First, a trip down memory lane on the use of bone drugs for the prevention of hip fractures. It is now 16 years since Merck’s widely prescribed Fosamax went on the market. In time, it was prescribed inappropriately to women with so-called “pre-osteoporosis” or osteopenia (yet-another drug maker invented “disease”). It was also prescribed inappropriately to women in their early 50s, thanks to Merck’s marketing strategies that made us think we would start crumbling inside right after menopause. Then came the reports of osteonecrosis of the jaw and spontaneous thighbone fractures in some women on Fosamax. And now, the latest bulletin on Fosamax and its knock-offs like Actonel, Reclast, and Boniva: If you have been on one of these drugs for five years, stop taking it.
What has happened to send out word that five years is enough and longer would be too risky? Two things: a paper by bone physiologist Susan Ott, MD, in the Cleveland Clinic Medical Journal published this month and the recent announcement that two FDA advisory panels will conduct a comprehensive safety review of the research supporting the use of these drugs called bisphosphonates. As noted often on this website: drug makers conduct the FDA-required studies of their own products; a new drug’s effectiveness is carefully studied to determine whether it is better than nothing, i.e., a placebo; and the full story on a new drug’s adverse reactions comes many years later, if at all.
Members of the FDA advisory committee that met early this month agreed that a time limit should be put on the duration of bisphosphonate therapy, but they could not agree on what that time limit should be. Anyone currently on a bisphosphonate drug should not wait for the FDA; and instead, go with Dr. Ott’s advice to stop taking the drug after five years. Her newly published paper entitled, “What is the optimal duration of bisphosphonate therapy?” is an in-depth assessment of all studies in which one of these bone drugs was compared with a placebo, as well as observational studies. Here is her conclusion:
Almost all the data about the safety and efficacy of bisphosphonate drugs for treating osteoporosis are from patients who took them for less than 5 years. Reports of adverse effects with prolonged use have caused concern about the long-term safety of this class of drugs. This is particularly important because these drugs are retained in the skeleton longer than 10 years, because there are physiologic reasons why excessive bisphosphonate-induced inhibition of bone turnover could be damaging, and because many healthy postmenopausal women have been prescribed bisphosphonates in the hope of preventing fractures that are not expected to occur for 20 to 30 years.
As someone who regularly visits Dr. Ott’s website (see below), I know that she has long been a supporter of appropriate use of bisphosphonates. The reason was given in her newly published paper: These drugs “reduce the incidence of devastating hip fractures”
I’ll stop quoting Dr. Ott right here to explain the operative words in her statement: reduce the incidence. This careful choice of words that is unlikely to be explained by many prescribing doctors. Consequently, many women go on bisphosphonate therapy mistakenly thinking they will not a have hip fracture. In truth and at best, only a small percentage of women who go on three to five years of bisphosphonate therapy will avoid a fracture.
One of the first important clinical trials to compare Fosamax with a placebo is the FLEX trial. After four years the FLEX trial found that 1.1% of the women in the placebo group had a hip fracture and 0.9% of the women taking Fosamax. Yes, that tiny fraction of a difference between taking Fosamax and going without treatment is what osteoporosis researchers get excited about. (If this described a woman’s chance of developing a serious drug side effect, it would be characterized as “rare.”)
The drugs always look better in osteoporosis studies when the authors throw all types of fracture (hip, forearm, spine, etc.) together. Again, using data from the FLEX trial: 21.3% of women on placebo had any type of fracture, compared with 19.9% of the women on Fosamax.
You might ask: Why haven’t I heard this before? Why do researchers report such findings as “significant”? Answers: Many prescribing doctors themselves don’t understand biostatistics; the word significant—to researchers—means “not due to chance,” the statistics can be trusted. Also, researchers tend to look at things in public health terms: a fraction of a 1% benefit means a lot when an estimated four million women in the U.S. are taking a bisphosphonate.
Back to Dr. Ott, who acknowledges “some emerging evidence of harm after 5 years of bisphosphonate treatment; to date the incidence of serious side effects is less than 1 in 1,000, but the risks beyond 10 years are unknown.” The serious side effects include spontaneous thighbone (femur) fracture, osteonecrosis of the jawbone.
The most obvious candidates for bisphosphonate therapy, according to Dr. Ott, are women whose risk of hip fracture is higher than 3% in the next decade and elderly women who already had compression fractures of the spine or a hip fracture. As for the risks the latter group might suffer, “women with a vertebral fracture have a one-in-five chance of fracturing another vertebra, which is a far higher risk than any of the known [emphasis mine] long-term side effects from bisphosphonate.
She is against prescribing bisphosphonates to women with osteopenia who have not had a fragility fracture, saying this common use is “based on hope, not evidence.”
Maryann Napoli, Center for Medical Consumers©
Effectiveness of the bisphosphonates’ fracture-prevention benefit in doubt click here
Fosamax-induced osteonecrosis of the jaw—more common thant preveiously thought click here
Spontaneous thighbone fracture—thought to be rare click here