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A Pooled Analysis of Vitamin D Dose: Requirements for Fracture Prevention

Bischoff-Ferrari, Heike A.; Willett, Calter C.; Orav, Endel J.; Lips, Paul; Meunier, Pierre J.; Lyons, Ronan A.; Flicker, Leon; Wark, John; Jackson, Rebecca D.; Cauley, Jane A.; Meyer, Haakon E.; Pfeifer, Michael; Sanders, Kerrie M.; Stähelin, Hannes B.; Theiler, Robert; Dawson-Hughes, Bess

Obstetrical & Gynecological Survey:
doi: 10.1097/01.ogx.0000422963.79411.8f
Gynecology: Infertility

ABSTRACT: Most fractures occur in people 65 years or older. It is unclear whether universal vitamin D supplementation can prevent fractures in this population. Results from several meta-analyses and other studies examining the possible association between vitamin D supplementation and fracture reduction in persons 65 years or older have been inconsistent.

This study was designed to estimate the effects of oral vitamin D supplementation (daily, weekly, or every 4 months) with or without calcium, as compared with controls (placebo or calcium alone) in persons 65 years or older. Effects of supplementation on fractures were estimated according to the actual intake of each participant, rather than the randomly assigned dose. A search of several databases, including MEDLINE, the Cochrane Central Register of Controlled Trials, and EMBASE, identified 11 double-blind, randomized controlled trials involving persons 65 years or older published on or before August 31, 2011, who met criteria for inclusion. Participant-level data from the 11 trials were pooled. Primary study end points were the risks of hip fracture and any nonvertebral fracture. The data were adjusted for subgroups of study, age, sex, and type of dwelling, as well as for each participant’s adherence to treatment according to a predefined protocol and additional calcium intake. In the primary analyses, adjusted data from quartiles of actual intake of vitamin D in the treatment groups of all trials and the controls were compared. The analysis was according to intention-to-treat.

Subjects in the 11 trials included 31,022 persons (91% women) at a mean age of 76 years with 1111 incident hip fractures and 3770 nonvertebral fractures. Compared with the control group, treated groups showed a nonsignificant 10% reduction in the risk of hip fracture (hazard ratio [HR], 0.90; 95% confidence interval [CI], 0.80–1.01) and a 7% reduction in the risk of nonvertebral fracture (HR, 0.93; 95% CI, 0.87–0.99). Based on quartiles of actual intake, there was reduction in the risk of fracture only at the highest intake level (median, 800 IU daily; range, 792–2000 IU), with a 30% reduction in the risk of hip fracture and a 14% reduction in the risk of any nonvertebral fracture; HRs were 0.70 (95% CI, 0.58–0.86) and 0.86 (95% CI, 0.76–0.96), respectively. In the adjusted data, benefits at the highest level of vitamin D intake were relatively consistent across subgroups.

These findings suggest that supplementation with high doses of vitamin D (≥800 IU daily) may reduce the risk of hip fracture and any nonvertebral fracture in persons 65 years or older.

© 2012 Lippincott Williams & Wilkins, Inc.