According to preliminary research presented this week at the 2010 Annual Meeting of the American Academy of Orthopaedic Surgeons held in New Orleans, LA, bisphosphonate drugs may adversely affect bone quality and increase the risk of atypical femur fractures in postmenopausal women with osteoporosis when used for four or more years, compared with women not treated with the drugs.

Results from two studies were presented at the meeting. Researchers from the first study, conducted at Columbia University Medical Center, evaluated the bone structure of 111 postmenopausal women with primary osteoporosis, including 61 patients who took bisphosphonates for a minimum of four years and 50 patients who did not take bisphosphonates. Findings indicated that while bisphosphonates initially help patients' bones, but things take a turn for the worse after years of treatment. “In the early treatment period, patients using bisphosphonates experienced improvements in all parameters, including decreased buckling ratio and increased cross-sectional area,” said Melvin Rosenwasser, MD, orthopaedic surgeon for Columbia University Medical Center. “However, after four years of use, these trends reversed, revealing an association between prolonged therapy and declining cortical bone structural integrity.”

In an unrelated prospective pilot study, researchers from the Hospital for Special Surgery in New York, NY evaluated the bone composition of 21 patients, including 12 patients who had taken bisphosphonate drugs for an average of 8.5 years and 9 patients who had not taken the drugs. Investigator Brian Gladnick, BS, explained that “patients who had been treated with bisphosphonates showed a reduction in tissue heterogeneity, specifically with mineral content and crystal size compared with the control group. This tells us that there may be some measurable differences in bone quality parameters in patients on long-term bisphosphonate therapy, which might contribute to the development of atypical fractures.”

Dr. Rosenwasser noted that “bisphosphonate use still is a very effective solution that prevents bone loss in most patients and no one is recommending that physicians avoid prescribing these.” The investigators emphasized that more research is needed to determine the efficacy of long-term clinical use of bisphosphonates for the treatment of osteoporosis. Results of these two studies are not expected to affect clinical practice in the near future.

In a separate safety announcement, the FDA said that its review of the long-term use of oral bisphosphonates is ongoing. In June 2008, the agency requested information from all bisphosphonate drug manufacturers regarding the potential increased risk of atypical subtrochanteric femur fractures in women with osteoporosis being treated with the products.