The authors state that they have no conflicts of interest.
Genetics of the Musculoskeletal System: A Pleiotropic Approach†
Article first published online: 11 FEB 2008
Copyright © 2008 ASBMR
Journal of Bone and Mineral Research
Volume 23, Issue 6, pages 788–802, June 2008
How to Cite
Karasik, D. and Kiel, D. P. (2008), Genetics of the Musculoskeletal System: A Pleiotropic Approach. J Bone Miner Res, 23: 788–802. doi: 10.1359/jbmr.080218
- Issue published online: 4 DEC 2009
- Article first published online: 11 FEB 2008
- Manuscript Accepted: 7 FEB 2008
- Manuscript Revised: 28 JAN 2008
- Manuscript Received: 14 NOV 2007
The risk of osteoporotic fracture can be viewed as a function of loading conditions and the ability of the bone to withstand the load. Skeletal loads are dominated by muscle action. Recently, it has become clear that bone and muscle share genetic determinants. Involution of the musculoskeletal system manifests as bone loss (osteoporosis) and muscle wasting (sarcopenia). Therefore, the consideration of pleiotropy is an important aspect in the study of the genetics of osteoporosis and sarcopenia. This Perspective will provide the evidence for a shared genetic influence on bone and muscle. We will start with an overview of accumulating evidence that physical exercise produces effects on the adult skeleton, seeking to unravel some of the contradictory findings published thus far. We will provide indications that there are pleiotropic relationships between bone structure/mass and muscle mass/function. Finally, we will offer some insights and practical recommendations as to the value of studying shared genetic factors and will explore possible directions for future research. We consider several related questions that together comprise the general paradigm of bone responses to mechanical loading and the relationship between muscle strength and bone parameters, including the genetic factors that modulate these responses. We believe that further progress in understanding the common genetic etiology of osteoporosis and sarcopenia will provide valuable insight into important biological underpinnings for both conditions and may translate into new approaches to reduce the burdens of both conditions through improved diagnosis, prevention, and early targeted treatment.