acid-phosphatase and deoxypyridinoline

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

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

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

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 turnover is characterized both by the formation of new bone by the osteoblasts and the resorption of old tissue by the osteoclast. This process takes place only on the surface of bone and can be described in terms of spatio-temporal events that are the bone metabolic unit and the bone remodelling cycle. The former consists of a discrete group of cells (osteoblasts and osteoclasts) involved in a particular remodelling event while the latter represents the succession of resorption and formation. In a typical remodelling cycle, resorption takes 7-10 days, whereas formation requires 2-3 months. Remodelling is regulated either by local or systemic factors, including electrical and mechanical forces, hormones (e.g. parathyroid hormone, sexual steroids, calcitriol, cortisol, thyroid hormones, calcitonin), growth factors and cytokines. Recently different circulating biochemical markers have been proposed for the investigation of bone turnover. In addition to classical parameters such as serum alkaline phosphatase and urinary calcium and hydroxyproline, new markers have gained clinical attention because of their accuracy in assessing the dynamic changes in bone remodelling (bone alkaline phosphatase, osteocalcin, propeptides PICP and PINP, tartrate-resistant acid phosphatase, deoxypyridinoline, pyridinoline, telopeptide CTx and NTx). The aim of this review is to present the recent advances in this field and the clinical application of markers of bone turnover in patients with bone metastases from solid tumors. Also the cellular and molecular bases of bone remodelling are reported with details.

Topics: Acid Phosphatase; Alkaline Phosphatase; Amino Acids; Biomarkers; Biomarkers, Tumor; Bone Neoplasms; Bone Remodeling; Collagen; Collagen Type I; Humans; Isoenzymes; Osteocalcin; Peptides; Procollagen; Tartrate-Resistant Acid Phosphatase

Chronic renal failure is often associated with bone disorders, including secondary hyperparathyroidism, aluminum-related low-turnover bone disease, osteomalacia, adynamic osteopathy, osteoporosis, and skeletal beta2-microglobulin amyloid deposits. In spite of the enormous progress made during the last few years in the search of noninvasive methods to assess bone metabolism, the distinction between high- and low-turnover bone diseases in these patients still frequently requires invasive and/or costly procedures such as bone biopsy after double tetracycline labeling, scintigraphic-scan studies, computed tomography, and densitometry. This review is focused on the diagnostic value of several new serum markers of bone metabolism, including bone-specific alkaline phosphatase (bAP), procollagen type I carboxy-terminal extension peptide (PICP), procollagen type I cross-linked carboxy-terminal telopeptide (ICTP), pyridinoline (PYD), osteocalcin, and tartrate-resistant acid phosphatase (TRAP) in patients with chronic renal failure. Most of the observations made by several groups converge to the conclusion that serum bAP is the most sensitive and specific marker to evaluate the degree of bone remodeling in uremic patients. Nonetheless, PYD and osteocalcin, in spite of their retention and accumulation in the serum of renal insufficient patients, are also excellent markers of bone turnover. The future generalized use of these markers, individually or in combination with other methods, will undoubtedly improve the diagnosis and the treatment of the complex renal osteodystrophy.

Topics: Acid Phosphatase; Alkaline Phosphatase; Amino Acids; beta 2-Microglobulin; Biomarkers; Bone Diseases; Bone Remodeling; Collagen; Collagen Type I; Glycation End Products, Advanced; Humans; Integrin-Binding Sialoprotein; Isoenzymes; Osteocalcin; Peptide Fragments; Peptides; Procollagen; Sialoglycoproteins; Tartrate-Resistant Acid Phosphatase; Uremia

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

Prescribing exercise based on intensity, frequency, and duration of loading may maximize osteogenic responses in bone, but a model of the osteogenic potential of exercise has not been established in humans. In rodents, an osteogenic index (OI) has been used to predict the osteogenic potential of exercise. The current study sought to determine whether aerobic, resistance, or combined aerobic and resistance exercise programs conducted over eight weeks and compared to a control group could produce changes in biochemical markers of bone turnover indicative of bone formation. We further sought to determine whether an OI could be calculated for each of these programs that would reflect observed biochemical changes. We collected serum biomarkers [bone-specific alkaline phosphatase (BAP), osteocalcin, tartrate-resistant acid phosphatase (TRAP), C-terminal telopeptide fragment of type I collagen (CTx), deoxypyridinoline (DPD), 25-hydroxy vitamin D (25(OH)D), and parathyroid hormone (PTH)] in 56 women (20.3+/-1.8 years) before, during and after eight weeks of training. We also measured bone mineral density (BMD) at regional areas of interest using DXA and pQCT. Biomarkers of bone formation (BAP and osteocalcin) increased in the Resistance and Combined groups (p<0.05), while biomarkers of bone resorption (TRAP and DPD) decreased and increased, respectively, after training (p<0.05) in all groups. Small changes in volumetric and areal BMD (p<0.05) were observed in the distal tibia in the Aerobic and Combined groups, respectively. Mean weekly OIs were 16.0+/-1.9, 20.6+/-2.2, and 36.9+/-5.2 for the Resistance, Aerobic, and Combined groups, respectively. The calculated osteogenic potential of our programs did not correlate with the observed changes in biomarkers of bone turnover. The results of the present study demonstrate that participation in an eight week physical training program that incorporates a resistance component by previously inactive young women results in alterations in biomarkers of bone remodeling indicative of increased formation without substantial alterations in markers of resorption.

Topics: Absorptiometry, Photon; Acid Phosphatase; Alkaline Phosphatase; Amino Acids; Anthropometry; Biomarkers; Bone and Bones; Collagen Type I; Diet; Exercise; Female; Humans; Isoenzymes; Osteocalcin; Osteogenesis; Parathyroid Hormone; Peptides; Physical Fitness; Tartrate-Resistant Acid Phosphatase; Time Factors; Tomography, X-Ray Computed; Vitamin D; Young Adult

There are conflicting data regarding the clinical benefit of the effect of HMG-CoA reductase inhibitors (statins) in osteoporosis. We have reported that fluvastatin (a statin) is effective in improving proteinuria and renal function in childhood IgA nephropathy with mild histological findings and moderate proteinuria. The aim of the present study was to clarify the effect of fluvastatin on the bone mineral density, bone metabolic markers, proteinuria, and renal function of children with minimal change glomerulonephritis with some focal mesangial cell proliferation whose glomeruli did not stain positive for IgA and on moderate proteinuria.. We conducted a prospective controlled study of 36 children who had recently been diagnosed with normocholesterolemic minimal change glomerulonephritis with some focal mesangial cell proliferation and moderate proteinuria, and in whom strenuous exercise was restricted. The 36 patients were randomly assigned to receive 20 mg of fluvastatin (group 1) or 5 mg/kg of dipyridamole (group 2) for two years.. By the end of the trial, there was no difference in BMD between the groups, and there were no changes in the four bone metabolic parameters. However, the urinary protein, hematuria and BUN levels had significantly decreased in group 1 compared to baseline, and the serum total protein and albumin levels and creatinine clearance had significantly increased in group 1 compared to baseline and group 2.. The results of this study suggest that fluvastatin therapy has an antiproteinuric effect and improves renal function in moderately proteinuric patients with mild histological glomerulonephritis, but does not increase BMD.

Topics: Acid Phosphatase; Adolescent; Adult; Alkaline Phosphatase; Amino Acids; Bone Density; Child; Fatty Acids, Monounsaturated; Female; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Indoles; Isoenzymes; Male; Nephritis; Nephrosis, Lipoid; Osteocalcin; Prospective Studies; Tartrate-Resistant Acid Phosphatase

Although there have been some case reports suggesting that bone in patients with pseudohypoparathyroidism (PHP) might respond to parathyroid hormone (PTH), no information is available as to whether serum PTH concentration is related to bone metabolic markers or to bone mineral density (BMD) in PHP.. To address these relationships, by comparing intact serum PTH, bone metabolic markers and BMD in patients with PHP with those in patients with idiopathic hypoparathyroidism (IHP) and postoperative hypoparathyroidism (OHP).. Intact serum PTH, bone metabolic markers (osteocalcin, tartrate-resistant acid phosphatase, pyridinoline, deoxypyridinoline) and BMD by dual-energy X-ray absorptiometry or single-photon absorptiometry were measured in patients with PHP Ia (n=2) and PHP Ib (n=8). The results were compared with those in patients with IHP (n=5) and OHP (n=14).. All bone metabolic markers measured were present in significantly greater amounts in patients with PHP Ib than in those with IHP+OHP. The Z score (standard deviation of average BMD at each age) of the BMD of femoral neck was significantly lower in patients with PHP Ib than in those with IHP+OHP. The Z scores of BMD of lumbar spine and radius were also lower in patients with PHP Ib than in those with IHP+OHP, but the difference was not significant. Moreover, the intact serum PTH concentrations were significantly and positively related to bone metabolic marker levels in all patients, and the intact serum PTH concentrations were significantly and negatively related to BMD of lumbar spine in PHP patients.. These results suggest that PTH stimulates bone turnover in PHP Ib patients, resulting in a relatively lower BMD in PHP Ib patients than in IHP+OHP patients. The present study indicates that bones of most cases of PHP could respond to PTH.

Topics: Acid Phosphatase; Adult; Aged; Amino Acids; Biomarkers; Bone Density; Cholecalciferol; Creatinine; Cyclic AMP; Erythrocyte Membrane; Female; GTP-Binding Protein alpha Subunits, Gs; Humans; Hypoparathyroidism; Isoenzymes; Kidney; Male; Middle Aged; Osteocalcin; Parathyroid Hormone; Phosphates; Postoperative Complications; Pseudohypoparathyroidism; Tartrate-Resistant Acid Phosphatase

Clinical biochemical markers of bone turnover are usually increased in Paget's disease. However, the analysis of "new" markers, such as serum bone alkaline phosphatase (BAP), carboxy-terminal propeptide of type I procollagen (PICP), tartrate-resistant acid phosphatase (TRAP), telopeptide carboxy-terminal propeptide of type I collagen (ICTP), and urinary pyridinoline (PYR) and deoxipyridinoline (D-PYR), may improve the diagnostic efficacy and the evaluation of Paget's disease compared with conventional markers, such as serum total alkaline phosphatase (TAP) and urinary hydroxyproline (HYP). To evaluate the diagnostic accuracy and the changes of biochemical markers of bone turnover according to Paget's disease activity, we measured the levels of all these markers in three groups of pagetic patients classified according to their serum TAP activity: G-I, patients with serum TAP lower than 250 U/l (upper limit) (n = 15); G-II, patients with serum TAP between 251 and 500 U/l (n = 18); and G-III, patients with serum TAP greater than 501 U/l (n = 26). Serum TAP and BAP showed the highest diagnostic accuracy among the markers of bone formation with a sensitivity of 78% and 84%, respectively, when the specificity was 100%. Urinary PYR was the most sensitive marker of bone resorption. Also, urinary PYR showed the highest proportion of increased values in pagetic patients (73%) compared with urinary HYP (64%), urinary D-PYR (60%), serum ICTP (41%), or serum TRAP (39%). In pagetic patients with normal serum TAP activity (G-I), serum BAP concentration was increased in 60% of patients, and urinary PYR was increased in 40% of patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acid Phosphatase; Adult; Aged; Aged, 80 and over; Alkaline Phosphatase; Amino Acids; Biomarkers; Bone Development; Bone Resorption; Collagen; Collagen Type I; Enzyme-Linked Immunosorbent Assay; Female; Humans; Hydroxyproline; Male; Middle Aged; Osteitis Deformans; Peptide Fragments; Peptides; Procollagen

The aim of this study was to determine the relationships among bone properties, bone metabolic markers, and types of jaw deformity. The subjects were 55 female patients with jaw deformities. Skeletal morphology was examined using lateral cephalograms, and the patients were divided into three groups according to the type of anteroposterior skeletal pattern. Serum osteocalcin, bone alkaline phosphatase, and tartrate-resistant acid phosphatase isoform 5b, as well as deoxypyridinoline in urine, were measured as bone metabolic markers. Quantitative ultrasound (QUS) measurements were used to assess bone properties at the calcaneal bone. The bone volume and bone density of the condylar process were measured in 43 patients by computed tomography. There were no significant differences in bone metabolic markers and QUS parameters between the groups, although bone formation and resorption markers tended to be higher in patients with a protrusive mandible. On the other hand, patients with mandibular retrusion had a higher tendency to have small and dense condylar processes. In conclusion, the results suggest that growth depression or a degenerative change in the mandibular condyle is involved in the pathogenesis of mandibular retrusion, although risk factors for progressive condylar resorption were not determined.

Topics: Acid Phosphatase; Adolescent; Adult; Alkaline Phosphatase; Amino Acids; Biomarkers; Bone and Bones; Bone Density; Cephalometry; Female; Humans; Jaw Abnormalities; Osteocalcin; Prospective Studies; Tartrate-Resistant Acid Phosphatase; Young Adult

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

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

Changes in bone remodeling during pathological states and during their treatment can be assessed noninvasively by measuring biomarkers of bone metabolism. Their application is limited, however, by the potential biological variability in the levels of these biomarkers over time. To determine the short-term variability in biomarkers of bone metabolism in adult sheep, the authors measured serum levels of alkaline phosphatase (ALP), bone-specific alkaline phosphatase (BALP), osteocalcin (OC), N-terminal propeptide of type-III procollagen (PIIINP), deoxypyridinoline (DPD), tartrate-resistant acid phosphatase (TRAP), calcium and phosphorus intermittently over a 12-week period. There were significant differences in mean ALP activity and in phosphorus concentrations over time, but all other biomarkers showed no significant short-term variability. The results suggest that biomarkers of bone metabolism in sheep, especially the bone resorption marker DPD and the bone formation marker BALP, can be used reliably to detect changes in bone cellular activity.

Topics: Acid Phosphatase; Alkaline Phosphatase; Amino Acids; Animals; Biomarkers; Bone and Bones; Bone Remodeling; Calcium; Isoenzymes; Osteocalcin; Peptide Fragments; Phosphorus; Portugal; Procollagen; Sheep; Statistics, Nonparametric; Tartrate-Resistant Acid Phosphatase; Time Factors

The relationship between biochemical markers of bone resorption (C-terminal telopeptide, deoxypyridinoline, tartrate-resistant acid phosphatase 5b) and osteosynthesis (bone alkaline phosphatase) and clinical manifestations of bone metastases were studied in 239 patients with breast cancer with and without signs of bone involvement. High levels of C-terminal telopeptide and bone alkaline phosphatase were associated with poor prognosis: more severe skeletal complications and lesser survival values. These biochemical markers can be used for prognosis and optimization of therapy for bone metastases in patients with breast cancer.

Topics: Acid Phosphatase; Alkaline Phosphatase; Amino Acids; Analysis of Variance; Biomarkers, Tumor; Bone Neoplasms; Bone Resorption; Breast Neoplasms; Collagen Type I; Enzyme-Linked Immunosorbent Assay; Female; Humans; Isoenzymes; Kaplan-Meier Estimate; Osteogenesis; Peptides; Prognosis; Radionuclide Imaging; Tartrate-Resistant Acid Phosphatase

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

The management of bisphosphonate-related osteonecrosis of the jaw (BRONJ) is still difficult in many cases that do not respond to conservative treatments. We report a case of BRONJ treated by adjunctive teriparatide therapy for 6 months with monitoring of bone turnover markers (at baseline, at 1, 3, and 6 months of treatment, and after 9 months off therapy) and bone scintigraphy (at baseline, 3 and 6 months, and after 9 months off therapy). The patient was a 78-year-old woman with osteoporosis and BRONJ. She had not responded to previous conventional treatment. Teriparatide was added for resolution of BRONJ. The pain disappeared after 1 month, and remarkable bone regeneration was obtained after 6 months, with significantly increasing bone formation and resorption markers. Bone scintigraphy showed regression of the uptake area. This case suggests the usefulness of monitoring bone turnover markers and using bone scintigraphy to increase the effectiveness of teriparatide therapy.

Topics: Acid Phosphatase; Aged; Alendronate; Alkaline Phosphatase; Amino Acids; Biomarkers; Bisphosphonate-Associated Osteonecrosis of the Jaw; Bone Density Conservation Agents; Bone Regeneration; Bone Resorption; Collagen Type I; Female; Follow-Up Studies; Humans; Isoenzymes; Mandible; Mandibular Diseases; Osteocalcin; Osteogenesis; Peptide Fragments; Peptides; Procollagen; Radionuclide Imaging; Radiopharmaceuticals; Tartrate-Resistant Acid Phosphatase; Technetium Tc 99m Medronate; Teriparatide

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

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

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

Insulin-dependent diabetes mellitus (IDDM) is known to be associated with an increased risk of osteopenia. However, the cellular and molecular mechanisms for IDDM-induced alterations of the bone are not well understood. The effects of IDDM on bone metabolism were investigated using rats rendered diabetic by an injection of streptozotocin (STZ). After 4 weeks, the diabetic rats exhibited bone loss, low levels of osteocalcin, insulin-like growth factor-I (IGF-I) and bone alkaline phosphatase (ALP) activity with normal levels of bone tartrate-resistant acid phosphatase (TRAP) and cathepsin K activity, and urinary excretion of deoxypyridinoline (Dpd). Histological analysis showed a decrease in the number of osteoblasts with a normal number of osteoclasts in the metaphysis of the proximal tibia. The decreased expression of ALP, osteoclacin and collagen mRNA was associated with a decrease in the expression of runt-related transcription factor 2 (Runx2), Osterix and distal-less homeobox 5 (Dlx5) and an unaltered expression of bone morphogenic protein-2 (BMP2). The protein levels of Runx2, phosphorylated glycogen synthase kinase 3β (GSK3β), active β-catenin and β-catenin decreased. The activation of Akt was inhibited. The mRNA and protein levels of sclerosteosis (Sost) and Dickkopf 1 (Dkk1), inhibitors of Wnt signaling, increased. The mRNA expression of IGF-I and the IGF-I receptor (IGF-IR) was suppressed. These changes observed in the bone of diabetic rats were reversed by treatment with insulin, but not by normalization of the circulating IGF-I levels by treatment with IGF-I. These results suggest that insulin-deficiency in IDDM decreases osteoblastogenesis associated with inhibition of Wnt signaling through the increased expression of Sost and Dkk1 and the inhibition of Akt activation.

Topics: Acid Phosphatase; Alkaline Phosphatase; Amino Acids; Animals; beta Catenin; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Cathepsin K; Core Binding Factor Alpha 1 Subunit; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Female; Genetic Markers; Glycogen Synthase Kinase 3; Glycogen Synthase Kinase 3 beta; Homeodomain Proteins; Insulin-Like Growth Factor I; Intercellular Signaling Peptides and Proteins; Isoenzymes; Osteoblasts; Osteocalcin; Proto-Oncogene Proteins c-akt; Rats; Rats, Wistar; Signal Transduction; Tartrate-Resistant Acid Phosphatase; Transcription Factors; Wnt Proteins

Associations between bone turnover markers and calcaneal ultrasound (quantitative ultrasound, QUS) were studied in a population-based sample of 810 elderly women. Baseline bone turnover markers correlated with baseline QUS as well as with 5-year prospective changes in QUS.. Bone turnover markers are associated with areal bone mineral density, but the knowledge on the association with QUS is limited.. Eight hundred ten women, all 75 years old, were investigated at baseline. Five hundred six completed a 5-year follow-up. Bone turnover markers and calcaneal QUS [speed of sound (SoS), broadband ultrasound attenuation (BUA), stiffness] were investigated at baseline. QUS was investigated at follow-up.. All bone turnover markers were correlated with baseline QUS [standardized regression (Beta(std)) values from -0.07, p < 0.05 to -0.23, p < 0.001], with the exception of bone-specific alkaline phosphatase (S-Bone ALP) which was not correlated with BUA and stiffness index. When the correlations between baseline bone turnover markers and 5-year changes in QUS were analyzed, three serum osteocalcins were correlated with changes of SoS and stiffness index (Beta(std) = -0.11, p < 0.05 to -0.17, p < 0.001). Also S-CTX-I correlated with changes of SoS and stiffness index (Beta(std) = -0.10 and -0.09, respectively, p < 0.05). S-TRACP5b, urinary deoxypyridinoline/crea, and U-MidOC/crea correlated with changes of SoS (Beta(std) = -0.10 and p < 0.05 for all). S-Bone ALP did not correlate with change of QUS. None of the bone turnover markers correlated with changes of BUA.. Bone turnover markers correlate with concomitantly assessed QUS as well as with longitudinal change in QUS.

Topics: Acid Phosphatase; Aged; Alkaline Phosphatase; Amino Acids; Biomarkers; Bone Remodeling; Calcaneus; Collagen Type I; Creatinine; Female; Humans; Isoenzymes; Longitudinal Studies; Organ Size; Osteocalcin; Peptide Fragments; Peptides; Postmenopause; Procollagen; Sweden; Tartrate-Resistant Acid Phosphatase; Ultrasonography

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

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

Curcumin is a potent inhibitor of the transcription factor activator protein-1 which plays an essential role in osteoclastogenesis. However, the effects of curcumin on bone metabolism have not been clarified in vivo. We reported herein the inhibitory effects of curcumin on the stimulated osteoclastic activity in insulin-dependent diabetes mellitus using rats with streptozotocin-induced diabetes. A dietary supplement of curcumin reversed the increase in levels of activity and mRNA of tartrate-resistant acid phosphatase (TRAP) and cathepsin K to control values. A histochemical analysis showed that the increase in TRAP-positive cells in the distal femur of the diabetic rats was reduced to the control level by the supplement. These results suggested that curcumin reduced diabetes-stimulated bone resorptive activity and the number of osteoclasts. When bone marrow cells were cultured with macrophage colony stimulating factor and receptor activator NF-kappaB ligand (RANKL), the increased activity to form TRAP-positive multinucleated cells and the increased levels of mRNA and protein of c-fos and c-jun in the cultured cells from diabetic rats decreased to control levels in the curcumin-supplemented rats. Similarly, the increased expression of c-fos and c-jun in the distal femur of the diabetic rats was significantly reduced by the supplement. These results suggested that curcumin suppressed the increased bone resorptive activity through the prevention of osteoclastogenesis associated with inhibition of the expression of c-fos and c-jun in the diabetic rats.

Topics: Acid Phosphatase; Amino Acids; Animals; Blood Glucose; Body Weight; Bone Marrow Cells; Bone Resorption; Calcium; Cathepsin K; Cell Differentiation; Curcumin; Diabetes Mellitus, Experimental; Dietary Supplements; Eating; Female; Femur; Glycosuria; Hydroxyproline; Isoenzymes; Osteocalcin; Osteoclasts; Rats; RNA, Messenger; Staining and Labeling; Stem Cells; Streptozocin; Tartrate-Resistant Acid Phosphatase

To clarify the pathogenesis of altered bone metabolism in diabetic state and its underlying mechanisms, the bone mineral content and fasting levels of serum intact parathyroid hormone (i-PTH), intact osteocalcin (i-OC), tartrate-resistant acid phosphatase (TRAP) and osteoclastgenesis inhibitory factor/osteoprotegerin (OCIF/OPG) were measured in male type 2 diabetic patients and their age-matched controls. In addition, urine levels of osteoclastic markers, C-telopeptide of type I collagen (CTx), deoxypyridinoline (DPD), and N-telopeptide of type I collagen (NTx) were simultaneously determined. Serum levels of i-PTH and i-OC in diabetic patients were significantly lower than those in the controls. Conversely, serum concentrations of TRAP were significantly elevated in diabetic patients. However, no clear correlation was observed between serum i-OC and TRAP. It was also observed that urinary excretion of CTx, DPD, and NTx was significantly increased in the diabetics as compared with the controls. Unexpectedly, serum levels of OCIF/OPG tended to be higher in the diabetic group, and these values exhibited a significantly positive correlation with those of serum TRAP. There was found a significantly negative correlation between serum TRAP and bone mineral density (BMD) and also between serum OCIF/OPG and bone mineral density. It seems probable that OCIF/OPG has a suppressive role on the increased bone resorption to prevent further loss of the skeletal bone mass in type 2 diabetic patients.

Topics: Acid Phosphatase; Amino Acids; Biomarkers; Bone Density; C-Peptide; Calcitriol; Calcium; Collagen; Collagen Type I; Data Interpretation, Statistical; Diabetes Mellitus, Type 2; Glycoproteins; Humans; Insulin; Isoenzymes; Magnesium; Male; Middle Aged; Osteocalcin; Osteoclasts; Osteoprotegerin; Parathyroid Hormone; Peptides; Phosphorus; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor; Sex Factors; Tartrate-Resistant Acid Phosphatase

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

Bone remodeling involves the interplay of bone resorption and formation and is accurately controlled to maintain bone mass. Both processes require transcellular Ca(2+) transport, but the molecular mechanisms engaged remain largely elusive. The epithelial Ca(2+) channel TRPV5 is one of the most Ca(2+)-selective transient receptor potential (TRP) channels. In this study, the functional role of TRPV5 in bone was investigated. TRPV5 mRNA was expressed in human and murine bone samples and in osteoclasts along with other genes involved in transcellular Ca(2+) transport, including calbindin-D(9K) and calbindin-D(28K), Na(+)/Ca(2+) exchanger 1, and plasma membrane Ca(2+)-ATPase 1b. TRPV5 expression in murine osteoclasts was confirmed by immunostaining and showed predominant localization to the ruffled border membrane. However, TRPV5 was absent in osteoblasts. Analyses of femoral bone sections from TRPV5 knockout (TRPV5(-/-)) mice revealed increased osteoclast numbers and osteoclast area, whereas the urinary bone resorption marker deoxypyridinoline was reduced compared with WT (TRPV5(+/+)) mice. In an in vitro bone marrow culture system, the amount of osteoclasts and number of nuclei per osteoclast were significantly elevated in TRPV5(-/-) compared with TRPV5(+/+) mice. However, using a functional resorption pit assay, we found that bone resorption was nearly absent in osteoclast cultures from TRPV5(-/-) mice, supporting the impaired resorption observed in vivo. In conclusion, TRPV5 deficiency leads to an increase in osteoclast size and number, in which Ca(2+) resorption is nonfunctional. This report identifies TRPV5 as an epithelial Ca(2+) channel that is essential for osteoclastic bone resorption and demonstrates the significance of transcellular Ca(2+) transport in osteoclastic function.

Topics: Acid Phosphatase; Amino Acids; Animals; Bone Resorption; Calcium; Calcium Channels; DNA Primers; Femur Head; Humans; Immunohistochemistry; Isoenzymes; Mice; Mice, Knockout; Osteoclasts; Polymerase Chain Reaction; RNA, Messenger; Tartrate-Resistant Acid Phosphatase; TRPV Cation Channels

The aim of the present study was to examine the effects of exercise on bone mass, bone metabolism, and calciotropic hormones in young growing rats. Twenty 6-week-old female Wistar rats were randomized into the following four groups with 5 animals each: 7 weeks of exercise, 7 weeks of sedentary control, 11 weeks of exercise, and 11 weeks of sedentary control. The exercise regimen consisted of running on a treadmill at 25 m/min for 1 h each day on 5 days a week. After each period of exercise, the bone mineral content (BMC) of the tibia and fifth lumbar spine was measured by dual-energy X-ray absorptiometry, using a Lunar DPX-L instrument. The femoral length and levels of bone markers and calciotropic hormones were also assessed. Seven and 11 weeks of exercise increased the serum osteocalcin and 1,25-dihydroxyvitamin D(3) levels, and decreased the serum parathyroid level. Seven weeks of exercise decreased the urinary deoxypyridinoline level, and 11 weeks of exercise increased the serum alkaline phosphatase level and decreased the serum tartrate-resistant acid phosphatase level. As a result, 7 and 11 weeks of exercise increased the femoral length and tibial BMC, but did not alter the lumbar BMC. The present study demonstrates that treadmill exercise stimulates bone formation and suppresses bone resorption, increases the serum 1,25-dihydroxyvitamin D(3) level, and decreases the serum parathyroid hormone level, resulting in an increase in bone mass with stimulation of longitudinal bone growth, especially at weight-bearing sites, in young growing rats. Further studies with long-term exercise may be needed to obtain a positive effect on the lumbar BMC.

Topics: Absorptiometry, Photon; Acid Phosphatase; Alkaline Phosphatase; Amino Acids; Animals; Body Weight; Bone and Bones; Bone Density; Bone Development; Calcitriol; Calcium; Female; Femur; Hormones; Isoenzymes; Lumbar Vertebrae; Muscle, Skeletal; Osteocalcin; Parathyroid Hormone; Phosphorus; Physical Conditioning, Animal; Rats; Rats, Wistar; Tartrate-Resistant Acid Phosphatase; Tibia

The aim of the present study was to clarify the therapeutic effects of 1alpha, 25[OH]2 vitamin D3 (calcitriol) pulse injection on bone lesions induced in a rat model of chronic cadmium toxicosis. Ovariectomized (OVX) and control-operated (sham-OVX) rats were given repeated intravenous injections of 0.5 mg/kg/day CdCl2 for 70 weeks. The rats were then treated intravenously with 0.02 microg/kg/day calcitriol 3 days per week for 8 weeks. CdCl2 treatment induced increases in osteoid volumes of the femur cortex and trabecula. This change was accompanied by an increase in the volume of iron deposition at the mineralization front of the trabeculae and a reduction in mineral density. Abnormalities of bone metabolic parameters, which were increases in the blood calcium, inorganic phosphorous, bone-specific alkaline phosphatase, parathyroid hormone (PTH) and osteocalcin levels, and in the urine deoxypyridinoline (D-PYR) level, were also induced. Calcitriol treatment increased the blood calcium and inorganic phosphorous levels, and reduced the blood PTH level. Decreases in blood tartrate-resistant acid phosphatase and urine d-PYR levels were also induced indicating that bone resorption was suppressed. The findings indicated that the increased osteoid volume of the cortex and Fe-deposition volume of the trabecula were improved. These effects or improvements were observed in the sham-OVX rats but not in the OVX rats.

Topics: Acid Phosphatase; Alkaline Phosphatase; Amino Acids; Analysis of Variance; Animals; Biomarkers; Bone and Bones; Bone Density; Cadmium; Cadmium Chloride; Cadmium Poisoning; Calcitriol; Chronic Disease; Erythrocyte Indices; Female; Femur; Hemoglobins; Iron; Models, Animal; Osteocalcin; Osteomalacia; Ovariectomy; Pulse Therapy, Drug; Rats; Rats, Sprague-Dawley

There have so far been no reports on the changes in bone histology in the early period after parathyroidectomy and autografting (PTX-AG). We investigated the effects of PTX-AG on bone histology during the initial 12 weeks after undergoing these surgical procedures.. We performed bone histomorphometry 3 times (before as well as 4 and 12 weeks after PTX-AG) in 6 patients and 2 times (before and 4 weeks after PTX-AG) in 3 hemodialysis patients. In addition, the circulating parameters of bone metabolism were also assessed before and after PTX-AG in all 9 patients. The changes in the histomorphometric (static) parameters between pre-surgery and 4 weeks after surgery and those between 4 weeks and 12 weeks after surgery were assessed by the t-test while changes in the circulating parameters of bone metabolism were analyzed by Friedman's test.. Bone formation parameters including carboxy terminal propeptide of human type I procollagen (PICP), alkaline phosphatase (ALP) and intact osteocalcin (i-OC) were all extremely high before surgery. These parameters initially increased after PTX-AG and thereafter gradually declined. In contrast, the circulating bone resorption parameters including tartrate-resistant acid phosphatase (TRAP) and deoxypyridinoline (Dpyr) were also extremely high at baseline but markedly declined after operation. Osteoid-related parameters including osteoid volume (OV/BV), osteoid surface (OS/BS), and osteoid thickness (O.Th) all initially increased at 4 weeks after PTX-AG. In contrast, osteoblast surface (Ob.S/BS), osteoclast surface (Oc.S/BS), eroded surface (ES/BS), and fibrosis volume (Fb.V/TV) all decreased at 4 weeks after surgery, while Ob.S/BS decreased further at 12 weeks in cases 1-6. Although bone mineralization was ongoing at 4 weeks after surgery, both the mineral apposition rate (MAR) and bone formation rate (BFR) remained below the mean for normal individuals.. The circulating bone formation parameters and osteoid-related parameters showed an initial increase after PTX-AG. The concomitant decline in the circulating bone resorption parameters reflected the reduction in bone resorption. BFR decreased, but bone mineralization did not stop after PTX-AG.

Topics: Acid Phosphatase; Aged; Alkaline Phosphatase; Amino Acids; Bone Resorption; Female; Humans; Male; Middle Aged; Osteocalcin; Osteoclasts; Osteogenesis; Parathyroid Glands; Parathyroidectomy; Procollagen; Renal Dialysis; Transplantation, Autologous

In the present study the osteoclast activity was monitored longitudinally in porcine blood samples by measuring the tartrate-resistant acidic phosphatase (TRAP) activity with several methods described for human samples. These methods differed in their specificity for bone-specific TRAP and in their practicability. The validity of TRAP measurements was evaluated by comparison with the peripheral concentrations of the N-terminal fragments of type I collagen with attached cross-links (NTx), a highly bone-specific parameter of bone collagen degradation, using a commercially available test kit developed for human samples. On selected days urine samples were collected for the determination of pyridinium cross-links. The determinations of cross-links in urine were normalized for the creatinine concentrations. However, they were not related to fluoride-sensitive TRAP (fsTRAP) and NTx measurements in serum. The fsTRAP activity in serum, which is assumed to be highly bone-specific, was highly correlated with the NTx concentrations in serum under different experimental conditions. As measurements in blood may be more easily standardized than those in urine, fsTRAP measurements in serum seem to be a highly practicable method to characterize osteoclastic activity in the pig.

Topics: Acid Phosphatase; Amino Acids; Animals; Biomarkers; Bone and Bones; Collagen; Collagen Type I; Isoenzymes; Longitudinal Studies; Male; Osteoclasts; Peptides; Swine; Tartrate-Resistant Acid Phosphatase

Weight bearing and physical activity are important mechanical stimuli to bone growth and metabolism, and microgravity, such a space flight and/or bed rest, induces bone resorption and bone loss. An increased excretion of urinary Ca, an increased bone resorption and a decreased bone mineral density (BMD) have been observed in bed rest experiment of healthy subjects. Bone resorption markers show the specific circadian rhythms in human. Cross-linked carboxyl-terminal telopeptide of type I collagen (ICTP) and the urinary excretion of deoxypyridinoline (Dpy) are the highest in the early morning and the lowest late at night. Bed rest immobilization might influence these rhythms, due to no mechanical loading with loss of daily life activity. Bone resorption markers in healthy subjects had been compared between before and during bed rest to determine disruption of diurnal rhythms of bone resorption.

Topics: Acid Phosphatase; Adolescent; Adult; Amino Acids; Bed Rest; Biomarkers; Bone Density; Bone Resorption; Circadian Rhythm; Collagen; Collagen Type I; Head-Down Tilt; Humans; Isoenzymes; Male; Peptides; 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

The objective of this study was to evaluate the effect of surgical menopause and hormone replacement therapy (HRT) on the new biochemical markers of bone turnover. Fourteen women who had undergone surgical menopause and began HRT 3 months after surgery were recruited for a 1-year study. Results were compared with a control group of 31 healthy premenopausal women of similar age. Serum samples were obtained to determine total alkaline phosphatase, bone alkaline phosphatase, propeptides carboxy- and amino-terminal of type I procollagen (PICP, PINP), osteocalcin, tartrate-resistant acid phosphatase, and carboxy-terminal telopeptides of type I collagen (ICTP and serum CTX). Urine samples were analyzed for hydroxyproline, pyridinoline, deoxypyridinoline, alpha- and beta-carboxy-terminal telopeptides of type I collagen (alpha-CTX and beta-CTX), and amino-terminal telopeptide of type I collagen (NTX). Determinations were performed after 3 months of surgical menopause and after 3 and 9 months of HRT. All biochemical markers increased after menopause, and most of them normalized after 9 months of HRT. Serum PINP showed the highest proportion of increased values after surgery among bone formation markers (62%), as well as the highest mean percent increase (101%). Among bone resorption markers in postmenopausal women, urinary beta-CTX, alpha-CTX, NTX, and serum CTX showed the highest proportion of increased values (100%, 67%, 58%, 58%, respectively) as well as the greatest mean percent increase. They were also the markers with the most marked response to HRT. In conclusion, serum PINP is the most sensitive marker of bone formation, whereas beta-CTX is the most sensitive marker of bone resorption after surgical menopause. In addition, both markers showed the highest response after HRT.

Topics: Acid Phosphatase; Administration, Cutaneous; Alkaline Phosphatase; Amino Acids; Biomarkers; Bone Development; Bone Resorption; Collagen; Collagen Type I; Estradiol; Estrogen Replacement Therapy; Female; Humans; Hydroxyproline; Isoenzymes; Menopause, Premature; Middle Aged; Osteocalcin; Ovariectomy; Peptide Fragments; Peptides; Procollagen; Tartrate-Resistant Acid Phosphatase

Pycnodysostosis (Pycno) is an autosomal recessive osteosclerotic skeletal dysplasia that is caused by the markedly deficient activity of cathepsin K. This lysosomal cysteine protease has substantial collagenase activity, is present at high levels in osteoclasts, and is secreted into the subosteoclastic space where bone matrix is degraded. In vitro studies revealed that mutant cathepsin K proteins causing Pycno did not degrade type I collagen, the protein that constitutes 95% of organic bone matrix. To determine the in vivo effects of cathepsin K mutations on bone metabolism in general and osteoclast-mediated bone resorption specifically, several bone metabolism markers were assayed in serum and urine from seven Pycno patients. Two markers of bone synthesis, type I collagen carboxy-terminal propeptide and osteocalcin, were normal in all Pycno patients. Tartrate-resistent acid phosphatase, an osteoclast marker, was also normal in these patients. Two markers that detect type I collagen telopeptide cross-links from the N and C termini, NTX and CTX, respectively, were low in Pycno. A third marker which detects a more proximal portion of the C terminus of type I collagen in serum, ICTP, was elevated in Pycno, a seemingly paradoxical result. The finding of decreased osteoclast-mediated type I collagen degradation as well as the use of alternative collagen cleavage sites by other proteases, and the accumulation of larger C-terminal fragments containing the ICTP epitope, established a unique biochemical phenotype for Pycno.

Topics: Acid Phosphatase; Adolescent; Adult; Amino Acids; Biomarkers; Bone and Bones; Bone Matrix; Cathepsin K; Cathepsins; Child; Collagen; Collagen Type I; Humans; Isoenzymes; Mutagenesis; Osteocalcin; Osteosclerosis; Peptide Fragments; Peptides; Procollagen; Tartrate-Resistant Acid Phosphatase

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

The influence of a nonskeletal disease with increased connective tissue synthesis or degradation in the collagen-related markers of bone turnover has been evaluated in 34 women with primary biliary cirrhosis (PBC; age range 41-81 years), a disease with increased hepatic fibrosis, often associated with osteoporosis. Serum osteocalcin (BGP), and carboxy-terminal (PICP) and amino-terminal (PINP) propeptides of type I collagen were assessed as indexes of bone formation, whereas serum tartrate-resistant acid phosphatase (TRAP), and cross-linked carboxy-terminal telopeptide of type I collagen (ICTP), and urinary hydroxyproline (HYP), pyridinoline (PYR), deoxypyridinoline (DPYR), and type I collagen cross-linked N- (NTX) and C-telopeptide (CTX) were measured as markers of bone resorption. The histologic stage of the disease and serum amino-terminal propeptide of type III collagen (PIIINP) as an index of liver fibrogenesis were also evaluated. BGP levels were significantly lower, whereas PICP and PINP levels were higher in patients than in controls. Among the bone resorption markers, serum ICTP and urinary PYR, DPYR, HYP, NTX, and CTX levels were significantly higher in patients than in controls. Serum PIIINP levels were also increased in PBC patients. BGP did not correlate with PICP and PINP, but these markers of bone formation as well as ICTP, PYR, DPYR, and NTX correlated with serum PIIINP levels. Serum TRAP did not correlate with collagen-related markers of bone resorption. Moreover, patients with PIIINP and bilirubin above normal levels had higher PICP, PINP, ICTP PYR, DPYR, CTX, and NTX. These markers correlated with the histologic stage of the disease, but not with osteopenia measured by densitometric procedures in 22 patients. In conclusion, collagen-related markers of bone turnover do not reflect bone remodeling in PBC. The close association of these markers with PIIINP and the clinical and histologic stage of the liver disease suggests that they are influenced by liver collagen metabolism.

Topics: Acid Phosphatase; Adult; Aged; Aged, 80 and over; Amino Acids; Biomarkers; Bone and Bones; Bone Density; Bone Development; Bone Resorption; Female; Humans; Hydroxyproline; Isoenzymes; Liver; Liver Cirrhosis, Biliary; Liver Function Tests; Middle Aged; Osteocalcin; Peptide Fragments; Procollagen; Tartrate-Resistant Acid Phosphatase

Biochemical markers of bone turnover may be useful to monitor patients taking hormone replacement therapy (HRT). The aim of this study was to assess the utility of markers in monitoring HRT by comparing the response of a large panel of markers to HRT with their within subject variability. We measured the response of markers to transdermal estradiol in 11 postmenopausal women over 24 weeks. We measured the within subject variability of markers in 11 untreated healthy postmenopausal women over the same period. The mean decrease in markers of bone formation after 24 weeks treatment ranged from 19% for procollagen type I C-terminal propeptide (PICP) to 40% for procollagen type I N-terminal propeptide (PINP). The mean decrease in markers of bone resorption ranged from 10% for tartrate-resistant acid phosphatase (TRAP) to 67% for C-terminal cross-linked telopeptide The least significant change (LSC at p < 0.05), calculated from the within subject variability in the untreated group, was used to define response. LSC for osteocalcin was 21%, bone alkaline phosphatase 28%, PICP 24%, PINP 21%, type I collagen telopeptide 28%, TRAP 17%, urinary calcium 90%, hydroxyproline 75%, total deoxypyridinoline 47%, free pyridinoline 36%, free deoxypyridinoline 26%, N-terminal cross-linked telopeptide 70%, and C-terminal cross-linked telopeptide 132%. The greatest number of responders after 24 weeks of treatment were found using PINP and osteocalcin (9 each), and free deoxypyridinoline (8 each) and total deoxypyridinoline (8 each) and total deoxypyridinoline (7 each). Lumbar spine bone mineral density defined four patients as responders. The ability to detect a response differs between markers and is not dependent on the magnitude of response to therapy.

Topics: Absorptiometry, Photon; Acid Phosphatase; Age Factors; Alkaline Phosphatase; Amino Acids; Biomarkers; Bone Density; Bone Remodeling; Estradiol; Estrogen Replacement Therapy; Female; Humans; Hydroxyproline; Isoenzymes; Lumbar Vertebrae; Middle Aged; Osteoporosis, Postmenopausal; Peptide Fragments; Procollagen; 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

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

Immobilization induces abnormal bone metabolism and severe decalcification of bone. To investigate the effect of middle-term immobilization on bone metabolism, we studied 10 young healthy males and females during bed rest for 20 days. Bone mineral density (BMD) rapidly decreased in both lumbar and metacarpal bones. No bone showed consistent BMD alterations, partial increase and partial decrease, and both lumbar and metacarpal bone showed similar rapid BMD change. Urinary excretion of pyridinoline tended to slightly increase by day 10, and to decline by day 20 (mean +/-SE: 34.2 +/-7.4, 26.3+/-4.6 nmol day-1, respectively). Neither alkaline phosphatase (isoform III) nor tartrate-resistant acid phosphatase, changed, suggesting that in the early stage of immobilization bone matrix in some part might increase or be resorbed without any activation of osteoblast or osteoclast, resulting in rapid calcification or decalcification, respectively.

Topics: Absorptiometry, Photon; Acid Phosphatase; Adult; Alkaline Phosphatase; Amino Acids; Bed Rest; Bone and Bones; Bone Density; Bone Remodeling; Bone Resorption; Calcium; Female; Humans; Immobilization; Male; Osteoclasts; Sex Factors; Tomography, X-Ray Computed; Weight-Bearing

Enhanced bone resorption is a characteristic finding in multiple myeloma (MM). The aim of this study was to assess the newer biochemical bone markers in patients with myeloma. We studied 17 MM patients--10 males (3 untreated, 5 in remission, 2 responding), 7 females (3 in remission, 4 responding) and 15 normal controls. Serum bone specific alkaline phosphatase (BSALP), osteocalcin (OC) and procollagen type 1 C-terminal peptide (PICP) were determined as markers of bone formation, while serum tartrate resistant acid phosphatase (TRAP), urinary deoxypyridinoline (Dpyr) and calcium (Ca) were determined as markers of bone resorption and the ratio of the levels of bone formation/resorption were determined. All markers were measured by enzyme immunoassays (Metra Biosystems), except for TRAP by an in-house enzymatic assay and Ca by the cresolphthalein method. The Dpyr and Ca were expressed as a ratio to urinary creatinine (Cr) excretion. There were significantly higher (i) (Dpyr/Cr)/PICP ratio in male MM patients than in controls (P < 0.05); (ii) (a) urinary Dpyr excretion (P < 0.001), (b) (Dpyr/Cr)/BSALP ratio (P < 0.0001) and (c) (Dpyr/Cr)/PICP (P < 0.0001) in the untreated male MM subgroup than controls; (iii) (Dpyr/Cr)/BSALP ratio (P < 0.05) in the untreated than in the responding male MM subgroup, (iv) (Dpyr/Cr)/PICP ratio (P < 0.05) in untreated male patients than in those in the remission subgroup. In conclusion, (a) Dpyr is a sensitive marker in assessment of bone resorption in MM patients; (b) (Dpyr/Cr)/BSALP or (Dpyr/Cr)/PICP ratio is even more sensitive in distinguishing the untreated from the other MM subgroups and controls. Therefore, the use of a combination of these markers may have a potential role in the management of patients with MM.

Topics: Acid Phosphatase; Adult; Aged; Aged, 80 and over; Alkaline Phosphatase; Amino Acids; Biomarkers, Tumor; Bone and Bones; Bone Resorption; Calcium; Creatinine; Female; Humans; Isoenzymes; Male; Middle Aged; Multiple Myeloma; Osteocalcin; Peptide Fragments; Procollagen; Sex Factors; Tartrate-Resistant Acid Phosphatase

Serum levels of hydroxylysyl pyridinoline and lysyl pyridinoline were quantified in uremic patients undergoing maintenance hemodialysis and in healthy subjects. Pre-hemodialysis serum levels of hydroxylysyl pyridinoline and lysyl pyridinoline in the hemodialyzed patients were significantly higher than those in healthy subjects. Serum levels of hydroxylysyl pyridinoline and lysyl pyridinoline decreased significantly after hemodialysis with reduction rates of about 40%. Pre-hemodialysis serum levels of hydroxylysyl pyridinoline and lysyl pyridinoline correlated significantly with intact parathyroid hormone, osteocalcin and bone-specific alkaline phosphatase. Lysyl pyridinoline showed better correlations with these parameters than hydroxylysyl pyridinoline. Parathyroidectomy markedly decreased serum levels of hydroxylysyl pyridinoline and lysyl pyridinoline. These results indicate that serum pyridinolines, especially lysyl pyridinoline, may be used as specific biochemical markers of bone resorption in hemodialyzed patients.

Topics: Acid Phosphatase; Adult; Aged; Aged, 80 and over; Alkaline Phosphatase; Amino Acids; Biomarkers; Bone Resorption; Chromatography, High Pressure Liquid; Female; Humans; Isoenzymes; Male; Middle Aged; Osteocalcin; Parathyroid Hormone; Parathyroidectomy; Renal Dialysis; Tartrate-Resistant Acid Phosphatase; Uremia

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

Bone is a dynamic tissue that functions not only as a mechanical support, but also as a major component of the metabolic and endocrine systems maintaining mineral homeostasis. It has been shown that immobilization induces decalcification of bone. To evaluate the effect of immobilization on bone mineral density and calcium metabolism, we investigated 9 young healthy males and females during 20 days bed rest. Three methods for measuring bone mineral density were performed to quantify whole body and regional bone changes: 1) dual energy X-ray absorptiometry, 2) quantitative computed tomography, and 3) multiple scanning X-ray photodensitometry, respectively. Bone mineral density showed a rapid decreasing tendency, especially in both lumbar and metacarpal bones (mean +/- SE: 4.6 +/- 0.6% and 3.6 +/- 0.4%, respectively). Urinary daily excretion of deoxypyridinoline, a sensitive marker of bone matrix resorption, tended to increase by day 10, and to decline by day 20 (mean +/- SE: 42.2 +/- 1.4, 27.6 +/- 2.2 nmol day-1, respectively). However, neither alkaline phosphatase nor tartrate-resistant acid phosphatase, both markers of osteoclast and mature osteoblast function, changed. These results showed that in the early stage of immobilization, bone matrix might be resorbed without any activation of osteoclasts, resulting in rapid decalcification of vertebral and cortical bones without any discernible changes in anatomical structure.

Topics: Absorptiometry, Photon; Acid Phosphatase; Adult; Alkaline Phosphatase; Amino Acids; Bed Rest; Biomarkers; Bone and Bones; Bone Density; Bone Development; Bone Resorption; Calcium; Collagen; Female; Humans; Male; Minerals; Tomography, X-Ray Computed

Immobilization induces abnormal bone metabolism and rapid decalcification. Measurements of bone mineral content disclosed rapid decalcification, especially in lumbar vertebral and metacarpal bones in our short-term 20-day bed rest study. Many factors could contribute to the marked demineralization. The activities of osteoclasts and osteoblasts were studied by following serum levels of tartrate-resistant acid phosphatase and alkaline phosphatase, biomarkers for osteocyte activity. There were no alterations in these enzymes during bed rest. However, urinary excretion of pyridinium cross-links, resorption markers of bone matrix itself, increased by day 10 with subsequent decrease at day 20. So decalcification was induced without any relation to osteoclast activity. As cytokines strongly modulate the function of osteoclasts, peripheral monocyte release of interleukin 1 alpha and tumor necrosis factor alpha were assayed to determine the contribution to this rapid demineralization. Cytokines were released transiently by day 7 and later rapidly decreased. However, there was no correlation between cytokine release and bone matrix resorption.

Topics: Acid Phosphatase; Adult; Amino Acids; Bed Rest; Biomarkers; Bone and Bones; Bone Matrix; Bone Resorption; Circadian Rhythm; Cytokines; Female; Humans; Interleukin-1; Male; Monocytes; Tartrates; Tumor Necrosis Factor-alpha

To study the mechanism of bone loss in physical unloading, we examined indices of bone formation and bone resorption in the serum and urine of eight healthy men during a 7 day -6 degrees head-down tilt bed rest. Prompt increases in markers of resorption--pyridinoline (PD), deoxypyridinoline (DPD), and hydroxyproline (Hyp)/g creatinine--during the first few days of inactivity were paralleled by tartrate-resistant acid phosphatase (TRAP) with significant increases in all these markers by day 4 of bed rest. An index of formation, skeletal alkaline phosphatase (SALP), did not change during bed rest and showed a moderate 15% increase 1 week after reambulation. In contrast to SALP, serum osteocalcin (OC) began increasing the day preceding the increase in Hyp, remained elevated for the duration of the bed rest, and returned to pre-bed rest values within 5 days of reambulation. Similarly, DPD increased significantly at the onset of bed rest, remained elevated for the duration of bed rest, and returned to pre-bed rest levels upon reambulation. On the other hand, the other three indices of resorption, Hyp, PD, and TRAP, remained elevated for 2 weeks after reambulation. The most sensitive indices of the levels of physical activity proved to be the noncollagenous protein, OC, and the collagen crosslinker, DPD. The bed rest values of both these markers were significantly elevated compared to both the pre-bed rest values and the post-bed rest values. The sequence of changes in the circulating markers of bone metabolism indicated that increases in serum OC are the earliest responses of bone to head-down tilt bed rest.

Topics: Acid Phosphatase; Adult; Alkaline Phosphatase; Amino Acids; Bed Rest; Biomarkers; Bone and Bones; Bone Development; Bone Resorption; Creatinine; Humans; Hydroxyproline; Male; Osteocalcin; Weightlessness

Estrogen deficiency-induced bone loss has been associated with accelerated bone turnover. Levels of some biochemical markers, such as serum osteocalcin (BGP), tartrate-resistant acid phosphatase (TRAP), and urinary hydroxyproline (OHP), have been shown to be related to the rate of bone turnover. They may therefore be useful in identifying the individual at risk for osteoporosis and monitoring the efficacy of the treatment. Two recently discovered markers, urinary pyridinoline (PYD) and deoxypyridinoline (DPD), are apparently directly related to bone matrix degradation and may be more accurate markers of bone resorption than OHP or TRAP. To evaluate the effects of menopause, osteoporosis, and estrogen replacement on the excretion of these new markers, we measured the levels of PYD and DPD and other biochemical markers of bone turnover in four groups of women, premenopausal healthy (PRE), postmenopausal healthy (POST), postmenopausal osteoporotic (UTO), and postmenopausal osteoporotic with estrogen treatment (ETO). Significant increases in PYD, DPD, BGP, TRAP, and OHP were found in POST and UTO groups compared with PRE. These increases were blunted by estrogen treatment when the levels of each of the markers returned to PRE levels. When comparing POST and UTO groups, significant increases were observed in UTO only for PYD, DPD, and urinary calcium but not for OHP, BGP, or TRAP. With subgroups matched for age and years from menopause, only DPD discriminated between POST and UTO. Indices of bone formation covaried with markers of bone resorption in the total population.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acid Phosphatase; Adult; Aged; Amino Acids; Biomarkers; Bone Density; Bone Resorption; Collagen; Cross-Sectional Studies; Estrogen Replacement Therapy; Female; Humans; Hydroxyproline; Menopause; Middle Aged; Osteoporosis, Postmenopausal

Topics: Acid Phosphatase; Amino Acids; Arthritis, Rheumatoid; Biomarkers; Bone and Bones; Humans; Hydroxyproline