Boning Up on Bone Drugs

Can a drug intended to prevent fractures cause them? The scoop on osteoporosis meds.

by Katharine Davis Fishman
Photograph: Photo: Coolife and Carole & Pauline

The subject of bisphosphonates and femur fractures was a point of controversy at the American Society for Bone and Mineral Research conference in the fall of 2008, when a case was made that these drugs were not the problem. Bo Abrahamsen, an endocrinologist at Copenhagen University Hospital, had studied registry data for all patients born in 1945 or earlier who entered Danish hospitals with fractures from 1996 to 2005. He fished out those who had been treated with bisphosphonates and matched them with controls who hadn’t taken those drugs but had experienced a fracture in the same place. If Lane’s hypothesis were true, the patients taking bisphosphonates would have gotten more of the atypical-femur fractures while the untreated controls would have gotten more of the old-fashioned osteoporotic fractures, yet that hadn’t happened.

Thus Abrahamsen concluded that the fractures Lane had deemed atypical were just ordinary osteoporotic fractures after all. The U.S. government, which is continuing to investigate the side effects of bisphosphonates, cited Abrahamsen’s study when it released a statement this March, saying, “At this point, the data that the FDA has reviewed have not shown a clear connection between bisphosphonate use and a risk of atypical subtrochanteric femur fractures.”

Merck, not surprisingly, concurs. While the company would not allow me to interview its researchers, a statement from its media-relations department said, “In clinical studies, Fosamax has not been associated with increased fracture risk at any skeletal site.” A recent analysis funded by Merck and another drug company also found no connection, though the investigators said their study was too small to be definitive.
On the other hand, two New York teams, one at Columbia and another (including Lane) at the Hospital for Special Surgery, recently presented small controlled studies of postmenopausal women with osteoporosis at the 2010 annual meeting of the American Academy of Orthopaedic Surgeons. The HSS team biopsied osteoporotic bone while the Columbia group analyzed the patients’ scans, and both studies buttress the theory that long-term bisphosphonate use alters bone properties so as to increase the risk of atypical femur fractures.

The risk appears quite small, however, relative to the odds of experiencing a hip fracture. This issue was explored in a large study done by orthopedist Richard Dell of -Kaiser-Permanente in Southern California. The study is important because Kaiser-Permanente is, as Dell puts it, “a closed shop,” meaning it provides comprehensive medical care and has complete medical records for large numbers of people. Dell looked at films and files of 172,000 people age 45 and older taking oral bisphos-phonates for more than three years, and he concluded that the drugs prevented 3,050 hip fractures that would have occurred in the untreated general population. At the same time, only 50 people in that group suffered bisphosphonate femur fractures like mine. (Merck is still looking into the question; it has funded a study run by Kaiser Pacific Northwest on the distribution and classification of femur fractures. Like Dell’s, this study will review X-rays and medical charts.)

Weighing the Risks
So the question is, How can doctors identify ahead of time the likely candidates for femur fractures—that is, patients who should not be given bisphosphonates, or at least not for very long? Dell, now analyzing his data before publication, has a few hints. Like Lane, he suspects that the most likely femur-fracture victims are younger (in their sixties and early seventies), more active and on the medication for a long time; some seem to be on other drugs as well, including prednisone and estrogen.

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