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 in doctors' offices with thigh pain that is easy to mistake for hip or knee arthritis. They have a unique constellation of radiologic findings on imaging, and they either have permanent titanium rods placed in their thigh bones or go on to full femur fractures—sometimes bilaterally—and permanent disability.
No one can yet say for sure whether they would have had those fractures regardless of bisphosphonate use, nor can anyone say if femur fractures are limited to alendronate (Fosamax) users or are a bisphosphonate class effect.
But a trend is emerging, and with it a treatment protocol.
“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 definitely 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 of the femur. 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.
There is a strong belief “from our sports medicine folks and rheumatologists” that there is a relationship with bisphosphonates, he said.
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 case, 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 their strength and ambulation during their convalescence, he added.
“The fractures are devastating,” said UCLA and Cedars-Sinai rheumatologist Dr. Solomon N. Forouzesh, who is the medical director of the rehabilitation department at Brotman Medical Center in Culver City, Calif. He said he's seen two cases in his practice.
Osteopenic Women 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.
In the past, she added, use of the drugs might have been “too aggressive.”
A Drug Holiday Is Advised
As the story unfolds, doctors are using bisphosphonates for shorter lengths of time than in the past, followed by a drug holiday and ongoing bone-density monitoring.