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Integrated Therapies for Osteoporosis and Sarcopenia: From Signaling Pathways to Clinical Trials

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Abstract

Sarcopenia and osteoporosis are two sides of the same coin. They represent different aspects of the same age-related process of musculoskeletal atrophy and together culminate in falls, fractures, deconditioning, and increased mortality in older individuals. However, the current therapeutic approach to the prevention of minimal trauma fracture is unilateral and focuses solely on bone. In theory, an integrated approach that recognizes the interaction between muscle and bone could break the vicious cycle of their combined involution and more effectively minimize falls/fractures. In this review, signaling pathways and cross-talk mechanisms that integrate bone/muscle, and the emergence of novel therapies that exploit these pathways to target osteoporosis/sarcopenia will be discussed. In broad terms, these agents act on nuclear receptors (e.g., VDR, AR) or transmembrane receptors (e.g., activins, GH/IGF-1) expressed in muscle and bone, and seek to alter biologic responses to musculoskeletal aging, loading, and injury. Challenges in the development of these dual bone–muscle therapies, early clinical trials examining their safety/efficacy, and novel targets that hold promise in the reversal of musculoskeletal aging will be discussed.

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Acknowledgments

CMG is funded by a National Health and Medical Research Council (NHMRC) Peter Doherty Early Career Research Fellowship. I also wish to acknowledge the kind assistance of A/Professor Jane Bleasel (Department of Rheumatology, Royal Prince Alfred Hospital, Sydney) for critically reviewing this manuscript.

Conflict of interest

Christian M. Girgis has no disclosures to report.

Human and Animal Rights and Informed Consent

All research discussed in this review has been subject to ethics approval and informed consent has been obtained in human studies.

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  1. Westmead Millennium Institute for Medical Research, 176 Hawkesbury Rd, Westmead, NSW, Australia

    Christian M. Girgis

  2. Faculty of Medicine, University of Sydney, Sydney, NSW, Australia

    Christian M. Girgis

  3. Garvan Institute of Medical Research, Sydney, NSW, Australia

    Christian M. Girgis

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Girgis, C.M. Integrated Therapies for Osteoporosis and Sarcopenia: From Signaling Pathways to Clinical Trials. Calcif Tissue Int 96, 243–255 (2015). https://doi.org/10.1007/s00223-015-9956-x

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