Letters Fall prevention with vitamin D

Institute of Medicine responds

BMJ 2011; 342 doi: http://dx.doi.org/10.1136/bmj.d4046 (Published 28 June 2011) Cite this as: BMJ 2011;342:d4046
  1. J Christopher Gallagher, professor of medicine, director1,
  2. Clifford Rosen, professor of medicine2
  1. 1Bone Metabolism Unit, Creighton University Medical School, Omaha, NE, USA
  2. 2Tufts University School of Medicine, Boston, MA, USA
  1. jcg{at}creighton.edu

The Institute of Medicine (IOM) criticised inconsistencies and misrepresentations of data in the meta-analysis of vitamin D and fall prevention by Bischoff-Ferrari and colleagues.1 2 The authors replied to the IOM,3 and we respond to them as members of the IOM committee.

In assessing the dose-response relation between vitamin D dose, serum 25-hydroxyvitamin D concentration, and risk of a fall the authors opted to compare subgroups of studies above or below a cut off point of vitamin D dose and serum 25 hydroxyvitamin D concentration selected by “visual inspection”—that is, in an entirely data driven way. They found significant differences in two subgroups (in a meta-regression framework) and interpreted them as evidence for an inverse relation. However, analyses using nearby cut off points are not significant. The IOM’s reanalysis of the authors’ data using vitamin D dose as a continuous variable showed no significant relation. Furthermore, trying to establish a “threshold” between falls and serum 25 hydroxyvitamin D concentration is too simplistic when non-comparable assays are performed over 12 years.

Bischoff-Ferrari and colleagues acknowledge that they included a trial conducted by Broe et al in violation of their stated eligibility criteria.3 4 They maintain that it was appropriate to do so because it had a high quality fall assessment. However, the study by Graafmans et al also violated the inclusion criteria since falls was only added as an end point in a cohort study two years after randomisation to a fracture study.5 Four of the five negative results relating to a threshold on “low dose” vitamin D and falls were by Broe et al and Graafmans et al.

Figure 3 in Bischoff-Ferrari and colleagues’ meta-analysis is misleading2: it was not simply misinterpreted by the Institute of Medicine. The figure uses the layout of a typical meta-regression plot and shows a “trend line” that resembles a meta-regression summary line. Using the same data, the IOM found that the meta regression analysis on falls was not significant (figure).1

Figure1

Meta-regression plot. Relative risk is 0.95 (95% confidence interval 0.89 to 1.02; P=0.13) per 100 IU/day increase in dose and 0.92 (0.80 to 1.05; P=0.17) per 10 nmol/L increase in mean achieved 25-hydroxyvitamin D concentration. Reproduced with permission from reference 1 by the National Academy of Sciences

The internal inconsistencies of the paper and the selectivity of the dose-response analyses justified the IOM’s reanalysis. Properly powered double blind studies of vitamin D on falls are needed but no more meta-analyses.

Notes

Cite this as: BMJ 2011;342:d4046

Footnotes

  • Competing interests: None declared.

References