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.”

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.

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

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.

  Michael J. Gardner
  Michael J. Gardner

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

— Michael J. Gardner, M
Orthopaedic Trauma
Service, Assistant Professor, Department of Orthopaedic Surgery Washington
University School of Medicine
Disclosure: Gardner has no relevant financial

Leave a Reply

Your email address will not be published.