The effects of combined calcium and vitamin D supplementation on bone mineral density and fracture risk in postmenopausal women with osteoporosis: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: This systematic review and meta-analysis assesses the efficacy of combined calcium and vitamin D supplementation on bone mineral density (BMD) and fracture risk among postmenopausal women with osteoporosis. METHODS: We conducted a comprehensive search across multiple medical databases including PubMed, Embase, Cochrane Library, and Web of Science, collecting randomized controlled trials (RCTs) published from database inception to present. Data extraction and analysis were performed to calculate standardized mean differences (SMDs) or risk ratios (RRs) with 95% confidence intervals (CIs), which were then presented in forest plots. RESULTS: Eleven RCTs with 43,869 participants were included. Combined supplementation modestly improved BMD at the pelvis (SMD = 0.20, 95% CI: 0.05–0.35, p = 0.01) without significant changes in BMD at the lumbar spine, femoral neck, or total hip. The overall fracture risk was not significantly reduced (RR = 0.98, 95% CI: 0.89–1.07, p = 0.68). Subgroup analyses revealed improvements in serum 25‑hydroxyvitamin D levels (25OHD), especially in participants with baseline deficiencies (Z = 10.48, p < 0.001). No dose-response effect was noted for supplementation duration. Fracture outcomes from three large trials (> 42 000 participants) yielded a neutral effect on any clinical fracture (pooled RR = 0.95; 95% CI 0.85–1.07; Z = 1.08, P = 0.28; I² = 0%). Sensitivity analyses affirmed the findings’ stability, with no evident publication bias. CONCLUSION: Combined calcium and vitamin D supplementation may improve pelvic BMD and correct serum 25OHD deficiencies in postmenopausal women with osteoporosis, but does not reduce clinical fracture risk in postmenopausal women with osteoporosis. Larger, highdose RCTs with rigorous adherence monitoring and adjudicated fracture endpoints are warranted. CLINICAL TRIAL NUMBER: Not applicable.