The Direct and Indirect Effects of Estrogen on Bone Formation

Abstract

This chapter discusses the direct and indirect effects of estrogen on bone formation. The central role of estrogen in the regulation of bone mass is well established. Estrogen is crucial to the attainment of normal skeletal mass during development and to the maintenance of this mass thereafter. Thus, there is a rapid increase in bone density in the vertebrae of females during puberty, while mutational inactivation of the estrogen receptor results in a low bone mass. Estrogen deficiency in adulthood, whether natural or pathological, is associated with bone loss, which can be prevented by estrogen administration. It is generally held that estrogen enhances and supports bone mass through suppression of bone resorption. Certainly bone loss in hypoestrogenic states is associated with increased bone resorption, and suppression of resorption by estrogen or other antiresorptive agents prevents osteopenia. The pubertal increase in bone mass by estrogen is also explicable as an effect on bone resorption. Theoretically, increased bone formation would also increase bone mass, but the prevailing view is that estrogen does not stimulate bone formation. Rather, the estrogen suppresses bone formation, because estrogen deprivation stimulates, and estrogen administration inhibits this. However, other antiresorptive agents such as bisphosphonates and calcitonin also reverse the increase in bone formation that occurs after estrogen deficiency.