Hormonal control of bone architecture throughout the lifespan: Implications for fracture prediction and prevention.

Skeletal modeling in childhood and adolescence and continuous remodeling throughout the lifespan are designed to adapt to a changing environment and resist external forces and fractures. The flux of sex steroids in men and women, beginning from fetal development and evolving through infancy, childhood, puberty, young adulthood, peri/menopause transition, and post-menopause, is critical for bone size, peak bone mass, and the risk for fractures. The contributions of estrogen and testosterone on skeletal development have been difficult to study due to the reciprocal and intertwining contributions of one on the other. While orchiectomy in men renders circulating testosterone absent, circulating estrogen also declines due to testosterone being the substrate for estradiol. The discovery of men with absent estradiol or resistance to estrogen and the study of mouse models led to the understanding that estrogen has a larger direct role in skeletal development and maintenance in men and women. The mechanistic reason for larger bone size in men is incompletely understood but related to indirect effects of testosterone on the skeleton, such as higher muscle mass leading to larger skeletal loads. Declines in sex steroids during menopause in women and androgen deprivation therapies in men have profound and negative effects on the skeleton. Therapies to prevent such bone loss are available, but how such therapies can be tailored based on bone size and architecture remains an area of investigation. In this review, the elegant interplay and contribution of sex steroids on bone architecture in men and women throughout the lifespan is described.