Overdosed America (33 page)

At the time that the WHO study group did its work, there were several new drugs for osteoporosis in the pipeline. The drug companies stood to benefit greatly if definitions of osteoporosis and osteopenia included large numbers of postmenopausal women and if bone mineral density testing was adopted into their routine medical care. It turns out that the WHO study group that developed the criteria for diagnosing osteoporosis and osteopenia was
funded by three drug companies
: the Rorer Foundation, Sandoz, and SmithKline Beecham. Of course, commercial funding does not necessarily impugn the conclusions of the study group, but its conclusions did happen to be in the drug companies’ interest.

In a 1994 paper published in the journal
Osteoporosis International,
the WHO study group recommended
that “an appropriate time to consider screening and intervention is at the menopause.” If BMD became part of routine care for postmenopausal women—based on the statistical definitions developed by the study group—the drug companies would be assured that millions of women would be seeking billions of dollars’ worth of their drugs, hoping to prevent and treat osteoporosis.

It may be hard to believe, especially with the debacle of routine HRT so fresh in our minds, but there has
never been a randomized controlled study
done to determine whether there is a benefit to screening women for osteoporosis with BMD tests. There simply is no gold-standard evidence showing that ordering all these tests and prescribing all those drugs is leading to better health for women. Nonetheless, the current recommendations call for women to have a BMD test at age 65 or earlier if there are risk factors for osteoporosis.

In 1995, Fosamax, the brand name for alendronate, was the first of the new generation of drugs approved by the FDA for the treatment of osteoporosis. Fosamax works by attaching itself to the surface of bone, interposed between the osteoclasts and the bone the osteoclasts are trying to absorb. Randomized clinical trials of Fosamax published in medical journals show dramatic reductions in the relative risk of hip fracture for women with osteoporosis. In a study published in JAMA in 1998, for example, women with
an average age of 68 and a T score of -2.5 or less
who took Fosamax for four years were 56 percent less likely to suffer a hip fracture than women in the control group.

This sounds like very good news for women with osteoporosis, but how many hip fractures were really prevented? With no drug therapy at all, women with osteoporosis had a 99.5 percent chance of making it through each year without a hip fracture—pretty good odds. With drug therapy, their odds improved to 99.8 percent. In other words, taking the drugs decreased their risk of hip fracture from 0.5 percent per year to 0.2 percent per year. This tiny decrease in absolute risk translates into the study’s reported 56 percent reduction in relative risk. The bottom line is that 81 women with osteoporosis have to take Fosamax for 4.2 years, at a cost of more than $300,000, to prevent one hip fracture. (This benefit does not include a reduction of less serious fractures, including wrist and vertebral fractures. Most vertebral fractures cause no symptoms.)

A study published in the NEJM in 2001 showed that even women with severe osteoporosis
*
derived only small benefit from these drugs. The study randomized
women between the ages of 70 and 79
to receive Actonel (the brand name of risedronate, a cousin of Fosamax) or a placebo for three years. Hip fractures were significantly reduced only in the women who already had a spine fracture when the study began (40 percent of the women in the study). One hundred such women would have to take Actonel for about one year to prevent one hip fracture. For the other 60 percent of women in the study without a preexisting spine fracture, Actonel did not significantly reduce the risk of hip fracture. Moreover, the drug appeared to have no beneficial effect on their overall health. There was no difference in the number of serious illnesses (causing death or hospitalization), including fractures, that occurred in the women who took Actonel compared with those who took the placebo.
The same result was found in younger women
, with an average age of 69, who had been diagnosed with osteoporosis and at least one spinal fracture: fewer fractures but no reduction in the occurrence of serious illness in the women who took Actonel. The net effect of drug treatment on the risk of serious illness in the highest risk women? Nothing—except the cost of the drug.

A study conducted in the Netherlands
helps to put these lackluster results into perspective. It turns out that bone mineral density tests identify only a small part of the risk of hip fracture. The study found that for women between the ages of 60 and 80, only one-sixth of their risk of fracturing a hip is identified by BMD testing. Other factors were just as important as T score: increased frailty, muscle weakness, the side effects of other drugs, declining vision, and cigarette smoking. As a result of the WHO study group’s definition of osteoporosis, however, women and their doctors mistakenly latch on to the results of BMD testing as the sole or primary predictor of fracture risk. Routine BMD testing may not be the best way to help women prevent hip fractures, but it is an excellent way to sell more drugs.

While nearly every postmenopausal woman fears osteoporosis, the reality is that
two out of three hip fractures
occur in women who have reached the age of 80. With
90 percent of hip fractures resulting from falls
, it makes sense that the oldest and frailest women would be at the greatest risk. It also makes sense that a broken hip in these frail elderly women often marks the transition to no longer being able to live independently or walk safely without assistance.

Do the osteoporosis drugs protect these women from hip fractures? They don’t appear to. The study of Actonel published in NEJM in 2001 included 3880 women over the age of 80 who had been diagnosed with osteoporosis or who had at least one major risk factor for falls (approximately 80 percent of the women in the study had osteoporosis). Treatment of these women with Actonel was reported in the article to have
“no effect on the incidence of hip fracture.”
So it looks as though the women who have by far the greatest risk of hip fracture, and for whom the consequences of hip fracture are the most devastating, do not benefit from the drugs that are sold to help women with osteoporosis.

What about using these drugs to prevent osteoporosis? Fosamax and Actonel were approved by the FDA to treat women with osteopenia based on studies that showed that they significantly increase the bone density of these women. It is important to remember, however, that bone density is only a surrogate end point; the real reason for taking these drugs is to reduce fractures, and hip fractures in particular. The study of Fosamax published in JAMA in 1998 (mentioned earlier) also included women with osteopenia. Did Fosamax reduce their risk of fracture? The results show that
the risk of hip fractures actually
went up
84 percent with Fosamax treatment.
*
The risk of wrist fractures increased by about 50 percent (that figure may be statistically significant—but this can’t be determined from the data as presented in the article).

How can it be that drugs approved for the prevention and treatment of osteoporosis succeed in increasing bone density but have such limited impact on reducing hip fractures? The answer can only inspire awe at Mother Nature’s elegance. There are two types of bone. Eighty percent of the body’s bone is made up of the hard and dense outer layer called cortical bone. In some areas of the body, bones also have an internal structure of trabecular bone, which works like an organic three-dimensional geodesic dome, providing additional strength in the areas of the skeleton most vulnerable to fracture, such as the hips, wrists, and spine.

The
lacelike structure of trabecular bone
creates a much greater surface area than the densely packed cortical bone and therefore allows the former to be more metabolically active when the body needs calcium. Its greater metabolic activity also makes trabecular bone more vulnerable than cortical bone to the changed balance between osteoclast and osteoblast activity. As a result, when bone mass starts to decline in women, trabecular bone is lost more quickly than is cortical bone. Once the architecture of these internal struts is lost, there is no structure left onto which calcium can be added. (See
Figure 13-1
.) The new bone, formed as a result of taking the osteoporosis drugs, is then formed primarily on the outer part of the bone, the cortical bone. This increases the score on the bone density test but does not necessarily contribute proportionately to fracture resistance.

FIGURE 13-1.
NORMAL BONE (
LEFT
) AND OSTEOPOROTIC BONE (
RIGHT
). REPRODUCED FROM
THE JOURNAL OF BONE AND MINERAL RESEARCH
1 (1986): 15–21, WITH PERMISSION OF THE AMERICAN SOCIETY FOR BONE MINERAL RESEARCH.

More drugs are now available to “help” women with osteoporosis. Evista (raloxifene) is in a new class of drugs called selective estrogen-receptor modulators, or SERMs. These drugs are designed to protect bones the same way that natural estrogen does, but without the risk of hormone therapy. Sounds great, but research shows that in women with osteoporosis,
Evista reduces only vertebral fractures
, not fractures of the hip or wrist. Nonetheless, Eli Lilly’s advertising for Evista, according to
an FDA letter to the company
dated September 2000, “misleadingly suggests” that it does just that. The letter requested that Eli Lilly “immediately discontinue the broadcast of this violative advertisement” along with other marketing material that contained “the same or similar violative claims or representations.”

Two other hormone-like drugs that regulate calcium metabolism are offered to treat osteoporosis; both were tested in women with osteoporosis and preexisting vertebral fractures.
Miacalcin, administered by a nasal spray
, has an inconsistent effect on hip fractures and vertebral fractures depending on the dose.
Forteo, administered by daily self-injection
, reduces fractures overall but has not been shown to significantly reduce hip fractures.

Even if loss of bone mass is a naturally occurring part of aging, hip fractures in old age are still a serious threat. So how can older women reduce their risk of hip fractures? As we’ve just seen, there are no magic pills. But there are ways to significantly strengthen bones and reduce the risk of fracture at any age.

Proper exercise and good nutrition are important through all stages of life to build and maintain strong bones. Reaching young adulthood with bones strengthened by routine exercise and a diet with adequate calcium makes future problems far less likely. There is good evidence that
exercise builds up trabecular bone
, which can then provide the internal support to vulnerable areas of the skeleton later in life.

The Study of Osteoporotic Fractures
, sponsored by the NIH, included almost 10,000 independently living women aged 65 and older. Over seven years, women who exercised moderately had 36 percent fewer hip fractures (statistically significant) than the least active women. In absolute terms, the reduction in hip fractures in the women who exercised most compared with those who exercised least was 6 per 1000 per year—twice the reduction achieved with Fosamax. At least two hours of moderate-to-vigorous exercise each week is best.

In a study in Sweden, nursing home residents
averaging 83 years of age, one-third of whom had dementia, were randomized to participate in a fall-prevention program (including exercise, medication reviews, hip protectors, and conferences among the staff after falls to minimize the risk of a repeat fall). During the course of the eight-month program, only 1.6 percent of the people in the fall-prevention program suffered a hip fracture compared with 6.1 percent in the control group—a dramatic reduction with no osteoporosis drugs involved (remember, Actonel did not reduce hip fractures in women of similar age).

Because nine out of 10 hip fractures result from falls, engaging in activities that increase strength and balance helps decrease the risk.
Strength training
is one of the best ways to increase bone density in the spine naturally and prevent falls.
Tai chi
, a form of exercise often used by elderly Chinese that is becoming popular throughout the world, improves balance and cuts the risk of falls in half for people 70 years of age and older.

Adequate calcium and vitamin D intake is also essential
: the daily goal should be 1200–1500 mg of calcium (usually no more than 1000 mg from supplements are needed), and 400 to 800 IU of vitamin D. The cost of generic calcium and vitamin D is about $3.60 per month. Studies also suggest that diets with a
higher ratio of animal to vegetable proteins
increase the rate of bone loss in women 65 and older. In an observational study, women whose diets contained the highest proportion of animal protein were almost four times more likely to suffer a fractured hip than women whose primary source of protein was vegetables.