Hip Fractures Associated with Low Vitamin D

Abstract & Commentary

By Mary Elina Ferris, MD, Clinical Associate Professor, University of Southern California. Dr. Ferris reports no financial relationship to this field of study.

Synopsis: Women who had low serum 25(OH) vitamin D concentrations were observed to have a higher hip fracture risk independent of other factors.

Source: Cauley JA, et al. Serum 25-hydroxyvitamin D concentrations and risk for hip fractures. Ann Intern Med 2008;149:242-250; summary for patients in Ann Intern Med 2008;149:I42.

Using a database of nearly 40,000 postmenopausal women from 40 U.S. sites who had no prior hip fractures and were not taking estrogens or other treatments for osteoporosis within the prior year, 400 cases of hip fracture were matched by age, ethnicity, and time of blood draw with 400 control cases without fractures. Serum was obtained at baseline visits, and cases were followed by annual survey with medical record confirmation for a median of 7.1 years (range, 0.7-9.3 years). Along with comparing serum 25-hydroxyvitamin D values, measurements of falls, physical function, frailty, renal function, and hormone levels were also utilized.

Mean serum 25(OH) vitamin D levels were lower in women with hip fractures compared to controls, and the lowest concentrations had higher fracture risk than the highest concentrations. The association was linear and did not differ by age. The risk of hip fracture decreased statistically with each quartile increase of serum 25(OH) vitamin D. Cases with subsequent hip fractures also had baseline labs showing higher cystatin C and bone resorption marker levels than did controls.

Compared with control participants, patients with hip fractures also had a lower body mass index, performed less physical activity, were more likely to report fair or poor health status, poor physical function, and smoking, and were more likely to be considered frail. After adjusting for physical activity and falls, the association was less robust, but remained. No differences were seen with vitamin D supplementation, alcohol use, or geographic location. Even though serum 25(OH) vitamin D levels were lower in obese women and those who lived in northern latitudes, there was no difference in hip fractures among the cases and controls.

Commentary

Although the importance of vitamin D for bone health is well established, there remains controversy over whether vitamin D supplementation should be recommended to prevent hip fractures. In the Women's Health Initiative (WHI), 36,282 postmenopausal women were randomly assigned to take either daily placebo or calcium with 400 IU of vitamin D3. After seven years, there was a small improvement in hip bone density, but no significant reduction in hip fracture, and an increase in the risk of kidney stones.1 Another epidemiologic study in Britain using 750 fracture cases and 1,400 controls found no increased fracture risk with lower serum 25(OH) vitamin D levels, although there were associations between the levels and multiple other factors.2

The authors of this current study find the opposite, and point out that their study used different cutoffs of serum 25(OH) vitamin D, and also used more accurate measurement technology. Their measurements did not distinguish between vitamins D2 and D3, which has caused confusion in the past. More than half the women in the WHI study took estrogen therapy, which may have been a confounding factor. Most other studies have compared all fractures rather than isolating hip fractures.

The authors admit that the association they found does not necessarily mean that vitamin D supplementation will reduce fracture risk, but a low serum level could be used to identify women with higher risk. It seems clear to me that the patient's report of taking vitamin D may not correlate with the serum levels for many other reasons, and that the occurrence of the dreaded hip fracture is a product of many interacting variables.

References

1. Jackson RD, et al; Women's Health Initiative Investigators. Calcium plus vitamin D supplementation and the risk of fractures. N Engl J Med 2006;354:669-683.

2. Roddam AW, et al. Association between plasma 25-hydroxyvitamin D levels and fracture risk: The EPIC-Oxford study. Am J Epidemiol 2007;166:1327-1336.