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Authors <> Avenell Alison, Gillespie William J, Gillespie Lesley D, O'Connell Dianne

Review Group <>Cochrane Bone, Joint and Muscle Trauma Group

Abstract <> 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.

Implications <> Frail older people confined to institutions appear to experience a reduction in hip and other non-vertebral fractures if given vitamin D with calcium supplements.The effectiveness in fracture prevention of administration of vitamin D with calcium supplements to community-dwelling older people is unclear. Supplementation with vitamin D and calcium, for fracture prevention, may be associated with a marginal reduction in mortality compatible with the reduction in hip fracture risk.Vitamin D alone, in the doses which have been used, appears unlikely to be effective in fracture prevention in older people.There is no evidence that related vitamin D compounds (analogues) have advantages in terms of effectiveness or reduced incidence of adverse effects compared with vitamin D.Calcitriol appears to be associated with an increased incidence of adverse effects such as hypercalcaemia.

Citation <>Avenell A, Gillespie WJ, Gillespie LD, O'Connell D. Vitamin D and vitamin D analogues for preventing fractures associated with involutional and post-menopausal osteoporosis. Cochrane Database of Systematic Reviews 2009, Issue 1. Art. No.: CD000227. DOI: 10.1002/14651858.CD000227.pub2.