Recent experimental and clinical findings in the skeleton associated with loss of estrogen hormone or estrogen receptor activity.
Studies on rodent models and rare human disorders of estrogen production or response have revealed an increased complexity of the actions of estrogen on bone. ERalpha disruption in human males results in delayed epiphyseal maturation, tall stature, trabecular thinning, marked cortical thinning, genu valgum and significantly reduced cortical vBMD, but trabecular number is preserved and there is normal to increased periosteal expansion. Aromatase deficiency results overall in a similar phenotype, although less is known about skeletal architecture. Importantly, estrogen replacement in these individuals, even if provided late in the third decade, may normalize aBMD. Less certain is whether there is complete recovery of normal skeletal architecture and strength. Rodent models, in general, are consistent with the human phenotype but are confounded by inherent differences between mouse and human physiology and issues regarding the completeness of the different knock-out lines. Both human and rodent studies suggest that residual effects of estrogen through ERbeta, truncated ERalpha forms or nonclassical estrogen receptors might account for different phenotypes in the hERKO man, aromatase deficient subjects and rodents. Importantly, androgen, particularly by preserving trabecular number and augmenting both periosteal and epiphyseal growth, also has significant actions on bone.
Smith
Eric P
EP
Department of Internal Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA. smithep@email.uc.edu
Specker
Bonny
B
Korach
Kenneth S
KS
D000728:Androgens / Q000378:metabolism*; D000818:Animals; D001846:Bone Development; D001842:Bone and Bones / Q000378:metabolism* / Q000473:pathology*; D004967:Estrogens / Q000378:metabolism*; D006801:Humans; D011960:Receptors, Estrogen / Q000378:metabolism*
D000728:Androgens; D004967:Estrogens; D011960:Receptors, Estrogen