SAGE-Hindawi Access to Research Journal of Osteoporosis Volume 2011, Article ID 702735, 4 pages doi:10.4061/2011/702735 Review Article The Bone-Muscle Relationship in Men and Women Thomas F. Lang Department of Radiology and Biomedical Imaging, School of Medicine, University of California, San Francisco, San Francisco, CA 94143-0946, USA Correspondence should be addressed to Thomas F. Lang, thomas.lang@ucsf.edu Received 30 June 2011; Accepted 10 August 2011 Academic Editor: Pawel Szulc Copyright © 2011 Thomas F. Lang. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Muscle forces are a strong determinant of bone structure, particularly during the process of growth and development. The gender divergence in the bone-muscle relationship becomes strongly evident during adolescence. In females, growth is characterized by increased estrogen levels and increased mass and strength of bone relative to that of muscle, whereas in men, increases in testosterone fuel large increases in muscle, resulting in muscle forces that coincide with a large growth in bone dimensions and strength. In adulthood, signiﬁcant age-related losses are observed for both bone and muscle tissues. Large decrease in estrogen levels in women appears to diminish the skeleton’s responsiveness to exercise more than in men. In contrast, the aging of the muscle-bone axis in men is a function of age related declines in both hormones. In addition to the well-known age related changes in the mechanical loading of bone by muscle, newer studies appear to provide evidence of age- and gender-related variations in molecular signaling between bone and muscle that are independent of purely mechanical interactions. In summary, gender diﬀerences in the acquisition and age-related loss in bone and muscle tissues may be important for developing gender-speciﬁc strategies for using exercise to reduce bone loss with aging. 1. Introduction Skeletal fractures occur when bones are subjected to mechan- ical loads which exceed their strength. Diminished skeletal strength is a primary risk factor for fracture, and gender diﬀerences in skeletal structure and strength play a powerful role in determining gender diﬀerences in fracture risk. Skel- etal structure adapts to the long-term loads exerted on the skeleton exerted as a result of physical activity, and the most powerful loading forces are conferred by muscles, which must exert enough force to move bones while acting against extremely short lever arms. Thus, skeletal muscle is one of the most powerful determinants of bone strength and gender diﬀerences in the bone-muscle relationship are of key interest in understanding gender diﬀerences in bone growth, in age-related bone loss, and in risk of fracture. The close coupling between muscle and bone and the gender diﬀerences in the relationship are often viewed in the context of the the mechanostat theory, ﬁrst elaborated by Frost [1, 2]. In this paradigm, the muscle-bone relationship, expressed as the “bone-muscle unit,” is viewed as a mechanical rela- tionship modulated by the systemic eﬀects (e.g., hormones). Bones respond to the varying strains imposed by increases or decreases of mechanical loading, with sharp losses or modeling eﬀects triggered when strains, respectively, fall below or exceed setpoints that are determined by the gender- speciﬁc interaction of systemic factors with bone tissue. These same endocrine factors also have direct gender-speciﬁc interactions with muscle tissues, altering muscle mass and strength and aﬀecting the loads placed on bone. Finally, newer research points to direct two-way signaling between muscle and bone tissues, broadening the relationship beyond that of a purely mechanical perspective. 2. Gender Differences in the Bone-Muscle Unit in Childhood and Adolescence Skeletal fragility in old age is a function of peak bone strength in young adulthood and age-related loss of bone strength.