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BACKGROUND: Postmenopausal osteoporosis (PMO) is a major cause of fragility fractures worldwide. While exercise and calcium/vitamin D are standard preventive measures, the synergistic effects of their combined use on bone mineral density (BMD) remain unclear. METHODS: We systematically searched eight databases through October 2025 and synthesized data using Review Manager version 5.4. Subgroup, sensitivity, and meta-regression analyses were conducted to examine heterogeneity and test the robustness of results. Risk of bias was assessed using the Cochrane RoB 2.0 tool, and the certainty of evidence was graded with the GRADE framework. RESULTS: 13 RCTs involving postmenopausal women were included. Compared with calcium and vitamin D supplementation alone, combined interventions significantly increased lumbar spine (SMD = 0.31, 95% CI [0.06, 0.55]) and femoral neck BMD (SMD = 0.47, 95% CI [0.09, 0.84]), with consistent but nonsignificant trends at other skeletal sites. Subgroup analyses showed that whole-body vibration produced the greatest and most consistent benefits at both sites, while mind-body or traditional Chinese exercises (e.g., Baduanjin) significantly improved lumbar spine BMD. Shorter interventions (≤6 months) yielded greater gains in BMD, whereas longer durations provided no additional advantage. CONCLUSIONS: Exercise combined with calcium and vitamin D supplementation effectively improves bone mineral density in postmenopausal women, especially at the lumbar spine and femoral neck. Whole-body vibration and mind-body exercises show the greatest benefits, with short-term interventions proving most effective. This combined approach offers a practical, evidence-based strategy to preserve skeletal health in aging women.

BACKGROUND: Diminished estrogen levels in women after menopause contribute to an elevated risk of decreased bone mineral density (BMD) and disturbed bone metabolism. Dietary supplements are extensively employed as substitutes for prescription drugs, serving as a significant approach to modulate bone metabolism and improve bone health. Nevertheless, a lack of robust evidence prevents clinicians and patients from making the best-informed choices at present. Accordingly, a network meta-analysis (NMA) was performed to provide a comprehensive comparison of the effects of different dietary supplements on bone turnover biomarkers among postmenopausal women. METHODS: PubMed, Embase, Cochrane Library, and Web of Science databases were retrieved from their inception to November 20, 2024. Randomized controlled trials (RCTs) assessing the strength of dietary supplements in women after menopause were adopted in this research. Primary outcome indicators encompassed C-terminal telopeptide of type I collagen (CTX), procollagen type I N-terminal propeptide (P1NP), osteocalcin (OC), bone alkaline phosphatase (BAP), alkaline phosphatase (ALP), and N-terminal telopeptide of type I collagen (NTX). Risk of bias assessment was performed for each enrolled trial utilizing the ROB 2.0. A Bayesian NMA was conducted utilizing the R software (V4.4.1). Publication bias was assessed utilizing Stata 15.1. RESULTS: Forty-three RCTs involving 5,184 postmenopausal women were adopted. Research findings revealed that CTX levels decreased most substantially with vitamin E supplementation (SUCRA: 82.37%). Combining vitamin D and vitamin K most effectively elevated P1NP (SUCRA: 100.00%) and OC (SUCRA: 97.05%) levels. The greatest increase in BAP levels (SUCRA: 95.50%) was observed with vitamin K supplementation. Calcium supplementation yielded the largest elevation in ALP levels (SUCRA: 96.68%). Furthermore, protein supplementation resulted in the most significant reduction in NTX levels (SUCRA: 81.20%). CONCLUSION: Dietary supplementation may serve as an important strategy for enhancing bone health in women after menopause by regulating bone metabolism. By promoting bone formation and inhibiting bone

OBJECTIVE: To evaluate the optimal choice of traditional Chinese exercise (TCE) for improving bone mineral density in postmenopausal women through a network meta-analysis. METHODS: The Chinese and English databases were searched, including China National Knowledge Infrastructure, Chongqing VIP, PubMed, Web of Science and Cochrane Library. The outcomes included BMD of lumbar L2-L4, femoral neck, ward triangle, and greater trochanter. Standardized mean differences (SMD) and 95% confidence intervals (CI) were used to assess the correlation between each group of interventions, and surface under the cumulative ranking (SUCRA) was used to rank the best interventions. RESULTS: A total of 20 randomized controlled trials (RCTs) including 1933 subjects and six interventions: [Tai Chi (TC), Baduanjin (BDJ), Wuqinxi (WQX), Yijinjing (YJJ), TA (Tai chi plus calcium supplementation), BA (Baduanjin plus calcium supplementation)] and three control measures: [Calcium supplementation (CA), Aerobic exercise (AE), Not exercise intervention (NEI)] were analyzed. Regarding BMD of lumbar L2-L4: TC [SMD = 0.99 (0.62, 1.37)], BDJ [SMD = 2.12 (1.39, 2.85)], TA [SMD = 1.12(0.17, 2.07)], BA [SMD = 2.24 (1.16, 3.31)] were superior in increasing BMD of lumbar L2-L4 relative to NEI. Regarding BMD of femoral neck: TC [SMD = 1.24 (0.70, 1.78)], BA [SMD = 3.77 (1.98, 5.56)] were superior in increasing BMD of femoral neck relative to NEI. Regarding BMD of ward's triangle: TC [SMD = 1.63 (1.09, 2.17)] was superior in increasing BMD of ward's triangle relative to NEI. Regarding BMD of greater trochanter: TC [SMD = 0.98 (0.28, 1.68)] were superior in increasing BMD of greater trochanter relative to NEI. TC topped the SUCRA with BMD of lumbar L2-L4: 53.8, femoral neck: 74.9, ward's triangle: 86.9 and greater trochanter: 77.7. CONCLUSION: Four TCE (TC, BDJ, TA and BA) are all effective in partially improving BMD indicators in postmenopausal women, while TC was effective on all four BMD indicators, which seems to be recommended as the most suitable exercise modality for postmenopausal women. SYSTEMATIC REVIEW REGISTRATION: This research follows the PRISMA Network statement. The protocol for this study

INTRODUCTION: Hip fractures have a huge impact in reducing the quality of life and increasing mortality. This review aims to assess the impact of daily oral supplementation of vitamin D3 plus calcium on the incidence of hip fracture in people over 65 years. METHODS: PRISMA guidelines were followed and RCTs that evaluated the effectiveness of daily oral supplementation of vitamin D3 plus calcium in preventing hip fracture in adults over 65 years were included in the study. The databases such as Cochrane Library, Embase, Medline, PubMed, CINAHL, Web of Science and Scopus were searched from October 2019- January 2020.The Cochrane risk of bias tool was used to check the quality of the included studies. A meta-analysis with fixed effect model using Review Manager (Revman 5.3) was used to analyse the data. RESULTS: The meta-analysis of seven RCTs on vitamin D3 plus calcium supplementation and hip fracture (n = 12,620) identified odds ratio (OR) of 0.75; 95% Confidence interval (CI): 0.64, 0.87; p = .0003. Daily oral supplementation of 800 IU of Vitamin D3 plus 1200 mg of calcium was found more effective (n = 5676 participants; OR = 0.69; 95% CI: 0.58, 0.82; p < .0001) than daily oral supplementation of 800 IU of Vitamin D3 plus 1000 mg of calcium (n = 6555,OR = 1.08; 95% CI: 0.74, 1.56; p = .70) in reducing hip fracture. A meta-analysis of the seven RCTs to identify the incidence of non-vertebral fracture gave the OR of 0.80; 95% CI: 0.72, 0.89; p < .0001. A meta-analysis of three RCTs on femoral neck bone mineral density (BMD) (n = 483) gave a mean difference of 1.21; 95% CI: -0.79, 3.20; p = .24. CONCLUSION: Daily oral supplementation 800 IU of vitamin D3 plus 1200 mg of calcium reduces hip fracture and non-vertebral fracture in older people. Administering vitamin D3 and calcium supplements had no effect in increasing the femoral neck BMD. IMPLICATIONS FOR PRACTICE: Even though it is evident from the review that optimal daily intake of vitamin D3 plus calcium supplementation help in the prevention of fracture, it is only one essential element in fracture prevention. Also, people who are on dietary supplements should be compliant with same for better result. Efforts

INTRODUCTION: In postmenopausal women, vitamin D deficiency (as defined by the circulating level of 25(OH)D being below 20 ng/ml (50 nmol/L)) is a regular occurrence. The effect of vitamin D supplementation on the muscle function of postmenopausal women has been controversial. This systematic review and meta-analysis of randomized controlled trials (RCTs) examines and summarizes the effects of vitamin D supplementation on the muscular strength and mobility of postmenopausal women. METHODS: RCTs that met the inclusion criteria for this study were identified by searching PubMed, EMBASE, and the Cochrane Library. Postmenopausal women who were included in the study were exposed to RCTs assessing the effectiveness of vitamin D supplements. Meta-analysis data were extracted by two independent reviewers and screened for methodological quality. RCTs that did not meet the minimum requirement for assessment were excluded. In the meta-analysis, the effect size (weighted mean differences, WMD) of handgrip strength (HGS) and timed-up and go test (TUG) with a 95% confidence interval (CI) was obtained to compare reported results across the included RCTs. RESULTS: A total of 19 trials were included in this systematic review, among which 13 trials were eligible for the meta-analysis. In the 13 included studies, supplementing with vitamin D produced a weighted mean difference of 0.876 kg (95% CI = 0.180 to 1.571, P = 0.014, I2 = 68.5%) for HGS, a measurement of muscle strength. However, an insignificant decrease of 0.044 s was observed after analyzing the TUG (95% CI = -0.979 to 0.892, P = 0.927, I2 = 95%). According to subgroup analysis, vitamin D supplementation increased HGS in patients over the age of 60 (P = 0.001), in those without calcium supplementation (P = 0.032), and in those whose baseline vitamin D level was greater than 75 nmol/L (30 ng/ml) (P = 0.003). CONCLUSIONS: Taking into account the studies in this systematic review, vitamin D supplementation improved muscle strength in postmenopausal women. However, an insignificant result was demonstrated in terms of mobility after vitamin D supplementation.

The aim of this systematic review and meta-analysis was to evaluate the effectiveness of different hormone therapies, including hormonal contraceptives, in women with premature ovarian insufficiency (POI). Thirty reports of 28 studies were included, with a total of 4004 participants with POI from diverse aetiologies, of whom 3785 received hormone therapies and 219 received calcium supplementation, vitamin D, placebo or no treatment. Hormone therapy was superior to non-treatment, placebo, calcitriol or calcium in preserving bone mineral density (BMD) in women with POI. Hormone therapy was associated with up to 80% reduction in the prevalence of hot flushes and with stability or improvement in the quality of life scores. Hormone therapy induced significant increases in uterine volume and endometrial thickness in women with POI. The studies yielded convergent results and were of good quality, although some lacked blinding or had incomplete outcome data. Moderate to high quality evidence was found that hormone therapy with oestrogen and progesterone or progestin (including contraceptives) is beneficial to women with POI, not only to mitigate hypoestrogenic symptoms but also to preserve BMD and avoid uterine atrophy. More studies are needed to confirm the long-term safety of this therapy and to assess its possible impact on the risk of hard outcomes such as bone fractures and cardiovascular events.

OBJECTIVE: The aim of the present study was to explore whether combined calcium and vitamin D supplementation is beneficial for osteoporosis in postmenopausal women. METHODS: We searched the PubMed, Cochrane library, Web of science and Embase databases and reference lists of eligible articles up to Feb, 2020. Randomized controlled trials (RCTs) evaluating the effect of combined calcium and vitamin D on osteoporosis in postmenopausal women were included in the present study. RESULTS: Combined calcium and vitamin D significantly increased total bone mineral density (BMD) (standard mean differences (SMD) = 0.537; 95% confidence interval (CI): 0.227 to 0.847), lumbar spine BMD (SMD = 0.233; 95% CI: 0.073 to 0.392; P < 0.001), arms BMD (SMD = 0.464; 95% CI: 0.186 to 0.741) and femoral neck BMD (SMD = 0.187; 95% CI: 0.010 to 0.364). It also significantly reduced the incidence of hip fracture (RR = 0.864; 95% CI: 0.763 to 0.979). Subgroup analysis showed that combined calcium and vitamin D significantly increased femoral neck BMD only when the dose of the vitamin D intake was no more than 400 IU d-1 (SMD = 0.335; 95% CI: 0.113 to 0.558), but not for a dose more than 400 IU d-1 (SMD = -0.098; 95% CI: -0.109 to 0.305), and calcium had no effect on the femoral neck BMD. Subgroup analysis also showed only dairy products fortified with calcium and vitamin D had a significant influence on total BMD (SMD = 0.784; 95% CI: 0.322 to 1.247) and lumbar spine BMD (SMD = 0.320; 95% CI: 0.146 to 0.494), but not for combined calcium and vitamin D supplement. CONCLUSION: Dairy products fortified with calcium and vitamin D have a favorable effect on bone mineral density. Combined calcium and vitamin D supplementation could prevent osteoporosis hip fracture in postmenopausal women.

BACKGROUND: The results obtained from previous trials regarding the effects of vitamin D supplementation on muscle strength and mobility in postmenopausal women have been inconsistent. This systematic review and meta-analysis of randomised controlled trials (RCTs) aimed to investigate the effect of vitamin D supplementation on muscle strength and mobility in postmenopausal women. METHODS: A comprehensive search on EMBASE, PubMed, MEDLINE and SCOPUS was performed to identify relevant articles published up to 28 March 2019. RCTs published in English measuring the effect of all forms and doses of vitamin D supplementation with or without calcium on muscle strength and mobility outcomes in postmenopausal women were included. RESULTS: In total, 29 eligible studies were included in the systematic review. The pooled findings using a random effects model showed that vitamin D supplementation insignificantly increased hand grip strength (HGS) as the measurement of muscle strength (MD = 0.656; 95% confidence interval = -0.037 to 1.350, P = 0.06). However, it did not affect timed-up-and-go (TUG) as the measurement of mobility (MD = 0.118; 95% confidence interval = -0.655 to 0.892, P = 0.76). The subgroup analyses showed that vitamin D supplementation improved HGS with respect to dosages >1000 IU day-1 (P = 0.016), a treatment duration of 3 months (P ˂ 0.001) and subjects with baseline vitamin D <30 ng mL-1 (P = 0.033). CONCLUSIONS: The present review demonstrates that vitamin D supplementation resulted in small but nonsignificant improvements in muscle strength compared to control in postmenopausal women. No significant effect was observed in mobility after vitamin D administration. © 2019 The British Dietetic Association Ltd.

Tai chi exercise may have positive effects on bone health in perimenopausal and postmenopausal women. This systematic review is the first to summarize evidence to clarify the efficacy of tai chi exercise in bone health. The benefits of tai chi exercise on bone health remain unclear; further studies are needed. Emerging randomized controlled trials (RCTs) exploring the efficacy of tai chi exercise on bone health among older women, but yielded inconclusive results. Our objective is to conduct a systematic review to evaluate evidence from RCTs to clarify the efficacy of tai chi exercise on bone mineral density (BMD), and bone turnover markers (BTM) in perimenopausal and postmenopausal women. Six electronic databases were searched, and reference lists of systematic reviews and identified studies from the search strategy were also screened. We included all RCTs that investigate tai chi exercise for bone health in perimenopausal and postmenopausal women. Data selection, extraction, and evaluation of risk of bias were performed independently by two reviewers. Ten trials detailed in 11 articles were included. Six of the 11 studies reported positive outcomes on bone health. Results of our meta-analysis showed a significant effect of tai chi exercise on BMD change at the spine compared with no treatment in perimenopausal and postmenopausal women. When tai chi exercise combined with a calcium supplement was compared with the calcium supplement alone, the result of BMD change at the spine showed no significant effect. Because the measurable effect observed was minimal, and due to the low quality of methodology of the studies, we conclude that the result is of limited reliability. Tai chi exercise may have benefits on bone health in perimenopausal and postmenopausal women, but the evidence is sometimes weak, poor, and inconsistent. Consequently, only limited conclusions can be drawn regarding the efficacy of tai chi exercise on bone health. Further well designed studies with low risk of bias are needed.

BACKGROUND: Osteoporosis is a systemic skeletal disease characterized by low bone mass and micro-architectural deterioration of bone tissue with a consequent increase in bone fragility and susceptibility to fracture. Osteoporosis represents an important cause of morbidity in people with beta-thalassaemia and its pathogenesis is multifactorial. Factors include bone marrow expansion due to ineffective erythropoiesis, resulting in reduced trabecular bone tissue with cortical thinning; endocrine dysfunction secondary to excessive iron loading, leading to increased bone turnover; and lastly, a predisposition to physical inactivity due to disease complications with a subsequent reduction in optimal bone mineralization.A number of therapeutic strategies have been applied to treat osteoporosis in people with beta-thalassaemia, which include bisphosphonates, with or without, hormone replacement therapy. There are various forms of bisphosphonates, such as clodronate, pamidronate, alendronate and zoledronic acid. Other treatments include calcitonin, calcium, zinc supplementation, hydroxyurea and hormone replacement therapy for preventing hypogonadism. OBJECTIVES: To review the evidence on the efficacy and safety of treatment for osteoporosis in people with beta-thalassaemia. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Date of most recent search: 04 February 2016. SELECTION CRITERIA: Randomised, placebo-controlled trials in people with thalassaemia with a bone mineral density z score of less than -2 standard deviations for: children less than 15 years old; adult males (15 to 50 years old); and all pre-menopausal females above 15 years and a bone mineral density t score of less than -2.5 standard deviations for post-menopausal females and males above 50 years old. DATA COLLECTION AND ANALYSIS: Two review authors assessed the eligibility and risk of bias of the included trials, extracted and analysed data and completed the review. We sum

BACKGROUND/OBJECTIVES: Adequate calcium and vitamin D intake, along with regular physical activity, is essential for maintaining skeletal health in postmenopausal women. In populations with low dairy consumption, sustainable and bioavailable calcium sources are required to support bone integrity. Eggshell powder offers a highly bioavailable, eco-friendly, and cost-effective calcium source consistent with environmental sustainability goals. This pilot randomized, double-blind, controlled trial investigated the effects of calcium- and vitamin D-fortified home meal replacements (HMRs) made with eggshell powder, combined with weight-bearing aerobic exercise, on bone mineral density (BMD) and bone turnover markers in postmenopausal women. METHODS: Thirty-six women aged 50-59 years were randomly assigned (1:2 ratio) to a control group (regular HMR) or an intervention group (HMR fortified with 418 mg eggshell-derived calcium and 837 IU vitamin D). Participants consumed one HMR daily, five days per week, and were encouraged to engage in weight-bearing aerobic exercise for 30-60 min, five times weekly, over six months. RESULTS: High adherence was observed for both dietary (94%) and exercise regimens. No significant differences were found between groups in overall BMD or bone metabolic markers after six months. Exploratory post hoc subgroup analysis suggested possible exercise-nutrition interactions in lumbar spine BMD. CONCLUSIONS: No significant overall BMD effect was found. Fortified HMRs achieved excellent adherence and corrected nutrient deficiencies, demonstrating feasibility. Future large-scale trials with adequate power based on realistic effect sizes are warranted to evaluate reproducibility of these exploratory findings.

OBJECTIVE: To determine associations between central adiposity, cognitive function, and randomized menopausal hormone therapy (MHT) in a reanalysis of the Kronos Early Estrogen Prevention Study-Cognitive and Affective (KEEPS-Cog) sub-study participants. METHODS: KEEPS randomized 727 women (ages 42-58) who were <36 months postnatural menopause to oral conjugated equine estrogens (o-CEE), transdermal 17-β-estradiol (t-E2), or placebo for 48 months. Participants with diabetes, body mass index >35 kg/m 2 , coronary artery calcium score >50 Agatston Units, and other cardiometabolic disease risk indicators were excluded from enrollment. In the ancillary KEEPS-Cog study, cognitive tests were completed at baseline, 18-, 36-, and 48-month post-randomization. In these analyses, cognitive variables were summarized as four cognitive domain-specific factor scores: verbal learning and memory, auditory attention and working memory, visual attention and executive function, and speeded language and mental flexibility. Waist-hip-ratio (WHR), an indicator of central adiposity, was measured at screening (baseline) and modeled as a covariate in linear latent growth models assessing associations of MHT with cognitive functions at baseline and over time. RESULTS: Higher baseline WHR was associated with poorer performance on all domain-specific cognitive outcomes at baseline and with changes in visual attention and executive function across time. Models including interaction effects were not significant for either o-CEE x WHR or t-E2 x WHR. CONCLUSION: Central adiposity is a risk factor for domain-specific cognitive decline, and thus, cognitive health effects should be investigated in early postmenopausal women, even in women with low cardiovascular risk statuses.

Background/Objectives: Post-menopausal women are at an increased risk of developing cardiovascular disease. Menaquinone-7 (MK-7) is a fat-soluble vitamin involved in coagulation and maintaining vascular health. The aim of the post hoc analysis of this one-year study is to investigate the effects of MK-7 supplementation on the vascular parameters in pre-, peri-, and post-menopausal women. Methods: In a clinical intervention trial (NCT02404519), a total of 165 women with a low vitamin K status received either 180 µg of MK-7 daily (n = 82) or a matching placebo (n = 83) for one year. Established vascular parameters were measured before and after one year of vitamin K2 supplementation. Pre-, peri-, and post-menopausal women were subdivided according to arterial stiffness, with a high b-stiffness index defined as being greater than the overall median of 9.83. Results: The post hoc analyses showed a significant decrease in desphospho-uncarboxylated matrix Gla protein (dp-ucMGP) plasma levels after MK-7 supplementation (pre/peri, p = 0.009; post, p < 0.001). MK-7 treatment significantly attenuated vascular stiffness in post-menopausal women (placebo +49.1% ± 77.4; MK-7 +9.4% ± 67.1; p = 0.035). Post-menopausal women with a high stiffness index showed significantly improved vascular markers after MK-7 treatment, e.g., a decreased blood pressure at brachialis (-3.0% ± 9.0; p = 0.007) and an increased distensibility coefficient (+13.3% ± 32.3; p = 0.040). Conclusions: Our results confirm that menopause affects vascular health status. Post-menopausal women with an increased stiffness benefit most from MK-7 supplementation, with a significantly improved blood pressure. Further research is needed to unravel the beneficial effects of MK-7 in post-menopausal women.

BACKGROUND/OBJECTIVES: Facial bone density, including the jawbone, declines earlier than that of the lumbar spine and calcaneus. Calcium maltobionate is reported to mitigate bone resorption and maintain bone density of the lumbar spine in post-menopausal women, but its effects on facial bone density remain understudied. Therefore, this study compared variations in facial bone mineral density with variations in calcaneal bone mineral density and bone resorption markers among healthy women, examining differences between pre- and post-menopause and the effects of continuous calcium maltobionate intake. METHODS: This randomized, double-blind, placebo-controlled, parallel-group trial involved 48 healthy Japanese women aged 30-69 years, divided into two groups. The test food group received tablets containing calcium maltobionate, while the placebo group received tablets containing a maltose and calcium carbonate mixture for 24 weeks. Calcaneal and facial bone densities were measured pre- and post-intervention in both groups. RESULTS: Post-intervention calcaneal bone mineral density and bone resorption marker deoxypyridinoline (DPD) showed no statistical difference between groups in pre-menopausal women. However, in post-menopausal women, the test food group exhibited significantly higher calcaneal bone density and lower DPD levels compared with the placebo group. Facial bone mineral density increased significantly in the test food group compared with the placebo group in post-menopausal participants, with similar trends observed in pre-menopausal participants. CONCLUSIONS: Facial bone mineral density could serve as a useful indicator for monitoring bone health from middle age onward. Moreover, continuous calcium maltobionate intake appears to mitigate bone density decline in pre- and post-menopausal women, contributing to osteoporosis prevention (UMIN-CTR ID: 000046391).

Vitamin D status has long been related to falls risk. In this planned secondary analysis of a vitamin supplementation trial in postmenopausal women, standardized 25-hydroxyvitamin D concentration up to 60 ng/mL was not associated with increased falls. Women with 25(OH)D ≥ 60 ng/mL had higher odds of ≥ 2 falls. PURPOSE: Falls are common and cause fractures. High circulating 25(OH)D may increase falls risk; thus, recent guidance recommends 25(OH)D not exceed 50 ng/mL. Prior falls studies have not reported standardized 25(OH)D (s25D) data. The purpose of this planned secondary analysis of a 4-year calcium/vitamin D supplementation trial was to evaluate the association of s25D with falls. METHODS: This study recruited 2,303 postmenopausal women. The analytic dataset consisted of pooled concatenated data from years 2-4 (NTotal = 5,732). Serum 25(OH)D was measured annually and subsequently retrospectively standardized using Vitamin D Standardization Program methods. Falls were recorded by diary. Incidence for ≥ 1 fall and ≥ 2 falls was assessed by s25D group (≤ 20, 20- < 30, 30- < 40, 40- < 50, 50- < 60 and ≥ 60 ng/mL) using multivariable logistic regression. RESULTS: Mean (SD) baseline s25D was 32.6 ng/mL (8.3) with no difference between supplement and placebo groups. s25D increased to 41.3 ng/mL at year 2 in the supplement group then remained stable. By s25D group, incidence for ≥ 1 fall varied from 22-32% (p = 0.19). For ≥ 2 falls incidence varied (p = 0.03) from 6% (< 20 ng/mL) to 17% (≥ 60 ng/mL.) There was no significant association between s25D and ≥ 1 fall. Those with s25D ≥ 60 ng/mL had a higher adjusted odds of ≥ 2 falls (OR = 1.99 ± 1.2-3.3) compared to women with s25D of 30- < 40 ng/mL. CONCLUSION: s25D up to 60 ng/mL was not associated with greater risk for ≥ 1 or ≥ 2 falls. Women with a s25D ≥ 60 ng/mL were at higher odds for ≥ 2 falls, however this group included only ~ 2% of study observations; therefore, confirmation in other cohorts is necessary. © 2024. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.

High dose bolus cholecalciferol supplementation has been associated with falls and fracture, and this does not appear to be due to hypercalcaemia. The primary aim of this study was to determine the change in free vitamin D and metabolites after high dose bolus supplementation. This was a single centre, double-blinded, randomised, controlled trial of three different oral bolus doses of vitamin D3 (50,000 IU, 150,000 IU, and 500,000 IU) in otherwise healthy, vitamin D deficient (total 25-hydroxylated vitamin 25(OH)D < 30 nmol/L) postmenopausal women. Thirty-three women were randomized to one of the three treatment groups. Twenty-seven vitamin D sufficient (25(OH)D > 50 nmol/L) postmenopausal women were recruited as a concurrent control group. Participants attended five study visits over three months. We measured total 25(OH)D3 and free 25(OH)D, total and free 1,25(OH)2D, parathyroid hormone, fibroblast-growth factor-23, serum calcium, ionised calcium, urinary calcium excretion, and bone turnover markers (procollagen I N-propeptide (PINP), serum C-telopeptides of type I collagen (CTX-I) and Osteocalcin (OC)). We assessed muscle strength and function with grip strength and a short physical performance battery. Postural blood pressure and aldosterone:renin ratio (ARR) was also measured. Total 25(OH)D3 and free 25(OH)D increased in response to dose, and there were proportionate increases in total and free metabolites. Treatment did not affect serum calcium, postural blood pressure, ARR, or physical function. Bone turnover markers increased transiently one week after administration of 500,000 IU. High dose bolus cholecalciferol supplementation does not cause disproportionate increases in free vitamin D or metabolites. We did not identify any effect on blood pressure regulation or physical function that would explain increased falls after high dose treatment. A transient increase in bone turnover markers one week after a 500,000 IU bolus suggests that very high doses can have acute effects on bone metabolism, but the clinical significance of this transient increase is uncertain.

Background Perimenopause is associated with a decline in estrogen levels, leading to decreased bone mineral density (BMD) and altered bone metabolism, increasing the risk of osteoporosis. Tai Chi Rouli Ball, a traditional Chinese sport, is thought to have beneficial effects on physical health, but its impact on bone health in perimenopausal women is not well understood. Methods This study involved a randomized controlled trial with 52 perimenopausal women aged 45-55 years from community senior centers. Participants were divided into two groups: the Tai Chi Rouli Ball group and the control group. Baseline assessments of bone density, bone mineral content (BMC), and bone metabolism markers, including estrogen levels, were conducted. The Tai Chi Rouli Ball group underwent regular training for a specific period, while the control group did not receive any intervention. Post-experiment assessments were then compared to the baseline. Results Post-intervention, the Tai Chi Rouli Ball group showed a significant increase in spine bone density and BMC in various body parts, including the whole body, trunk/torso, and spine, compared to the control group. Bone metabolism indicators also improved, with increased levels of estrogen and a decrease in follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Calcium levels showed a significant increase, while other markers like alkaline phosphatase (ALP), phosphorus (P), and magnesium (Mg) had non-significant changes. Conclusions Tai Chi Rouli Ball exercise may positively influence bone health by improving bone density, BMC, and altering bone metabolism markers in perimenopausal women. These findings suggest that Tai Chi Rouli Ball could be a viable non-pharmacological approach to prevent osteoporosis in this demographic.

BACKGROUND: Statins are the first-line treatment for dyslipidemia, which is a major modifiable risk factor for atherosclerotic cardiovascular disease. Studies have shown that in addition to the beneficial lipid-lowering effect, statins also exhibit a number of pleiotropic effects that may find application in other diseases, including osteoporosis. This study aimed to assess the effect of statins on bone turnover, as measured by the concentration of bone turnover markers, and to compare the effect of atorvastatin as a lipophilic statin and rosuvastatin as a hydrophilic statin. METHODS: This study included 34 postmenopausal women aged < 65 years with newly diagnosed dyslipidemia requiring statin therapy. Patients were randomly assigned to receive a statin drug. Statins were initiated at standard doses of 5 to 10 mg of rosuvastatin and 20 mg of atorvastatin. The levels of C-terminal telopeptide of type I collagen as a bone resorption marker and N-terminal propeptide of procollagen type I as a marker of bone formation, lipid concentrations and other biochemical parameters were assessed at baseline and after 6 and twelve months of treatment. RESULTS: There were no statistically significant differences between the levels of bone turnover markers before and 6 months after statin implementation (P > .05) - for all patients or subgroups according to statin use. Analysis of the results showed that after 12 months, there was a statistically significant decrease in N-terminal propeptide of procollagen type I concentration in all subjects (P = .004). By statin subgroup, a statistically significant decrease in N-terminal propeptide of procollagen type I was observed only in patients receiving rosuvastatin (P = .012) and not in those receiving atorvastatin (P = .25). Moreover, changes in bone turnover markers did not correlate with changes in lipid concentrations. CONCLUSIONS: These results may indicate the superiority of atorvastatin over rosuvastatin in inhibiting adverse changes in bone turnover in postmenopausal women. Confirmed by studies involving a larger population, the observed differences might find particular applications in clinical practice, and the choice of ator

Calcium and vitamin D deficiencies have been ongoing problems in Koreans due to a lack of food sources of calcium and vitamin D. Postmenopausal women aged 50 to 64 years (n = 25) were randomly assigned to consume three home meal replacements (HMRs)/week with (treatment) and without (control) eggshell powder and vitamin D for 6 months. Additionally, subjects who agreed to continue the study consumed the same three HMRs/week for an additional 6 months in this randomized double-blind study. We confirmed the high compliance of the study participants by analyzing carotenoids, the bioactive substances of HMRs, in the blood. The treatment group consumed an additional 261 mg/d of calcium and 10.3 μg/d of vitamin D from the HMRs, thus meeting the recommended intakes of calcium and vitamin D for Koreans. As a result of consuming fortified HMRs for 6 months, the decline in femoral neck bone density was significantly reduced in the treatment group (p = 0.035). This study indicates that inexpensive eggshell powder may be a good source of calcium for populations with low consumption of milk and dairy products. Additionally, functional HMRs fortified with eggshell powder and vitamin D can be a good dietary strategy for bone health.

Bone strength estimates are important for fracture prevention. This study compared bone strength changes in postmenopausal women with low bone mass who were assigned to 12 months of exercise, a bone medication, or control. Exercise and bone medications benefited structure at the hip. Structure should be considered in fracture prevention research. PURPOSE: Exercise and bisphosphonates reduce fracture risk, but their impact on estimates of bone strength remains uncertain. This study compared changes in tibial bone strength using peripheral quantitative computed tomography (pQCT) and hip structure analysis (HSA) outcomes from dual-energy X-ray absorptiometry (DXA) scans in postmenopausal women with low bone mass assigned to 12 months of exercise, risedronate, or control. METHODS: In this RCT, 276 postmenopausal women within 6 years of menopause were randomly assigned to three groups: exercise (92), risedronate (91), or control (93). Exercise included weighted jogging and progressive resistance exercises; risedronate treatment was 150 mg monthly; all groups received calcium and vitamin D. pQCT and DXA images were obtained at baseline and 6 and 12 months and compared between groups over time. RESULTS: Participants had a mean (± SD) age of 54.5 (± 3.2) years with an average of 36.7 (± 40.7) months postmenopause. No significant differences were found between groups for the change in pQCT outcomes (volumetric bone mineral density, area, and strength estimates). At 12 months, mean percent differences (95% CI) in HSA measures between exercise and controls were as follows: intertrochanteric, cross-sectional area 2.25% (0.28, 4.12) (p = .03), cross-sectional moment of inertia (CSMI) 5.67% (1.47, 9.87) (p < .01), and section modulus (SM) 4.38% (1.02, 7.74) (p = .01), and narrow neck, average cortical thickness 2.37% (-0.08, 4.83) (p = .031). Mean percent differences (95% CI) in HSA measures between risedronate and control were as follows: intertrochanteric, CSMI 4.28% (-0.24, 8.81) (p = .03) and SM 3.35% (-0.21, 6.91) (p = .03), and shaft, subperiosteal width 0.82% (0.05, 1.58) (p = .047), CSMI 2.53% (0.88, 4.18) (p = .004), and SM 1.57% (0.34, 2.8) (p = .008). Exercise main

OBJECTIVE: Recent studies show that vitamin D (VitD) deficiency is associated with metabolic syndrome (MetS). Current evidence suggests that estrogen and VitD have similar physiological functions and potentially interact with bone health. We investigated the association between estradiol (E2) and 25-hydroxyvitamin-D [25(OH)D] with MetS and its components in Chinese postmenopausal women. METHODS: In this cross-sectional study, we examined 616 postmenopausal women (aged 49-86 y) from southern China who were not taking estrogen and VitD/calcium supplements. At the end of data collection, serum E2 and 25(OH)D were measured for each participant. MetS was defined according to the 2006 International Diabetes Federation standard. RESULTS: There was a positive correlation between 25(OH)D and E2. Higher 25(OH)D was associated with a favorable lipid profile, blood pressure, and glucose level. E2 was negatively associated with cholesterol, triglycerides, and blood pressure. The odds ratio for MetS was 2.19 (95% CI, 1.19-4.01, P value for trend=0.009) for deficient compared with sufficient women after multivariable adjustment. This association remained unchanged after further adjusting for E2 levels. After stratified analysis by VitD status, low E2 increased MetS risk in women with VitD deficiency (odds ratio = 3.49, 95% CI, 1.45-8.05 for the lowest vs the highest tertile). CONCLUSIONS: These results suggest a synergistic role of VitD and E2 deficiency in MetS in Chinese postmenopausal women.

PURPOSE: In postmenopausal women under L-T4 therapy, which was subsequently accompanied by calcium carbonate (CC) supplementation taken 6-8 h after tablet L-T4, TSH levels were greater than prior to adding CC. Total cholesterolemia [CHOL], fasting glycemia [FG], systolic and diastolic blood pressure [SBP, DBP] were also greater than baseline. Our aim was to explore the effects of either liquid or softgel capsule L-T4, while maintaining CC ingestion 6-8 h, later on TSH levels, CHOL, FG, SBP, and DBP. METHODS: We proposed to 50 hypothyroid postmenopausal women under tablet L-T4 therapy, to switch to either liquid or softgel capsule L-T4 at the same daily dose while maintaining CC ingestion 6-8 h later. Sixteen women accepted [group I; liquid (n = 9), capsule (n = 7)], while 34 continued tablet L-T4 [group II, (n = 34)]. RESULTS: After 3 months, in group I, TSH decreased significantly (1.23 ± 0.49 vs. 1.80 ± 0.37 mU/L, P < 0.01), as did FG (80.7 ± 7.9 vs. 83.4 ± 6.3 mg/dL, P < 0.05); CHOL, SBP, and DBP decreased, though insignificantly. In contrast, in group II, TSH, FG, CHOL, SBP increased insignificantly, and DBP increased borderline significantly (69.7 ± 9 vs. 66.3 ± 6.5, P < 0.10). Compared to baseline (before adding CC), in group I, TSH was significantly lower (P < 0.01) and the other indices similar; in group II, TSH, FG, and SBP were significantly higher (P < 0.05), DBP borderline significantly higher (P < 0.10) and CHOL insignificantly higher. Performance of liquid L-T4 and capsule L-T4 was similar. CONCLUSION: Delaying CC ingestion even by 6-8 h after taking tablet L-T4 is not entirely satisfactory, unlike liquid or softgel L-T4.

OBJECTIVE: This study aims to test the added value of calcium and vitamin D (CaD) in fracture prevention among women taking postmenopausal hormone therapy (HT). METHODS: This is a prospective, partial-factorial, randomized, controlled, double-blind trial among Women's Health Initiative postmenopausal participants aged 50 to 79 years at 40 centers in the United States with a mean follow-up of 7.2 years. A total of 27,347 women were randomized to HT (0.625 mg of conjugated estrogens alone, or 0.625 mg of conjugated equine estrogens plus 2.5 mg of medroxyprogesterone acetate daily), and 36,282 women were randomized to 1,000 mg of elemental calcium (carbonate) plus 400 IU of vitamin D3 daily, each compared with placebo. A total of 16,089 women participated in both arms. The predefined outcomes were adjudicated hip fractures and measured bone mineral density. RESULTS: Interaction between HT and CaD on hip fracture (P interaction = 0.01) was shown. The effect of CaD was stronger among women assigned to HT (hazard ratio [HR], 0.59; 95% CI, 0.38-0.93) than among women assigned to placebo (HR, 1.20; 95% CI, 0.85-1.69). The effect of HT on hip fracture was stronger among women assigned to active CaD (HR, 0.43; 95% CI, 0.28-0.66) than among women assigned to placebo (HR, 0.87; 95% CI, 0.60-1.26). CaD supplementation enhanced the antifracture effect of HT at all levels of personal calcium intake. There was no interaction between HT and CaD on change in hip or spine bone mineral density. CONCLUSIONS: Postmenopausal women at normal risk for hip fracture who are on CaD supplementation experience significantly reduced incident hip fractures beyond HT alone at all levels of personal baseline total calcium intake.

OBJECTIVE: The aim of this study was to evaluate the efficacy of Fructus Ligustri Lucidi (FLL) and Puerariae radix (PR) combination treatment in bone and mineral metabolism in ovariectomized (OVX) rats in our search for an alternative regimen for the management of postmenopausal osteoporosis. METHODS: Six-month-old OVX rats were used as postmenopausal osteoporotic models, and PR water extract (PR) and FLL water extract (WE) were added to commercial diets individually or in combination and administered to OVX rats for 12 weeks. Bone properties, calcium and phosphorus absorption, and bone biochemical markers were measured to investigate the potential interactions between the actions of PR and the actions of WE on bone and mineral metabolism in OVX rats. RESULTS: Long-term treatment with PR did not significantly improve bone properties but greatly ameliorated the secondary hyperparathyroidism induced by ovariectomy in the animals. WE significantly enhanced the intestinal calcium absorption rate and decreased the enlarged trabecular bone surface at the site of metaphysic tibia in OVX rats. However, the positive effects of WE or PR alone on bone and mineral metabolism were diminished when OVX rats were cotreated with WE and PR. CONCLUSIONS: The combination of these two herbs offsets their independent actions on bone and mineral metabolism in vivo. The results of the present study could provide insights to medical professionals to further their understanding of the potential negative impact of herb-herb interactions when a combination of herbal mixtures is used for the management of osteoporosis.

Vitamin D is known to increase Ca absorption in adults. However, the threshold vitamin D status to benefit Ca absorption is lower than the target vitamin D status for higher bone mineral density and lower fracture risk, pointing to another pathway for vitamin D to benefit bone. One possibility is by affecting osteoblast and osteoclasts directly. Vitamin D-related bone metabolism may also be affected by soy isoflavones, which selectively bind to the estrogen receptor &#946; and may reduce bone loss in postmenopausal women. We discuss a possible synergistic effect of soy isoflavones and vitamin D on bone by affecting osteoblast and osteoclast formation and activity in postmenopausal women.

CONTEXT: Vitamin D is often recommended for use with calcium supplements to increase absorption. There are no systematic studies of vitamin D on calcium absorption that indicate what dose should be recommended. OBJECTIVE: Our objective was to study the effect of increasing doses of vitamin D3 on calcium absorption. DESIGN AND SETTING: We conducted a randomized double-blind placebo-controlled trial at Creighton University Medical Center, Omaha, NE. PARTICIPANTS: Participants included 163 postmenopausal Caucasian women with vitamin D insufficiency, defined as a serum 25-hydroxyvitamin D (25OHD) below 20 ng/ml (50 nmol/liter). INTERVENTION: Participants were randomized to receive one of the vitamin D3 doses, 400, 800, 1600, 2400, 3200, 4000, or 4800 IU/d, or placebo for 1 yr. Calcium intake was increased to 1200-1400 mg daily by giving daily calcium citrate. MAIN OUTCOME: We evaluated the change in calcium absorption on vitamin D. RESULTS: Mean serum 25OHD increased from baseline 15.6 ng/ml (39 nmol/liter) to 46.5 ng/ml (112 nmol/liter) in subjects randomized to the highest dose of vitamin D (4800 IU). Calcium absorption was more significantly related to serum 25OHD (R2=0.50; P=0.001) than dose (R2=0.47; P=0.033). Calcium absorption of a 100-mg dose increased from 52-58% (6 mg) over a serum 25OHD range of 20-66 ng/ml (50-165 nmol/liter). CONCLUSIONS: There was no evidence of a threshold for reduced calcium absorption in the serum 25OHD range of 10-66 ng/ml (25-165 nmol/liter). The increase in absorbed calcium of 6% on high doses of vitamin D is so small that the same amount could be obtained from half a glass of milk (100 ml) or 100 mg elemental calcium. The results challenge assumptions about the value of adding vitamin D to increase calcium absorption except when serum 25OHD is very low that is less than 10 ng/ml (25 nmol/liter).

OBJECTIVE: Prebiotics and phytoestrogens have sparked great interest because evidence indicates that the consumption of these dietary constituents leads to lower cholesterol levels and inhibition of postmenopausal bone loss. The aim of this study was to determine the effect of both a prebiotic (Synergy) and a phytoestrogen (genistein) on bone and blood lipid levels in an animal model of postmenopausal women. METHODS: A 4-week feeding study was conducted in 5-month-old ovariectomized (OVX) Sprague-Dawley rats to examine the effect of genistein, Synergy (a prebiotic), and genistein and Synergy combined on bone density and strength, calcium metabolism, and lipid biomarkers. There were six treatment groups: sham control, OVX control, OVX rats receiving daily estradiol injections, and OVX rats receiving an AIN-93M diet supplement with 200 ppm genistein, with 5% Synergy or with 200 ppm genistein and 5% Synergy combined. RESULTS: The rats receiving genistein had significantly lower total serum cholesterol concentrations than OVX rats in the control group (17%), OVX rats receiving daily estradiol injections (14%), and OVX rats fed the 5% Synergy diet (19%). Consumption of Synergy improved calcium absorption efficiency (41%) compared with nonconsumption (OVX control). Sham control rats had a significantly higher femoral bone density, as determined by underwater weighing, than did the rats in all of the OVX groups. Genistein consumption restored total and trabecular bone mineral density at the distal femur similar to the levels of sham rats. CONCLUSIONS: Genistein supplementation imparts modest heart health benefits and improves bone geometry at the distal femur, and prebiotic consumption (Synergy) results in improved calcium utilization strength in ovariectomized rats, but the combination produced no synergistic effects.

The commonest medical conditions following menopause are osteoporosis and atherosclerotic disease. This review considers the safety of pharmacotherapy of osteoporosis in cardiology patients. Drugs used for osteoporosis treatment may have adverse effects on the cardiovascular system. This article has detailed analysed of current drug classes, such as the bisphosphonates and strontium ranelate, as well as reviewed of the controversy surrounding hormone replacement therapy (HRT) and the selective estrogen receptor modulators (SERMs). Additionally, we discuss the adverse effects on the heart of calcium and drugs influencing calcium metabolism such as vitamin D, parathormone and calcitonin. We look at the interference between osteoporosis treatment and the drugs used for atherosclerosis. Moreover, the side effects on bones of cardiology drugs are analysed. Lastly, the possible advantages of selected drugs used for cardiovascular diseases in terms of osteoporosis prevention are evaluated.

INTRODUCTION: Epilepsy is a major public health problem worldwide which is clinically characterized by recurrent seizures. AIM: The aim of this position statement is to provide evidence-based advice on management of the menopause in postmenopausal women derived from the limited data available. MATERIALS AND METHODS: Literature review and consensus of expert opinion. RESULTS AND CONCLUSIONS: Women with epilepsy may undergo an earlier natural menopause, between 3 and 5 years depending on seizure frequency, but the data are limited. Data regarding the effects of the perimenopause and menopause on epilepsy are conflicting: some studies show an increased risk of seizures but others do not. With regard to hormone therapy (HT) one study has shown an increase in seizures with oral therapy with conjugated equine estrogens and medroxyprogesterone acetate, but no data are available for other regimens. Women starting HT should be closely monitored as their antiepileptic drug (AED) needs may change. As vitamin D and calcium metabolism can be affected by AEDS, supplements should be considered. Herbal preparations should be avoided as their efficacy is uncertain and they may interact with AEDs. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

In the estrogen-regulated RANK ligand (RANKL)/RANK/osteoprotegerin (OPG) pathway, estrogen deficiency favors osteoclast maturation, leading to increased bone resorption compared with bone formation. Treatment of low bone mineral density (BMD) should be based on fracture risk, assessed using the WHO Fracture Risk Algorithm (FRAX(R)). Criteria for treatment are 10-year overall fracture risk ≥ 20% or 10-year hip fracture risk ≥ 3%. Vitamin D supplementation at levels higher than those traditionally recommended may be appropriate for healthy menopausal women. Multiple strategies are needed to effectively manage osteoporosis in postmenopausal women.