FDA will continue review of bisphosphonate, femur fracture risk

Two small studies presented this week highlight potential risk.

The FDA has ruled out a suggested link between bisphosphonate use and risk for atypical subtrochanteric femur fractures.

“Recent news reports have raised the question about whether there is an increased risk in this type of fracture in patients with osteoporosis using these medications. At this point, the data that FDA has reviewed have not shown a clear connection between bisphosphonate use and a risk of atypical subtrochanteric femur fractures,” according to an FDA Drug Safety Communication statement.

In June 2008, the FDA requested information from all bisphosphonate drug manufacturers regarding a potential safety signal of atypical subtrochanteric femur fractures in women with osteoporosis using bisphosphonates, such as alendronate (Fosamax, Merck), risedronate (Actonel, Proctor & Gamble), ibandronate (Boniva, Roche) and zoledronic acid (Reclast, Zometa, Novartis). The agency’s review of all requested case reports and clinical trial data did not show an increase in this risk for women using bisphosphonates.

The FDA also reviewed a December 2008 study published in the Journal of Bone and Mineral Research by Abrahamsen et al. The researchers analyzed data from two large, observational studies in patients with osteoporosis, and concluded that atypical subtrochanteric femur fractures had many similar features as classical osteoporotic hip fractures (patient age, sex, trauma mechanism). Data showed that patients taking bisphosphonates had similar numbers of atypical subtrochanteric femur fractures relative to classical osteoporotic hip fractures compared with those not taking bisphosphonates.

The FDA urged health care professionals to continue to follow recommendations on the bisphosphonate drug label when prescribing the drug. The agency further recommended that health care professionals be aware of the possible link between bisphosphonates and atypical subtrochanteric femur fracture; discuss known benefits and potential risks with patients; and report any adverse events to the FDA’s MedWatch program.

The FDA said it will continue to work with outside experts, including members of the American Society of Bone and Mineral Research Subtrochanteric Femoral Fracture Task Force, to gather additional information to provide further insight into the link between bisphosphonates and fracture.

New data this week

Two preliminary studies presented at the 2010 Annual Meeting of the American Academy of Orthopedic Surgeons suggest that long-term suppression of bone remodeling by bisphosphonates may alter material properties of bone, and may potentially affect the bone’s mechanical integrity and contribute to the risk for atypical fractures.

Researchers at Columbia University Medical Center evaluated the bone structure of 111 postmenopausal women with primary osteoporosis; 61 had been taking bisphosphonates for at least four years and 50 controls were taking calcium and vitamin D supplements. Bisphosphonates improved structural integrity early in the course of treatment; however, those gains were diminished with long-term treatment, according to an AAOS press release.

“In the early treatment period, patients using bisphosphonates experienced improvements in all parameters, including decreased buckling ratio and increased cross-sectional area,” Melvin Rosenwasser, MD, orthopedic surgeon at Columbia University Medical Center, said in the release. “However, after four years of use, these trends reversed, revealing an association between prolonged therapy and declining cortical bone structural integrity.”

The second unrelated, prospective, pilot study evaluated the bone composition of 21 postmenopausal women who were treated for femoral fractures; 12 had a history of bisphosphonate treatment for an average 8.5 years and nine had no history of treatment. Researchers at the Hospital for Special Surgery analyzed microarchitecture and material properties of the bone, using samples removed from each patient’s femur during surgical placement of a femoral nail. The researchers reported no between-group differences in bone microarchitecture. However, material properties of the bone displayed reduced bone tissue heterogeneity in bisphosphonate-treated patients. This may be associated with reduced strength and may potentially contribute to the presentation of atypical fractures, according to the release.

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