Clinical Review

Treating and preventing osteoporosis: in the wake of WHI

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The recent findings regarding hormone replacement therapy aren’t the only new developments on the osteoporosis front. Here, 3 experts discuss trends in prevention, diagnosis, and treatment, as well as what’s on the horizon.



  • Hormone replacement therapy is a viable option for the prevention of osteoporosis.
  • The US Preventive Services Task Force recently recommended that women over the age of 65 get a bone densitometry test.
  • Although bone loss is a side effect of depot medroxyprogesterone acetate (DMPA) injections and gonadotropin-releasing hormone agonists (GnRH), physicians should not halt therapy in women for whom these agents are indicated.
  • Data suggest that the current vitamin D recommendation of 400 to 800 IU daily is probably inadequate.
  • Many physicians need further education on the use of dual-energy x-ray absorptiometry.
In some respects, the estrogen-progestin arm of the Women’s Health Initiative (WHI) offered hormone replacement therapy (HRT) advocates encouragement. While it is true that this particular study was terminated due to an increased number of events for breast cancer, heart attack, and stroke, it was also the first large-scale clinical trial to prove that HRT can reduce fracture occurrence.

Osteoporosis threatens the public health, particularly for women. According to the National Institutes of Health (NIH), of the 10 million Americans who suffer from osteoporosis, 8 million are women over the age of 50. In addition, an estimated 18 million women with low bone mass have yet to be diagnosed or treated.1

Still, this is not an irreversible trend. Thanks to recent educational efforts, many more Americans know how to prevent this disease. Advances in detection and treatment protocols, meanwhile, have given physicians new options for managing patients at risk.

As protectors of women’s health, Ob/Gyns have the unique opportunity to provide patients with the information they need to achieve and maintain optimal bone mass, as well as to ensure that proper preventive measures start early in life. Here, 3 experts review recent advances in the field of osteoporosis, and offer guidance for effective prevention and treatment.


Robert Lindsay, MD, is chief, internal medicine, Helen Hayes Hospital, West Haverstraw, NY; professor, clinical medicine, Columbia University, New York, NY; and board member, National Osteoporosis Foundation.

Wulf Utian, MD, is executive director, North American Menopause Society, Mayfield Heights, Ohio; consultant gynecologist, Cleveland Clinic Foundation, Cleveland, Ohio; and president, Rapid Medical Research, Cleveland, Ohio.

Robert Wild, MD, MPH, is professor and chief, reproductive endocrinology, adjunct professor of medicine and epidemiology, Oklahoma University Health Sciences Center, Oklahoma City, Okla.

HRT and osteoporosis

OBG Management: In light of the WHI findings, women at an increased risk for osteoporosis may be more likely to forego HRT. Are there better agents than HRT for preventing osteoporosis?

Wild: The WHI was a well-done clinical trial that had the advantage of recruiting a large number of women. Its endpoints included a favorable effect on fracture prevention. However, in view of the deleterious effects of this particular estrogen-progestin combination, the risk-benefit ratio may not be favorable for chronic disease prevention for more than 4 years in older women. But this question is still open as we await the results of the WISDOM trial, a large scale clinical trial in the United Kingdom using similar agents and evaluating similar clinical endpoints as in the WHI.

While HRT does remain a good choice, fortunately, many other therapies to prevent osteoporosis and its consequences are available ( TABLE). Many patients, particularly older women without estrogen-deficiency symptoms, are good candidates for raloxifene, bisphosphonates, and selective estrogen receptor modulators (SERMs) soon to be on the market. It really depends on an individual’s needs. Unfortunately, we do not have any long-term data on the use of bisphosphonates in younger women. Some animal data have given cause for concern, at least theoretically, that the protective effects of these agents will not continue after several years of use.

The estrogen-progestin arm of the Women’s Health Initiative was a very large and powerful study that demonstrated a fracture benefit in women who were not selected because they had osteoporosis.

Lindsay: Women have been drifting away from HRT for quite some time, particularly for long-term use in preventing osteoporosis. But it’s important to realize that the WHI was a very large and powerful study that demonstrated a fracture benefit in people who were not selected because they had osteoporosis. Research on other anti-osteoporosis agents has shown no reduction in fracture risk for people who do not have osteoporosis. This means that HRT is a viable option for the prevention of osteoporosis, regardless of the other issues surrounding it. I think it will remain one of the agents we’re likely to use.

Utian: I agree with Dr. Lindsay. What’s interesting is that the breast cancer increase reported in the WHI study was not statistically significant, but the rate of fracture reduction was. If we actually look at the WHI and the Heart and Estrogen/Progestin Replacement Study (HERS)—2 very large, randomized studies that have caused this antihormone brouhaha—we are certainly dealing with older women exclusively. I’d be interested to hear what Dr. Lindsay has to say about a woman who is under 50 with significant osteoporosis risk. Would he put her on a longterm bisphosphonate or would he prefer that younger women take HRT for the short-term and then consider some therapeutic change?


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