How a risk factor (bone loss) became a disease (osteoporosis) by Maryann Napoli. Originally published in American Journal of Nursing, May 2009

Nurses probably get the same question I often get as a consumer advocate.  Should I be on this drug? You’re asked because you’re seen as the expert or simply a knowledgeable friend.  In fact, it’s a valid question not only to ask but also to look beyond the prescribing health care provider for answers.

In the name of prevention, millions of Americans have accepted the idea that it is reasonable to treat a risk factor (e.g., high cholesterol, bone loss) as if it were a disease. Think back to the 1990s when virtually all menopausal women were advised—pressured, according to accounts that came my way—by their gynecologists to go on hormone therapy to prevent heart disease and hip fractures.

More people should question the wisdom of going on long-term drug therapy. Often the magnitude of the risk factor has been overestimated; or the danger of the disease itself may be exaggerated by people trying to sell us something—like a drug you must take for the rest of your life.

Osteoporosis provides an excellent example of how the pharmaceutical industry begins creating a market for a new prevention drug years before it is approved.  The disease has become a major health concern for older women, though it was unknown to the general public until the early 1980s when the drug industry-led awareness campaign began.  It used to be that osteoporosis was not diagnosed until a fragility fracture had occurred.[1]

But a new definition, one based on bone mineral density, was established in 1993 at a World Health Organization meeting of osteoporosis researchers.  Its ostensible purpose was to determine the global prevalence of osteoporosis, but this meeting is where the definition of osteoporosis was radically changed.  What had been simply a risk factor (bone loss) became a disease (osteoporosis), complete with an arbitrary cutoff (bone density more than 2.5 standard deviations below the normal bone mass in young women).[2]

Overnight, the market for bone drugs had been expanded. Years after that WHO meeting, I would learn that it was sponsored by several pharmaceutical companies.² Hormone drugs were the standard preventive treatment at the time of the meeting, but three years later the first non-hormonal drug for bone loss—alendronate (Fosamax)—was launched.

Getting symptom-free women to accept drug therapy requires scarey statistics that imply the danger period starts right after menopause, leaving the impression that hip fractures, the most disabling consequence of osteoporosis, often occur soon after the hot flashes are over.  Here’s one stat you would see often: 24% women, aged 50 and over, die within a year of a hip fracture.[3]  And here’s one you don’t see often: over 90% of the hip fractures occur in people over 70 and the average age is 80.[4]  Elderly men have hip fractures, too, but the early marketing of alendronate was all about the ladies.

How Predictive are Bone Scans?

In the initial phase of the industry-funded osteoporosis awareness campaign, the scan known by the acronym DEXA was advised for women at the time of menopause. Scanning caught on in a big way, especially after Merck, the maker of alendronate, began financing the installation of DEXA machines in doctors’ offices.[5]  Nothing creates drug customers faster than getting people to be routinely scanned.

Unfortunately, scanning is not good at predicting which women in their early 50s will have a hip fracture at age 80. This was known in 1997 thanks to a report from the British Columbia Office for Health Technology Assessment, which—to my knowledge—is the first to reveal industry sponsorship of that 1993 WHO meeting where osteoporosis was redefined.[6]

Unfortunately, the report had no effect on U.S.testing guidelines, but consumer advocate Barbara Mintzes, Universityof British Columbia, summed up the situation nicely, “Bone mineral density testing is a poor predictor of future fractures, but an excellent predictor of start of drug use.”[7] Merck’s ads aimed at women did not even mention alendronate, they simply said, “Ask your doctor whether a bone density test is right for you.”  Sure, low calcium/vitamin D intake, scatter rugs, poor muscle strength, certain medications, impaired vision were given lip service as contributing factors to osteoporotic fractures, but loss of bone density always seemed front and center.

How Good is the Drug?

In the initial phase of DEXA promotion, many women in early middle-age, with low bone density but no history of fracture, were put on alendronate, despite the fact that the drug was tested only in elderly women with vertebral fractures. The results, even for this supposedly high-risk elderly group, were not impressive. In the Merck-sponsored three-year trial that received Food and Drug Administration approval, hip fractures occurred in 1% of those on alendronate, compared with 2% of those on a placebo. [8] (A “50% reduction in hip fracture” is the accurate, though misleading, way these results were often portrayed.)

Here is where the nurse/advocate can serve as a sounding board for patients deciding whether to go on drug therapy, helping them consider questions like:  Are you similar in age and fracture history to the women in this trial? What does that 1% fewer hip fractures mean to you? Let’s compare that 1% benefit with the 1.5% risk for a alendronate-induced esophageal ulcer found in this trial? Consider what happened to the study participants who did not take alendronate (98% of the untreated women—i.e., the placebo group—did not have a hip fracture).  The “script” for this discussion is the drug’s official FDA-approved label and the Physicians’ Desk Reference where the trials that won FDA approval are described.

When alendronate was put to the test for elderly women with bone loss but no vertebral fractures, the four-year trial showed that the hip fracture rate was no different for the drug-treated participants than it was for the women taking a placebo.In short, the drug is good at improving bone density but not so good at reducing hip fractures. This did not stop other drug companies from introducing their own alendronate knockoffs—risedronate, ibandronate, pamidronate, etidronate and zoledronic acid.  All are in the same drug class called bisphosphonates.  In an example of how long a drug has to be on the market before the full picture of harm is known, the FDA reported early this year that all bisphosphonates carry the risk of severe and sometimes incapacitating musculoskeletal pain.[9]

Drug Ad Campaign Misled Doctors

Why younger rather than elderly women became the likely recipients of a bisphosphonate prescription is no mystery.  Merck’s initial ads aimed at physicians encouraged it.  A multi-page glossy ad campaign that ran frequently in Annals of Internal Medicine featured a thin fortysomething white woman with a crumbling ancient stone column in the background.  “Don’t wait for a fracture… No matter what her degree of osteoporotic bone loss…” [10]  I wrote to the editor-in-chief of Annals, pointing out that alendronate had no proven benefit for women in early middle age.  Never got a reply, but Annals stopped running the ad about six months later.  Still, the message had already gone out, there and elsewhere—early middle age is the appropriate time to start fracture prevention with alendronate.  From the drug industry’s point of view, the younger customer is far more desirable than, say, the  elderly nursing home resident with a limited remaining lifespan in which to take drugs.

Today, women in the osteoporosis drug ads are usually in their early sixties.  The guidelines for bone density measurement currently recommend bone mineral testing not begin before age 65 (or 60 in some high-risk cases)[11], but now there’s a bigger problem.   Researchers have known, at least since 2000, that bone strength or bone quality are better predictors of hip fracture than bone density.  In 2001, the National Institutes of Health redefined osteoporosis as a combination of bone mineral density and bone quality. But there is no test for bone  quality or bone strength. ¹

It’s going to take time for the word to get out.

How relevant is this story to other drugs people take to treat a risk factor?  In a word: very.  Three-fourths of all Americans on cholesterol-lowering statins, the country’s top-selling drugs, do not have heart disease and are thus far less likely to benefit than people who do. [12]  (Statins are terrific at lowering cholesterol, but much less impressive at reducing the risk for heart attack[13]—sound familiar?)  The thresholds for high cholesterol[14] and high blood pressure were lowered several times over the years, each time making millions more people eligible for drug therapy. ⁵ 

Drug ads and industry-sponsored “education” programs are no longer the only major sources of biased information. Industry funding compromises the directives of non-profits like the American Heart Association and the American Cancer Society, as well as the experts who write treatment guidelines. [15]  One example of the latter: eight of the nine doctors who served on the 2004 government committee that expanded the guidelines for cholesterol-lowering drug therapy had financial ties to statin companies.[16]

More than ever, nurses must be knowledgeable advocates for their patients. You may be the last of the independent health professionals.

For More Information:

http://courses.washington.edu.bonephys    Web site of bone physiologist and osteoporosis researcher Susan Ott, MD, Associate Professor, Department of
Medicine, University of Washington.  Mostinteresting section: “When [drug] studies don’t give clear answers.”  Definitely take the quiz. (Accessed June 12, 2008.)