Splits Form Over How to Address Bone Loss

This is a New York Times article published on 7th September 2009

By KATE MURPHY

As people age, their bones lose density and they grow ever more vulnerable to osteoporosis, with its attendant risk of a disabling fracture. But how do you know just how vulnerable you are?

The question has been complicated by a relatively new diagnosis: osteopenia, or bone density that is below what is considered normal but not low enough to be considered osteoporosis.

Millions of people worldwide, most of them women, have been told they have osteopenia and should take drugs to inhibit bone loss. But the drugs carry risks, so many public-health experts say the diagnosis often does more harm than good.

Now the World Health Organization has developed an online tool meant to help doctors and patients determine when treatment for deteriorating bones is appropriate.

A preliminary version of the tool, called FRAX, was released last year and can be found at www.shef.ac.uk/FRAX/index.htm. A revised version is to be released later this year.

But FRAX is proving almost as controversial as the diagnosis of osteopenia. While some experts applaud it for taking factors besides bone density into account, others say that the formula on which the tool is based is faulty and that the advised threshold for medication is too low.

“FRAX is coming from the same people who came up with osteopenia in the first place,” said Dr. Nelson Watts, director of Bone Health and Osteoporosis Center at the University of Cincinnati, who said the diagnosis unnecessarily frightened women and should be abolished.

Indeed, it was a W.H.O. panel financed by the pharmaceutical industry that in 1994 defined normal bone mass as that of an average 30-year-old woman. Because bone naturally deteriorates with age, anyone much older than 30 is likely to qualify for a diagnosis of osteopenia; using similar logic, a middle-aged woman might be said to have a skin disorder because she had more wrinkles than her 30-year-old daughter.

Rebecca Doll, 36, received a diagnosis of osteopenia after a bone density test this year. “The nurse didn’t tell me how bad it was,” said Ms. Doll, a computer consultant who lives in Thousand Oaks, Calif. “She just wanted to know where to call in the prescription.”

The W.H.O. panel said its definitions of osteopenia and osteoporosis were not intended to provide reference points for diagnoses, much less for prescribing drugs. But Dr. Watts and other experts warn that this is what is happening, as more drugs become available to treat thinning bones and drug companies pay for the installation of bone-density measuring devices in doctors’ offices — not to mention in drugstores, shopping malls and health clubs.

Since 2003, annual sales of osteoporosis drugs have about doubled to $8.3 billion, according to Kalorama Information, a provider of market research on medicine.

Dr. Watts said that while FRAX was a useful tool because it took factors like family history into account, it had significant flaws.

For example, he said, it does not consider factors like vitamin D deficiency, physical activity and use of epilepsy drugs and antidepressants that can erode bone. And while it accounts for tobacco andalcohol use, which can increase the risk of osteoporosis, it does not ask how long or how much a patient has been smoking or drinking.

Other experts object that the mathematical formula used to calculate FRAX scores has not been released to the public.

“I have asked for it repeatedly,” said Dr. Nananda Col, director of the Center for Outcomes Research and Evaluation at Maine Medical Center in Portland. “There’s no way to validate the equation if you can’t tell the independent contribution or weight of each risk factor.”

Dr. John A. Kanis, an emeritus professor of medicine at the University of Sheffield in England and the director of the W.H.O. center that developed FRAX, said the formula, or algorithm, had been kept secret so “the tool is not tampered with and remains authentic.”

Dr. Kanis added that he was in “advanced negotiations” to license the formula to two leading manufacturers of bone-scanning equipment, GE Lunar and Hologic. That would allow them to incorporate it into their software, so patients would receive a calculation for risk of fracture, along with a T score, the standard measure of bone density.

The main controversy, however, involves whether and when to start taking bone-loss drugs, whose side effects can include gastrointestinal and other problems. Merck’s popular drug Fosamax is the subject of hundreds of lawsuits by patients who assert that it caused osteonecrosis of the jaw, a rare disease that breaks down the jawbone. (The company says there is no proof of cause and effect.)

The FRAX guidelines in the United States call for medication when the calculated risk for hip fracture in the next 10 years is 3 percent or the combined risk of a broken hip, vertebra, shoulder or wrist is 20 percent.

The recommendations “don’t mean you have to take drugs or you are crazy if you don’t,” said Dr. Bess Dawson-Hughes, senior scientist and director of the Bone Metabolism Laboratory at Tufts, who helped devise the United States guidelines. (Recommendations differ by country, she said, because of varying health care costs.) Indeed, Ms. Doll’s FRAX calculation indicates that she does not need medication, even though her mother has osteoporosis.

But Dr. Pablo Alonso-Coello, an epidemiologist at the Iberian-American Cochrane Center in Barcelona, Spain, said the guidelines implied that “a hip fracture is greater in magnitude and patient importance than a cardiovascular event, because risk thresholds for treating the latter are usually stated as 20 to 30 percent at 10 years.”

Dr. Alonso-Coello was the lead author of an analysis of osteoporosis drugs published last year in The British Medical Journal, concluding that they were largely ineffective and unnecessary in women with osteopenia.

To determine when drugs are appropriate, FRAX’s developers said they undertook an extensive cost-benefit analysis comparing the expense of hospitalization and rehabilitation for a major fracture with the cost of drugs, which can range from $105 to about $1,800 a year.Dr. Ethel S. Siris, director of the Toni Stabile Osteoporosis Center at Columbia University, said she hoped FRAX would end the fixation on “that horrible term” osteopenia and focus treatment decisions on individual risk of fracture.

“Clearly, doctors have been at fault,” Dr. Siris said. “But women need to educate themselves about the risks” before consenting to treatment.

Dr. Steven Cummings, professor of medicine and epidemiology at the University of California, San Francisco, said it was also important to understand when medication was likely to help. “The drugs work if you have osteoporosis,” Dr. Cummings said. “But some studies suggest there is little benefit, if any benefit at all, if you take these drugs when you have osteopenia.”