Hop rho iso-alpha acids, berberine, vitamin D3 and vitamin K1 favorably impact biomarkers of bone turnover in postmenopausal women in a 14-week trial
Michael F. HolickJoseph J. LambRobert H. LermanVeera Reddy KondaGary DarlandDeanna M. MinichAnuradha DesaiTai C. ChenMelissa A. AustinJacob KornbergJyh‐Lurn ChangAlex HsiJeffrey S. BlandMatthew L. Tripp
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Bone remodeling
Osteopenia
Development of optimal bone mass during early adulthood is determined by the balance between bone formation and resorption. The utility of minimally invasive biomarkers for monitoring bone turnover balance in maturing non-human primates has received limited attention. This study evaluated the biological variation of osteocalcin (a marker of bone formation), carboxyterminal cross-linking telopeptide of type 1 collagen (CTX, a marker of bone resorption), and the ratio of osteocalcin to CTX (reflecting bone turnover balance), in 136 rhesus and cynomolgus macaques aged 3.8-11.6 years. In a subsample of the animals (n = 28), blood samples were collected at monthly intervals over 4 months. Between-subject analysis revealed that there were no sex or species differences for CTX. Osteocalcin and the ratio of osteocalcin to CTX were higher in males than in females, and in rhesus macaques than in cynomolgus macaques. There were no changes in osteocalcin, CTX, or the ratio of osteocalcin to CTX across 4 months for any of the groups. In contrast, there was considerable within-subject variation in osteocalcin and CTX concentrations. However, differences in values exhibited no discernible pattern, suggesting that within-subject variation can be reduced by averaging repeat measurements. In summary, the data provide reference values for male and female rhesus and cynomolgus macaques and support the utility of osteocalcin and CTX as biomarkers to monitor bone turnover at the population level.
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Osteocalcin (OC) is produced by osteoblasts during bone formation. OC is excreted into urine by glomerular filtration and can be found as fragments in urine. The presence of three vitamin K-dependent γ-carboxyglutamic acid residues is critical for osteocalcin's structure, which appears to regulate the maturation of bone mineral. Recent bone biology research have highlighted the importance of bone not only as a structural scaffold to support the human body, but also as a regulator of a metabolic processes that are independent of mineral metabolism. Circulating osteocalcin is present either as carboxylated or as undercarboxylated forms. Increased serum level of osteocalcin is linked with increased bone mineral density. The importance of the bone–kidney relation in physiologic regulation of mineral ion has also been extensively studied and documented. Several workers have uncovered the role of insulin as an additional factor involved in the skeletal remodelling process. Evidences are available which shows that osteoblastic insulin signalling is important for glucose metabolism. The measurement of OC in urine samples could be used as an index of bone turnover in monitoring bone metabolism. In this review, we have tried to explain different roles of OC, however further studies are required to elucidate the metabolic and hormonal role of OC in human body.
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Osteocalcin (OC) is non-collagenous bone matrix protein produced by osteoblasts. OC binds to hydroxyapatite and is deposited in the bone matrix. Concentration of OC in the blood seems to reflect both osteogenesis and increased bone metabolism and depends on age, sex, menopausal status. The aim of our study was to evaluate changes in the concentration of osteocalcin and selected biochemical parameters of bone turnover in different stages of life in healthy people. We found that the mean serum levels of OC were significantly greater in women than in men. The highest OC levels were found in men under the age of 30 with a decrease in the fourth decade of life. In the group of women of up to 40 years of age, OC concentrations were comparable with the equivalent group of men. The lowest concentration of OC was found in the age group 40-49, with the significant increase in the subsequent decades of life. In both men and women, we found a significant correlation of OC with the calcium concentrations and alkaline phosphatase activity. Osteocalcin determinationa, particulary in women, may be useful laboratory parameters of osteoporosis process.
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The recent development of biochemical markers gives the opportunity to assess bone metabolism. Osteocalcin is a non collagenous protein of the bone matrix specifically synthesized by osteoblasts. The concentration of osteocalcin in serum reflects osteoblastic function and bone turnover. It has emerged as a more specific index of bone metabolism than serum alkaline phosphatase activity. Great care must be taken in blood sampling, processing and storage to avoid protein degradation. Inasmuch, we have shown in human clinical settings, the interest of this marker in patients with bone metabolic disorders characterized by increased bone turnover such as primary and secondary hyperparathyroidism or postmenopausal osteoporosis. Conversely, exogenous or endogenous high levels of corticosteroids rapidly induced a reversible decrease in osteocalcin levels.
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The recent development of biochemical markers gives the opportunity to assess bone metabolism. Osteocalcin is a non collagenous protein of the bone matrix specifically synthesized by osteoblasts. The concentration of osteocalcin in serum reflects osteoblastic function and bone turnover. It has emerged as a more specific index of bone metabolism than serum alkaline phosphatase activity. Great care must be taken in blood sampling, processing and storage to avoid protein degradation. Inasmuch, we have shown in human clinical settings, the interest of this marker in patients with bone metabolic disorders characterized by increased bone turnover such as primary and secondary hyperparathyroidism or postmenopausal osteoporosis. Conversely, exogenous or endogenous high levels of corticosteroids rapidly induced a reversible decrease in osteocalcin levels.
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Objective To investigate the changes of bone metabolism markers in patients with hyperthyroidism before and after treatment and the characteristics of bone turnover rate.Methods Forty-six patients with hyperthyroidism and thirty healthy controls were included into this study.Electrochemical luminescence immunoassay(ECLIA) method was used to measure serum osteocalcin and β-cross laps levels in all the hyperthyroid patients before and after antithyroid (methimazole) therapy and thirty healthy volunteers.Results The mean concentrations of both osteocalcin and β-cross laps in hyperthyroid patients before and after treatment were significantly higher than those in the healthy subjects (P0.000),increased by 1.74 folds and 1.80 folds respectively before treatment and 2.26 folds and 2.16 folds respectively after treatment.The correlation analysis showed that the serum FT3 was positively correlated with osteocalcin(P0.05) and FT4 was positively correlated with osteocalcin and β-cross laps (P0.05) before methimazole treatment.The serum osteocalcin was positively correlated with β-cross laps (P0.01) as well.Compared with the untreated hyperthyroidism group,serum osteocalcin and β-cross laps were further increased after methimazole treatment for 2 months (P0.05).Conclusions High bone turnover rate characterizes the bone metabolism in the patients with hyperthyroidism.The activity of bone may dominant with osteoclast resulting in abnormal bone metabolism in the untreated hyperthyroidism patients.However,in the patients who under treatment,both bone resorption and bone formation were further increased and bone formation were more prominent,which suggested that the osteoblast activity dominant the whole progress in favor of bone remodeling.
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The assessment of bone metabolism by biochemical markers remains difficult problem. Serum osteocalcin, synthesized in bone cells, is now becoming a sensitive indicator of bone turnover in patients with metabolic bone diseases. We measured serum osteocalcin levels by radioimmunoassay in 18 patients with osteoporosis and examined whether they reflect bone formation, resorption or both. We found that serum osteocalcin levels in biopsy-identified osteoporotics were widely ranged (1.8 – 18.8 ng/ml). Tetracycline double labeling method exibited two types of labeling pattern in the iliac bone, that is double labeled or no double labeled (impaired labeled) pattern. Serum concentrations of osteocalcin in patients with double labeling were significantly higher than those with impaired labeling (11.2±4.0 vs 4.1 ±2.1 ng/ml, P<0.01). Furthermore, serum osteocalcin levels showed a significantly positive linear correlation with the parameters reflecting bone formation, but not with bone resorption. These data indicate that serum osteocalcin levels reflect bone formation in osteoporotics and thereby could be a useful indicator of osteoblastic function in osteoporosis.
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Bone metabolism is the course of dynamic balance between bone formation and bone resorption, and can produce some metabolites. These metabolites are named for markers of bone turnover, and classified into markers of bone formation and markers of bone resorption. Markers of bone formation represent the activity of osteoplast and metabolite of bone formation, and markers of bone resorption represent the activity of osteoclast and metabolite of bone resorption. In this review, the researches on neonatal markers of bone turnover were discussed.
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Osteocalcin is one of the biochemical markers of bone metabolism, produced by mature osteoblasts. It has been shown that serum osteocalcin is a marker of osteoblastic activity, and the levels reflect the rate of bone formation and bone turnover. Bone metabolism after spinal cord injury (SCI) initially reflects a disproportion between highly bone resorption and almost normal or lightly elevated bone formation, indicating an increase in bone turnover. Osteocalcin and other biochemical markers may be helpful to know the bone metabolism after SCI and to evaluate the effect of all kinds of methods in treating and preventing osteoporosis after SCI.
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