Low vitamin D related to decreased response to bisphosphonates

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, according to researchers at Hospital for Special Surgery.

“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,” study author Richard Bockman, MD, PhD, 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.”

A retrospective chart review

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, risedronate, ibandronate or zolendronate for at least 18 months. The women also had undergone at least two densitometry 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.

Retooling vitamin D recommendations

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 … 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.”

For more information:

  • Shieh A, Carmel A, Bockman RS. Vitamin D insufficiency is associated with decreased bisphosphonate response. Paper #P1-228. Presented at The Endocrine Society’s 93rd Annual Meeting & Expo. June 4-7, 2011. Boston.

Disclosure: Bockman has no relevant financial disclosures.


These authors have presented some critical information for clinicians who treat osteoporosis. In this study, the authors have discovered a direct link between serum 25-hydroxyvitamin D levels and the ability of bisphosphonates to maintain or improve bone mineral density. Vitamin D is a critical cofactor for the efficaciousness of prescription antiresorptive medications, specifically bisphosponates.

There has been a recent resurgence in attempting to raise the awareness of all physicians regarding the undertreatment of osteoporosis following a fragility fracture. Dialogue around the barriers to timely osteoporosis diagnosis and treatment has tended to focus on bisphosphonates. Often calcium and vitamin D are overlooked because they are not prescription medications, and because they alone are not considered sufficient to treat osteoporosis. However, this study has demonstrated that these supplements are not only necessary for normal bone metabolism, but are a prerequisite for maximum clinical benefit of bisphosphonate therapy. Interestingly, the authors also found that this is not an all-or-none phenomenon, but occurs in a dose-dependent manner, underscoring the importance of appropriate vitamin D dosing.

— Michael J. Gardner, MD
Orthopaedic Trauma Service
Assistant Professor
Department of Orthopaedic Surgery
Washington University School of Medicine

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