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Review
. 2025 Jun;21(6):375-390.
doi: 10.1038/s41574-025-01088-x. Epub 2025 Feb 26.

Bone and muscle crosstalk in ageing and disease

Affiliations
Review

Bone and muscle crosstalk in ageing and disease

Ben Kirk et al. Nat Rev Endocrinol. 2025 Jun.

Abstract

Interorgan communication between bone and skeletal muscle is central to human health. A dysregulation of bone-muscle crosstalk is implicated in several age-related diseases. Ageing-associated changes in endocrine, inflammatory, nutritional and biomechanical stimuli can influence the differentiation capacity, function and survival of mesenchymal stem cells and bone-forming and muscle-forming cells. Consequently, the secretome phenotype of bone and muscle cells is altered, leading to impaired crosstalk and, ultimately, catabolism of both tissues. Adipose tissue acts as a third player in the bone-muscle interaction by secreting factors that affect bone and muscle cells. Physical exercise remains the key biological stimulus for bone-muscle crosstalk, either directly via the release of cytokines from bone, muscle or adipocytes, or indirectly through extracellular vesicles. Overall, bone-muscle crosstalk is considered an inherent process necessary to maintain the structure and function of both tissues across the life cycle. This Review summarizes the latest biomedical advances in bone-muscle crosstalk as it pertains to human ageing and disease. We also outline future research priorities to accommodate the understanding of this rapidly emerging field.

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Conflict of interest statement

Competing interests: The authors declare no competing interests.

References

    1. Novotny, S. A., Warren, G. L. & Hamrick, M. W. Aging and the muscle-bone relationship. Physiology 30, 8–16 (2015). - PubMed - PMC
    1. Kirk, B., Feehan, J., Lombardi, G. & Duque, G. Muscle, bone, and fat crosstalk: the biological role of myokines, osteokines, and adipokines. Curr. Osteoporos. Rep. 18, 388–400 (2020). - PubMed
    1. Kirk, B. & Piasecki, M. in Sarcopenia (eds Cruz-Jentoft, A. J. & Morley, J. E.) 35–43 (Wiley, 2021).
    1. Gostage, J. et al. Extra-osseous roles of the RANK-RANKL-OPG axis with a focus on skeletal muscle. Curr. Osteoporos. Rep. 22, 632–650 (2024). - PubMed - PMC
    1. Lai, Y. et al. Multimodal cell atlas of the ageing human skeletal muscle. Nature 629, 154–164 (2024). - PubMed - PMC

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