MARINA DEL REY, CALIF. — As the debate unfolds over both whether bisphosphonates cause femur fractures and the degree to which the benefits of drugs still outweigh the risks, a phenomenon has emerged.
Women who have taken bisphosphonates for years are being seen with thigh pain that is easy to mistake for hip or knee arthritis. They have a unique range of radiologic findings, and they either have permanent titanium rods placed in their thigh bones or go on to full femur fractures—sometimes bilaterally—and permanent disability.
“The thinking [among colleagues] is that this is novel and specific to bisphosphonate treatment, but only time will tell,” Dr. Benjamin C. Bengs, an orthopedic surgeon at the University of California, Los Angeles, said in an interview.
The possibility must be added to the hip pain differential in women with long-standing use of the drugs, according to Dr. Bengs and others who were interviewed for this story.
Unusual Radiology Findings
For many of the doctors who were interviewed, the question isn't so much whether bisphosphonates cause femur fractures, but rather how to care for women with a long history of using the drugs, and how to recognize signs and symptoms of impending trouble.
Any woman with pain over the thigh and those x-ray findings is a candidate for prophylactic rodding, said Dr. Bengs.
The unique findings on x-ray are cortical thickening that is most pronounced on the lateral side of the femur, accompanied by a beaking lesion, also on the lateral side. Intramedullary edema is often present.
The beaking lesion is the start of a horizontal or oblique stress fracture. In time, there generally develops a “little, lucent, dark line extending from the beak to the middle of the bone,” Dr. Joseph Robinson, a radiology fellow at Cedars-Sinai Medical Center in Los Angeles, said in an interview.
“Lateral stress fractures are unusual. In our area, they are all related to bisphosphonates,” Dr. Kambiz Motamedi, a diagnostic radiologist at UCLA Medical Center.
Both Legs Must be Examined
Standard hip x-rays don't go far enough down to detect the lesion, which is closer to the knee than the typical femur fracture would be, Dr. Robinson said. When they do a hip series, Cedars-Sinai radiologists are careful to image lower down so they don't miss it, he said, noting that they are also putting markers on skin to identify the source of pain.
If the lesion is found, it is imperative to image the other femur as well, said Dr. Stuart L. Silverman, a rheumatologist in private practice in Beverly Hills, Calif. The other femur can go on to fracture, often within 18 months, he said in an interview.
Dr. Bengs noted that in most cases, rodding is the usual treatment. It takes only a matter of weeks to recover from hip-to-knee rod placement, he said. It takes months to recover from a fracture, however, and older patients usually lose 10%–15% of strength and ambulation during convalescence, he added.
“The fractures are devastating,” said UCLA and Cedars-Sinai rheumatologist Dr. Solomon N. Forouzesh, who has seen two cases in his practice.
Who is at Risk?
Active women who have osteopenia—not osteoporosis—appear to be most at risk, Dr. Nancy Lane, a University of California, Davis, rheumatologist, said in an interview. “What I think is going on” is that bisphosphonates, by reducing bone turnover, lead to the overmineralization of cortical bone, she explained. “Over time, the bones become brittle [and] fail from too much mineralization. They cannot dissipate the load.”
It's “probably best not [to use bisphosphonates] in people with low risk of fractures who are very active,” she said, adding that use of the drugs might have been “too aggressive” in the past.
A Drug Holiday Is Advised
As the story unfolds, doctors are using bisphosphonates for shorter lengths of time, followed by a drug holiday and ongoing bone-density monitoring.
The risk of fracture seems to “start at about 3 years and peaks between 5 and 6 years,” Dr. Forouzesh said. To be ahead of the game, he advises not waiting until the risk peaks. “Back off ahead of time. I do a drug holiday in 3 or 4 years,” he said.
It's not clear at this point if the phenomenon—if it is truly real—is limited to alendronate or a bisphosphonate class effect.
Alendronate has been on the market the longest and has been the most widely used agent, Dr. Lane noted. “I am sure over time” it will emerge with other members of the class, as well, she said.