It’s never fails to amaze me how long a drug can be in use before its benefits and harms are fully understood. This is particularly troubling where it concerns drugs given to healthy people to prevent something that might happen to them sometime in the future. On my mind right now is the bone drug Fosamax prescribed since the mid-1990s to symptomless women with bone loss usually detected on a bone density measurement test.

Concern over the lack of good information about this widely prescribed drug and it multiple knockoffs (Actonel, Boniva, Didronel, Reclast, Aredia) has galvanized several research teams around the world. The impetus is the unusual thigh bone fractures initially reported over six years ago in women taking Fosamax click here. The international researchers analyzed all relevant studies to determine whether these bone drugs “prevent or cause bone fractures”. Their unenthusiastic conclusion: The drugs have “some effectiveness” in preventing vertebral fractures in the short-term (one to three years). Brace yourself for this clarification: Effectiveness is limited to “vertebral fractures demonstrated by x-ray” (translation: tiny symptomless spinal fractures that the women themselves are unaware of). The researchers go on to point out, “The efficacy with regard to preventing hip fractures is uncertain.”

Wait a minute…wasn’t hip fracture prevention the big selling point of Fosamax and its knockoffs? Remember those scary statistics indicating how many of us would die within the year of a hip fracture.

The harms of these bone drugs are usually determined to be rare, for example, the rotting jawbones (osteonecrosis of the jaw) of women given oral surgery while on Fosamax click here. So are the esophageal ulcers and those spontaneous thigh bone fractures we’ve been hearing about for at least five years. Has anyone tallied up all these “rare” harms so they can be weighed against the small, uncertain benefits of bone drugs? The researchers addressed this question, but said, in effect, “Hold off, we still don’t have a good count yet”. In other words, people on one of these bone drugs are participating in one long, ongoing experiment.

Most of the studies, by the way, were done on Fosamax because it has the longest track record. There is no evidence that the other drugs in this class known as bisphosphonates are any safer or more effective because no head-to-head comparison has been done.

In case you’re wondering how these drugs got FDA approval in the first place, the new analysis gives a brief history. Merck, maker of Fosamax, had only to prove its drug increased bone density… on the shaky assumption that this would translate to fracture prevention. (To gain FDA approval, drug makers test their products against a placebo which means they need only to prove their drug is better than nothing.) In time, the aforementioned x-ray evidence of fracture reduction became acceptable proof of a bone drug’s effectiveness. Only a third of the people with vertebral fractures that show up on x-ray have symptoms.

By 2006 long-term data came from a trial, known by its acronym FLEX, that followed women taking Fosamax for three to ten years. The aim of this trial was to determine whether Fosamax can achieve what matters most to women taking this drug: Does it reduce hip fractures? It found no significant difference between Fosamax and placebo in terms of preventing any type of fracture.

And so it goes. This new analysis is available online at Therapeutics Initiative, published by the University of British Columbia (UBC), Vancouver, click here. It is based on the combined findings of the Cochrane Collaboration and other independent groups in France and Spain. The conclusion: “Given that bisphosphonates can cause severe adverse effects including fractures, which they are meant to prevent, it is urgent that the overall benefits and harms of long-term treatment be clarified. The available evidence suggests that the benefit-harm balance may be unfavorable for their use in osteoporosis.”

The UBC research team plans to take it from there and conduct “a full systematic review and critical appraisal of this widely prescribed class of drugs.”

More to consider about these drugs
-If you have no bone symptoms and have decided that you’ll never take one of these drugs, think twice about having your bone density measured. This screening test is all about unproven predictions of who will suffer a fracture after age 70 and directing them to long-term drug therapy.

-If you think you’ve been injured by a bisphosphonate drug, contact the FDA’s Medwatch Program click here.

Maryann Napoli, Center for Medical Consumers©