Aging Bones: A Short History of Osteoporosis

Chapter Six. Therapeutic Expansion

CHAPTER SIX Therapeutic Expansion F F F Although concern with osteoporosis accelerated during and after the 1980s, the therapeutic armamentarium remained relatively limited. ERT was by far the most frequently prescribed medication , even though there were disagreements on how it should be used. Other therapies, including calcitonin, anabolic steroids, sodium fluoride, and human parathyroid hormone, did not compare with ERT. Vitamin D and calcium supplementation were not controversial regimens, and patients were often urged to use them. But the preponderant view was that none of these interventions could compare with the effectiveness of estrogen. As long as the boundaries of the diagnosis of osteoporosis were circumscribed, drug companies had little incentive to develop alternative therapies and challenge Ayerst’s Premarin. But as the numbers of women diagnosed as either osteopenic or osteoporotic grew, interest in developing new therapies increased accordingly, particularly as doubts about the safety of ERT were raised. During and after the 1990s, a variety of new drugs entered the medical armamentarium. They were accompanied by recommendations from specialty groups and organizations stating that virtually all women should consider pharmacological therapy to prevent hip and vertebral fractures. The pharmaceutical industry 147 148 Aging Bones played a major role through its financial support of both research and clinical trials, to say nothing of publicity campaigns designed to persuade clinicians and patients of the importance and effectiveness of pharmacological therapy to prevent or treat osteopenia and osteoporosis. ESTROGEN By the 1980s Premarin—one of the five best-selling prescription drugs in the United States—was the leading drug prescribed for the prevention and treatment of osteoporosis. Its competitors lagged far behind, partly because the Ayerst pharmaceutical company had been promoting it in enthusiastic terms as an antidote for both osteoporosis and menopause. The only other competitor was calcitonin, a drug made by two European pharmaceutical firms. Calcitonin, however, had to be injected every day. Aside from its inconvenience and discomfort, its daily cost ($6 and $7) was beyond the means of many people. Yet the debate about the health benefits and risks of ERT had never been completely resolved, and uncertainty concerning the public health implications of long-term exposure to supplemental estrogen persisted.1 The WHI was just getting started, and results from that study were still some years away. Nevertheless, it was clear that there was no agreement about the risks of long-term ERT. Uncertainty, if not confusion, characterized recommendations concerning its use. In 1992 the American College of Physicians published guidelines designed to counsel postmenopausal women about preventive hormone therapy. Its recommendations were based on a review of the medical and scientific literature since 1970 dealing with the use of long-term hormone therapy to prevent disease or prolong life. Their review of 265 studies summarized the effect of estrogen-only therapy and estrogen therapy plus progestin on endometrial cancer, breast cancer, coronary heart disease, osteoporosis , and strokes. It found evidence that ERT decreased the risk of coronary heart disease and hip fractures. Long-term therapy, on the other hand, increased the risk of endometrial cancer and may Therapeutic Expansion 149 have been associated with a small increase in the risk of breast cancer . The heightened risk in the former could probably be avoided by adding a progestin to the estrogen regimen for women with an intact uterus, but the effect of combination hormones on the risks of contracting other diseases was unknown.2 Based on their literature survey, the American College of Physicians could only come to tentative recommendations. It suggested that all women, regardless of race, consider hormone therapy. Women who had a hysterectomy and those with or at high risk for coronary heart disease would benefit from such therapy. “For other women,” the guidelines stated, “the best course of action is unclear.”3 In many respects such guidelines were a mirror image of the divisions in the osteoporosis community. The American College of Physicians noted that estimates of risks and benefits came from observational studies, which could not provide conclusions about cause and effect. Randomized trials were required in order to prove effects and define their magnitude. Such trials, however, needed to be very large and would have to continue for many years, an undertaking that faced nearly insuperable obstacles. Hence the organization’s recommendations were based on the best available current data, but they were subject to possible change as the results of randomized trials...