The reputation of bisphosphonates, the most widely prescribed osteoporosis drugs on the market, has taken a beating lately.
Last month, a study in the New England Journal of Medicine by the U.S. Food and Drug Administration found inconsistencies in the ability of bisphosphonates to reduce fractures and suggested the drugs may not have much benefit for many women. In an accompanying article, researchers questioned whether women who are at a high risk for fractures and are currently taking the drugs would be better off only using them for a short period.
The same month, a study in the Archives of Internal Medicine found women taking bisphosphonates appear to actually face a higher risk of suffering rare, but very serious, atypical femoral fractures which account for less than 1 per cent of all hip and femur fractures. Unlike most fractures, atypical femoral fractures aren't usually the result of a fall or other trauma; the thigh bone appears to snap for no reason. Healing can take months or years and the fractures may lead to complications.
Last December, Health Canada announced it was updating the warning label on bisphosphonate drugs in light of evidence they are linked to a higher risk of rare atypical femoral fractures. Plenty of credible research has also suggests the drugs may lead to osteonecrosis of the jaw, a rare and painful deterioration of the jaw bone, and even esophageal cancer.
These are just the latest blows to a class of drugs that, for years, was prescribed to millions of women with osteoporosis or believed to be at risk of developing the disease.
In light of the evidence, a growing segment of the medical community says it's time to revamp the way bisphosphonates are prescribed in order to restrict use in women who clearly won't benefit from them. At the same time, many osteoporosis doctors seem reluctant to admit there's a big problem, which is leading to widespread confusion.
"I think it's a huge problem for patients," said Clifford Rosen, professor of medicine at Tufts University, senior scientist at Maine Medical Center's Research Institute and one of the authors of the NEJM article that was published last month.
Bisphosphonates are a class of drugs, such as Fosamax and Aclasta, that are thought to prevent bone loss by binding to the surface of bones. Depending on the type, they can be taken daily, monthly or even yearly and some research indicates they continue to provide protective effects long after patients stop taking them.
The main points of contention over the drugs are who should be taking them, and for how long. When the drugs first came on the market in the mid-1990s, they were believed to help prevent osteoporosis and halt its progression, which meant many women, including those without the disease, were put on them, Dr. Rosen said.
Within a few years, reports began emerging of rare but serious side effects and more research was done to assess these drugs.
Much of the concern centres on the risk of rare, but potentially devastating, atypical femoral fractures. The Archives of Internal Medicine study published last month found that 82 per cent of patients with atypical fractures had taken bisphosphonates. Estimates suggest the risk of atypical fractures for women taking bisphosphonates is as low as 1 in 1,000.
Osteoporosis Canada mentions bisphosphonates first in its online list of medications to treat the disease. The website, which provides information to those with osteoporosis, says the medications are effective at reducing fractures and increasing bone density. A section on side effects lists problems such as nausea or joint pain, but makes brief mention of the fact atypical femoral fractures and osteonecrosis of the jaw have been reported.
"These are valuable drugs that have been shown to reduce the risk of fracture," said Aliya Khan, an osteoporosis specialist and member of the society's scientific advisory council.
While Dr. Khan acknowledges that bisphosphonates shouldn't be prescribed as widely as they once were, she said the evidence they help most women is overwhelming.
"All the scientific communities are united in agreement with the fact bisphosphonates are clearly of benefit," she said. "The bottom line is that everybody agrees, after five years of use [in an individual patient] we should review the use of these medications."
But that's the problem: not everyone is in agreement.
In fact, a growing number of researchers studying bisphosphonates say there is little reason for many older women, including those with osteoporosis, to take them.
Jim Wright, managing director and chair of the Therapeutics Initiative, an independent drug review body at the University of British Columbia, reviewed the evidence on bisphosphonates and concluded "there are no clinically meaningful benefits for bisphosphonates in postmenopausal women" with no history of fractures or vertebral compression.
"There's really no proven benefit in women who just have a low bone mineral density. That's probably the bulk of women who are getting it," Dr. Wright said.
Dr. Rosen, a bone specialist, said he believes some women can benefit from the drugs, but that they're a select group: women over age 65 who have either previously suffered a fracture or who have very low bone density. The big question now facing researchers is how long this group of women should take the medications. Dr. Rosen said it's becoming clearer that women don't need to be on the drugs for long, as they continue to provide protection even after a person goes off them.
"If you've been on a drug for three to five years and you haven't had any fractures and bone density is better, it's time to talk to your doctor. It's very likely you can come off the drug," he said.
However, he isn't surprised the message bisphosphonates should be prescribed to a smaller group of women for a shorter period of time isn't quickly taking hold.
"I think there's such an established thinking process that...it's hard to waver from a bottom line message which has been out here for a long time," Dr. Rosen said.
Merck, the drugmaker that sells Fosamax, declined to respond to questions. In an e-mail statement, the company said the drug has been proven effective at treatment and prevention of osteoporosis in patients with a heightened fracture risk for up to 10 years. But the company noted the "optimal duration" of use of the drug hasn't been established.
"How long they need to be on [bisphosphonates] is the biggest question," Dr. Rosen said. "That's what people want to know."
Bisphosphonate use in Canada
Bisphosphonates are the most widely-prescribed osteoporosis drugs in Canada. Here is a breakdown of how many prescriptions for some of the major bisphosphonates (generic and brand name versions of the drugs are available in Canada) retail pharmacies dispensed in 2011.
- Risedronate (generic name for Actonel): 3.4 million
- Alendronate (generic name for Fosamax): 2.8 million
- Etidronate (generic name for Didronel): 5,943
- Zoledronic acid (generic name for Aclasta): 32,154