Controversy over Bone Drugs Builds

Yesterday's New York Times reported on increasing evidence that long-term use of bisphosphonates, a class of drugs used to decrease the risk of fractures in people with osteoporosis, may lead to weaker bones in some people. The concern arises mainly from case reports of fractures that occurred with little or no trauma, including an unusual type of fracture to the upper thigh bone. In addition, patients on bisphosphonates may experience delayed fracture healing.

Studies of bisphosphonates which include alendronate (Fosamax), risedronate (Actonel), and ibandronate (Boniva), show the drugs increase bone density and decrease fracture risk. The drugs, which are heavily advertised (think Sally Fields and Boniva) are used by large numbers of women and a smaller number of men with osteoporosis.

Bone remodeling is the process by which old bone is dissolved and new bone added. Bisphosphonates slow the dissolving of old bone and thus preserve bone density. However, there has long been a concern, based on theory and animal studies, that microscopic bone cracks that occur through normal wear and tear ("microdamage") may not be repaired when bone remodeling is suppressed. This concern is increased when bisphosphonates are combined with another drug that may inhibit bone turnover, such as estrogen.

In 2005, the Journal of Clinical Endocrinology and Metabolism published a report on nine patients who had nontraumatic fractures after 3 to 8 years on alendronate. Bone biopsies revealed severe reductions in bone formation rates. Six of these patients had fractures that did not heal properly.

Since then, there have been other similar case reports.

Based on these reports, some experts have suggested that bisphosphonates should be stopped after five years, and that studies should be conducted to determine the risks and benefits of long-term therapy. In addition, use of the drugs should be limited to people who are at a high enough risk of fracture to justify the possible risks.

-- PM