New Cautions About Long-Term Use of Bone Drugs
WELL WOMAN | By TARA PARKER-POPE |
In an unusual move that may prompt millions of women to rethink their use of popular bone-building drugs, the Food and Drug Administration published an analysis that suggested caution about long-term use of the drugs, but fell short of issuing specific recommendations.
The F.D.A. review, published in The New England Journal of Medicine online on Wednesday, was prompted by a growing debate over how long women should continue using the drugs, known as bisphosphonates, which are sold as generic versions of brands like Fosamax and Boniva, as well as Novartis’s Reclast.
The concern is that after years of use, the drugs may in rare cases actually lead to weaker bones in certain women, contributing to “rare but serious adverse events,” including unusual femur fractures, esophageal cancer and osteonecrosis of the jaw, a painful and disfiguring crumbling of the jaw bone.
Although the concerns about the long-term safety of bone drugs are not new, the F.D.A. performed its own systematic review of the effectiveness of bisphosphonates after years of use. The agency’s analysis, which found little if any benefit from the drugs after three to five years of use, may prompt doctors around the country to rethink how they prescribe them.
The F.D.A. review analyzes only long-term use and does not address whether a woman should be prescribed a bone drug in the first place to reduce her fracture risk. Because serious complications are so rare, most doctors believe that for women with documented osteoporosis who are at very high risk for spinal fractures, the benefits of the drugs far outweigh the risks. However, some women with moderate bone density and no other risk factors continue to take the drugs for years even though they are unlikely to gain any benefits.
“I think a lot of people are going to come off this drug,” said Dr. Clifford J. Rosen, an endocrinologist and researcher at the Maine Medical Center Research Institute.
Bones are in a constant state of remodeling, but after age 30 or so, a woman’s bones start to dissolve faster than they can be rebuilt, and after menopause she may develop thin, brittle bones that are easily broken. Bisphosphonates slow this process. The drugs are incorporated into newly formed bone and can persist there for years, long after a patient stops taking them.
The F.D.A. report offered little specific guidance about long-term use, saying that the decision to continue or stop treatment should be based on an individual assessment of risks, benefits and preferences discussed between a patient and her doctor. The agency did say that women at low risk for fracture or with a bone density near normal may be good candidates to stop therapy after three to five years, but older patients at higher fracture risk and bone density “in the osteoporotic range” may benefit from continued therapy.
But an accompanying article by Dr. Rosen and others, also published in The New England Journal of Medicine, offers more specifics, concluding that the women most likely to benefit from long-term use of the drugs are those who, after three to five years of treatment, continue to have very low bone density, as measured by something called a “T score” that is lower than minus 2.5. Women with a history of spinal fracture or with an existing fracture also are most likely to benefit from long-term use of the drugs, the researchers concluded.
However, many women who are prescribed bone drugs have been given a diagnosis of osteopenia, moderate to low bone density that is not low enough to be called osteoporosis. These women are unlikely to benefit from long-term use and should probably stop taking the drugs after about three years, the researchers said.
It is not clear how many women would be affected based on those recommendations, but many women tire of the therapy and stop taking it on their own anyway, partly because of inconvenient requirements like remaining upright after taking the drugs and common side effects of heartburn, nausea and flulike symptoms. Even so, the researchers estimate that perhaps 60 percent to 70 percent of current users would be candidates for stopping the drugs after three to five years.
The recommendations are based on findings from two industry-sponsored studies led by the University of California, San Francisco, that focused on long-term use of the drugs. A study of Fosamax, which is sold generically as alendronate, continued for 10 years, and a study of Reclast, an injectable form of the drug zoledronic acid, continued for six years. According to the F.D.A. analysis, both studies showed significant reductions in fracture risks during the first three to four years of use but little or no benefit with longer use.
In the Fosamax trial, 10.6 percent of Fosamax users suffered a fracture during the first three years of use, compared with 21 percent of those in the placebo group, according to the F.D.A. analysis. But there was no benefit seen among women who continued the drug for the next 5 to 10 years. In the Reclast trial, 9.8 percent of women taking the drug suffered a fracture in the first three years of the study, compared with 20 percent of women who were taking a placebo. By four to six years, the benefit had narrowed, with 8.6 percent of Reclast users suffering fractures, compared with 12 percent in the placebo group.
The two studies did not show any increased risk of serious side effects with long-term use of bisphosphonates, but experts say the studies simply were not large enough to detect a relatively rare adverse event. Even so, there have been numerous case reports of the unusual fractures and other side effects, prompting widespread concern about the risks with long-term use. No one knows how common the femur fractures are, but estimates have ranged from 1 in 10,000 users to 10 in 10,000.
Women should be reassured that serious complications are rare, saidDennis M. Black, a professor of epidemiology and biostatistics at U.C.S.F. and the lead author of the article that accompanied the F.D.A. report.
“The reality is there is a lot of uncertainty in this situation,” Dr. Black said. “The F.D.A. report was very general, and we tried to be much more specific and use evidence from the best trial available. Hopefully people who are using this drug will be reassured.”
Dr. Rosen said that even though the F.D.A. report was vague on specific recommendations, he was pleased to see the analysis published.
“It’s a very new thing that they submit a paper to The New England Journal that presents all sides of the argument,” Dr. Rosen said. “I think it’s a good thing, because I’ve been on these advisory committees for years, and we get a big crowd in Washington, but the doctors never see the results.”
80 Comments
Is there more knowledge about the effects - or lack thereof - of estrogen replacement on bone health - strength, density, the ability to break down and recreate bone - now that we have a somewhat better sense that estrogen is not as dangerous as once tho't?
The newer bone medicine , ATELVIA, does not cause gastointestinal problems because it is enteric coated, and you do not have to stay upright after taking it on a full breakfast ...
The ATYPICAL fractures of the femur are VERY uncommon, somewhere between 1/10,000 - 10/10,000, and occur in women who do not take the medicine as well ... risk of getting killed in your car on the way home tonight is 1/6,000.
Oesphogeal cancers from the bone medicine, is so rare it cannot be stated what the true incidence is ...
Just be careful before you trash these bone medicines, or worse still , have the older population stop them, and see how devastating a hip fracture really is .
When will this "Health" column deal with the profusion of prescription drug advertising that has permeated our society and, more important, our thinking. There was a time that advertisement of prescription drugs were not allowed on TV. We now have aggressive advertising campaigns that have done nothing for our well being and have done irreparable damage in the amount of confusion and fear mongering.
I have yet to see this topic treated with any seriousness from this column and I have no idea why not.
http://www.newsinferno.com/pharmaceuticals/stopping-bisphosphonates-may-...
I'm glad you found relief from your migraine miseries with the right medication. The overall experience in the US, however, is an aggressive over-reliance on medications. Studies show, for example, that aggressively dosing hospitalized diabetics to drive their blood sugar to "normal" levels caused more deaths than a more moderate regimen.
Given the risks involved, "All things in moderation" would seem especially apt for our medical care - yet this is more the exception than the rule. And it's our doctors, not the drug companies, that write the prescriptions.
Bone density: Stop smoking and do weight-bearing exercise. Works wonders.
I agree with the poster about direct to consumed pharma ads, it has to stop.
Majid Ali, M.D.
Institute of Integrative Medicine
140 West End Ave. New York, NY 10023
212-873-2444
support from pharmaceutical industry giants Eli Lilly and Novartis, and has
served on the speaker’s bureau for Procter & Gamble. Procter & Gamble
markets the controversial bisphosphonate osteoporosis drug Actonel®."
[Source: LEF].
If correct, this sheds the not unexpected deep dark shadow on the accompanying article in the NEJM, where Dr. Rosen is listed as co-author and, seemingly, as a
damage control rescuer . . .
Here is substantially more on this subject than I could ever say in 100 years,
by Dr. Harriet Hall in his blog published on Jan 5, 2010:
"Osteoporosis Drugs: Good Medicine or Big Pharma Scam?"
http://www.sciencebasedmedicine.org/index.php/osteoporosis-drugs-good-me...
ne-or-big-pharma-scam/
an enlightening blog with many comments from/among medical doctors.
Highly recommended reading.
The widely suspected "Scam" starts with a DXA Scan, which may be considered
the true and lucrative beginning of the scam; it seems to be controlled
(by setting standards, writing/supplying scanning and evaluation software)
by the downstream benefactors - a well-greased industry including the radiologic testing labs ("osteoporosis factories"), the highly rewarded specialists evaluating
the scans, the GPs, who hand the dire warnings of "Osteoporosis!" (anything lower than -2.5 T score) to the poor patients opening the floodgates of drug treatment
to further benefit the pharmacist and Big Pharma.
A smart doctor and a smart patient will weigh the facts and draw the proper conclusion. Taking the drug and then stopping for a "drug holiday" is an intelligent approach.
No one wants to experience sudden thigh bone fractures or necrosis of the jaw; but neither do they want to break a hip and experience its sometimes devastating consequences.
Anyone who is cynical enough to infer that this is just a plot on the part of drug manufacturers to make money has not seen first-hand the results of osteoporosis. As someone who was diagnosed with the disease at a young age (and watched her mother and other close relatives struggle with the same disease) I have been taking these drugs for more than 10 years with the appropriate "holidays" in between. The drugs, coupled with a diligent weight training regimen and healthy lifestyle have made it possible for me to escape the fate of so many older women who never had a choice.
It's all about moderation and thinking it through with a competent specialist.
www.losingtogether.com
If we're going to be guinea pigs, shouldn't we be the ones being paid?