Postmenopausal Osteoporotic Women Research Articles

Muscle performance in post-menopausal women at different risk of falling: A cross-sectional study

Falls are very common in older people and in post-menopausal osteoporotic women might lead to disability and hospitalization, with a significant health care burden. The relationship among the several risk factors for falls is still not well clarified. The aim of this study was to investigate muscle performance of post-menopausal women, according to their risk of falling. In this cross-sectional multicentre study, we included post-menopausal women aged ≥ 55 years, referring to 10 Italian centers specialized in bone health. The cohort was stratified in three groups according to a fall screening test (FST): mild, moderate, and high-risk of falling. We assessed the physical performance using the Unipedal Stance Test (UST) and the gait speed. According to the FST, 752 women, mean aged 71.6 ± 10.4 years, were divided into 3 groups: 365 (48.6%), 254 (33.8%), and 133 (17.6%) at mild, moderate and high-risk of falling respectively. There were statistically significant differences among the 3 groups for both UST (15.70 ± 15.04 vs. 8.39 ± 10.37 vs. 3.17 ± 2.87; P < 0.001) and gait speed (0.89 ± 0.34 vs. 0.57 ± 0.38 vs. 0.37 ± 0.20; P < 0.001). We observed a significant negative correlation between FST and UST (ρ = −0.527; P < 0.001) and between FST and gait speed (ρ = −0.575; P < 0.001). Our data suggest that the risk of falling is moderately correlated to the reduced muscle function and there is progressive worsening of muscle performance with the increase in the risk of falling.

Identification of an Epigenetic Signature of Osteoporosis in Blood DNA of Postmenopausal Women.

Osteoporosis is one of the most common age-related progressive bone diseases in elderly people. Approximately one in three women and one in five men are predisposed to developing osteoporosis. In postmenopausal women, a reduction in BMD leads to an increased risk of fractures. In the current study, we delineated the DNA methylation signatures in whole blood samples of postmenopausal osteoporotic women. We obtained whole blood DNA from 22 normal women and 22 postmenopausal osteoporotic women (51 to 89 years old) from the Canadian Multicenter Osteoporosis Study (CaMos) cohort. These DNA samples were subjected to Illumina Infinium human methylation 450 K analysis. Illumina 450K raw data were analyzed by Genome Studio software. Analysis of the female participants with early and advanced osteoporosis resulted in the generation of a list of 1233 differentially methylated CpG sites when compared with age-matched normal women. T test, ANOVA, and post hoc statistical analyses were performed, and 77 significantly differentially methylated CpG sites were identified. From the 13 most significant genes, ZNF267, ABLIM2, RHOJ, CDKL5, and PDCD1 were selected for their potential role in bone biology. A weighted polygenic DNA methylation score of these genes predicted osteoporosis at an early stage with high sensitivity and specificity and correlated with measures of bone density. Pyrosequencing analysis of these genes was performed to validate the results obtained from Illumina 450 K methylation analysis. The current study provides proof of principal for the role of DNA methylation in osteoporosis. Using whole blood DNA methylation analysis, women at risk of developing osteoporosis can be identified before a diagnosis of osteoporosis is made using BMD as a screening method. Early diagnosis will help to select patients who might benefit from early therapeutic intervention. © 2018 American Society for Bone and Mineral Research.

Serum adiponectin level in osteoporotic postmenopausal women with type 2 diabetes mellitus

BackgroundDiabetes Mellitus (DM) is a major health burden worldwide. Patients with type 2 DM has various complications, including impaired bone health. Adiponectin is novel adipocytokine that could influence bone metabolism. ObjectiveWe investigated the relationships between serum adiponectin versus lumbar bone mineral density (BMD) in type 2 diabetic osteoporotic postmenopausal women. Subjects and methodsThis study is a case control study included 90 postmenopausal women; divided as (group A) composed of 30 type 2 diabetic osteoporotic postmenapausal,(group B) composed of 30 non diabetic osteoporotic postmenopausal and 30 apparently healthy non osteoporotic postmenopausal women as a control group. All participants underwent Dual Energy X-ray Absorptiometry to measure the lumbar Bone Mineral Density (BMD).Serum adiponectin was measured by ELISA Kits. SPSS was used to analyze the data. ResultsAmong the studied subjects, group B showed a significant negative correlation between serum adiponectin and lumbar BMD. The diabetic osteoporotic postmenapausal group (group B) showed the lowest concentration of serum adiponectin (μg/mL): 5.14 compared with 11.02 and 8.63 in group A, and the control, respectively. Lumbar BMD of group B was significantly higher than that of group A. ConclusionsSerum adiponectin is associated with lumber BMD in diabetic osteoporotic postmenopausal women. These findings suggest that serum adiponectin was involved in bone metabolism in this group.

Effect of denosumab on fasting glucose in women with diabetes or prediabetes from the FREEDOM trial.

RANKL is a key regulator of bone resorption that may also modulate glucose metabolism. Denosumab (DMAb) is a fully human monoclonal antibody that binds RANKL and was associated with fracture risk reduction in the FREEDOM trial. We hypothesized that DMAb treatment decreased fasting serum glucose (FSG) relative to placebo in women with diabetes or prediabetes enrolled in FREEDOM trial. Post hoc analysis of FREEDOM, in which 7808 postmenopausal osteoporotic women were randomized to receive DMAb or placebo every 6months for 36months. All diabetes group included subjects with a self-report of diabetes, use of antidiabetic medication (ADM), or an FSG≥126mg/dL at baseline. The diabetes group without prior ADM use included subjects with a self-reported history of diabetes or FSG level≥126mg/dL at baseline. Prediabetes was defined as an FSG of 100 to 125mg/dL on no ADM. Average postbaseline FSG across visits was estimated and compared between DMAb and placebo. Main outcome measures are the difference in average postbaseline FSG across follow-up visits between DMAb and placebo. Estimated average postbaseline FSG across visits was not different between DMAb and placebo in either all diabetes group (P=.20) or those with prediabetes (P=.42); in diabetic women not on ADM, estimated average postbaseline FSG across visits was lower with DMAb than placebo (-6.8mg/dL; 95% CI, -12.6 to -1.0; P=.02). DMAb did not affect FSG in postmenopausal osteoporotic women with prediabetes or diabetes. There was evidence of modest FSG lowering with DMAb in those with diabetes who were not on ADM. It remains to be determined whether blockade of RANKL has a clinically important effect on glucose metabolism.

Serum osteocalcin levels in postmenopausal osteoporotic women receiving alendronate

Osteoporosis is characterized by low bone mass, changes in the microscopic structure of bone, and increased bone fragility. Monitoring response to treatment is critical for the appropriate management of osteoporosis. Serum osteocalcin has become known as a bone formation biomarker for the evaluation of treatment response in postmenopausal osteoporosis. The present study assessed the effect of alendronate on serum osteocalcin levels in patients with postmenopausal osteoporosis. Thirty-four women with postmenopausal osteoporosis diagnosed by DEXA received alendronate 10 mg/day for 3 months. Serum osteocalcin, calcium, phosphorus, and alkaline phosphatase (ALP) were measured at baseline and after 45 and 90 days. Mean age and duration of menopause were 57.91±7.68 and 9.37±8.43 years, respectively. Mean serum osteocalcin at baseline was 15.27±3.7 ng/ml, which decreased significantly after 45 and 90 days of treatment with alendronate (p=0.009 and p<0.001, respectively). The levels of serum osteocalcin at days 45 and 90 in patients aged < 60 and ≥ 60 years were not significantly different. The levels of serum osteocalcin at days 45 and 90 in patients with a menopause duration of < 5 and ≥ 5 years were not significantly different. No significant difference was observed in serum osteocalcin levels at days 45 and 90 in patients with osteoporosis only in the femoral neck (n=7), only in the lumbar spine (n=20), and in both femoral neck and lumbar spine (n=7). Measurement of serum osteocalcin is a less expensive, more available tool for monitoring the results of treatment in osteoporotic patients. It provides a practical suggestion about the effectiveness of treatment earlier than densitometry. As expected, osteocalcin levels decreased after treatment of osteoporosis.

Association of vitamin D receptor gene polymorphism (TaqI and Apa1) with bone mineral density in North Indian postmenopausal women

Vitamin D receptor (VDR) gene has an important role as a candidate gene for the regulation of bone mass in osteoporosis. However, its association with bone mineral density (BMD) is controversial and has not been established in different ethnic populations. To enhance the understanding of VDR gene polymorphism in the context of BMD, we investigated the plausible genetic association of TaqI and ApaI polymorphism with BMD in North Indian postmenopausal women with osteoporosis.254 osteoporotic women (Age 55.82 ± 6.91) and 254 postmenopausal non osteoporotic women (Age 54.76 ± 6.26) were included in the study. VDR TaqI and ApaI polymorphism were determined by PCR (polymerase chain reaction) and RFLP (restriction fragment length polymorphism). BMD was assessed by dual energy X-ray absorptiometry (DXA) at the lumbar spine (L1-L4), hip, forearm and femoral neck. The average BMD with TT genotype was significantly lower at lumbar spine, hip and forearm. The Frequency of TT genotype and t allele was significantly high in osteoporotic women when compared with controls. The average BMD with Aa genotype was higher in ApaI. Furthermore, comparison of frequency distribution of genotype and allele for VDR ApaI between osteoporotic patients and controls did not show any significant difference. Our findings revealed that TaqI gene TT genotype was associated with low BMD in North Indian osteoporotic women. Moreover, TT genotype and t allele associated significantly with osteoporosis in postmenopausal women. Therefore, VDR TaqI gene is an important determinant of risk factor for osteoporosis.

Effects of discontinuing oral bisphosphonate treatments for postmenopausal osteoporosis on bone turnover markers and bone density

Bisphosphonates (BPs) continue to suppress bone turnover markers (BTMs) after treatment has stopped, leading to the suggestion that a pause in treatment could be considered for low-risk patients. Indirect comparisons suggest that after cessation of treatment, the effects on bone may differ between drugs. We investigated the effects of stopping oral BP treatments for postmenopausal osteoporosis on BTMs and bone mineral density (BMD). We studied postmenopausal osteoporotic women who had previously taken part in a 2-year randomised study of three oral BPs (ibandronate, alendronate, or risedronate). At the end of the study, women with hip BMD T-score > - 2.5 and considered clinically appropriate to discontinue treatment were invited to participate in a further 2-year observational study. Biochemical response was assessed using BTMs, and BMD was measured by dual-energy X-ray absorptiometry. All BTMs increased after treatment withdrawal but remained below the pre-treatment baseline with less suppression of BTMs for the risedronate group compared to alendronate and ibandronate up to 48weeks. There was no difference between the BP groups 96weeks after stopping treatment. The change in BMD during the 96weeks after stopping treatment was - 1.6% (95% CI - 1.9 to - 1.2, P < 0.001) for the total hip and - 0.6% (95% CI - 1.1 to - 0.2, P = 0.17) at the lumbar spine with no difference between the three BP groups (P = 0.85 and P = 0.48, respectively). For all treatment groups, there was an increase in BTMs and a decrease in hip BMD after stopping BPs for 2years; however, none returned to pre-treatment baseline values.

MiRNA-133a is involved in the regulation of postmenopausal osteoporosis through promoting osteoclast differentiation.

The important role of miR-133a in the progress and development of postmenopausal osteoporosis has been reported, however, the underlying mechanism is not clear yet. In this study, qRT-PCR analysis was performed to assess miR-133 expression in serum isolated from postmenopausal osteoporosis patients (PMOP) and healthy controls. Bone mineral density (BMD) was measured at the lumbar spine by dual-energy X-ray absorptiometry (DXA). The results showed that miR-133a was significantly upregulated and negatively correlated with lumbar spine BMD in serum of postmenopausal osteoporotic women. The miR-133a mimic, miR-133a inhibitor, and the corresponding controls were transfected into RAW264.7 and THP-1 cells, respectively. TRAP-positive cells were counted and the protein expression of NFATc1, c-Fos and TRAP were detected by western blot analysis. We found that MiR-133a was upregulated during osteoclastogenesis, and overexpression of miR-133a promoted RANKL-induced differentiation of RAW264.7 and THP-1 cells into osteoclasts, whereas miR-133a knockdown showed the reversed results. In in vivo experiment, rats were bilaterally ovariectomized (OVX) and injected with antagomiR-133a or antagoNC, and were sacrificed for collecting serum and lumbar spine for ELISA, micro-computed Tomography (CT) and bone histomorphology analysis, respectively. It was found that, in OVX rats, miR-133a knockdown altered the levels of osteoclastogenesis-related factors in serum and increased lumbar spine BMD and changed bone histomorphology. Collectively, miRNA-133a is involved in the regulation of postmenopausal osteoporosis through promoting osteoclast differentiation.

Association of cystatin C- and creatinine-based eGFR with osteoporotic fracture in Japanese postmenopausal women with osteoporosis: sarcopenia as risk for fracture.

Coexistence of chronic kidney disease (CKD) is regarded as a risk for osteoporotic fracture particularly in postmenopausal women, not only because of increased parathyroid hormone level but also uremic sarcopenia. We examined the relationships of cystatin C-based glomerular filtration rate (eGFRcys) and creatinine-based GFR (eGFRcr), as well as their ratio with occurrence of osteoporotic fracture in postmenopausal osteoporotic women. This cross-sectional study included 555 postmenopausal women with osteoporosis. eGFRcr and eGFRcys were simultaneously measured, while occurrence of osteoporotic fracture was obtained by a medical chart review. Patients with osteoporotic fractures (n=211) exhibited significantly lower levels of physical activity, eGFRcr, eGFRcys, and eGFRcys/eGFRcr ratios, while a higher percentage was CKD stage 3 or more, estimated by eGFRcr or eGFRcys (CKDcys), than those without (n=344). Lower eGFRcys, but not lower eGFRcr, was independently associated with osteoporotic fracture in the entire cohort and that association was retained in CKDcys patients. Of great interest, higher eGFRcr was associated with osteoporotic fracture independent of eGFRcys in CKDcys patients. Furthermore, lower eGFRcys/eGFRcr ratio was independently associated with osteoporotic fracture in both CKDcys patients and the entire cohort. eGFRcys reduction might be associated with osteoporotic fracture in postmenopausal osteoporotic women, indicating the involvement of renal osteopathy in its occurrence. Furthermore, the association of higher, but not lower, eGFRcr with osteoporotic fracture in CKDcys cases might be explained by underestimation of renal dysfunction by eGFRcr resulting from decreased muscle mass and quality in those patients.

Effects of Bazedoxifene on Bone Mineral Density and Fracture in Post-Menopausal Osteoporotic Women: a Systematic Review and Meta-Analysis

Bazedoxifene (BZA) is a selective estrogen receptor modulator that reduces the risk of fracture and improves bone mineral density in post-menopausal women with osteoporosis. The aim of the present systematic review and meta-analysis was to investigate effects of BZA on bone mineral density (BMD) and fracture in post-menopausal osteoporotic women. We searched PubMed, Cochrane Central Register of Controlled Trials, Web of Sciences, Embase, and Scopus from until November 30, 2016. All randomized controlled trials that compared the effects of BZA on BMD and the incidence of vertebral and non-vertebral fractures in post-menopausal osteoporotic women compared with a control group were eligible for inclusion. Meta-analyses were conducted to calculate relative risk (RR) with 95% confidence interval (CI) for the association of BZA and vertebral and non-vertebral fractures compared with placebo. Nine randomized clinical trials met our inclusion criteria. Studies results showed that BZA significantly improves BMD, although we were not able to pool the results. Meta-analysis showed that the pooled effect of BZD on vertebral fracture was protective and significant (RR = 0.63; 95% CI 0.48, 0.83; P = 0.001). But pooled results did not show any association between taking BZD and the incidence of non-vertebral fracture (RR = 0.97; 95% CI 0.83, 1.13; P = 0.683). Evidence suggests that bazedoxifene is generally effective and safe in preventing bone loss and vertebral fracture in post-menopausal women with osteoporosis.

Relation Between Circulating Vitamin K1 and Osteoporosis in the Lumbar Spine in Syrian Post-Menopausal Women.

Background:In the past two decades, Vitamin K has been receiving more attention due to its role in bone health and metabolism. The bone mineral density does not remain steady with age, particularly declining after menopause.Objective: This study is aimed to investigate the relationship between bone mineral density and serum vitamin K1 levels in post-menopausal women, and to evaluate serum vitamin K1 levels as a potential biomarker for postmenopausal osteoporosis.Methods:Serum levels of vitamin k1 were measured in 23 postmenopausal osteoporotic women, and in 15 postmenopausal healthy control women using a standardized Enzyme-Linked Immune Sorbent Assay (ELISA) kit. Bone mineral density BMD was assessed at the lumbar spine.Results:The mean serum vitamin k1 level was significantly lower in the postmenopausal osteoporotic women group than in the normal control group (mean=0.794 vs3.61ng/ml, P< 0.0001), and serum vitamin k1 concentration was positively correlated with lumbar spine BMD among postmenopausal osteoporotic women (R=0.533, p = 0.009), and in postmenopausal healthy control (R=0.563, p = 0.02).Diagnostic sensitivity and specificity of vitamin k1 for osteoporosis were 90% and 98%, respectively (cut-off value: 0.853 ng/ml). The area under the ROC curve (AUC) value for vitamin k1 was 0.984 the odd ratio result was 18.66.Conclusion:Our results suggest that vitamin K1 may contribute to maintain bone mineral density. Vitamin K1 may have a role in diagnosing post-menopausal osteoporosis. Vitamin K1 may be a valuable diagnostic as well as therapeutic marker in post-menopausal osteoporosis.

The effect of protein diets in postmenopausal women with osteoporosis: Systematic review of randomized controlled trials

ABSTRACTThe main objective of this systematic review was to examine the effectiveness of protein supplementation through diet or dietary supplements on osteoporosis in postmenopausal women as evidenced by randomized controlled trials (RCTs). Five RCTs were included using dietary protein (N = 2), protein supplements (N = 2), and proteins through diet and supplements (N = 1). A total of 677 postmenopausal woman were included, all diagnosed with osteoporosis (T score < –2.5) and aged between 50 and 80 years. Results have found that combined protein administration through diet, mainly from animal sources and supplemental proteins (whey proteins, 86 g/d PRO including 6 g WPI), for a short period of time (up to 12 months) may positively affect osteoporosis in postmenopausal women. In addition, a positive effect can also be achieved by the single administration of a 250 mg/d supplement in which 10 g was WPI for a six-month period. In this review, it is shown that both combined administration of proteins through diet and supplements and single administration through protein supplements may reduce the risk of fracture in postmenopausal osteoporotic women. In contrast, dietary proteins alone, in doses similar to and/or higher than the RDA values, may not have any positive effect on treating osteoporosis.

High Serum Retinol as a Relevant Contributor to Low Bone Mineral Density in Postmenopausal Osteoporotic Women.

There is controversial information about the impact of vitamin A on bone. Some epidemiological studies show that excessive intake of vitamin A, or an excess of serum vitamin A, has related with adverse impact on bone mass; however, other studies did not find these links, and some authors have proposed that this vitamin might promote a better bone health. The present work aims to contribute to clarify the real role of vitamin A in bone tissue. For this purpose, a cross-sectional study of 154 osteoporotic non-treated postmenopausal women (> 65years old) was carried out. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry. We assessed concentrations of serum retinol, osteocalcin, parathyroid hormone, alkaline phosphatase, calcium, and phosphorus. We also studied demographic and anthropometric parameters. Spearman's correlations between retinol levels and other variables found negative correlations with BMD in both lumbar spine (R=- 0.162, P < 0.01) and femoral neck (R=- 0.182, P < 0.01), as well as alkaline phosphatase (R=- 0.110; P < 0.05) and phosphorus (R=- 0.110; P < 0.05). A positive correlation between retinol and fertile window was observed (R = 0.158; P < 0.01). After multivariable adjustment, we still found a negative correlation between serum retinol and BMD, both at the lumbar spine (R=- 0.210; P < 0.01) and at the femoral neck (R=- 0.324, P < 0.001). It is concluded that elevated serum-retinol levels are associated with an increased risk of low bone mass and thus with osteoporotic fractures. Therefore, osteoporosis-risk assessment should include quantification of serum metabolite of vitamin A.

The effects of treatment with biphosphonates on the remodelation of cortical bone microarhitecture in patients with postmenopausal osteoporosis – research on morphological, clinical and experimental aspects

Background. The dynamics on the remodelation of cortical bone microarchitecture are revealed with increasing accuracy by the use of newly infrared absorption spectra, providing more complex data compared to classical osteodensitometry. The aim of this study was to assess the impact of 2-year biphosphonate treatment on bone loss in a cohort of osteoporotic postmenopausal women with radius fragility fractures. Materials and method. A longitudinal, randomized, 5-year experimental and observational survey was conducted on 156 eligible patients, treated with alendronate, risedronate or zolendronate. Results. Fourier transform infrared spectra from bone biopsy samples revealed compositional information regarding crystalline texture and collagen matrix, allowing a comparative analysis between the initial bone demineralization and the cancellous trabecular bone architecture formed by cortical remodeling exerted by biphosphonates. Conclusions. Monitoring bone remodeling activity is important for guiding biphosphonate therapy.

Effect of a sequential treatment combining abaloparatide and alendronate for the management of postmenopausal osteoporosis

ABSTRACTThe recently published results of the sequential treatment of postmenopausal osteoporotic women with subcutaneous abaloparatide (80 µg/day) (ABL) for 18 months followed by 6 months of oral alendronate (70 mg/week) (ALN) support the administration of an anti-resorptive agent after completion of a treatment course with an osteoanabolic agent. The ABL/ALN sequence resulted in greater bone mineral density gains at all skeletal sites and in a reduction of vertebral, non-vertebral, major and clinical fractures compared to what is observed after 18 months of placebo followed by 6 months of ALN. Whereas questions remained unanswered about the ideal anti-resorptive agent to be used after ABL, the optimal duration of the administration of the anti-resorptive drug or the potential interest of re-initiating a course of ABL after a limited administration of ALN, these results support the use of the ABL/ALN sequence in the management of postmenopausal osteoporosis.

The effect of consumption of garlic tablet on proteins oxidation biomarkers in postmenopausal osteoporotic women: A randomized clinical trial.

BackgroundOsteoporosis (OP) is one of the most prevalent metabolic bone diseases at higher ages, especially in postmenopausal women.ObjectiveTo determine the effect of consumption of garlic tablet on proteins oxidation biomarkers in postmenopausal osteoporotic women.MethodsThe present study was a double-blind randomized controlled clinical trial that included 42 postmenopausal women in Yazd during 2014–2015. Osteoporotic women were randomly assigned into two groups: the garlic group (GG) and the placebo group (PG). Participants in GG took two garlic tablets daily for 1 month and the participants in PG took placebo tablets in the same manner. After 30 days, the plasma level of carbonyl groups (PCO), total antioxidant capacity (TAC), and advanced oxidation protein products (AOPPs) were assessed by spectrophotometric assays. Also, Malondialdehyde (MDA) content was measured according to the procedure of Thiobarbituric Acid (TBA). Data were analyzed by SPSS version 18, using paired-samples t-test, independent-samples t-test, Wilcoxon, and Mann-Whitney U test.ResultsThis study showed that garlic tablets had decreased PCO plasma levels (47.37±5.98 vs. 19.62±3.40 nM, p≤0.001, before and after the study, respectively), AOPPs (738.95±151.86 vs. 585.12±209.99 μM, p≤0.008, before and after the study, respectively), and increased TAC (11.34±10.80 vs. 47.93±17.80, p≤0.001, before and after the study, respectively). The parameters in placebo groups showed no significant differences before and after the study, respectively. The levels of MDA before taking the drug in comparison to before Garlic group was also reduced (1.30±1.04 vs. 0.92±0.81 μM, p=0.01, before and after the study, respectively).ConclusionThe role of oxidative stress in the pathophysiology of many diseases such as osteoporosis has been demonstrated. The present study showed that garlic consumption can reduce the oxidative stress.Trial registrationThe protocol of trial was registered at the Iranian clinical trial register (www.irct.ir) with ID: IRCT138811183273N1.FundingThis study funded by Shahid Sadoughi University of Medical Sciences (Yazd, Iran).

Circulating osteoprotegerin in postmenopausal osteoporotic women: marker of impaired glucose regulation or impaired bone metabolism.

Osteoprotegerin (OPG) is closely related to insulin resistance and bone remodeling. However, no studies have examined the role of OPG in postmenopausal women with coexistent impaired glucose and bone regulation. The present study investigated the relationship of OPG to glucose homeostasis and insulin resistance in postmenopausal osteoporotic women with different types of glucose tolerance. In all, 114 postmenopausal osteoporotic women were divided into three groups according to glucose tolerance status: 51 with normal glucose tolerance (NGT, group 1), 31 with impaired glucose tolerance (IGT, group 2), and 32 with type 2 diabetes mellitus (DM, group 3). Study participants were evaluated for metabolic parameters, OPG, Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), and bone mineral density parameters. The OPG levels differed significantly across groups and increased from group 1 to group 3 in a continuous fashion (analysis of variance, P < 0.0001). In post-hoc analysis, OPG was significantly lower in osteoporotic women with NGT, than participants with IGT and DM (P < 0.05 and P < 0.0001, respectively). OPG was positively associated with HOMA-IR (P < 0.0001). No association between serum OPG levels and measures of BMD was observed. In a multiple regression analysis, OPG emerged as an independent predictor of HOMA-IR even after controlling for age, body mass index, and creatinine. OPG is significantly higher in postmenopausal osteoporotic women with impaired glucose regulation (IGT and DM) than women with NGT. OPG was independently associated with insulin resistance assessed by HOMA-IR. Thus, measurement of OPG may potentially be considered as a prediabetic state screening in postmenopausal osteoporotic women.

RELATIONSHIP BETWEEN SERUM OC AND SCTX WITH BONE MINERAL DENSITY IN PREDICTING BONE LOSS AND TREATING FOR POSTMENOPAUSAL OSTEOPOROSIS WOMEN OVER 45 YEARS OLD WITH FOSAMAX PLUS THERAPY

Backgrounds: Serum OC and ssCTX are correlated with BMD and have early changes under antiresorptive therapies. This study was aimed to find correlations between serum OC, sCTX and BMD changes in women over 45 and evaluated early changes of the two markers in postmenopausal osteoporotic women with Fosamax plus therapy. Materials and Methods: Cross-sectional and prospective study. 142 women over 45 were tested for serum OC and sCTX and determined BMD at lumbar spine and femur neck. 37 postmenopausal osteoporotic women of the group were treated with Fosamax plus therapy. Results: OC and sCTX showed negative correlation with BMD of lumbar spine and femur neck in all of women over 45. The correlation between sCTX and BMD of femur neck was not significant. The lowest values of OC and sCTX to predict bone loss in non-osteoporotic women were 14.46ng/ml (ss = 76.1%, sp = 40%) and 396.25pg/ml (ss = 66%, sp = 52%). The decreasing rates of serum OC and sCTX after 3 and 6 months with Fosamax plus therapy were 41.6%, 55% (p ˂ 0.0001) and 78.3%, 72% (p ˂ 0.0001), respectively. Slow increasing rates of BMD at two sites were 4.2% (p ˂ 0.001) and 3.6% (p ˃ 0.05), irrespectively. Conclusions: OC and sCTX were inversely correlated to BMD of lumbar spine and femur neck in all of women over 45. The lowest values of OC and sCTX to predict bone loss in non-osteoporotic women were 14.46ng/ml and 396.25pg/ml. Serum OC và sCTX decreased early in comparision to BMD improvement in postmenopausal osteoporotic women with Fosamax plus therapy. Key words: oC, sCTX, postmenopausal osteoporotic women, Fosamax plus

Association of Vitamin D Receptor (FokI and BsmI) Gene Polymorphism with Bone Mineral Density and Their Effect on 25-Hydroxyvitamin D Level in North Indian Postmenopausal Women with Osteoporosis.

Osteoporosis is a systemic disease with a strong genetic component. Vitamin D receptor (VDR) has been suggested as a candidate gene for osteoporosis. Therefore the present study was aimed to investigate the pattern of allelic variants of VDR gene polymorphism (FokI and BsmI), its influence on vitamin D levels and bone mineral density (BMD) in North Indian postmenopausal women with osteoporosis for possible genetic association. 254 postmenopausal osteoporotic women and 254 postmenopausal non osteoporotic women were included in the study. VDR FokI and BsmI gene polymorphism gene were assessed by the PCR-RFLP method. Serum 25-hydroxyvitamin D was measured by the ELISA. BMD at the L1-L4 lumbar spine, hip, forearm and femoral neck was assessed by dual energy X-ray absorptiometry. The average BMD at spine and hip in postmenopausal women with bb and spine, hip, femoral neck and forearm with ff genotype had significantly low BMD. The frequency of ff genotype and f allele was significantly higher in postmenopausal osteoporotic women when compared with postmenopausal non osteoporotic women. However, no significant association was found between the genotypes and vitamin D levels. Our study reveals that VDR gene FokI and BsmI polymorphism is significantly associated with low bone mineral density. Therefore the ff genotype and f allele of VDR FokI gene may be used as an important risk factor for osteoporosis.

Sclerostin Antibody Reverses Bone Loss by Increasing Bone Formation and Decreasing Bone Resorption in a Rat Model of Male Osteoporosis.

Sclerostin antibody (Scl-Ab) restored bone mass and strength in the ovariectomized rat model of postmenopausal osteoporosis. Increased bone mineral density (BMD) and decreased skeletal fragility fracture risk have been reported in postmenopausal osteoporotic women receiving Scl-Ab. In males, loss of androgen leads to rapid decreases in BMD and an increased risk of fragility fractures. We hypothesized that Scl-Ab could reverse the loss of bone mass and strength caused by androgen ablation in the orchiectomized (ORX) rat model of male osteoporosis. We treated 9-month-old ORX Sprague Dawley rats (3 months after ORX) subcutaneously twice weekly with vehicle or Scl-Ab (5 or 25 mg/kg) for 6 weeks (n = 10 per group). Both doses of Scl-Ab fully reversed the BMD deficit in the lumbar spine and femur and tibia in ORX rats. Microcomputed tomography showed that the bone mass in the fifth lumbar vertebral body, femur diaphysis, and femoral neck were dose-dependently restored by Scl-Ab. The bone strength at these sites increased significantly with Scl-Ab to levels matching those of sham-operated controls and correlated positively with improvements in bone mineral content, demonstrating bone quality maintenance. Dynamic histomorphometry of the tibial diaphysis and second lumbar vertebral body demonstrated that Scl-Ab significantly increased bone formation on periosteal, endocortical, and trabecular surfaces and significantly decreased bone resorption on endocortical and trabecular surfaces. The effects of Scl-Ab on increasing bone formation and decreasing bone resorption led to restoration of bone mass and strength in androgen-deficient rats. These findings support the ongoing evaluation of Scl-Ab as a potential therapeutic agent for osteoporosis in men.