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Submitted on August 4, 2005
Accepted on November 15, 2005
Laboratory for Experimental Medicine and Endocrinology, Leuven University Center for Metabolic Bone Diseases and Division of Geriatric Medicine, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium
* To whom correspondence should be addressed. E-mail: dirk.vanderschueren{at}uz.kuleuven.ac.be.
Context: Traditionally, differences in periosteal bone formation between men and women have been assumed to reflect two diverging endocrine effects: stimulatory effects of androgens in men and inhibitory effects of estrogens in women. In line with this concept, it is tempting to speculate that men experience more periosteal bone expansion than women because they are more exposed to endogenous androgens and less to estradiol. However, recent data challenge this traditional concept.
Evidence acquisition: A PubMed search was conducted for relevant most recent findings in both humans and animals in the context of an intriguing observation of ongoing periosteal expansion following estrogen treatment in an aromatase deficient boy.
Evidence Synthesis: Human experiments of nature have provided evidence that androgens and estrogens are both required for the process of pubertal periosteal bone expansion typically associated with the male bone phenotype. Androgens alone appear insufficient to drive male periosteal bone formation. In both sexes, androgens may stimulate periosteal bone formation but low levels of estrogen may increase the mechanical sensitivity of the periosteum. Higher concentrations of endogenous estrogen however inhibit periosteal bone apposition and/or its interaction with mechanical loading. This biphasic action of estrogen on the periosteum may result from a direct effect on its receptor, either 
or 
, but may also depend on changes in serum IGF-I.
Conclusions: Simple concepts of the role of sex steroids in periosteal apposition have to be reconsidered in the context of these recent findings.
Introduction: the traditional concept of skeletal sexual dimorphism
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