Vitamin D Concentration Linked to Hip Fracture Risk

By Todd Neale
PITTSBURGH, 19 aug 2008 -- In postmenopausal women, low serum vitamin D concentrations were associated with an increased risk for hip fracture in a nested case-control study here.
Women with the lowest serum concentrations of 25-hydroxyvitamin D were 71% more likely to have a hip fracture than those with the highest (OR 1.71, 95% CI 1.05 to 2.79), Jane Cauley, Dr.P.H., of the University of Pittsburgh, and colleagues, reported in the Aug. 19 issue of Annals of Internal Medicine.
Adjusting for C-terminal telopeptide of type I collagen -- a marker for bone resorption -- seemed to eliminate the association (OR 1.58, 95% CI 0.97 to 2.60), the researchers said, but the overall trend remained significant in a multivariate model (P=0.029).
"Our findings suggest that low serum 25-hydroxyvitamin D concentrations might help identify women at high risk for hip fracture," they said.
Past studies examining the link between serum vitamin D concentrations and risk of fracture have yielded mixed results, they said.
To explore the issue, the researchers turned to the Women's Health Initiative Observational Study, a large prospective cohort study of participants ages 50 to 79.
They selected 400 women who had an incident hip fracture and 400 controls from 40 clinical centers around the U.S. for a case-control study nested within the larger study.
All of the participants were postmenopausal (mean age 71, 95% white) and were not using estrogens or other osteoporosis medications.
Serum vitamin D concentrations were measured at baseline and the participants were followed annually with questionnaires for a mean of 7.1 years (range 0.7 to 9.3).
At baseline, concentrations were lower in the case patients than in the controls (55.95 nmol/L versus 59.60 nmol/L, P=0.007).
For each 25-nmol/L decrease in vitamin D concentration, the risk of hip fracture was increased by 33% (OR 1.33, 95% CI 1.06 to 1.68).
Risk of hip fracture decreased significantly from women in the lowest quartile of vitamin D concentration (≤ 47.5 nmol/L) to those in the highest (≥ 70.7 nmol/L) (P=0.016 for trend).
The association did not vary by age and remained significant when adjusted for the number of falls, physical function, frailty, renal function, sex-steroid hormone levels, geographic location, and obesity.
The researchers said that the mechanism of the association remained unclear but suggested several ways that serum vitamin D concentration and fractures could be related.
Vitamin D concentration could influence muscle strength and balance, and consequently, falls and disability, they said.
In addition, they said, the relationship could be influenced by sex-steroid hormones, bone turnover, and renal insufficiency, which has been linked to both fracture risk and vitamin D deficiency.
The authors acknowledged several limitations of the study, including the possibility of seasonal variability in the blood tests, the fact that almost all participants were white, the lack of distinction between 25-hydroxyvitamin D2 and D3, the failure to measure parathyroid hormone, the inclusion of few women with a serum vitamin D concentration greater than 75 nmol/L, and potential residual confounding.
In addition, they did not measure bone mineral density, which may provide varying information on fracture risk so they could not determine whether 25(OH) vitamin D concentrations give different information about fracture risk than that offered by bone-mineral density.
The Women's Health Initiative was funded by the National Heart, Lung, and Blood Institute. Additional support was provided by U.S. Public Health Service Research grants. One of Dr. Cauley's co-authors is supported by a grant from the National Center for Research Resources.
Dr. Cauley and her co-authors reported potential conflicts of interest with Novartis, Eli Lilly, Merck, Roche Diagnostics, Johnson & Johnson, Procter & Gamble, Amgen, GlaxoSmithKline, Zelos, sanofi-aventis, General Electric, Pfizer, MicroMRI, and Abbott.
Primary source: Annals of Internal MedicineSource reference:Cauley J, et al "Serum 25-hydroxyvitamin D concentrations and risk for hip fractures" Ann Intern Med 2008; 149: 242-250.