The role of SERMs in the treatment of osteoporosis

Abstract

Osteoporosis is currently defined as 'a skeletal disorder characterized by compromisedbone strength predisposing to an increased risk of fracture. Bonestrength reflects the integration of two main features: bone density and bonequality' (NIH Consensus 2001). Thus, osteoporosis is a debilitating conditionof the skeleton that propends to fractures and is associated with advancedage. The disease has a high prevalence in western countries, as it isa condition associated with advanced age, and it is on the rise since life expectancyhas risen dramatically in the last several decades. It is, therefore,a major public health problem because it not only induces morbidity (fracturesand chronic sequelae) with a substantial impact on health-related qualityof life, but is also associated with increased mortality (Badia et al. 2001,2004).Although osteoporosis affects both men and women, the ratio of female tomale patients is as high as 6 to 1. This is related not only to the lower total boneacquisition in women during development but also to the abrupt estrogen deficiencyas a result of menopause. It has been demonstrated that estrogens playan important role in female bone homeostasis, and their deficiency increasesbone resorption. Thus, in recent years the administration of estrogens hasbeen extensively used as the main therapy to prevent osteoporosis in women.Estrogens not only reduce the rate of bone remodeling, acting as an antiresorptiveagent, but also offer positive effects on the undesirable symptoms ofmenopause. There is still much discussion, however, on the overall benefits ofan exclusive hormone replacement therapy (HT) either with estrogens aloneor combining estrogens and progestogens, because these therapies increasethe risk of serious health disorders, such as breast cancer (Writing Groupfor the Women's Health Initiative Investigators 2002; Million Women StudyCollaborators 2003).Some years ago breast cancer patients treated with tamoxifen showed protectionagainst loss of bone in postmenopausal women (Powles et al. 1996).This clinical result led to a revision of the traditionally accepted role of tamoxifen as an antiestrogen. It is clear that a number of substances can act insome organs or tissues as estrogen agonists and be antagonists in others. Asa result of these observations and a better knowledge of the molecular featuresof estrogen receptors (ERs), the term selective estrogen receptor modulator(SERM) was coined. Tamoxifen and raloxifene belong to this group of substances.This chapter will review the scientific evidence supporting the role ofSERMs as bone antiresorptive agents. © Springer-Verlag Berlin Heidelberg 2006.