Long-term use of osteoporosis drugs seems to change bones in a way that could lead to unusual leg fractures, according to two reports presented earlier this month at a meeting of orthopedic surgeons. Doctors have reported seeing the unusual fractures in some patients on bisphosphonate drugs such as Fosamax.
It seems paradoxical that a medicine designed to protect against bone fractures in fact might be the cause of broken legs. Adding to the confusion, the U.S. Food and Drug Administration released a statement in the same week as the medical conference that said there is no clear connection, based on available evidence, between the bisphosphonates — including Actonel, Boniva and Reclast in addition to Fosamax — and atypical femur fractures.
The unusual bone breaks — called atypical subtrochanteric femur fractures — were first documented in small clinical reports and through the FDA's MedWatch system, which monitors side effects of drugs after they've been approved. Such reports do not necessarily mean the drug is the cause of the problem, but multiple reports of the same side effect with the same drug can spur additional investigation. Other potential side effects of bisphosphonate drugs have been identified through the FDA's reporting system, including serious jaw deterioration and esophageal cancer.
Here's a closer look at what's known about the safety and effectiveness of bisphosphonates.
What is osteoporosis?
Osteoporosis is a weakening of bones that results from bone loss occurring with age or because of disease. People with osteoporosis can suffer pain, lose inches from their height and are at high risk of fractures in their wrists, hips and vertebrae. Ten million Americans, men and women, have osteoporosis, and the disease causes about 1.5 million fractures every year, according to the National Institute of Arthritis and Musculoskeletal and Skin Diseases.
Doctors use bone density measurements to diagnose the condition, and recommend screening in women over age 65 and men over age 70. Earlier screening should be done in people with certain risk factors, such as those with a family history of osteoporosis or who have broken a bone after age 50; women who went through early menopause or recently stopped hormone therapy; and people taking medications such as prednisone, aromatase inhibitors or anti-seizure drugs.
How do bisphosphonates work?
Normal healthy bone is constantly being renewed through a cycle of dismantling and replacement of bone cells and minerals. Bisphosphonates get incorporated into newly formed bone in place of naturally occurring phosphate, along with calcium. They inhibit the breakdown of bone, thereby favoring the building-up side of the cycle.
The bisphosphonates are extremely effective at reducing the bone loss that occurs in osteoporosis. Clinical trials have shown that drugs such as Fosamax reduce the risk of fractures by 30% to 50% in people with osteoporosis, according to Dr. Daniel Solomon, a professor of medicine at Harvard Medical School, who studies the drugs.
How might bisphosphonates make bones brittle?
Since the drugs interfere with normal bone turnover, it's not hard to imagine that bisphosphonate drugs may affect bone structure.
The atypical fractures in people taking Fosamax — the first of the drug class to be approved, in 1995 — now being noticed by orthopedic surgeons across the country are happening in the thigh bone below the hip rather than within the joint, which is the more normal pattern seen for bones with osteoporosis. And they're straight across the bone, unlike most osteoporotic breaks. They occur among people who have been taking the drug for five years or more.
The reports at the meeting of the American Academy of Orthopaedic Surgeons were detailed studies of bone structure in osteoporosis, in which bones of patients taking bisphosphonates were compared with those of patients receiving other osteoporosis treatments. In one of the reports, a research team led by Dr. Joseph Lane at New York's Hospital for Special Surgery did bone biopsies and found qualitative differences in bone that might explain the atypical fractures. A second study, by a group at New York Presbyterian Hospital, used sophisticated bone density scans and found that bisphosphonate drugs initially increased structural integrity of the femur but that the effect tapered off over four years of treatment.
What's the risk for people taking the drugs?