resorption and osteogenesis. The analysis of correlations has shown that there is a close correlation between the level of TRAP, bone mineral density scores and indices of pack-years (r = -075, p < 0.01; r = -0.6, p < 0.01, respectively). Anamnesis of smoking has a positive correlation with TRAP (r = 0.85, p < 0.001) and a negative correlation with bone density (r = -0.8, p < 0.01) and OC (r = -0.55, p < 0.01).. Duration of smoking (total pack-years) is an additional marker of osteopenic syndrome in COPD. This is confirmed by close correlation of this parameter with bone density and markers of bone resorption.

Topics: Acid Phosphatase; Aged; Biomarkers; Bone and Bones; Bone Density; Bone Diseases, Metabolic; Bone Resorption; Calcium; Female; Humans; Hypercalcemia; Male; Osteocalcin; Phosphorus; Pulmonary Disease, Chronic Obstructive; Smoking

The P2X7 nucleotide receptor is an ATP-gated ion channel that plays an important role in bone cell function. Here, we investigated the effects of L: -tyrosine derivatives 1-3 as potent P2X7 antagonists on human primary osteoclasts. We found that the level of expression of P2X7 receptor increased after treatment with the derivatives 1-3, together with the induction of high levels of apoptosis. This effect is associated with activation of caspase-3 and inhibition of expression of IL-6. Interestingly, no pro-apoptotic effect of compounds 1-3 was found on human osteoblasts. Our results suggest that the development of specific P2X7 receptor antagonists may be considered a useful tool to modulate apoptosis of human osteoclasts. Since bone loss due to osteoclast-mediated resorption represents one of the major unsolved problem in osteopenic disorders, the identification of molecules able to induce apoptosis of osteoclasts is of great interest for the development of novel therapeutic strategies.

Topics: 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; Acid Phosphatase; Apoptosis; Bone and Bones; Bone Diseases, Metabolic; Caspase 3; Caspases; Cell Nucleus; Cells, Cultured; Enzyme Activation; Enzyme Inhibitors; Humans; Immunohistochemistry; In Situ Nick-End Labeling; Interleukin-6; Isoenzymes; Models, Chemical; NF-kappa B; Osteoblasts; Osteoclasts; Piperazines; Purinergic P2 Receptor Antagonists; Receptors, Purinergic P2X7; Tartrate-Resistant Acid Phosphatase; Tetrazolium Salts; Thiazoles; Time Factors

The main task of the present study is to investigate the influences of normobaric gas mixture with lowered PO2 (90-110 mm Hg) on the bones metabolism in rats after hind limb unloaded (HLU). We observed increased the glycosaminoglicans (GAG) concentration in blood serum rats with hind limb unloaded in atmospheric air (AA). An increased activity of acid phosphatase (AcP) and tartratresistant acid phosphatase (TRAcP) in blood serum of rats after HLU was observed. The activities of the alkaline phosphatase (AIP) in blood serum did not change. An increased osteocalcin (OST) and C-terminal Propeptide of type I Collagen (CICP) concentration in blood serum, but parathyroid hormone (PTH) decrease comparatively with the control. The above mentioned biochemistry markers in animals after 28 days unloading in normobaric gas mixture (NGM) were more stable and in spite of the same procedure in AA, all dates were near to the controls.

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Biomarkers; Bone Diseases, Metabolic; Bone Remodeling; Glycosaminoglycans; Hindlimb Suspension; Isoenzymes; Male; Osteocalcin; Oxygen; Parathyroid Hormone; Partial Pressure; Peptide Fragments; Procollagen; Rats; Rats, Wistar; Tartrate-Resistant Acid Phosphatase; Weightlessness Simulation

The pathophysiological processes underlying the development of diabetic osteopenia has not hitherto been elucidated. Induction of streptozotocin diabetes leads in our experiments to decrease of bone density, ash, mineral content and to thinner cortical width compared to control male rats. In order to investigate the pathogenetic role of bone resorption by osteoclasts in streptozotocin-induced diabetes, we determined the circulating levels of tartrate-resistant acid phosphatase (TRAP), a biochemical marker for bone resorption. Plasma TRAP values in diabetic rats did not differ from their corresponding controls. Streptozotocin diabetes by itself did not have any effect on the weight of seminal vesicles which are highly testosterone-dependent. Low doses of nitric oxide cause bone resorption, but higher doses of NO inhibit bone resorbing activity. We examined the effect of L-NAME (inhibitor of nitric oxide production) after six weeks of administration to diabetic rats. There was no further significant loss of bone mineral density, ash and mineral content or tibia weight in diabetic rats treated with L-NAME. L-NAME itself did not decrease bone metabolism. In our study no evidence of an increased bone resorption was found. Our results have indicated that a predominance of bone resorption over bone formation is not involved in the pathogenesis of diabetes-associated osteopenia. Inhibition of NO neither increased osteoclastic activity (TRAP) nor induced osteopenia in L-NAME-treated rats. This suggests a possibility that NO is not involved in the pathogenesis of diabetic osteopenia.

Topics: Acid Phosphatase; Animals; Blood Glucose; Body Weight; Bone and Bones; Bone Density; Bone Diseases, Metabolic; Diabetes Mellitus, Experimental; Enzyme Inhibitors; Femur; Glycated Hemoglobin; Insulin; Isoenzymes; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase; Rats; Rats, Wistar; Seminal Vesicles; Tartrate-Resistant Acid Phosphatase; Tibia; Treatment Outcome

To assess how two different serum markers of bone resorption may reflect changes in bone turnover, we compared age- and sex-related changes in serum C-terminal telopeptide of type I collagen (betaCTx) and tartrate-resistant acid phosphatase activity (TRAP) in 136 healthy men and 184 normal women. Serum levels of the two markers were also assessed in several groups of patients of both sexes presenting with the most common metabolic and endocrine bone diseases: established osteoporosis (n = 77), primary hyperparathyroidism (n = 44), glucocorticoid excess (n = 17), chronic renal failure (n = 39), active Paget's disease of bone (n = 5), humoral hypercalcemia of malignancy (n = 3), osteomalacia (n = 3), hyperthyroidism (n = 10), post-surgical hypoparathyroidism (n = 10), acromegaly (active disease, n = 8) and Cushing's syndrome (n = 10). In men the regression of betaCTx with age showed an initial decrease in bone resorption followed by an increase thereafter, starting from the sixth decade of life. No age-related change in serum TRAP activity was observed. In women, by contrast, a slight but significant linear correlation of both serum betaCTx and TRAP with age (r = 0.223, p<0.003 and r = 0.333, p<0.0001, respectively) was found, the two markers being positively correlated (r = 0.238, p<0.002). In each class of patients the mean Z-scores of betaCTx were significantly higher than those of TRAP activity. Moreover, compared with normal subjects, serum betaCTx seems to be characterized by a superior sensitivity relative to TRAP measurement, at least in the disorders studied.

Topics: Acid Phosphatase; Adult; Aged; Aged, 80 and over; Aging; Biomarkers; Bone Diseases; Bone Diseases, Endocrine; Bone Diseases, Metabolic; Bone Resorption; Collagen; Collagen Type I; Female; Humans; Isoenzymes; Male; Middle Aged; Peptides; Sex Characteristics; Tartrate-Resistant Acid Phosphatase

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

Tartrate-resistant acid phosphatase (TRAP) is a standard histochemical marker of differentiated osteoclasts and has been proposed as a serum/plasma marker for osteoclast activity. Enzyme assays have been described that show elevated TRAP enzyme activity in the serum or plasma of patient groups known to have increased bone metabolism. However, the poor stability of the enzyme and potential contribution from nonosteoclastic sources make it problematic to measure in patient samples. Immunoassays developed to measure TRAP in serum and plasma have yielded widely varying TRAP levels in both normal and disease states. It is not clear if this variability is caused by differences in assay calibration, antibody specificity, and/or TRAP instability. In this paper, we report that purified TRAP spiked into serum forms high molecular weight complexes. Complex formation results in greatly decreased TRAP enzyme activity and immunoreactivity. The complexing protein in serum has been identified as alpha2-macroglobulin (alpha2M). Similar complexes are observed in stored patient samples. In vitro studies with purified components show that TRAP binds to alpha2M primarily through noncovalent ionic interactions. Our results demonstrate that one mechanism of TRAP instability in serum is complex formation with alpha2M and suggest further that current TRAP enzyme and immunoassays may not accurately measure the circulating level of TRAP.

Topics: Acid Phosphatase; alpha-Macroglobulins; Biomarkers; Bone Diseases, Metabolic; Child; Enzyme Stability; Humans; Immunoenzyme Techniques; In Vitro Techniques; Isoenzymes; Macromolecular Substances; Molecular Weight; Osteitis Deformans; Osteoclasts; Protein Binding; Tartrate-Resistant Acid Phosphatase

Tartrate-resistant acid phosphatase (TRAP) activity is regarded as an important cytochemical marker of osteoclasts; its concentration in serum is utilized as a biochemical marker of osteoclast function and degree of bone resorption. This study was carried out to assess the sensitivity of TRAP activity both as a cytochemical marker in histological sections and as a biochemical marker in serum in comparison with the standardized histomorphometric variables of osteoclasts. To this end we investigated 24 patients (21 women, 3 men; 60 +/- 17 years of age) affected with various metabolic bone diseases. Osteoclast surface (OcS/BS) and osteoclast number (OcN/BS) were evaluated by standardized histomorphometry in iliac crest biopsies. On the basis of TRAP cytochemical activity, TRAP-positive osteoclast surface (TRAP + OcS/BS) and number (TRAP + OcN/BS) were measured. TRAP-positive cells adjacent to bone and showing one nucleus or no nuclei at all in the plane of section were included in the counts as osteoclasts. Serum TRAP activity was determined by spectrophotometric assay. Values of OcS/BS and OcN/BS were much lower than those of TRAP + OcS/BS (-50%) and TRAP + OcN/BS (-60%), respectively. Correlations between OcS/BS and TRAP + OcS/BS, and between OcN/BS and TRAP + OcN/BS, were highly significant. Serum TRAP was significantly correlated with OcS/BS, OcN/BS, and TRAP + OcN/BS. These correlations, however, were rather low. Moreover, serum TRAP did not correlate with TRAP + OcS/BS. From these results, the conclusion can be drawn that while TRAP activity is confirmed as a valid cytochemical marker for identification of osteoclasts, serum TRAP activity is an osteoclastic marker of weak sensitivity. This may be due to known factors, such as synthesis of the enzyme not being unique to osteoclasts, enzyme instability, and the presence of inhibitors in serum. Mononucleated osteoclasts do not significantly influence the serum enzyme levels.

Topics: Acid Phosphatase; Aged; Biomarkers; Bone Diseases, Metabolic; Cell Nucleus; Cell Size; Female; Humans; Isoenzymes; Male; Middle Aged; Osteoclasts; Sensitivity and Specificity; Tartrate-Resistant Acid Phosphatase

We examined the effects of nandrolone decanoate (25 mg im every 3 weeks) on bone mass, serum biomarkers, and bone histomorphometric endpoints in 52 female cynomolgus macaques randomized into four treatment groups: (1) sham-ovariectomized (sham); (2) ovariectomized + placebo for 2 years (ovx); (3) ovx + nandrolone decanoate for 2 years (Nan); and (4) ovx + nandrolone decanoate beginning 1 year after ovx (dNan). Serum alkaline phosphatase (ALP), osteocalcin, and tartrate-resistant acid phosphatase (TRAP) were assayed every 3 months, and X-ray densitometry of the lumbar spine was done every 6 months. Fluorochrome-labeled iliac biopsies collected at baseline and 1 year, and lumbar vertebrae and midshaft femur collected at 2 years, were evaluated histomorphometrically. Body weight increased over 50% with administration of nandrolone. After 2 years, ovx animals had lower spinal BMC and BMD than all other groups. Ovx animals also had higher bone turnover rates than all other groups, as indicated by higher levels of the serum and urine biomarkers, and by at least twofold higher label-based bone formation rates in the femur diaphysis and in both cancellous and cortical bone of the ilium and vertebral bodies. Nandrolone-treated animals had similar serum estradiol levels as the sham animals, presumably due to conversion of endogenous or exogenous androgens. The effects of nandrolone on bone in this experiment are consistent with estradiol action and may be attributable to the increased serum estradiol. Despite >50% higher body weight, nandrolone-treated, ovariectomized animals did not have higher bone mass than sham animals.

Topics: Absorptiometry, Photon; Acid Phosphatase; Alkaline Phosphatase; Amino Acids; Anabolic Agents; Animals; Biomarkers; Body Composition; Bone Density; Bone Development; Bone Diseases, Metabolic; Disease Models, Animal; Estradiol; Female; Femur; Humans; Ilium; Isoenzymes; Lumbar Vertebrae; Macaca fascicularis; Nandrolone; Nandrolone Decanoate; Osteocalcin; Osteoporosis, Postmenopausal; Ovariectomy; Random Allocation; Tartrate-Resistant Acid Phosphatase

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

We have recently shown that administration of long-term, low-dose methotrexate (MTX) causes severe osteopenia in female rats. This osteopenia is characterized both by decreased osteoblast function without a decrease in osteoblast numbers, and by increased bone resorption that is believed to represent a physiologic remodeling response by osteoclasts. The present study investigates the effects of varying doses of MTX on mouse bone cells in culture.. Cells were obtained by sequential digestion of neonatal mouse calvariae, and cultured with fetal calf serum (10% for osteoblast-like cells and 2% for osteoclast-like cells). After 1 week, MTX was added to each culture in concentrations of 0.6 microM, 0.4 microM, 0.2 microM, 0.1 microM, 1 nM, and 0.5 nM. All experiments were done on 24 wells for each MTX concentration and for the controls. The effect on osteoblastic cells was assessed, at 7 days, by cell counts and by measurement of lysate alkaline phosphatase and supernatant osteocalcin levels, and, at 21 days, by analysis of the calcified matrix production, which was cultured with ascorbic acid and beta-glycerophosphate. For osteoclastic cells, cell count and lysate acid phosphatase levels were determined.. Levels of osteoblastic cells and lysate alkaline phosphatase were not changed by any of the concentrations of MTX. Matrix calcification and supernatant osteocalcin levels were diminished by MTX in a dose-responsive manner. Osteoclast-like cell numbers and acid phosphatase levels were not significantly affected by MTX.. These results suggest that diminished mouse osteoblastic cell function occurs with very low mean concentrations of MTX, in a dose-responsive manner. The mechanism seems to be inability of the cell to synthesize and calcify matrix, possibly through defective osteocalcin production. Thus, low-dose MTX may have an important impact on bone density by slowing osteoblastic matrix production.

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Bone Diseases, Metabolic; Calcium; Cell Count; Cells, Cultured; Dose-Response Relationship, Drug; Female; Methotrexate; Mice; Mice, Inbred ICR; Osteoblasts; Osteoclasts; Pregnancy; Skull

The etiology of bone disease seen in long-term total parenteral nutrition patients is poorly defined. This study examined the question of whether abnormal bone could be induced in otherwise normal weanling rats fed a balanced nutrient solution intravenously. Young adult, male Wag/Rij rats were divided into three groups. One group was fed a commercial liquid research diet, one group received an indwelling jugular catheter and was fed an intravenous elemental solution formulated to be nutritionally complete, and one group received an indwelling catheter but was fed the commercial liquid diet orally. Significant differences were seen between groups in percent bone, femur length, growth-plate width, endosteal label area, periosteal mineral apposition rate, and periosteal and endosteal bone-formation rates. This study suggests that intravenous administration of otherwise adequate nutrients to rats results in altered bone remodeling compared to orally fed cohorts.

Topics: Acid Phosphatase; Administration, Oral; Animals; Bone and Bones; Bone Diseases, Metabolic; Catheterization, Central Venous; Catheters, Indwelling; Male; Minerals; Nutritional Requirements; Parenteral Nutrition, Total; Rats

The propensity of crosslinked collagen matrices to calcify when implanted in animals and human beings is well documented. This article demonstrates that the covalent binding of the biphosphonate, 3-amino-1-hydroxy-propane-1-1-diphosphonic acid, to active bone matrix inhibits bone formation as well as dystrophic calcification. The inhibitory effects on calcium accumulation and alkaline phosphatase activity are greater than those achieved by inactivation of the matrix by protease digestion of the bone morphogenetic factors present in demineralized bone. Whereas bone formation is a cell-mediated effect, artificially crosslinked collagen matrices calcify extensively inside diffusion chambers, reflecting a non-cell-mediated nucleation process. The fundamental differences described should shed light on new modalities to modulate these processes in living systems.

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Bone Demineralization Technique; Bone Diseases, Metabolic; Bone Transplantation; Calcinosis; Collagen; Diphosphonates; Femur; Humans; Male; Models, Biological; Osteocalcin; Pamidronate; Protein Binding; Rats; Tibia

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 preventive effect of beta-alanyl-L-histidinato zinc (AHZ) on the toxic action of aluminium on bone metabolism was investigated in the femoral diaphysis of weanling rats. Aluminium chloride (5.0, 10.0 and 20.0 mumol A1/100 g body weight) was orally administered for 3 days. The dose of 10.0 and 20.0 mumol A1/100 g caused a significant increase in serum calcium concentration and bone acid phosphatase activity, while bone alkaline phosphatase activity and calcium content were not altered significantly. Moreover, the bone DNA content was significantly decreased by the doses of 10.0 and 20.0 mumol A1/100 g. Meanwhile, the increase in serum calcium concentration caused by the administration of aluminium (20 mumol/100 g) was completely prevented by the simultaneous administration of AHZ (1.0 and 2.5 mg/100 g) for 3 days, although AHZ alone did not have any effect. Also, the effects of aluminium (20.0 mumol/100 g) to increase bone acid phosphatase activity and to decrease the bone DNA content were completely blocked by the simultaneous administration of AHZ (1.0 and 2.5 mg/100 g). AHZ (1.0 and 2.5 mg/100 g) alone had the effect to increase bone DNA content but not bone acid phosphatase activity. The present study indicates that AHZ can prevent the revelation of the toxic effect of aluminium on bone metabolism in rats.

Topics: Acid Phosphatase; Aluminum; Animals; Anti-Ulcer Agents; Bone and Bones; Bone Diseases, Metabolic; Calcium; Carnosine; Dipeptides; DNA; Dose-Response Relationship, Drug; Femur; Male; Organometallic Compounds; Rats; Rats, Inbred Strains; Zinc; Zinc Compounds

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

Lumbar vertebrae (L4) from CW-1 female mice were examined for age-related changes in alkaline and acid phosphatase activities from young to old age. Histochemically, both enzymes were encountered along the bony surfaces of both trabecular and cortical bones with no significant age-related changes in their distribution. Biochemical determinations of bone alkaline phosphatase (Alk'ase) activity revealed that for a given unit level of bone or the bone as a whole no significant changes took place, whereas acid phosphatase (Acid'ase) activity was found to have increased significantly with age. A high positive correlative relationship was noted between the calcium content and the trabecular bone volume of the same vertebrae. It may, therefore, be proposed that age-related bone loss in mice could be attributed to an enhanced resorption rather than to a substantial reduction in the formative potential of bone cells.

Topics: Acid Phosphatase; Aging; Alkaline Phosphatase; Animals; Bone Diseases, Metabolic; Female; Histocytochemistry; Levamisole; Lumbar Vertebrae; Male; Mice; Sodium Fluoride

We improved the spectrophotometric assay of tartrate-resistant acid phosphatase (TrACP; EC 3.1.3.2) activity in serum. During development of the assay we found that human serum contains a dialyzable, mixed-type noncompetitive inhibitor(s) of TrACP activity, the effects of which on the assay were substantially lessened by diluting the serum sample with water before assay and increasing the substrate concentration. Hemolysis releases into serum a significant amount of TrACP activity from erythrocytes, which can be inactivated by incubating the serum at 37 degrees C for 1 h before assay. Our improved assay was reproducible (CV = 5%), and measured within 10% of the amount of added bovine skeletal TrACP activity. Preliminary application of the assay revealed that the amount of serum TrACP activity in patients with skeletal diseases differed from normal values and changed in the same direction as the expected change in bone turnover, suggesting that TrACP activity in serum could be useful clinically as a marker of bone metabolism, possibly of bone resorption.

Topics: Acid Phosphatase; Adult; Aged; Animals; Bone Diseases, Metabolic; Bone Resorption; Cattle; Drug Resistance; Erythrocytes; Female; Humans; Isoenzymes; Male; Middle Aged; Tartrates

Osteoclasts are known to have a high acid phosphatase content. We have adapted the simple simultaneous mono-coupling azo-dye method of Grogg and Pearse to undecalcified bone sections. A cold embedding in a mixture of glycol and methyl methacrylate was shown to well preserve the enzyme activity. Sodium alpha-naphtyl phosphate (1 mg/ml) and fast violet B (2 mg/ml) are used in 0.1 M acetate buffer, pH 5.0. The addition of 1 mM L(+) sodium tartrate selectively inhibits the acid phosphoprotein phosphatase ("osteoblastic acid phosphatase") but not osteoclastic lysosomal acid phosphatase. Counterstaining with phosphomolybdic aniline blue WS leads to well contrasted sections, providing accurate measurements of osteoclast number.

Topics: Acid Phosphatase; Bone Diseases, Metabolic; Cell Count; Histocytochemistry; Histological Techniques; Humans; Ilium; Osteoclasts; Staining and Labeling