Only high intake of vitamin D supplementation with 800 IU or more per day appears to reduce the risk of fracture significantly in the elderly, according to the latest meta-analysis on the subject reported online July 4 in the New England Journal of Medicine.
Such high levels of supplementation appear to reduce the risk of hip fracture by 30% and the risk of nonvertebral fracture by 14% in people aged 65 years and older, said Dr. Heike A. Bischoff-Ferrari, of the Center on Aging and Mobility at the University of Zurich, and her associates.
Many previous meta-analyses of the protective effect of vitamin D supplements, like the numerous clinical trials they reviewed, have produced markedly conflicting results. Some have found reductions in fracture risk of up to 20%, others have found no beneficial effect, and a few have even found negative effects on fracture risk.
Dr. Bischoff-Ferrari and her colleagues reasoned that many of these clinical trials, as well as the meta-analyses that pooled their findings, were flawed by relying on the doses of vitamin D that were prescribed for subjects rather than the actual amount that subjects took. Many also were flawed in that they did not take into account subjects’ baseline levels of 25-hydroxyvitamin D, an indicator of the degree of their vitamin D deficiency.
So for their meta-analysis, the investigators included only double-blind, randomized, controlled trials that either recorded subjects’ actual intake of oral vitamin D supplements or controlled for their adherence to prescribed supplementation. Thus, the investigators were able to include only 11 studies, with a pooled population of 31,022 subjects, in their meta-analysis.
The intention-to-treat analysis, which examined the prescribed supplementation, showed a nonsignificant 10% reduction in the risk of hip fracture. However, a comparison of subjects’ actual intake of vitamin D supplements showed a significant 30% reduction in risk of hip fracture at the highest levels of intake (800-2,000 IU daily).
"Notably, there was no reduction in risk of hip fracture at any actual intake level lower than 792 IU per day," Dr. Bischoff-Ferrari and her associates said (N. Engl. J. Med. 2012 July 4 [doi: 10.1056/NEJMoa1109617]).
Similarly, the intention-to-treat analysis showed a nonsignificant 7% reduction in the risk of nonvertebral fracture, while a comparison of actual intake levels showed a significant 14% decline in risk at the highest levels of intake.
Internal validation analyses supported these results, and indicated that there was a dose-response relationship between vitamin D dose actually ingested and fracture risk. Several sensitivity analyses also bolstered the findings, and showed that the benefit of vitamin D supplements extended across several subgroups of patients, including all ages and both sexes.
"Previous meta-analyses have suggested that the benefits of vitamin D may be limited to older persons who live in institutions. Our subgroup analyses suggest that at the highest actual intake level, the risk of hip fracture is reduced among all persons 65 years of age or older, whether they live in the community or in an institution.
"Our data further suggest that persons who are most vulnerable to vitamin D deficiency – those 85 years of age or older and those with very low baseline levels of 25-hydroxyvitamin D – benefit from vitamin D supplementation at least as much as others do," they added.
Overall, the study results support the Institute of Medicine’s recommendation that people aged 65 years and older receive 800 IU of vitamin D each day, the investigators noted.
In addition, "our findings suggest that some previous high-quality trials of vitamin D supplementation either showed no benefit owing to lower-than-intended doses of vitamin D or showed an unexpected benefit owing to higher-than-intended doses," they said.
This study was supported by the Swiss National Foundation, the European Commission Framework 7 Program, and DSM Nutritional Products. Dr. Bischoff-Ferrari reported ties to DSM Nutritional Products, Amgen, MSD, Novartis, Roche, and Nestle, and her associates reported ties to numerous industry sources.