Selective Estrogen Receptor Modulator (SERM) Drugs for the Prevention of Osteoporosis

Abstract

It has been well established that estrogens in any form in doses equivalent to 0.3–1.25 mg esterified estrogens per day when administered by oral, percutaneous, or transdermal routes are effective in preventing postmenopausal bone loss [1–3]. The results of a variety of epidemiological studies designed to analyze the effects of hormone replacement therapy (HRT) on cardiovascular function also reveal a reduced relative risk of morbidity and mortality from cardiovascular diseases in woman taking HRT [4,5]. Despite these observations it is becoming increasingly obvious that a low prevalence of HRT use exists [6–8]. Factors which dispose to noncompliance and/or lack of acceptance of HRT treatment in the postmenopausal female include a dislike for withdrawal bleeding which results from cyclic estrogen/progestin therapy, breast engorgement and pain, poor compliance with progestins, and the fear of breast cancer [9,10]. In fact, many women either never have their prescriptions filled, follow treatment either intermittently or sporadically, or discontinue therapy completely after 21–24 months [7,8]. Although nonhormonal therapies for preventing bone loss in postmenopausal women such as the bisphosphonates have been recommended as effective substitutes for HRT [11–13], these pharmacological agents often require rigorous dosing schedules because of a variety of gastrointestinal complications [11]. SERM drugs which are also available to women who can not, will not, or should not utilize HRT characteristically react with estrogen receptors with resultant transcriptional pathways unlike those identified for estrogens [14–16].