Vitamin D and vitamin D analogues for preventing fractures associated with involutional and post-menopausal osteoporosis

BACKGROUND: Vitamin D and related compounds have been used to prevent osteoporotic fractures in older people. OBJECTIVES: To determine the effects of vitamin D or related compounds, with or without calcium, for preventing fractures in older people. SEARCH STRATEGY: We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register, the Cochrane Central Register of Controlled Trials (The Cochrane Library 2007, Issue 3), MEDLINE, EMBASE, CINAHL, and reference lists of articles. Most recent search: October 2007. SELECTION CRITERIA: Randomised or quasi-randomised trials comparing vitamin D or related compounds, alone or with calcium, against placebo, no intervention, or calcium alone, reporting fracture outcomes in older people. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality, and extracted data. Data were pooled, where admissible, using the fixed-effect model, or random-effects model if heterogeneity between studies appeared high. MAIN RESULTS: Forty-five trials were included. Vitamin D alone appears unlikely to be effective in preventing hip fracture (nine trials, 24,749 participants, RR 1.15, 95% CI 0.99 to 1.33), vertebral fracture (five trials, 9138 participants, RR 0.90, 95% CI 0.42 to 1.92) or any new fracture (10 trials, 25,016 participants, RR 1.01, 95% CI 0.93 to 1.09).Vitamin D with calcium reduces hip fractures (eight trials, 46,658 participants, RR 0.84, 95% CI 0.73 to 0.96). Although subgroup analysis by residential status showed a significant reduction in hip fractures in people in institutional care, the difference between this and the community-dwelling subgroup was not significant (P = 0.15).Overall hypercalcaemia is significantly more common in people receiving vitamin D or an analogue, with or without calcium (18 trials, 11,346 participants, RR 2.35, 95% CI 1.59 to 3.47); this is especially true of calcitriol (four trials, 988 participants, RR 4.41, 95% CI 2.14 to 9.09). There is a modest increase in gastrointestinal symptoms (11 trials, 47,042 participants, RR 1.04, 95% CI 1.00 to 1.08, P = 0.04) and a small but significant increase in renal disease (11 trials, 46,537 participants, RR 1.16, 95% CI 1.02 to 1.33). AUTHORS' CONCLUSIONS: Frail older people confined to institutions may sustain fewer hip fractures if given vitamin D with calcium. Vitamin D alone is unlikely to prevent fracture. Overall there is a small but significant increase in gastrointestinal symptoms and renal disease associated with vitamin D or its analogues. Calcitriol is associated with an increased incidence of hypercalcaemia.