Where do we stand on vitamin D?

A meta-analysis of primary prevention high-quality trials published in 2005 found that oral cholecalciferol (D3) in a daily dose of 700-800 IU or intermittently 100,000 IU every 4 months with or without calcium, should reduce both hip and non-vertebral fracture risk significantly compared to placebo. Trials that administered 400 IU vitamin D did not achieve fracture efficacy. Notably, there was a significant association between higher achieved 25-hydroxyvitamin D levels (25(OH)D) in the treatment groups and fracture efficacy: The minimal mean level where fracture efficacy was observed was 74 nmol/l (25(OH)D). Epidemiological data for bone density and lower extremity strength support this threshold, and high-quality trials that used 700 to 800 IU D3 suggested fall risk reduction by 35 to 65% in institutionalized and community-dwelling older individuals. However, since the 2005 meta-analysis, benefits of vitamin D on fracture and fall reduction have been questioned by results from several recent trials. This review proposes that the interpretation of these recent trials is hindered by different doses of vitamin D, different types of supplemental vitamin D (D3 or ergocalciferol D2), low adherence, concurrent use of supplements outside the study protocol, open study design, short follow-up, and/or different patient risk profiles including primary and secondary fracture prevention. In most recent trials, low adherence, the use of the relatively less potent D2, or a too low dose of D3 (400 IU) may have prohibited a shift of (25(OH)D) levels in the treatment groups to the desirable range of at least 75 nmol/l. In summary, from recent trials, two lesson may be learned: (1) Adherence less than 60% is insufficient to achieve fracture efficacy with daily 800 IU D3 plus calcium, (2) D2 in any application or any previously studied dose may not reduce fractures in institutionalized or community-dwelling older individuals.