acid-phosphatase and pyridinoline

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

Bone loss in rheumatoid arthritis (RA) patients results from chronic inflammation and can lead to osteoporosis and fractures. A few bone remodeling markers have been studied in RA witnessing bone formation (osteocalcin), serum aminoterminal propeptide of type I collagen (PINP), serum carboxyterminal propeptide of type I collagen (ICTP), bone alkaline phosphatase (BAP), osteocalcin (OC), and bone resorption: C-terminal telopeptide of type 1 collagen (I-CTX), N-terminal telopeptide of type 1 collagen (I-NTX), pyridinolines (DPD and PYD), and tartrate-resistant acid phosphatase (TRAP). Bone resorption can be seen either in periarticular bone (demineralization and erosion) or in the total skeleton (osteoporosis). Whatever the location, bone resorption results from activation of osteoclasts when the ratio between osteoprotegerin and receptor activator of nuclear factor kappa-B ligand (OPG/RANKL) is decreased under influence of various proinflammatory cytokines. Bone remodeling markers also allow physicians to evaluate the effect of drugs used in RA like biologic agents, which reduce inflammation and exert a protecting effect on bone. We will discuss in this review changes in bone markers remodeling in patients with RA treated with biologics.

Topics: Acid Phosphatase; Amino Acids; Animals; Arthritis, Rheumatoid; Biomarkers; Bone Remodeling; Collagen Type I; Humans; Isoenzymes; Tartrate-Resistant Acid Phosphatase

Bone tissue is subject to remodeling throughout the lifetime of an individual. Through a continuous remodeling cycle, actuated via the so-called 'bone remodeling units', old bone is resorbed by osteoclasts with the formation of cavities that are subsequently filled by osteoblasts. Bone loss observed in old age and in women after menopause is due to an imbalance between bone resorption and formation. Biochemical markers provide a dynamic view of the remodeling process, which covers rate of turnover and pathogenesis, and should improve fracture risk prediction. Furthermore, they can be used to monitor the short-term effects of therapy, and indicate if an excessive slowing of the remodeling process is occurring. When searching for markers of bone remodeling, biochemists have focused mainly on skeletal molecules that can be dosed in plasma and/or urine, as indicators of osteoblast function (i.e. bone alkaline phosphatase, osteocalcin, procollagene I C- and N-terminal propeptides) or osteoclast function (i.e. pyridinium crosslinks, collagen I C- and N-terminal telopeptides). The clinical significance of any marker for bone remodeling depends on two fundamental characteristics: specificity and variability. If the objective is to monitor therapeutic efficacy, it seems most rational to use a resorption marker for drugs that act principally on osteoclast, such as estrogens or bisphosphonates, while for drugs that act principally on osteoblast, such as PTH-peptides a marker for bone formation would be more appropriate.

Topics: Acid Phosphatase; Alkaline Phosphatase; Amino Acids; Biomarkers; Bone Remodeling; Collagen Type I; Humans; Hydroxyproline; Isoenzymes; Osteocalcin; Peptides; Practice Patterns, Physicians'; 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

Currently, biomarkers are available which have considerably increased the possibility of monitoring changes in bone turnover. Assays for carboxy-terminal procollagen I fragments, osteocalcin and the bone-specific isoenzyme of alkaline phosphatase allow a more precise assessment of the complex osteoblastic functions in health and disease; osteocalcin appears at present to be the most satisfactory one. With respect to bone resorption, the measurement of urinary pyridinoline cross-links seems to be the most reliable assay. It has to be emphasized, however, that a single biomarker may be of value in some metabolic bone diseases but not in others.

Topics: Acid Phosphatase; Alkaline Phosphatase; Amino Acids; Biomarkers; Bone and Bones; Bone Remodeling; Bone Resorption; Humans; Hydroxyproline; Osteocalcin; Peptide Fragments; Procollagen; Reproducibility of Results

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

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

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

We have examined the response of different biochemical bone turnover markers to intravenous pamidronate administration (15 mg for 5 days) in 14 patients with Paget's disease, on days 8, 15 and 30 after pamidronate treatment. Urinary parameters of bone resorption, free pyridinolines (Pyr) and hydroxyproline (OHP), as well as serum tartrate-resistant acid phosphatase (TRAP) were measured. Two serum biochemical osteoblastic markers, alkaline phosphatase (AP) and osteocalcin (OC), were also analysed. In addition, ionic calcium (Ca2+) was measured in blood, and parathyroid hormone and calcitriol were measured in serum. All the biochemical markers of bone resorption tested decreased throughout the study. TRAP levels decreased slowly, meanwhile Pyr decreased maximally, below OHP values on day 8. However, the latter were lowest and were lower than those of Pyr on days 15 and 30. AP serum values also decreased during the study. Conversely, OC serum levels increased on days 8 and 15, decreasing to baseline levels on day 30. Ca2+ blood levels decreased while PTH plasma levels increased at all times during the period studied. Calcitriol serum levels increased on day 15. In conclusion, intravenous pamidronate administration was found to modify several biochemical parameters of bone turnover, including Pyr. Moreover, the changes in these parameters were different in intensity and "time course" during the study.

Topics: Acid Phosphatase; Adult; Aged; Amino Acids; Biomarkers; Bone and Bones; Bone Resorption; Calcitriol; Diphosphonates; Female; Humans; Injections, Intravenous; Isoenzymes; Male; Middle Aged; Osteitis Deformans; Osteocalcin; Pamidronate; 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

We studied the influence of normobaric hyperoxia on bone metabolism in 3- and 12-month-old male Wistar rats. Maintaining young rats (3 months) during the 14-hour daily sessions under normobaric hyperoxia (90% O2) was accompanied by a significant decrease in the concentration of C-terminal propeptides of collagen type I (by 36%), the acid phosphatase activity (by 32%), an increased activity of alkaline phosphatase (by 64%), an increased concentration of pyridinoline (by 37%) and 3-CrossLaps (by 8%), glycosaminoglycans (by 72%) in the blood serum. We believe that normobaric hyperoxia (90%) is accompanied by the disturbance of collagen synthesis. In adult rats under the same conditions for 14 sessions, the concentration ofglycosaminoglicans significantly increased by 60% relative to the control values. After 28 sessions of breathing the normobaric gas mixture containing 90% O 2 this parameter increased by 195%. Breathing normobaric gas mixture containing both 40% and 90% of O2 for 14 and 28 days decreased the acid phosphatase activity and the tartrat-resistant acid phosphatase activity by 18-25%. We believe that in adult animals 90% hyperoxia does not affect the activity of osteoblasts, but breaks the link between glycosaminoglicans and collagen fibrils, decreases the activity oflysosomal enzymes which are produced by osteoclasts and which can inhibit osteogenesis.

Topics: Acid Phosphatase; Alkaline Phosphatase; Amino Acids; Animals; Bone and Bones; Collagen; Glycosaminoglycans; Hyperoxia; Male; Osteoblasts; Osteogenesis; Oxygen; Oxygen Consumption; Protein Precursors; Rats

Matrix metalloproteinase (MMP) has been implicated in joint destruction of chronic arthritis diseases, such as rheumatoid arthritis. FR217840 (2R)-1-([5-(4-fluorophenyl)-2-thienyl]sulfonyl)-N-hydroxy-4-(methylsulfonyl)-2-piperazinecarboxamide is a potent, orally active synthetic MMP inhibitor that inhibits human collagenases (MMP-1, MMP-8 and MMP-13), gelatinases (MMP-2 and MMP-9) and membrane type MMP (MT-MMP) (MT1-MMP/MMP-14). FR217840 also inhibits rat collagenase and gelatinase. We studied the effect of FR217840 on a rat adjuvant induced arthritis model. Although oral administration (days 1-21) of FR217840 (3.2, 10, 32 mg/kg) to adjuvant injected Lewis rats did not affect inflammation, as indicated by both hind paw swelling and histological inflammatory infiltration, FR217840 suppressed both bone destruction and serum pyridinoline content in a dose-dependent manner. Also, FR217840 (32 mg/kg) reduced tartrate-resistant acid phosphatase (TRAP) cell number in the ankle joints of rats with arthritis. These results indicate that FR217840 successfully suppressed joint destruction and suggest that FR217840 may have potential as a novel anti-rheumatic drug.

Topics: Acid Phosphatase; Amino Acids; Animals; Ankle Joint; Arthritis, Experimental; Cell Line; Cells, Cultured; Collagenases; Disease Progression; Female; Humans; Isoenzymes; Joint Diseases; Matrix Metalloproteinase 1; Matrix Metalloproteinase 13; Matrix Metalloproteinase 8; Matrix Metalloproteinase 9; Matrix Metalloproteinase Inhibitors; Matrix Metalloproteinases; Piperazines; Protease Inhibitors; Radiography; Rats; Rats, Inbred Lew; Tartrate-Resistant Acid Phosphatase; Tumor Necrosis Factor-alpha

Circadian rhythmicity is an essential feature of bone metabolism. The present study was undertaken to (Aoshima et al., 1998) determine the changes in bone resorption and formation in rats over 24h, (Black et al., 1999) evaluate the effect of the consecutive administration of etidronate on circadian rhythms of serum bone markers, and (Blumsohn et al., 1994) determine whether the effect of etidronate on bone metabolism is circadian time-dependent. One hundred twenty male Wistar rats, which had been adapted to a 12/12h light/dark cycle, were injected subcutaneously once daily with either 0.5 mgP/kg etidronate or 0.9% NaCl (control group) at 0090, 1300, 1700, 2100, 0100, or 0500h for 10d. Serum was collected and tibiae were dissected 24h after the last injection. Serum pyridinoline (Pyd), tartrate-resistant acid phosphatase (TRAP), osteocalcin (OC), alkaline phosphatase (ALP), calcium (Ca), phosphorus (Pi), calcitonin (CT), and parathyroid hormone (PTH) were determined. Bone mineral density (BMD) in the proximal tibia, and the rate of formation of longitudinal trabecular bone over the past 48h were also determined using a chronological labeling method with NTA-Pb. The results showed characteristic circadian rhythms in serum bone markers in rats, with peaks in both bone resorption and bone formation during the animals' rest span. The administration of etidronate at the different times of the day decreased the level of bone-resorption markers (Pyd and TRAP) without affecting the circadian patterns of markers of bone formation (OC and ALP). However, the magnitude of the decrease due to etidronate was not uniform throughout the day, and was greatest during the daytime. Etidronate increased the BMD in the tibial metaphysis in all of the time-treatment groups, but the magnitude of the increase did not vary with the time of etidronate administration. The present data provide a physiological basis for future studies on bone metabolism and may be important in the design of future experiments and in the interpretation of experimental data.

Topics: Acid Phosphatase; Alkaline Phosphatase; Amino Acids; Animals; Biomarkers; Bone and Bones; Bone Density; Bone Resorption; Circadian Rhythm; Etidronic Acid; Isoenzymes; Male; Osteocalcin; Osteogenesis; Rats; Rats, Wistar; Tartrate-Resistant Acid Phosphatase

Sex hormones, including estradiol, play important physiological roles in bone metabolism. The purpose of this study was to investigate whether there is estrous-cycle-dependent variation in orthodontic tooth movement, and, if so, to determine the mechanism. Ten-week-old female Wistar rats were used. They received repeated orthodontic force during specific phases in the estrous cycle. Tooth movement in animals that received force principally in estrus was about 33% greater than that in animals that received such force principally in pro-estrus (p < 0.05). Serum estradiol levels also varied according to the estrous cycle, with a peak during pro-estrus and a nadir during estrus, and were inversely related to tooth movement. Furthermore, there were negative correlations between estradiol and both serum TRAP activity and pyridinoline (r = -0.42, p < 0.05; r = -0.59, p < 0.001). These results suggest that cyclic changes in the estradiol level may be associated with the estrous-cycle-dependent variation in tooth movement through its effects on bone resorption.

Topics: Acid Phosphatase; Amino Acids; Analysis of Variance; Animals; Bone Remodeling; Calcium; Estradiol; Estrous Cycle; Female; Isoenzymes; Osteocalcin; Phosphorus; Progesterone; Rats; Rats, Wistar; Statistics, Nonparametric; Tartrate-Resistant Acid Phosphatase; Tooth Movement Techniques

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

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 and increased bone turnover are recognized local changes after a fracture, 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 ankle fracture. Fourteen subjects (7 postmenopausal women and 7 men, mean age 63 years) were recruited following fracture of the distal tibia and fibula. Bone mineral density (BMD) of the ankle and proximal femur were measured by dual-energy X-ray absorptiometry (DXA) and quantitative ultrasound (QUS) of the calcaneus 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), deoxypyridinoline (iFDpd), N-telopeptides of type I collagen (NTx). We used the nonfractured limb to calculate values for baseline BMD and QUS. There was a significant decrease in BMD at the ultradistal ankle (p<0.001), the trochanteric region of the hip (p<0.01) and QUS of the heel after ankle fracture. This bone loss was maximal for ultradistal ankle BMD by 6 weeks at 13% (p<0.001) and for the trochanter by 26 weeks at 3% (p<0.01). The ankle BMD returned to baseline at 52 weeks but the trochanter BMD did not. Velocity of sound (VOS) decreased at 6 weeks by 2% (p<0.01) and broadband ultrasound attenuation (BUA) by 15% (p<0.01). VOS recovered completely by 52 weeks, but BUA did not return to baseline. Bone formation markers increased significantly between 1 and 4 weeks by 11-78% (p<0.01), and iBAP returned to baseline at 52 weeks but PINP and Oc remained elevated. Bone resorption markers did not increase and NTx was decreased at 52 weeks. We conclude that BMD decreased distal and immediately proximal to the fracture line when measured with DXA and QUS. Ankle BMD and heel VOS recovered at 52 weeks (trochanteric BMD and heel BUA did not) and the bone turnover markers returned toward baseline.

Topics: Absorptiometry, Photon; Acid Phosphatase; Aged; Aged, 80 and over; Alkaline Phosphatase; Amino Acids; Analysis of Variance; Ankle Injuries; Biomarkers; Bone Density; Bone Remodeling; Collagen; Collagen Type I; Female; Fractures, Bone; Humans; Isoenzymes; Male; Middle Aged; Osteocalcin; Peptide Fragments; Peptides; Procollagen; Reflex Sympathetic Dystrophy; Statistics, Nonparametric; Tartrate-Resistant Acid Phosphatase; Time Factors

We have developed a new and simple system of human osteoclast formation by fusing peripheral blood monocytes with anti-Fusion Regulatory Protein-1 (anti-FRP-1) monoclonal antibody (mAb). When human blood monocytes were cultured in the presence of anti-FRP-1/CD98 mAbs, polykaryocytes began to appear at approximately 15 h and increased in size with time until 3-4 days of incubation with anti-FRP-1 mAb. These fused cells showed positive staining in tartrate-resistant acid phosphatase, possessed numerous calcitonin receptors, and were capable of bone resorption. These results strongly suggest that anti-FRP-1 antibody-induced multinucleated cells are osteoclasts. Furthermore, FRP-1 antigens were detected in osteoclasts isolated from human bone and in the osteoclast-like cells obtained from human giant cell tumors of bone.

Topics: Acid Phosphatase; Amino Acids; Antibodies, Monoclonal; Antigens, CD; Antigens, Surface; Carrier Proteins; Cells, Cultured; Child; Femur; Fusion Regulatory Protein-1; Giant Cell Tumors; Giant Cells; Humans; Isoenzymes; Monocytes; Osteoclasts; Receptors, Calcitonin; Staining and Labeling; Tartrate-Resistant Acid Phosphatase

This study was undertaken to observe osteoclast differentiation related to inflammatory progression in aggressive periodontitis induced in beagle dogs by ligature of the gingival sulcus. To monitor osteoclastic activity, we used histochemical methods (staining for tartrate-resistant acid phosphatase [TRAP]) to visualize osteoclasts and their TRAP-positive precursors and biochemical methods (ELISA assay of pyridinium crosslinks) to detect bone matrix degradation products in gingival crevicular fluid (GCF), serum, and urine. For histochemical study, tissue specimens were prepared from 3 adult female beagle dogs induced with experimental periodontitis by silk ligature placement below the gingival margin of mandibular molars ligated for 3, 7, and 21 days. For biochemical study for pyridinoline measurement, the 24 mandibular molars of 4 male beagle dogs were ligated. GCF, urine, and serum were collected at day 0 and at 3, 7, 14, and 21 days after ligation. In the early inflammatory phase of ligature-induced periodontitis (day 3), TRAP+ mononuclear and TRAP+ multinucleated cells were present in the gingival connective tissue, and active bone-resorbing cells were found in excavated lacunae at the alveolar crest, but osteoclasts were not infiltrating the periodontal ligament during this early phase. During later stages of the inflammatory process (7 and 21 days), osteoclasts appeared at both the gingival and ligament side of the alveolar bone. Osteoclastic bone resorption appeared to be more severe on the bone surface at the gingival side than on the bone surface of the periodontal ligament side. Measurement of pyridinoline significantly increased in GCF and urine 3 days after ligation. The results suggested that bone at the crest of the alveolar bone is rapidly resorbed within 3 days of inducing experimental periodontitis.

Topics: Acid Phosphatase; Alveolar Bone Loss; Alveolar Process; Amino Acids; Animals; Biomarkers; Cell Differentiation; Coloring Agents; Connective Tissue; Cross-Linking Reagents; Disease Progression; Dogs; Enzyme-Linked Immunosorbent Assay; Female; Giant Cells; Gingiva; Gingival Crevicular Fluid; Histocytochemistry; Isoenzymes; Leukocytes, Mononuclear; Male; Osteoclasts; Periodontal Ligament; Periodontitis; Pyridinium Compounds; Tartrate-Resistant Acid Phosphatase

Moderate increases in "classical" biochemical markers of bone turnover have been described only in some patients with Camurati-Engelmann disease. However, the determination of the following "new" markers has not been previously performed: serum osteocalcin (BGP), bone alkaline phosphatase (BAP), carboxyterminal propeptide of type I procollagen (PICP), aminoterminal propeptide of type I procollagen (PINP), tartrate-resistant acid phosphatase (TRAP), telopeptide carboxyterminal of type I collagen (ICTP), urinary pyridinoline (PYR), crosslinked N-telopeptides of type I collagen (NTX), and Crosslaps (CL). Such a determination may improve the evaluation of the disease activity. To evaluate the usefulness of biochemical markers of bone turnover reflecting Camurati-Engelmann disease activity we measured the levels of all these markers in four affected patients. The results were compared with bone scintigraphic indices of disease activity. Except for PICP and TRAP, bone formation and resorption markers were abnormal in all patients and were related to bone scan indices of disease activity. Among the markers of bone formation PINP, BAP, and BGP showed the highest values, whereas NTX and CL were the most sensitive markers of bone resorption. These results suggest that the determination of NTX or CL, and PINP or either BAP and BGP, associated with bone scan evaluation, provides the best assessment of Camurati-Engelmann disease activity.

Topics: Acid Phosphatase; Adult; Alkaline Phosphatase; Amino Acids; Biomarkers; Bone Development; Bone Resorption; Camurati-Engelmann Syndrome; Chromatography, High Pressure Liquid; Collagen; Collagen Type I; Female; Humans; Isoenzymes; Male; Middle Aged; Osteocalcin; Peptide Fragments; Peptides; Procollagen; Tartrate-Resistant Acid Phosphatase

Urinary excretion of the cross-linked alpha 2(I) N-telopeptide (NTx) of type I collagen has proven in clinical studies to provide a highly responsive and specific index of bone resorption. In order to understand better the biological basis of the specificity and responsiveness of this marker, we examined whether osteoclasts cultured on human bone could generate immunoreactive NTx peptide. Mouse bone marrow cultures stimulated with 1,25 diliydroxyvitamin D3 (1,25(OH)2D3) and hydrocortisone to produce osteoclasts, were cocultured on human bone particles or dentin slices. Aliquots of culture medium were assayed for NTx by enzyme-linked immunosorbent assay (ELISA). NTx was detected in the medium 5 days after the addition of bone and continued to be produced linearly over the 14-day culture period. NTx production required attachment to the bone particles or dentin slices of mononuclear and multinuclear cells that stained for tartrate-resistant acid phosphatase. Surface area of resorbed dentin was highly correlated with medium NTx concentration (R2 = 0.84). Production of NTx was suppressed by the osteoclast inhibitors, calcitonin and alendronate, in a dose-dependent manner. Two other markers of bone resorption, hydroxylysyl pyridinoline and lysyl pyridinoline, were found in peptide linkage in the culture medium but not in free form; indicating that the osteoclasts had degraded the bone collagen to peptides but not to the free cross-linking amino acids.

Topics: Acid Phosphatase; Alendronate; Amino Acids; Animals; Anti-Inflammatory Agents; Biomarkers; Bone Marrow; Bone Resorption; Calcitonin; Calcitriol; Cells, Cultured; Chromatography, High Pressure Liquid; Collagen; Collagen Type I; Culture Media; Dentin; Dose-Response Relationship, Drug; Enzyme-Linked Immunosorbent Assay; Female; Femur; Humans; Hydrocortisone; Isoenzymes; Mice; Mice, Inbred BALB C; Osteoclasts; Peptide Biosynthesis; Peptides; Receptors, Calcitonin; Tartrate-Resistant Acid Phosphatase

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

We examined the response of different biochemical markers of bone resorption to bisphosphonate therapy (400 mg of etidronate daily for 6 months) in mild Paget disease (n = 14). Urinary markers included hydroxyproline (OHP), total (T) and free (F) pyridinolines (Pyds) determined by HPLC, immunoreactive FPyds, immunoreactive TPyds, and the N- and C-terminal telopeptides of type I collage (NTx, CL). Serum measurements included tartrate-resistant acid phosphatase (TRAcP) and the C-terminal telopeptide of type I collagen (ICTP). ICTP and TRAcP showed a minimal response to therapy (% change at 6 months, -13.1 +/- 6.8 and -6.7 +/- 3.4, respectively). The response was greatest for urinary telopeptides (NTx and CL; % change -75.7 +/- 7.5 and -73.4 +/- 8.9, respectively). The response was somewhat greater for TPyds than for FPyds. We conclude that: (a) ICTP and TRAcP are unreliable indicators of changes in bone turnover; (b) oligopeptide-bound Pyds and telopeptide fragments of type I collagen in urine show a somewhat greater response to therapy than do FPyds and may be more sensitive indicators of bone resorption; and (c) as yet no evidence suggests that these markers are substantially better predictors of the clinical response to therapy than serum total alkaline phosphatase or urinary OHP. There are several problems with the interpretation of these measurements in Paget disease, and the clinical utility of these measurements remains uncertain.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Amino Acids; Biomarkers; Bone Resorption; Chromatography, High Pressure Liquid; Collagen; Drug Resistance; Etidronic Acid; Female; Humans; Hydroxyproline; Male; Middle Aged; Osteitis Deformans; Peptide Fragments; Tartrates; Testosterone

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

Despite these potential problems, biochemical bone markers are the single most sensitive method for monitoring acute changes in bone metabolism. For example, subcutaneous injections of recombinant human insulin-like growth factor I cause a measurable increase in both procollagen and urinary DPD in as little as 1 day. Similarly, it is possible to measure a significant decrease in bone formation as determined by decreases in serum levels of ALP, OC, and C-PCP within 12 hours after the beginning of a PTH infusion study. Additionally, an increase in DPD/cr was determined within 24 hours of the start of bed rest. These changes, seen within 24 hours, are far earlier than could be detected by any other method of monitoring bone metabolism. Thus, biochemical assays have opened a new era where changes in bone metabolism can be detected in hours to days. This acute detectability should be especially helpful to the development of new drugs and the optimization of the use of approved drugs. Accordingly, definite dose-response studies can now be done in a reasonable time. For osteoporosis therapy there are reasons to consider cyclic drug administration, such as avoiding drug resistance (PTH or calcitonin), avoiding overtreatment (bisphosphonates), or avoiding a possible mineralization defect (fluoride). By using biochemical assays, we can determine the optimum amount of "on time" and "off time" in cyclic therapy. Of the bone formation assays, ALP, OC, and PCP, we recommend for routine use the OC assay because of its high discriminant power and because it has been better characterized, in terms of clinical application, than the PCP assays and the ALP IRMA. If, however, the serum cannot be drawn at a specific time in all patients to be studied, we recommend the ALP assay because, unlike the OC assay, it shows no diurnal variation. Of the bone resorption assays, HYP, TRAP, GHYL, and PYD/DPD, we recommend the urine PYD/DPD assay (adjusted for creatinine) because it is commercially available and because, along with the urine GHYL assay, it is the most sensitive bone resorption assay. Established guidelines for the use of assays in patient care is not yet available, largely because of the large intrapatient variation seen with most assays. Once this problem is resolved, it should be possible to apply biochemical assays to routine clinical practice. For example, if the patient has a urine DPD/cr (indicating a high bone resorption rate), the patient would be selected for anti

Topics: Acid Phosphatase; Alkaline Phosphatase; Amino Acids; Biomarkers; Bone Development; Bone Resorption; Humans; Hydroxylysine; Hydroxyproline; Osteocalcin; Procollagen; Reproducibility of Results

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