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

Abstract

Background: Vitamin D and related compounds have been used to prevent fractures.

Objectives: To determine the effects of vitamin D or analogues, with or without calcium, in the prevention of fractures in older people.

Search strategy: We searched the Cochrane Bone, Joint and Muscle Trauma Group trials register, the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1, 2005), MEDLINE, EMBASE, CINAHL, and reference lists of articles. Most recent search: March 2005.

Selection criteria: Randomised or quasi-randomised trials comparing vitamin D or an analogue, alone or with calcium, against placebo, no intervention, or calcium, 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 the relative risks were heterogeneous.

Main results: Vitamin D alone showed no statistically significant effect on hip fracture (seven trials, 18,668 participants, RR 1.17, 95% CI 0.98 to 1.41), vertebral fracture (four trials, 5698 participants, RR (random effects) 1.13, 95% CI 0.50 to 2.55) or any new fracture (eight trials, 18,903 participants, RR 0.99, 95% CI 0.91 to 1.09). Vitamin D with calcium marginally reduced hip fractures (seven trials, 10,376 participants, RR 0.81, 95% CI 0.68 to 0.96), non-vertebral fractures (seven trials, 10,376 participants, RR 0.87, 95% CI 0.78 to 0.97), but there was no evidence of effect of vitamin D with calcium on vertebral fractures. The effect appeared to be restricted to those living in institutional care. Hypercalcaemia was more common when vitamin D or its analogues was given compared with placebo or calcium (14 trials, 8035 participants, RR 2.38, 95% CI 1.52 to 3.71). The risk was particularly high with calcitriol (three trials, 742 participants, RR 14.94, 95% CI 2.95 to 75.61). There was no evidence that vitamin D increased gastro-intestinal symptoms (seven trials, 10,188 participants, RR (random effects) 1.03, 95% CI 0.79 to 1.36) or renal disease (nine trials, 10,107 participants, RR 0.80, 95% CI 0.34 to 1.87).

Authors' conclusions: Frail older people confined to institutions may sustain fewer hip and other non-vertebral fractures if given vitamin D with calcium supplements. Effectiveness of vitamin D alone in fracture prevention is unclear. There is no evidence of advantage of analogues of vitamin D compared with vitamin D. Calcitriol may be associated with an increased incidence of adverse effects. Dose, frequency, and route of administration of vitamin D in older people require further investigation.