Boning Up on Bone Drugs

Can a drug intended to prevent fractures cause them? The scoop on osteoporosis meds.

by Katharine Davis Fishman
Photograph: Photo: Coolife and Carole & Pauline

Both psychological and physiological factors account for this rapid decline and high death rate. Ethel Siris, MD, director of the Toni Stabile Osteoporosis Center at Columbia University Medical Center and a past president of the National Osteoporosis Foundation, explained to me that many formerly active patients in their seventies and eighties become depressed after undergoing surgery, spending months in a rehab facility and then finding they still can’t get around.

Very low bone density, or osteoporosis, is not the only factor in fracture risk, but it is the most important and the easiest to measure. Osteoporosis most often becomes a concern around menopause. When you’re younger, your bones stay healthy through a mineral process called turnover, in which breakdown cells (osteoclasts) remove the old, calcium-deficient bone, and buildup cells (osteoblasts) replace it with new, calcium-rich bone. In the years just before and after menopause, the breakdown osteoclast cells become more active, and the buildup osteoblasts grow sluggish, partly because estrogen, now being rapidly lost, is a key element in the turnover process. The result is bone that is less dense and more fragile and at its laciest is labeled osteoporotic. Only 4 percent of women in their fifties suffer from osteoporosis, while 52 percent of women over 80 meet criteria for the disease.

Before the Food and Drug Administration approved Fosamax in 1995, the only drug available for treating osteoporosis was estrogen, prescribed to prevent bone loss and thereby fractures. Fosamax, like the bisphosphonates developed later, blocks the work of the breakdown osteoclast cells but does not stimulate the buildup osteoblasts, so it slows decline but cannot rebuild bone.

In 1997 the FDA allowed for a broader use of Fosamax, as an osteoporosis preventive. And while the agency says it conducted its own analysis of clinical data before approving that use of the drug, in September 1998 an agency statistician re—evaluated the numbers Merck had submitted. Merck had pooled data from two studies, with different time spans, populations and goals, and the statistician raised the possibility that this may have distorted the results. He also suggested that the drug’s effectiveness varied over time with the test populations’ medical histories: it worked best with patients who had either full-fledged osteoporosis or prior fractures, a finding that called into question how useful the drug would be at preventing fractures among women who simply had low bone mass and had never broken their bones.

Still, once the FDA approval was granted, the drugs, which had been given primarily to people with osteoporosis, could now be dispensed to a much larger group on the basis of bone scans produced by a machine called a DXA (or sometimes DEXA). The scan, which came into wide use in the late 1990s, generates a “T-score” that rates a patient’s bone-mineral density relative to that of healthy women at age 30, when bone mass peaks. A T-score below –2.5 equals osteoporosis; a score of –1 to –2.5 is low enough to make the patient a candidate for preventive treatment.

This ability to measure below—normal bone density fed into the grand old American notion of proactivity, of nipping a disease in the bud before it could get troublesome. Soon many doctors were prescribing bisphosphonates to patients in their midfifties in hopes of warding off osteoporosis and the grim consequences of hip fractures. The change also fed the drug manufacturers’ bottom lines. When pharmaceutical companies add osteopenic patients to those with osteoporosis, the market more than triples.

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