Osteoporosis Drugs, Like Fosamax May Increase Risk of Broken Bones in Some Women
Long-term Use of Popular Class of Osteoporosis Drugs May Have Opposite Effect for Some Women, Experts Say
By CHRISTINE ROMO and LARA SALAHI|
March 8, 2010
Sandy Potter, 59, of Queens, N.Y., was jumping rope with neighborhood children when she felt her thigh bone snap.
Commonly prescribed drug meant to strengthen bones may have the opposite effect.
"I went up in the air and I came straight down to the ground," Potter said. "The pain was excruciating."
Potter, who was diagnosed with osteoporosis at age 48, had been taking the popular osteoporosis drug Fosamax for eight years before breaking her femur.
Fosamax, one in a class of drugs called bisphosphonates, is supposed to make bones stronger, and for many women, it is safe and effective. But now there's mounting evidence that, for some women, taking these medications for more than five years could cause spontaneous fractures.
"We are seeing people just walking, walking down the steps, patients who are doing low-energy exercise," said Dr. Kenneth Egol, professor of orthopedic surgery at NYU Langone Medical Center. "Very unusual, the femur is one of the strongest bones in the body."
Egol said X-rays of some of his patients look more like injuries from car accidents than from an otherwise-minimal fall.
"Over the last 18 months, we are seeing this more frequently," he said.
Sue Heller, 60, of Castle Rock, Colo., had been on Fosamax for almost 10 years. She broke both of her femur bones.
"I'm sure there are a lot of women who have brittle bones right now that maybe are ready to break, and they're not aware of it," said Heller. "And my heart aches for them."
Sales of the popular drug increased when doctors began prescribing it, not only to women with osteoporosis, but to others who were osteopenic -- with reduced bone density that might lead to the disease. Now some doctors worry that staying on the drug for more than five years can cause some women's bones to become more brittle.
Weighing the Risks
This is not the first time that many doctors have reported an opposite effect for people taking the drug. Fosamax has already been linked to severe musculoskeletal pain, as well as a serious bone-related jaw disease called osteonecrosis.
Also, the Food and Drug Administration asked the manufacturer, Merck, in 2008 to add information about the report of femur fractures.
After 16 months, Merck added patients' reports of femur fractures to the list of possible side effects included in the drug's package insert.
Photo: Risk of Break in Bone-Building Drug: Popular Class of Osteoporosis Drugs May Have Opposite Effect, Experts Say
Fosamax, one in a class of drugs called bisphosphonates, is supposed to make bones stronger. But now there's mounting evidence that, for some women, taking these medications for more than five years could cause spontaneous fractures.
"It took Merck an entire year to respond," said ABC News senior health and medical editor Dr. Richard Besser. In small print on the package insert listing possible side effects from the drug, he said, there are "just six words: 'low energy femoral shaft and subtrochanteric fractures.'"
The FDA has also never made an effort to inform the public or doctors across the country who prescribe bisphosphonates of the possible side effect, said Besser.
Both the FDA and Merck declined ABC News' request for interviews. The FDA said it is looking into reports of fractures.
"Nothing is more important to Merck than the safety of its medicines," said a written statement from Merck to ABC News. "A causal association has not been established between long-term bisphosphonate use and subtrochanteric femoral fractures. In clinical studies, FOSAMAX (alendronate sodium) has not been associated with increased fracture risk at any skeletal site. The company currently has several ongoing epidemiological studies to further investigate the issue of subtrochanteric femoral fractures."
Dr. Joseph Lane, orthopedic trauma surgeon at the Hospital for Special Surgery in New York City, said, "The drug companies have to recognize when there is a problem, they have to be up front with the public. If there's a concern, they have to voice it and at least give everybody a fair chance to look at this carefully."
How Much for How Long?
Many studies suggest an overall benefit from taking the medication for women who are at risk for osteoperosis. In fact, bisphosphonates can help to prevent hip and spine fractures, which for many women may lead to death.
"Normally your bone is constantly being remade," Lane said. "These patients don't remake their bone and they acquire damage, microdamage, the collagen gets altered and we need to rejuvenate the skeleton."
In 2008, bisphosphonate sales exceeded $3.5 billion according to data from IMS Health. In 2008, over 37 million prescriptions were written for the osteoporosis medications.
While some physicians use bone density scans to help drive their decisions, doctors generally prescribe them to women who are at an increased risk for either osteoporosis or fractures from osteoporosis they already have. A new tool developed by the World Health Organization can determine the risk of having fractures and can help doctors determine which women with osteoporosis should be treated with medications.
Although bisphosphonates are generally recommended for postmenopausal women, research does not indicate how long women should be on the drug. Many doctors now recommend a five-year limit.
"When they are on it for five, six, seven or eight years, they lost their ability to remodel and regenerate their skeleton," said Lane. "[A subset of women] are very vulnerable and they will then develop problems of brittle bone."
Additional time on the medication depends on doctors' orders, said Besser.
Bone Loss Drug Linked to Rare Fracture
Long-Term Use of Osteoporosis Drug Fosamax May Weaken Long Bones
By Daniel J. DeNoon
WebMD Health News
Reviewed by Louise Chang, MD
March 19, 2008 -- Long-term use of the osteoporosis drug Fosamax may weaken the bones in a small subset of people taking the drug.
Patients who suffer this unusual side effect suffer broken legs after minor falls. It's likely that other drugs in the same class as Fosamax -- the bisphosphonates -- have the same rare side effect. It is seen in only a small number of patients who took the drug for more than five years.
Joseph M. Lane, MD, chief of the metabolic bone disease service at New York/Presbyterian Hospital and professor of special surgery at Weill Medical College of Cornell University and colleagues report the side effect in a letter to the March 20 issue of The New England Journal of Medicine.
"There is a subset of patients for whom the longer they take bisphosphonates, the more they turn off the internal repair of the bone. This sets them up for bone fractures after trivial falls," Lane tells WebMD. "Is everyone who takes a bisphosphonate going to get this? No. This is a subset of patients. But we cannot say what makes these patients unique. And is it unique to this one bisphosphonate, or to all drugs in this class? We don't know."
Lane and colleagues report 15 cases of unusual bone fractures in postmenopausal women who had been taking Fosamax for more than five years. All had fractures along the length of the femur, the long bone in the thigh, after falls from standing position or lower.
Ten of the patients had a distinct and unusual fracture pattern. These patients had been taking Fosamax for more than seven years on average; the other five patients averaged less than three years of Fosamax use.
"People on prolonged bisphosphonates -- and Fosamax is the only one we have seen so far -- after five to seven years they are at risk of fractures in the long bone of the leg," Lane says. "They complained of thigh pain for months before the breaks. So it seems they start off with a stress fracture that is unrecognized, and it goes on to full fracture."
Susan Bukata, MD, director of the center for bone health at the University of Rochester, New York, says orthopaedic surgeons and specialists in metabolic bone disease are well aware of this problem. Bukata was not involved in the Lane report.
"This is not seen only with Fosamax. We see this in cancer patients given high doses of Zometa as well," Bukata tells WebMD. "Fosamax was the most commonly used bisphosphonate for the longest time. And it takes several years on the drug before it seems to be a problem. So more people have been on Fosamax long term than on Actonel or the several other bisphosphonates."
What's going on? Bisphosphonates keep the body from reabsorbing bone. That slows bone loss in osteoporosis. But it also interferes with the body's natural bone-repair process.
That's why a growing number of bone experts suggest that after about five years of bisphosphonate use, patients should take a "drug holiday" until blood tests show their bone turnover increasing. It's done in Europe and in Australia, and in a growing number of U.S. bone centers -- including Lane's and Bukata's institutions.
"Remember, bisphosphonates go into the bone like money goes into an IRA. Put money in now and it comes out, slowly, later," Lane says. "The general thought is that after about five years of bisphosphonate treatment, you stop for a year or two. And if bone-turnover markers go up, restart, and if not, watch. Some patients on bisphosphonate holiday followed for up to four years have not shown any change in these markers and are steady."
Meanwhile, Bukata warns patients not to stop taking their osteoporosis drugs.
"The average person should not worry about this -- and certainly should not stop taking their bisphosphonates," she says. "We as doctors need to be aware of this and start finding out who is at risk and why. But the last thing we want is for people to stop taking their bisphosphonates because of this type of fracture."
Lane notes that the rare leg fractures linked to Fosamax use are far less dangerous than the hip fractures the drug prevents.
"Public-health-wise, I will take these [leg] fractures, because hip fractures, which are lethal, go down 50% with use of these drugs," he says.
Bisphosphonate drugs for osteoporosis include Actonel, Actonel+Ca, Boniva, Fosamax, Fosamax+D, Reclast, and Zometa.
Other bisphosphonates include Aredia, Didronel, Skelid, and Zometa.
Merck, the drug company that makes Fosamax, did not respond to WebMD's request for a response to the Lane report.