Previous studies have shown that there is a clear relationship between physical activity and higher bone mineral density (BMD). Exercise and the force that muscle contraction applies to bone improve skeletal health by stimulating the formation of new bone. Conversely, off-loading muscle, such as in astronauts, can lead to bone loss and an increased fracture risk. But the question of how muscle function regulates bone mass has remained largely unresolved despite their close anatomical proximity. A key question is whether muscle contraction connects to bone mass regulation through a secreted molecule.
My team, along with researchers from the Department of Experimental and Clinical Medicine at University of Ancona in Italy, and the Department of Basic Medical Science, Neuroscience and Sense Organs at the University of Bari in Italy, recently published our findings in the Proceedings of the National Academy of Sciences (PNAS), identifying the bone active properties of a molecule, irisin, known to be released from muscle following exercise. Irisin has been shown to be a major regulator of metabolic health, wherein it permits the conversion of white, storage fat into brown, energy-generating fat. We find that irisin, when injected into mice at remarkably low doses, increases bone mass and improves the strength of cortical bone–the key function of which is to resist bending and torsion. Thus, from our work, it appears that irisin is fundamental to muscle-bone communication, in essence, translating the skeletal anabolic action of exercise by directly stimulating new bone synthesis by osteoblasts, cells that create new bone. Indeed, our research establishes for the first time that a molecule released from muscle during exercise can act directly on long bones, such as the femur, to increase bone strength.
The discovery of irisin is not just the identification of the molecule responsible for muscle-bone connectivity, but it could also become a therapy for both sarcopenia and osteoporosis. During normal aging, bones can become weak and brittle, and this can sometimes occur together with the gradual loss of muscle mass, thus causing significant disability in our increasingly older population.
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By Mone Zaidi, MD, PhD, Professor of Medicine and of Structural and Chemical Biology at the Icahn School of Medicine at Mount Sinai, and Director of the Mount Sinai Bone Program.