March 10, 2010— -- Twice doctors have prescribed medications for Jeanette McLearen with great certainty, only to second-guess the outcomes.
After taking hormone replacement for 15 years, the Warren, Mich., retiree was diagnosed with breast cancer. And now, after seven years of taking the controversial drug Fosamax, she is terrified of bone fractures.
Just this week ABC's Dr. Richard Besser reported that Fosamax, one of a class of bisphosphonates used to treat osteoporosis that is supposed to make bones stronger, may actually weaken them after long-term use.
The U.S. Food and Drug Administration announced today that it will look into whether or not a link exists between the use of certain osteoporosis drugs and a particular type of leg fracture after ABC News reports investigated the possible connection.
In numerous cases of women who had taken the drug for long periods of time, their femur bones had just snapped while doing little more than taking a walk.
"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."
Now, at 66, McLearen said her doctor wants her to have further injections for bone loss, but she cancelled her first appointment this week.
"I am scared and I am confused," she said. "I don't know what I think. I don't know what to do."
McLearen, like millions of post-menopausal women, was treated with bisphosphonates for osteopenia, a term used to describe bone mineral density that is lower than normal, but not yet osteoporotic.
The controversy is reminiscent of the medical world's turn-about on use of hormone replacement therapy in 2002. Thought to reduce women's risk of heart disease, combined estrogen and progestin actually increased risks for both that and for breast cancer.
"This is two things for me now, hormone treatment and now this," McLearen said. "They put me on Fosamax thinking it was one thing, and years go by, and they find out it's wrong."
Like osteoporosis, osteopenia occurs more frequently in post-menopausal women as a result of the loss of estrogen. It may affect more than 17 million American women, according to some studies.
Bisphosphonates like Fosamax -- which is also now sold as generic alendronate -- and its pharmaceutical cousins Actonel, Boniva and others, were developed in the mid-1990s to treat osteoporosis, but have been increasingly prescribed for osteopenia.
Doctors use a so-called T-score to determine the amount of bone loss that naturally occurs with aging. A mineral bone density score of -1.5 to -2.5 is considered osteopenia. Over -2.5 is osteroporosis, according to the World Health Organization.
T-scores are measured by bone density machines, known as DXA or dual X-ray absorptiometry.
Though osteopenia is considered a precursor to osteoporosis, not every person diagnosed will go on to develop the disease.
This is not the first time that doctors have reported an opposite effect for Fosamax. The drug, made by Merck & Co., has already been linked to severe musculoskeletal pain, as well as to a serious bone-related jaw disease called osteonecrosis.
After taking Fosamax for eight years, Stephanie George said she was advised not to have dental surgery for an absess on her wisdom tooth until she had been off the drug for five years.
"They said there was a rare, but real chance that my bottom jaw would become infected and might have to be removed," said George, a 67-year-old retired college teacher from Frisco, Texas.
Drug Companies Push Bone-Loss Drugs
She said she was put on Fosamax at age 50 because her thyroid was not processing calcium properly.
"People like Sally Field are pushing Boniva, which is the same damn thing and people are listening and saying, 'Oh, I should really be on that,'" George said.
"The ads say if you are small-boned or tall or white, you may get osteoporosis, but I am all three," she said. "People think that's all there is and they don't know the other side of the story. They don't know what the side effects are."
Though the drug was linked to osteonecrosis in 2004, Merck added no warning until 2005.
"Most reported cases of osteonecrosis in bisphosphonate users have been in cancer patients treated with intravenous bisphosphonates, but cases have also been reported in patients taking oral bisphosphonates, including Fosamax," says Merck on its Web site.
In 2008, the Food and Drug Administration reached out to Merck about the reports of femur fractures. After 16 months, Merck added those patients' reports to the list of possible side effects reported by patients included in the drug's package insert.
"Nothing is more important to Merck than the safety of its medicines," said Merck in a prepared release. "As part of our commitment, Merck closely monitors post-marketing data and reports that information to FDA and other regulatory agencies."
"A causal association has not been established between long-term bishphosphonate use and low energy femoral shaft and subtrochanteric fractures," it said. "In clinical studies, Fosamax (alendronate sodium) has not been associated with increased fracture risk at any skeletal site."
The company did say that these femoral fractures had been reported in non-bisphosphonate users and is doing further investigation.
They cite statistics from the U.S. Surgeon General that show osteoporosis is a national health threat for women over 50 and increases with age.
Doctors disagree on the use of bisphosphonates for those with osteopenia. They say bisphosphonates have helped those with osteoporosis fight bone thinning, but put others with osteopenia at risk with a medication that may not necessarily help them.
McLearen, who now has full-blown osteoporosis, understands the paradox: "I know that they have to help some people, but with these drugs it's money first and I don't think they have researched it enough to give Fosamax it to all these people."
Dr. Nortin Hadler, professor of medicine and microbiology at University of North Carolina at Chapel Hill, is opposed to the treatment of osteopenia, which he says is the "the natural course of aging."
"We have a history of over treatment and over-medicalization of people in this country and we need a discussion that's out loud and up front," said Hadler, author of "Worried Sick" and "The Last Well Person."
For those who are in their 50s and "otherwise healthy," there is no reason to have a bone density test, he said.
A 50-year-old woman with osteopenia has a much lower risk of fracture within a five-year period than an 80-year-old with the same bone density.
In some cases, however, testing makes sense, especially for people prone to osteoporosis because they have taken steroids, have nutritional issues or have inflammatory bowel disease.
The data against testing is persuasive, according to Hadler.
"You have to treat a hundred for a year and maybe you spare one hip fracture," he said. "Most hip fractures are symptoms of frailty. We need more focus on the frailty and the falling."
"Our nation has been taught to fear the consequences of our thinning bones," he said in a 2007 column for ABCNews.com.
But, he said the reason so many elderly die of hip fractures is because of their "decrepitude -- it's a reflection of their ripe old age. Their time is near."
Dr. Ethel Siris, professor of clinical medicine at Columbia University's College of Physicians and Surgeons and director of the Toni Stabile Osteoporosis Center, said she agrees that not all women with osteopenia should be on bisphosphonates, but the issue is a "complicated" one.
"When we get stuff like this on the news, we get millions of calls and people with bad osteoporosis on the drug and at risk for fractures throw away the drugs and are afraid," she said.
"First of all, these are unusual fractures and hard to interpret and a fair number occur in people without bisphosphonates," she said. "This is a rare complication."
Doctors still don't understand why Fosamax might weaken bones in some women. These atypical fractures tend to occur in women with "low turnover" -- the loss and replacement of bone material.
Bone Quality Declines With Age
Bone density tests fail to capture a poorly understood factor known as bone quality, which declines with age.
Women who have been on a combination of bisphosphonates with estrogen or with steroids like prednisone also seem to be more susceptible to femur fracture.
One theory for these unusual bone breaks is that small stress fractures occur and cannot heal.
"You see the doctor and he doesn't see anything and you keep living with the pain, thinking it's a pulled muscle," said Siris. "You go out there and keep moving and it gets worse and worse. But you probably need to go back for an X-ray or an MRI if you are really worried."
The National Osteoporosis Foundation now recommends women be screened with FRAX, a new algorhythm that gives a 10-year probability percentage for bone fracture.
It is a cost-effect way to evaluate additional risk factors: Did the woman have any fractures after menopause? Does she smoke? Is she small and thin? Does she have a family history of osteoporosis? Is she taking drugs that suppress the immune system and can increase risk?
"If you calculate the risk of fracture and it's quite low and the major factors are quite low, we have a choice [about treatment]," she said.
Five years past menopause "the worst bone loss is behind you," according to Siris. Women who are relatively young with no risk factors might just be advised to take more calcium and vitamin D and get more exercise to combat their risk for fractures.
"The message we are giving people with osteopenia is if you are worried about your risk factor, see a doctor, get FRAX and if the risk is low, don't have treatment and get reevaluated," Siris said.
She also recommends taking a "holiday" from bisphosphonates from time to time.
But she adds, "It's very important not to scare the ones who need these drugs into stopping because they think they are going to get these rare complications."
But for women like Janet Cornish, a retired psychiatric nurse from Maggie Valley, N.C., who broke both her femurs without even falling, she is angry that she never questioned her doctor.
Cornish, 74, said she had been on Fosamax for seven or eight years for osteoporosis.
Her first fracture happened in 2007 when she was bracing herself on a step and she heard her leg break. The other leg broke in a motel room last Christmas, when she was just sitting down on a bed to take her socks off.
"Now that I know Fosamax might have been part of it, I am quite angry because I am getting thousands of dollars in medical bills coming in right now," she said. "I would even consider a class action lawsuit."
Cornish's case points to the need for doctors and their patients to discuss risk versus benefit when it comes to taking bisphosphonates.
"Can the patient afford it, will they take it, are there interactions with other meds?" asked Ivy Alexander, director of the nurse practioner program at Yale University and a medical advisor to HealthyWomen.org.
"What is the total risk for fracture and is it worth it to pay for these drugs and have some side effects even if they are rare? It's not black and white."