Estrogen receptor subtype-specific effects on markers of bone homeostasis

To further elucidate the processes involved in the physiology of bone-protection by estrogens, ovariectomized (OVX) rats were treated subcutaneously with 17beta-estradiol (E(2)), the ERalpha-specific agonist (16alpha-LE2) and the ERbeta-specific agonist (8beta-VE2). OVX and intact animals served as controls. Biomarkers of bone-formation (osteocalcin (OC), osteopontin (OPN)) and bone-resorption (telopeptides of collagen type I (CTx), pyridinoline cross-links (Pyd)) were quantified. Bone mineral density was measured by computed tomography. OVX-induced bone loss could be antagonized by subcutaneous administration of 17beta-estradiol and 16alpha-LE2. Serum levels of CTx, OC and OPN were significantly elevated in OVX compared to intact animals and reduced by 17beta-estradiol and 16alpha-LE2. Treatment of OVX rats with 8beta-VE2 did not affect bone mineral density (BMD) or bone-marker serum levels. Taken together, the complex expression pattern of bone-markers in OVX rats following subcutaneous administration of ER subtype-specific agonists indicates that 17beta-estradiol exerts its bone-protective effects by modulating the activity of osteoclasts and osteoblasts via ERalpha.