Vitamin D and vitamin D analogues for preventing fractures in post-menopausal women and older men.

Systematic review and meta-analysis of randomized and quasi-randomized trials in post-menopausal women and older men, mostly aged over 65 years, recruited from community, nursing home, assisted living, hospital, and long-stay geriatric settings. Active vitamin D regimens or analogues, with or without calcium, were compared with placebo or no treatment.

The review evaluated oral and occasional intramuscular vitamin D2 or D3, often with calcium co-supplementation, and the active vitamin D analogues alfacalcidol and calcitriol. Doses ranged from daily 400 to 800 IU vitamin D3 with about 1000 mg calcium to intermittent regimens such as 100,000 IU every 4 months, 300,000 IU intramuscular annually, and 500,000 IU oral annually; alfacalcidol and calcitriol were typically given orally in microgram doses.

Vitamin D alone did not prevent fractures: hip fracture RR 1.12 (95% CI 0.98 to 1.29), non-vertebral fracture RR 1.05 (0.96 to 1.14), vertebral fracture RR 1.03 (0.76 to 1.39), and any new fracture RR 1.03 (0.96 to 1.11). Vitamin D plus calcium modestly reduced hip fractures (RR 0.84, 0.74 to 0.96) and any fracture (RR 0.95, 0.90 to 0.99), with stronger effects in institutional residents for hip fracture (RR 0.75, 0.62 to 0.92). Alfacalcidol reduced vertebral fractures (RR 0.57, 0.49 to 0.65) but not hip or non-vertebral fractures, whereas calcitriol did not show consistent fracture benefit. Hypercalcaemia was more common with vitamin D analogues, especially calcitriol (RR 4.41, 2.14 to 9.09), and vitamin D plus calcium was associated with small increases in gastrointestinal symptoms and renal disease.

The evidence base was heterogeneous in population, formulation, dose, route, and duration, and several trials were small or had incomplete follow-up. Some alfacalcidol findings were driven by a quasi-randomized study, and adverse-event estimates were limited by sparse reporting and reliance on a few large trials. Generalizability is strongest for older women and institutional populations rather than all older adults.