The use of biochemical markers of bone turnover in osteoporosis: state of the art
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The assay features of biochemical markers of bone turnover have markedly improved in the past few years. The most sensitive and specific markers of bone formation include serum bone alkaline phosphatase, total osteocalcin (including the intact molecule and the large N-Mid fragment) and the N extension peptide of type I collagen (PINP) measured with a recently developed radioimmunoassay. Among the various markers of bone resorption, measurements of the urinary excretion of the (deoxy) pyridinoline crosslinks and of N- and C- related telopeptides (NTX and CTX respectively) are the most sensitive and specific ones. In addition, a two-site immunoassay of serum CTX is now widely available. Bone markers can be used to predict the rate of bone loss in postmenopausal women. Three independent studies have shown that high bone turnover is associated with increased bone loss over 4 to 15 years in women aged 50 to 70 years. In addition, we have shown in elderly women that increased bone resorption, i.e. above the premenopausal range, is associated with a two-fold increase in the risk of hip fractures and that those with both a low BMD (T score < -2.5) and increased bone resorption have a 4- to 5- fold increase in hip fracture risk. We have recently confirmed that increased bone turnover predicts the risk of fragility fractures in a younger cohort of postmenopausal women followed for an average of 5 years. The mechanisms underlying the increased bone turnover in some (but not all) postmenopausal women are unknown. The increase appears to be independent from the residual secretion of 17 s estradiol (E2), assessed by a highly sensitive radioimmunoassay. Indeed, we found that a low serum E2 predicts the risk of fragility fractures in late postmenopausal women (but not in the elderly) independently of the rate of bone turnover. Bone markers can be used to monitor the efficacy of antiresorptive therapy such as hormone replacement therapy, raloxifene and bisphosphonates. We and others have shown that the short-term (3 to 6 months) decrease of bone turnover is significantly correlated with the long-term (2 years) increase in BMD of the spine. In addition, the decrease of serum osteocalcin is associated with the risk of vertebral fractures in osteoporotic women treated with raloxifene. Similar studies in patients using alendronate or risedronate show that the short-term decrease of bone turnover markers is correlated with the risk of subsequent fractures. Thus, with adequate cut-offs, individual patients can be monitored with bone markers earlier than with DXA. It remains to be assessed if such a monitoring can improve long-term compliance with therapy.Keywords:
Bone remodeling
Pyridinoline
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Trabecular bone score
N-terminal telopeptide
Zoledronic Acid
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Pyridinoline
Deoxypyridinoline
Bone remodeling
N-terminal telopeptide
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Pyridinoline
Deoxypyridinoline
Bone remodeling
N-terminal telopeptide
Densitometry
Tartrate-resistant acid phosphatase
Hydroxyproline
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Biochemical markers of bone turnover have been suggested to be useful in monitoring the efficacy of antiresorptive therapy. In this study, we investigated the predictive value of bone turnover markers to determine short-term response in bone mineral density (BMD) and to identify nonresponders in 138 postmenopausal women (mean age 58 years) with osteoporosis given with either hormone thearpy (HT) or alendronate. Urinary type I collagen N-telopeptide (NTx) and serum osteocalcin (OC) at baseline, 3, and 6 months after treatment as well as spine and femoral neck BMD at baseline and 12 months were measured. Significant decreases in both NTx and OC were evident in women on treatment with antiresorptive agents as early as 3 months (p<0.01). Percent change of NTx at 3 months correlated with the percent change of spinal BMD at 12 months of treatment. When bone turnover markers were stratified by tertiles, the average rate of lumbar spine BMD gain increased significantly with increasing tertiles of baseline value (p<0.05) and percent change (p<0.05) of urinary NTx at 3 month of treatment. In terms of BMD response, urinary NTx at 3 months decreased significantly more in BMD responders group than in nonresponders group. Logistic regression analysis demonstrated that percent change of NTx at 3 months is an independent predictor to identify BMD nonresponders, defined as those whose BMD gain remained within the precision error range of dual energy X-ray absorptiometer (DXA). We conclude that biochemical markers of bone turnover, especially percent change in urinary NTx levels, can be used to determine BMD response to antiresorptive therapy in Korean postmenopausal women with osteoporosis.
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Bone remodeling
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Although bone mineral density (BMD) measurement is the common method for the diagnosis of postmenopausal osteoporosis (PMO, bone turnover markers have been proposed as good indicators for monitoring the efficiency of antiresorptive treatment. We aim to evaluate course of bone turnover markers in the follow-up of treatment osteoporosis and compare the results of these markers with bone mineral densities. 47 postmenopausal patients were included in this study. The age average of the patients was 59.1±7.6 (48-81). Patients were divided into 5 groups depending on the type of the treatment: Calcium and vitamin D (8 patients); calcium, vitamin D and risendronate (10 patients); calcium, vitamin D and alendronate (10 patients); calcium, vitamin D and hormone replacement therapy (tibolone) (9 patients) and calcium, vitamin D and calcitonine (10 patients). Samples were taken from each group, prior to treatment and in the third and sixth months of the treatment. Bone mineral density measurements were carried out before the treatment and in the sixth month. The basal concentrations of bone turnover markers [serum Type I collagen C-telopeptide (CTX), N-mid-Osteocalcin (OC) and urinary deoxypridinoline (Dpd)] and Interleukin-1b (IL-1b) were compared to the values in the third and sixth month of the therapy and also to BMD.OC, CTX and Dpd are good markers for the evaluation the effectiveness antiresorptive therapy. The changes in CTX and OC seems to be reflect the changes in bone mass in the early period. However, the changes in Dpd levels come out later. HRT (tibolone) and biphosphonates especially risendronate are thought to be effective therapeutic approaches, because a significant decrease in bone turnover markers and an improvement in BMD – especially in lombar vertebra - were observed in the follow up of treatment. A good correlation found between the changes in levels of CTX and Dpd and changes in BMD during treatment, which suggest that these two markers would be useful for monitoring response to antiresorptive therapy. Keywords: Postmenopausal osteoporosis, bone turnover markers, serum Type I collagen C-telopeptide, N-mid-Osteocalcin, urinary deoxypridinoline, Interleukin-1b DOI: 10.7176/JHMN/80-14 Publication date: September 30 th 2020
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Menopause is associated with adverse changes in bone turnover. When bone resorption exceeds formation, bone loss and osteoporosis will occur. This is explained by Biochemical marker of bone turnover profile. Though Bone Mineral Density (BMD) measurements are the gold standard in calculating bone mass, the changes are usually late and the damage is irreversible. Combined use of biochemical markers of bone turnover helps in early identification of women who are at increased risk of fractures. rnObjective: To compare Serum Total Alkaline Phosphates (ALP), Total Calcium, Urinary OHP in postmenopausal cases and pre-menopausal controls. rnMethods: The study included 25 healthy postmenopausal women as cases, and 25 healthy Premenopausal women. Estimation of ALP was done by kinetic method Recommended by International Federation of Clinical Chemistry (1FCC), Serum total Calcium by modification of Ortho- Cresolphthalein Complexone (OCPC) method, Urinary OHP by modified Neumann and Logan method. rnResults: Bone formation markers, serum total ALP was significantly increased (p<0.001) and total calcium was significantly decreased (p<0.001) in postmenopausal women compared to premenopausal women. Bone resorption marker, urinary OHP was significantly increased (p<0.001) in postmenopausal womenrnConclusion: This study concluded that, Serum total ALP, total calcium and Urinary OHP combined together provided a fairly useful index of bone resorption in postmenopausal women and these common biochemical parameters can be used to categorize postmenopausal women into rapid and slow bone losers. Preventive measures like calcium supplementation or Hormone replacement therapy can be initiated early in those who are rapid bone losers and prevent the osteoporotic fractures.
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Antiresorptive agents are widely used to treat osteoporosis. Both reduction in bone turnover and increase in BMD may be necessary to decrease the fracture risk. The aim of the study was to evaluate the effects of aledronate on bone turnover markers and bone mineral density in postmenopausal women with osteoporosis. The study involved a group of 56 postmenopausal women with osteoporosis treated with alendronate (70 mg) weekly at the Institute of Nuclear Medicine Clinical Center University of Sarajevo during a 12-months period. Bone mineral density (BMD) at lumbar spine and proximal femur and bone turnover markers (serum β-CrossLaps, urinary N-telopeptides of type I collagen (NTx), total serum alkaline phosphatase (AP) and serum osteocalcin) were measured at baseline and after 12 months of the treatment with aledronate. BMD values significantly increased both at lumbar spine by 13.46% and proximal femur by 21.96% during the study period (-3.12±0.24 vs. -2.7±0.19 and -2.55±0.2 vs. -1.99±0.19 respectively; p<0.001). Bone turnover markers significantly decreased during the study period; C-terminal telopeptides of type I collagen fragment (β-CrossLaps) 49.0% (0.51±0.05 vs.0.26±0.028 ng/mL), NTX 33.4% (48.3±4.9 vs.32.15±3.25 nMBCE/mM Cr), AP 24.3% (81.1±5.2 to 61.43±5.2 IU/L) and serum osteocalcin by 29.7% (34.3±2.65 to 24.1±1.36 ng/mL)(p<0.001). Alendronate treatment increased BMD and reduced the level of bone turnover markers. Therefore, the treatment with aledronate during 12 months period can be recommended in postmenopausal women with osteoporosis.
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Bone remodeling
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