OSTEOPOROSIS: How Effective is Prevention?

by Maryann Napoli

When osteoporosis emerged as a major health problem in the 1980s, experts in the field believed that the devastating fractures suffered by some women in old age could be prevented. Most of the diet and exercise advice was aimed at mid-life women who were warned that they would be rapidly losing bone right after menopause. The bone loss, they were told, was largely due to the body's declining level of estrogen. In time, bone density testing became a rite of passage for many menopausal women.

The increased awareness of osteoporosis plus the overemphasis on estrogen's role in bone loss had the unfortunate consequence of making mid-life women believe that an inevitable hip fracture loomed in the near future. Once bone density testing continued to show bone loss, something had to be done. And that something often turned out to be a lifelong prescription for estrogen. This hormone drug proved itself many times over to be good at stopping bone loss. However, estrogen had never been proven to reduce the fracture rate.

That proof arrived in 2002 with the results from the Women's Health Initiative (WHI) trial. Estrogen, in combination with progestin, slightly reduced the rate of hip fractures in the WHI. Unfortunately, this hormone combination is too risky for lifelong use because the WHI showed that it raised the risk of developing blood clots, stroke, breast cancer and Alzheimer's disease. (Progestin was added to the regimen to protect the uterus from estrogen's cancer-causing effect.)

Now, the tide of expert opinion is slowly changing its focus away from mid-life women to those of advanced age. As Dr. Susan Love said in her Menopause & Hormone Book, “The usual line is that prevention is always better than treatment, and this has certainly driven the use of HRT [hormone replacement therapy] in postmenopausal women. This may not actually be the case.”

Dr. Love sees the newer osteoporosis medication--from a drug class known as the bisphosphonates (brand names: Fosamax, Actonel, Didronel)--as safer alternatives to 30 years on estrogen.

Bisphosphonates will modestly reduce the hip and spinal fracture rate, but the published evidence for this benefit is primarily confined to elderly women with low bone mineral density and at least one other major risk, such as a previous spinal fracture.

An osteoporosis-related hip fracture is rare in women younger than 70 (the average age at which it occurs in women is 79), and only 18% of all white women will ever have a fracture. One reason to reserve treatment for high-risk older women is the lack of long-term information--beyond seven years--about bisphosphonate's safety and continued effectiveness.

The shift in thinking about osteoporosis prevention is reflected in the revised recommendations about when to start bone density testing. Several medical organizations, such as the National Osteoporosis Foundation, now suggest that women not start until age 65, unless they are at extremely high risk. Some osteoporosis researchers have made a case for the quality of bone strength as the more important indicator of a future fracture than bone density. There is no available test for bone strength.

How Good are the Best Drugs?

The bisphosphonates cannot improve bone strength, but they are the only drugs proven to reduce the rate of hip and spinal fractures. Actonel, for example, modestly reduced the fracture rate in a study of 10,000 high-risk elderly women with low bone density or osteoporosis and at least one risk factor for hip fracture, such as an unsteady gait. At three years, there was a 1% lower rate of hip and spinal fractures among the women taking Actonel than those taking the placebo. Interestingly, the three-year fracture rate was low in these supposedly high-risk women, even among those not taking the drug. Overall, the fracture rate was 4% among those taking a placebo versus 3% among those on Actonel (New England Journal of Medicine, 2/1/01).

The fracture prevention value of bisphosphonates in younger women is yet to be demonstrated. In another trial, 1,609 postmenopausal participants, aged 45 to 59 years, were chosen because they did not have osteoporosis. Short-term treatment with Fosamax (5 mg/daily or 2.5 mg/daily) was compared with estrogen plus progestin. The idea was to see whether Fosamax had a sustained effect once the drug was discontinued. The study was paid for in part by a grant from Merck, maker of Fosamax. Some of the women in the Fosamax group took the drug for two years and were than switched to a placebo; others remained on the drug for the four-year duration of the study.

At the end of this study, bone loss had been prevented in those taking Fosamax and in those on estrogen/progestin. Continuous Fosamax treatment, however, was more effective in preventing bone loss than the shorter two-year regimen. The fracture rate is low in this age group, and the study lasted only four years; therefore, this trial could not show that Fosamax reduced fractures (Annals of Internal Medicine, 12/21/99).

 

What about Diet and Exercise?

Osteoporosis research has clearly shown that increased calcium intake and certain exercises will stop bone loss and/or improve bone density, but few studies have lasted long enough to prove the ultimate goal of fracture reduction. In 2002, the Cochrane Library published an updated review of all studies that assessed the value of exercise in preventing osteoporosis. The reviewers conclusions favored aerobics, weight bearing and resistance exercises as the most effective in increasing bone mineral density of the spine. And walking was effective for the hip. Of the few studies that showed fracture reduction, two found walking to be the best for older men and women. In fact, a moderate amount of walking (2-4 hours a week), and even standing, reduced the hip fracture rate. Interestingly, one study showed that the people who spent more time walking did not have a lower rate of fractures than those did just the 2-4 hours a week.

Where diet is concerned, emphasis has been almost entirely--and perhaps, inappropriately--placed on calcium. For over 20 years, women have been advised to increase their daily calcium intake with diet and/or supplements to 1,000 mg daily, and then raise it to 1,500 mg after age 50.

Studies show that calcium supplements will stop bone loss, but they typically did not last long enough to provide information about fractures. As for any fracture-reduction benefit from high dietary calcium intake, the famed Nurses' Health Study produced some bad news. About 77,000 of the participants were singled out because they did not take calcium supplements. All were between the ages of 30 and 55 years in 1980 when they began filling out extensive questionnaires biannually about their health habits. After 18 years, there was a modest but significantly increased incidence of fracture among the women who reported the highest dietary intake of calcium, primarily from milk and other dairy foods (American Journal of Public Health, 6/97).

To determine whether this study was an aberration, Diane Feskanich, D.Sc., and colleagues at Harvard Medical School, looked at all the trials in which calcium supplementation was compared to a placebo, as well as the longer studies, such as the Nurses' Health Study, in which women were asked about their diet, calcium supplement usage and other health habits while being followed for many years. The Harvard researchers concluded that the first category of trials, those that lasted only a few years, typically showed that calcium supplements reduced bone loss. But “the longer observational studies did not generally find a lower risk of hip fracture with higher-calcium diets” (American Journal of Clinical Nutrition, 2/03).

In a telephone interview, Dr. Feskanich was asked why women continue to be told to increase their calcium intake. “Calcium's importance is overrated--–we have a strong milk industry [in this country], and the U.S. Department of Agriculture was started with the mission to promote the idea that certain foods, especially dairy foods, must be consumed,” she answered, adding the importance of the Dairy Council, which has had a major influence on doctors as well as the general public. Contradictions abound. “We know from worldwide population studies that the high-calcium intake is associated with high hip fracture rates--Scandinavian countries, for example,” Dr. Feskanich continued, noting that Asian and Mediterranean countries with very low calcium intake have low fracture rates.

Vitamin A

The emphasis on the importance of calcium has led many women to drink low-fat or non-fat milk to prevent osteoporosis, a practice that is counterproductive, according to Dr. Feskanich. Drawing, once again, from 18-year data provided by the Nurses' Health Study, Dr. Feskanich and her colleagues found that a certain type of vitamin A, is associated with an increase in hip fractures (JAMA, 1/2/02). They identified the fortification of dairy products as the chief culprit. “Because the fat has been removed, the vitamin A has to be put back,” explained Dr. Feskanich, adding that people typically take a one-a-day vitamin supplement and eat a fortified breakfast cereal, and they might eat a power bar--all of which are fortified with vitamin A.

The fortification is usually done with the cheaper form of the vitamin called retinol, the type that is not good for bones in the long term, according to Dr. Feskanich. You can get beta carotene [the other form of vitamin A] from orange and yellow vegetables and fruits, she added, “and you can get plenty without eating animal products or taking a supplement.” Consumption of just one multivitamin often provides an excessive amount of vitamin A if the label says 5,000 IU with retinol as the major source. But some vitamin manufacturers have begun to reduce or eliminate retinol from their products.

To Dr. Feskanich and other nutrition researchers, the current RDA of 5,000 IU daily of vitamin A is too high, a point made in the editorial that accompanied her study. The editorial cites, approvingly, the Institute of Medicine's new recommendations for vitamin A intake as 800 IU daily for men and 700 IU daily for women.

Vitamin D

At the end of the telephone interview, Dr. Feskanich said, “I can't say that there is no benefit to calcium, but I think there's a bigger benefit from vitamin D.” Unfortunately, Dr. Feskanich and colleagues found that only a few studies focused on this vitamin as a way to prevent fractures. One of them, published in 2003 in the British Medical Journal, had over 2,600 participants, aged 65 to 85 years at the onset. All were living in the community (as opposed to a nursing home) and had been randomly assigned to take a placebo or vitamin D.

The study was conducted entirely by mail. The participants were sent one capsule containing 100,000 IU of vitamin D3 (cholecalciferol) or a placebo every four months for five years. The total fracture incidence was reduced by 22%. The research team led by Daksha P. Trivedi cautioned that the fracture incidence was extremely low even in those who had been taking the placebo, possibly due to the fact that most of the participants were men.

This was a small pilot study, and as such cannot be considered the last word on the role of vitamin D and fracture prevention. Dr. Trivedi and colleagues wrote, “The results, nonetheless, indicate that isolated vitamin D supplementation prevents fractures.” In discussing their findings, Dr. Trivedi and colleagues wrote that the every-four-month dose of 100,000 IU averages out to be a daily equivalent of 800 IU of vitamin D. And this might explain why their results were different from those of earlier trials, which used a lower dose (400 IU) and found no fracture-reduction benefit due to vitamin D.

The rapid responses to this article, or letters to the editor, can be read at no charge on the British Medical Journal's Web site (www.bmj.com, see March 1,2003). Several raised the concern about the potential toxicity of high doses of vitamin D. This was answered by one of the study's co-authors, Kay Tee Shaw, who wrote that several earlier trials showed that extremely high doses of vitamin D are safe. In one Scandinavian trial, nursing home residents were safely given single-dose injections of 300,000 IU of vitamin D annually for four to five years.

Dr. Feskanich's response to the same concern was that vitamin D is fat-soluble so people don't need to take a little bit every day. What's more, “vitamin D is stored in the liver, and this is good,” she explained, because elderly people don't metabolize vitamins well as they age, and the body's capacity to produce vitamin D when exposed to sunlight also declines with age. Her studies found that women typically consume less than the recommended intake of vitamin D. Therefore, they should consider supplement use or dark fish consumption.

 

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Maryann Napoli is the associate director of the Center for Medical Consumers in New York City.

December 2003