Low vitamin D related to decreased response to bisphosphonates

Issue: July 2011

ENDO 2011

BOSTON — Women with 25-hydroxyvitamin D levels greater than 33 ng/mL are seven times more likely to benefit from bisphosphonate therapy compared with women with lower levels, researchers found in a new study.

“Maintaining adequate vitamin D levels above those recommended by the Institute of Medicine is important for optimizing a standard therapy for osteoporosis, which is bisphosphonates,” Richard Bockman, MD, PhD, chief of the endocrine service at the Hospital for Special Surgery and a professor of medicine at Weill Cornell Medical College in New York, said at a press conference. “Nearly 20 million Americans take bisphosphonates for osteoporosis. Many of those who take bisphosphonates have suboptimal levels of 25-hydroxyvitamin D.

The Institute of Medicine (IOM) issued recommendations for vitamin D intake in November 2010, suggesting that most adults up to age 70 years need no more than 600 IU per day to maintain bone health. This dose is said to achieve the minimum adequate vitamin D level of 20 ng/mL.

For their study, Bockman and colleagues conducted a retrospective chart review of patients at a specialty osteoporosis practice. They identified postmenopausal women who had been taking alendronate (Fosamax, Merck), risedronate (Actonel, Warner Chilcott), ibandronate (Boniva, Roche) or zolendronate (Aclasta, Reclast, Zomera and Zometa; Novartis) for at least 18 months. The women also had undergone at least two DXA scans that were taken at 18 to 60 months apart.

The researchers collected data about age, BMI, bisphosphonate usage, concurrent calcium supplementation, fractures before or during therapy, bone mineral density and T-scores at the lumbar spine, femoral neck, trochanter and total hip. Measurements of 25-hydroxyvitamin D were obtained either with or between the two most recent DXA scans.

Patients were classified as responders to bisphosphonate therapy or non-responders. Non-responders were classified as having more than a 3% decrease in BMD at any site between DXA scans; incident low-fracture despite more than 12 months of bisphosphonate use; or a T-score of less than –3.0 at any site despite 24 or more months of bisphosphonate use.

The study included 160 patients: 89 responders and 71 non-responders. Among the responders, 16.8% were vitamin D insufficient, whereas 54.9% of the non-responders were vitamin D insufficient. Patients with 25-hydroxyvitamin D levels of 20 ng/mL or less had a non-response rate of 83.3%. Those with 25-hydroxyvitamin D levels of 20 to 30 ng/mL had a non-response rate of 77.8%. Patients with a 25-hydroxyvitamin D level of 30 to 40 ng/mL had a non-response rate of 42.3% and those with a 25-hydroxyvitamin D level of more than 40 ng/mL had a non-response rate of 24.6%.

“The value of at least 33 ng/mL [found to be associated with bisphosphonate benefit in this study] is higher than the level considered adequate by the IOM report for the general population, and most likely requires a vitamin D intake higher than 600 IU for this therapeutic outcome,” Bockman said. “In the future, I think we’re going to see vitamin D recommendations based on specific conditions.” – by Emily Shafer

Disclosure: Dr. Bockman reports no relevant financial disclosures.

For more information:

Bockman R. #P1-228. Presented at: The Endocrine Society 93rd Annual Meeting & Expo; June 4-7, 2011; Boston.

The investigators appear to prove what many endocrinologists would like to believe: the FDA has recommended too low a daily dose of vitamin D. There are a few caveats. This study is not a randomized clinical trial and may be biased by unknown confounders that might affect the outcome. Also, some patients were vitamin D-deficient and yet met the criteria for response to a bisphosphonate. Finally, the definition used in this paper of what is a bisphosphonate response (other than fracture risk reduction) might not be agreed upon by all (acknowledging the outstanding credentials of the researchers).

– Donald A. Bergman, MD
Endocrine Today Editorial Board member

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