NEED FOR ADDITIONAL CALCIUM TO REDUCE THE RISK OF HIP OR ANY NONVERTEBRAL FRACTURE WITH VITAMIN D SUPPLEMENTATION: EVIDENCE FROM A COMPARATIVE META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS

Abstract

Objectives: A recent meta-analysis (JAMA. 2005;293:2257–2264) reported that supplementation with oral vitamin D 700–800 IU/day reduces the risk of hip or any nonvertebral fracture in elderly individuals by approximately 25%. However, this metaanalysis was unable to define the role of additional calcium supplementation. The aim of the current study was to assess the need for calcium supplementation in individuals receiving vitamin D for the prevention of hip and nonvertebral fractures.

Methods: MEDLINE (search terms: ‘vitamin D’ AND ‘hip fracture’), bibliographies of articles retrieved, and the authors’ reference files were used to identify randomized controlled trials (RCTs) of oral vitamin D supplementation with or without calcium supplementation vs placebo/no treatment in postmenopausal women and/or older men (over 50 years) specifically reporting hip fracture risk. Data extraction was independent by

Results: All pooled analyses are based on random-effects models. Based on 4 RCTs (9083 subjects), the pooled relative risk (RR) of hip fracture for vitamin D supplementation alone was 1.10 (95% confidence intervals [CI], 0.89 to 1.36). No between-trial heterogeneity was observed. For the 5 RCTs (9227 subjects) of vitamin D supplementation with calcium supplementation, the pooled RR for hip fracture was 0.79 (95% CI, 0.64 to 0.97). There was no heterogeneity between trials. The RRs for all nonvertebral fracture were 0.98 (0.83 to 0.16) for vitamin D alone and 0.84 (0.73 to 0.96) for vitamin D with calcium, with moderate heterogeneity between trials. In an adjusted indirect comparison of the summary RRs from the 2 meta-analyses, the RR for hip fracture for vitamin D with calcium vs vitamin D alone was 0.72 (95% CI, 0.53 to 0.96) and the RR for all non-vertebral fractures was 0.77 (95% CI, 0.60 to 0.99).

Conclusions: Oral vitamin D supplementation appears to reduce the risk of hip and any nonvertebral fractures only when calcium supplementation is added. Our findings suggest that to optimize clinical efficacy, vitamin D supplementation should be complemented with calcium supplements.