The adaptive response of bone to mechanical loading in female transgenic mice is deficient in the absence of oestrogen receptor-α and -β

Abstract

Postmenopausal osteoporosis represents a failure of the response by which bone cells adapt bone mass and architecture to be sufficiently strong to withstand loading without fracture. To address why this failure should be associated with oestrogen withdrawal, we investigated the ulna's adaptive response to mechanical loading in adult female mice lacking oestrogen receptor-α (ERα-/-), those lacking oestrogen receptor-β (ERβ-/-) and their wild-type littermates. In wild-type mice, short periods of physiologic cyclic compressive loading of the ulna in vivo over a 2-week period stimulates new bone formation. In ERα-/- and ERβ-/- mice this osteogenic response was respectively threefold and twofold less (P<0·05). In vitro, primary cultures of osteoblast-like cells derived from these mice were subjected to a single short period of mechanical strain. Twenty-four hours after strain the number of wild-type cells was 61 ± 25% higher than in unstrained controls (P<0·05), whereas in ERα-/- cells there was no strain-related increase in cell number. However, the strain-related response of ERα-/- cells could be partially rescued by transfection with functional human ERα (P<0·05). ERβ-/- cells showed a 125 ± 40% increase in cell number following strain. This was significantly greater than in wild types (P<0·05). These data support previous findings that functional ERα is required for the full osteogenic response to mechanical loading and particularly the stage of this response, which involves an increase in osteoblast number. ERβ appears to depress the ERα-mediated strain-related increase in osteoblast number in vitro, but in female transgenic mice in vivo the constitutive absence of either ERα or ERβ appears to diminish the osteogenic response, to loading. © 2004 Society for Endocrinology.