High doses of vitamin D prevent fractures in older people – as long as they take the substance regularly, researchers reported.
In a meta-analysis, oral doses of at least 800 IU were associated with reductions in the risk of both hip and nonvertebral fractures, according to Heike Bischoff-Ferrari, MD, DrPH, of University Hospital in Zurich, and colleagues.
The analysis differs from previous studies and other meta-analyses in that it looked at how much vitamin D participants actually took, rather than what dose they were assigned to take, Bischoff-Ferrari and colleagues reported in the July 5 issue of the New England Journal of Medicine.
Fractures are common in older people and one strategy to prevent them might be vitamin D supplements, the researchers noted, but studies of the issue have been inconsistent. To try to clarify the matter, they looked for all controlled studies of oral vitamin D, with or without calcium, among people 65 and older.
They included 12 studies and had participant-level data on 30,011 volunteers.
The primary end points were the risks of hip fracture and any nonvertebral fracture, and the primary analyses compared the actual intake of vitamin D supplementation, in quartiles, to the controls, with actual intake calculated as the assigned dose plus any additional supplemental dose, adjusted for adherence.
The study design is important, because it takes into account the biology of vitamin supplementation, according to Robert Heaney, MD, of the Creighton University Medical Center in Omaha, Neb.
In an accompanying editorial in the journal, Heaney argued that the inconsistent outcomes of earlier work might be the result of an overfocus in meta-analyses on the methods used in individual trials.
"The question of how much vitamin D is enough is likely to remain muddled as long as meta-analyses focus on trial methodology rather than on biology," he argued.
But Heaney noted that the results of the current meta-analysis are in accordance with recommendations of the Endocrine Society. "It would appear to be prudent, and probably helpful as well, to ensure an intake at the upper end of the range" that the researchers found effective.
Bischoff-Ferrari and colleagues found that, in an intention-to-treat analysis, there was a nonsignificant 10% reduction in the risk of hip fracture and a significant (at P=0.03) 7% reduction in the risk of nonvertebral fracture.
On the other hand, when they took into account actual vitamin D intake, they found a 30% reduction in the risk of hip fracture but only for those in the highest quartile of intake – 792 to 2,000 IU a day.
The relative risk in that group, compared with controls, was 0.70, with a 95% confidence interval from 0.58 to 0.86, and was significant at P<0.001.
They also found a 14% reduction in the risk of any nonvertebral fracture, but again only in the highest quartile. The relative risk was 0.86, with a 95% confidence interval from 0.66 to 0.96, and was significant at P=0.007.
A sensitivity analysis, not including any outside supplements, had similar results, they reported.
Heaney commented that the benefits of supplements might be affected by baseline levels of vitamin D but noted that such information has not been routinely collected in trials of the substance.
Indeed, baseline levels of hydroxyvitamin D were only available for 4,383 participants, Bischoff-Ferrari and colleagues reported. Despite that, the results among those participants were similar to those in the whole group, they found.
In addition to the absence of baseline hydroxyvitamin D levels, other study limitations included inability to separate calcium and vitamin D intake as those receiving high doses of vitamin D were all taking calcium and lack of trial level data for two of the 14 included trials.