Studies show that the drugs do have proven benefits in preventing osteoporosis fractures for the first three years of treatment, but continuing beyond five years does not demonstrate such benefits over no drug use at all, the report said. And women who stop taking the drugs after five years have similar levels of increased bone density and reduced fracture risk as those who continue taking them, it said.
“These results suggest no significant advantage of continuing drug therapy beyond 5 years,” according to agency’s 45-page review of scientific evidence.
As for side effects, the report said, there is no solid evidence the drugs, called bisphosphonates, cause unusual breaks of the femur bone, a jaw injury called osteonecrosis, or esophageal cancer. At the same time, the agency said, those rare but dangerous outcomes cannot be ruled out because it has been so difficult to study them for various reasons.
“The safety of long-term bisphosphonate therapy continues to be unclear as study results are conflicting,” according to the F.D.A. report.
The drugs under review include Fosamax from Merck, first approved in 1995, Boniva from Roche Therapeutics, Actonel and Atelvia from Warner Chilcott, and generic copies. The F.D.A. has never conducted a broad review of the long-term safety and efficacy of the drugs.
A so-called “drug holiday” may be warranted for many of the women who take the drugs for longer terms, the report said, but adding a note of caution: “There are no substantial data available to inform decisions regarding the initiation or duration of a drug holiday.”
Between 5.1 million and 5.7 million patients in the United States have received prescriptions for the drugs for each of the years 2005 through 2009, the agency said, citing drug tracking from the data firm SDI. Most patients were over 55 years old. At least one in 11 women in that age group received the bone drugs, the agency said.
Sally Fullman, 69, of Murray Hill, N.J., started taking Fosamax in 2006 after being diagnosed with osteoporosis. She stopped taking it last year partly because of concern about the possible side effects.
“I’m troubled by all the confusion and the stress that’s out there with respect to the advisability of taking them,” Ms. Fullman said in an interview shortly before the F.D.A. issued its report. “I’m still on a drug holiday. But when I talk to people, everybody is confused and angry about this.”
Perhaps the F.D.A. safety review will help patients like Ms. Fullman – at least more than media reports on conflicting studies, anecdotal cases and lawsuits. “When I read articles or see things on TV, what I hear are side effects that are taken out of context,” she said. “So they’re catchy and they kind of scare you a little bit, but they don’t really tell you the risks of not taking the medication.”
Drug makers including Merck issued their own safety reports on Wednesday at the F.D.A.’s request.
The Merck report, using the chemical name for Fosamax, said: “The available data support a favorable benefit to risk profile during long-term (10-year) treatment with alendronate in osteoporotic patients who remain at risk of osteoporotic fracture and who have not experienced adverse reactions that required discontinuation of therapy.”
But Merck also said it would support the notion of taking a break from the bone drugs.
“A drug holiday may be considered for patients who have previously received long-term treatment and are no longer considered to have a sufficiently high fracture risk,” the company said.