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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: The purpose of this investigation was to determine risk factors for osteoporosis (OP) in patients with rheumatoid arthritis (RA) through comprehensive literature review and meta-analysis. METHODS: A comprehensive database exploration covered PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang, VIP, and Chinese Biomedical databases from inception to December 31, 2024. Study quality was assessed using the Newcastle-Ottawa Scale for Healthcare Research and Quality (AHRQ). Data analyses involved STATA 18 to calculate odds ratios (ORs) with 95% confidence intervals (CIs). Publication bias assessment involved funnel plots in conjunction with Egger's test. RESULTS: Fifty-seven articles were incorporated in the meta-analysis. Significant risk factors for OP in RA patients included female (OR = 2.10), advancing age (OR = 1.11), prior fracture (OR = 2.83), disease duration (OR = 1.16), and postmenopausal status (OR = 3.96). Laboratory and clinical parameters that correlated with increased risk included elevated CTX (OR = 1.01), higher DAS28 scores (OR = 1.60), increased ESR (OR = 1.05), higher Sharp Scores (OR = 1.12), and RF titers (OR = 1.01). Glucocorticoid therapy constituted a significant risk factor (OR = 2.34). Protective factors included higher BMI (OR = 0.86), adequate 25-(OH)-D levels (OR = 0.88), and calcium and/or vitamin D supplementation (OR = 0.49). No significant associations were found between OP in individuals with RA and smoking history, alcohol consumption, PTH levels, or DMARD therapy. This meta-analysis systematically identified risk factors for OP among individuals with RA. Female, advanced age, prior fracture, longer disease duration, postmenopausal status, CRP, ESR, CTX, RF titers, DAS28, Sharp Score, and glucocorticoid therapy increased OP risk. Conversely, higher BMI, adequate 25-(OH)-D status, and calcium/vitamin D supplementation demonstrated protective effects. CONCLUSION: This meta-analysis reveals female, age, postmenopausal status, prior fracture, and glucocorticoid therapy as major risk factors for osteoporosis in rheumatoid arthritis, with higher BMI as protective factors to quantify the impact of each risk factor

3. Osteoporos Int. 2025 Jun;36(6):981-993. doi: 10.1007/s00198-025-07479-0. Epub 2025 Apr 9. Clinical presentation, risk factors and management of pregnancy-associated osteoporosis: a systematic review and meta-analysis. Orhadje E(1), Makaram N(1), Berg K(1), Hauser B(1)(2), Ralston SH(3)(4). A

BACKGROUND & OBJECTIVES: Calcium and vitamin D, separately or in combination are usually prescribed to prevent fragility fractures in elderly population. However, there are conflicting results regarding the ideal dosage and overall efficacy obtained from randomized controlled trials (RCTs) conducted in the past. The objective of this study was to assess the fracture risk with the administration of calcium or vitamin D alone or in combination in elderly population (>60 yr). METHODS: PubMed, Cochrane and Embase databases were searched to identify the studies from inception to February 2021 with keywords, 'vitamin D', 'calcium' and 'fracture' to identify RCTs. The trials with comparing vitamin D, calcium or combination with either no medication or placebo were included for final analyses. The data were extracted and the study quality was assessed by two reviewers. The principal outcome measure was fractures around hip joint and secondary outcomes assessed were vertebral and any other fracture. RESULTS: Eighteen RCTs were considered for the final analysis. Neither calcium nor vitamin D supplementation was associated with risk of fractures around hip joint [risk ratio (RR) 1.56; 95% confidence interval (CI), 0.91 to 2.69, I[2]=28%; P=0.11]. In addition, the combined administration of calcium and vitamin D was also not associated with fractures around the hip joint in comparison to either no treatment or placebo. The incidence of vertebral (RR 0.95; 95% CI, 0.82 to 1.10, I[2]=0%; P=0.49) or any other fracture (RR 0.83; 95% CI 0.65 to 1.06, I[2]=0%; P=0.14) was not significantly associated with the administration of calcium and vitamin D either individually or in combination. Further subgroup analysis of the results did not vary with the dosage of calcium or vitamin D, dietary calcium intake sex, or serum 25-hydroxyvitamin D levels. INTERPRETATION & CONCLUSIONS: The present meta-analysis of RCTs on calcium, vitamin D or a combination of the two in comparison to no treatment or placebo did not support the routine administration protocol of calcium and vitamin D either alone or in combination to lower the risk of fractures in elderly population.

BACKGROUND: Many nutritional supplements and pharmacological agents have been reported to show preventive effects on colorectal adenoma and colorectal cancer (CRC). We performed a network meta-analysis to summarize such evidence and assess the efficacy and safety of these agents. METHODS: We searched PubMed, Embase, and the Cochrane Library for studies published in English until October 31, 2021 that fit our inclusion criteria. We performed a systematic review and network meta-analysis to assess the comparative efficacy and safety of candidate agents (low-dose aspirin [Asp], high-dose Asp, cyclooxygenase-2 inhibitors [coxibs], calcium, vitamin D, folic acid, ursodeoxycholic acid [UDCA], estrogen, and progesterone, alone or in combination) for preventing colorectal adenoma and CRC. Cochrane risk-of-bias assessment tool was employed to evaluate the quality of each included study. RESULTS: Thirty-two randomized controlled trials (278,694 participants) comparing 13 different interventions were included. Coxibs significantly reduced the risk of colorectal adenoma (risk ratio [RR]: 0.59, 95% confidence interval [CI]: 0.44-0.79, six trials involving 5486 participants), advanced adenoma (RR: 0.63, 95% CI: 0.43-0.92, four trials involving 4723 participants), and metachronous adenoma (RR: 0.58, 95% CI: 0.43-0.79, five trials involving 5258 participants) compared with placebo. Coxibs also significantly increased the risk of severe adverse events (RR: 1.29, 95% CI: 1.13-1.47, six trials involving 7109 participants). Other interventions, including Asp, folic acid, UDCA, vitamin D, and calcium, did not reduce the risk of colorectal adenoma in the general and high-risk populations compared with placebo. CONCLUSIONS: Considering the balance between benefits and harms, regular use of coxibs for prevention of colorectal adenoma was not supported by the current evidence. Benefit of low-dose Asp for chemoprevention of colorectal adenoma still requires further evidence. REGISTRATION: PROSPERO, No. CRD42022296376.

Milk contains a number of bone-beneficial nutrients. However, milk, due to the D-galactose content, might have unfavorable effects on bone health. A meta-analysis of randomized controlled trials (RCTs) was performed to clarify the effects of milk supplementation on bone mineral density (BMD), bone turnover markers [N-terminal telopeptide of type I collagen (NTx), C-terminal telopeptide of type 1 collagen (CTx), osteocalcin, bone alkaline phosphatase (BALP), and procollagen type 1 N-propeptide (P1NP)], and hormonal indices related to bone metabolism [parathyroid hormone (PTH), 25-hydroxyvitamin D [25(OH)D], and insulin-like growth factor 1 (IGF-1)] in adults. The PubMed and Web of Science databases were searched. A random-effects model was used to estimate the pooled effect sizes. A total of 20 RCTs were included. The trial duration ranged from 1 mo to 36 mo. Milk supplementation resulted in a small but significant increase in BMD at the hip (+0.004 g/cm2; n = 9 RCTs) and lumbar spine (+0.025 g/cm2; n = 7), but did not significantly affect whole-body BMD (n = 3) and femoral neck BMD (n = 7). Milk supplementation reduced the concentrations of P1NP (-5.20 ng/mL; n = 9), CTx (-0.16 ng/mL; n = 9), and NTx (-8.66 nmol bone collagen equivalents/mmol creatinine; n = 3). The concentrations of osteocalcin (n = 9) and BALP (n = 3) were not affected by milk supplementation. Reduced parathyroid hormone PTH (-1.01 pg/mL; n = 13) concentrations and increased IGF-1 (+1.79 nmol/l; n = 4) concentrations were observed with milk supplementation. 25(OH)D (+3.73 ng/mL; n = 11) concentrations were increased with vitamin-D fortified milk supplementation. The addition of milk to the diet may potentially increase the likelihood of preventing bone loss by restoring bone homeostasis through the modulation of the calcium-vitamin D-PTH axis, bone remodeling rate, and growth hormone/IGF-1 axis. © The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.

BACKGROUND: Magnesium plays a key role in bone health and may, therefore, represent an interesting nutrient for the prevention of bone loss and osteoporosis. The aim of this systematic review and meta-analysis was to investigate the impact of magnesium intake from any source on bone mineral density (BMD), bone mineral content (BMC), bone turnover markers, and fracture risk in older adults. METHODS: A systematic search was conducted using Embase, Medline Ovid and Cochrane Central from database inception to October 2020. All studies that related magnesium intake with bone health outcomes among adults aged ≥60 years were included. Two investigators independently conducted abstract and full-text screenings, data extractions, and risk of bias assessments. Authors were contacted for missing data. RESULTS: Once 787 records were screened, six cohort studies, one case-control study and five cross-sectional studies were included. Qualitative evaluation demonstrated a positive trend between higher magnesium intake and higher hip and femoral neck BMD. Meta-analysis of four studies showed a significant positive association between magnesium intake and hip BMD (pooled beta: 0.03, 95% CI: 0.01-0.06, p < 0.05). CONCLUSIONS: This systematic review indicates that a higher magnesium intake may support an increase in hip and femoral neck BMD. Due to limited research no associations with BMD at other sites or fractures were found. There is a need for properly designed cohort studies to determine the association between magnesium intake and bone health in older adults. Next, large and long-term randomized controlled trials in older adults are needed to determine whether an increase in magnesium (supplementation) intake can improve bone health. The combination of several bone nutrients (calcium, vitamin D, protein, magnesium and potentially more) may be needed for the most optimal effect on bone health and to delay or prevent the development of osteoporosis.

The objective of this review was to assess the impact of preventive nutrition interventions on health and nutritional status of adolescents aged 10-19 years in low- and middle-income countries (LMICs). We searched the databases until 5 February 2019 without any restrictions on publication, date, language, or publication status. A total of 10 studies (15 papers) including 10,802 participants assessing the impact of micronutrient supplementation/fortification were included in this review. We did not find any study assessing the impact of nutrition education and counseling or macronutrient supplementation among adolescents. Among primary outcomes, we are uncertain of the effect of iron supplementation with or without folic acid on anemia (daily supplementation; relative risk (RR): 1.04, 95% confidence interval (CI) 0.42, 2.57; one study; 1160 participants; low-quality evidence; weekly supplementation; RR: 1.07, 95% CI: 0.46, 2.52; one study; 1247 participants; low-quality evidence). We are also uncertain of the effect of various micronutrient supplementation/fortification on body mass index (BMI) (calcium/vitamin D supplementation; (MD: -0.01 kg/m2; 95% CI: -1.20, 1.17; two studies; 730 participants; I2 94%; very-low-quality evidence, iron supplementation with or without folic acid; MD: 0.47 kg/m2; 95% CI: -0.17, 1.11; two studies; 652 participants; I2 37%; very-low-quality evidence, zinc supplementation; MD: 0.35 kg/m2; 95% CI: -0.15, 0.85; one study; 382 participants; very-low-quality evidence) and multiple micronutrient (MMN) fortification; MD: 0.23 kg/m2, 95% CI: -0.11, 0.57; two studies; 943 participants; I2 22%; very-low-quality evidence). None of the included studies reported any other primary outcomes including morbidity or adverse effects. Among secondary outcomes, iron supplementation with or without folic acid may improve hemoglobin concentrations, and calcium/vitamin D supplementation may improve serum 25(OH)D levels, while calcium only supplementation and calcium and vitamin D supplementation may marginally improve total body bone mineral density (BMD). We are uncertain of the effect of MMN fortification on hemoglobin concentrations, calcium supplement

OBJECTIVE: Inconsistent findings in regard to association between different concentrations of vitamin D, calcium or their combination and the risk of fracture have been reported during the past decade in community-dwelling older people. This study was designed to compare the fracture risk using different concentrations of vitamin D, calcium or their combination. DESIGN: A systematic review and network meta-analysis. DATA SOURCES: Randomised controlled trials in PubMed, Cochrane library and Embase databases were systematically searched from the inception dates to 31 December 2017. OUTCOMES: Total fracture was defined as the primary outcome. Secondary outcomes were hip fracture and vertebral fracture. Due to the consistency of the original studies, a consistency model was adopted. RESULTS: A total of 25 randomised controlled trials involving 43 510 participants fulfilled the inclusion criteria. There was no evidence that the risk of total fracture was reduced using different concentrations of vitamin D, calcium or their combination compared with placebo or no treatment. No significant associations were found between calcium, vitamin D, or combined calcium and vitamin D supplements and the incidence of hip or vertebral fractures. CONCLUSIONS: The use of supplements that included calcium, vitamin D or both was not found to be better than placebo or no treatment in terms of risk of fractures among community-dwelling older adults. It means the routine use of these supplements in community-dwelling older people should be treated more carefully. PROSPERO REGISTRATION NUMBER: CRD42017079624. © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the effect of calcium-vitamin D co‑supplementation on insulin, insulin sensitivity, and glycemia. A systematic search was carried out in Web of Science, PubMed, EMBASE, Scopus, and Cochrane library without any language and time restriction up to 12 August 2018, to retrieve the RCTs, which examined the effect of calcium and vitamin D co-supplementation on fasting blood glucose (FBG), insulin, HOMA-B, HOMA-IR, and QUICKI. Meta-analyses were carried out using a random effects model, and I2 indexes were used to evaluate the heterogeneity. Search yielded 2225 publications. Twelve RCTs with 4395 patients were eligible. Results demonstrated that calcium and vitamin D co‑supplementation had significantly reducing effects on FBG, HOMA-IR and circulating levels of insulin. As the subgroup analysis demonstrated, short-term (≤12 weeks) calcium and vitamin D co‑supplementation had a significant reducing effect on FBG. However, beneficial effects of calcium and vitamin D co‑supplementation on circulating level of insulin and HOMA-IR were seen in both short-term and long-term (>12 weeks) supplementations. Furthermore, we found that high doses of vitamin D and calcium co-supplementation (vitamin D≥2000 mg/day and calcium≥1000 mg/day) had significantly reducing effects on FBG, HOMA-IR and insulin. Present meta-analysis indicated the beneficial effects of high-dose and short-term combined vitamin D and calcium supplementation on insulin, insulin resistance and glycemia; however, further large-scale RCTs with adequate and multiple dosing schedules are needed. © Georg Thieme Verlag KG Stuttgart · New York.