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Rheumatoid sarcopenia: loss of skeletal muscle strength and mass in rheumatoid arthritis

Nature Reviews Rheumatology volume 19, pages 239–251 (2023)Cite this article

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Abstract

Sarcopenia, a disorder that involves the generalized loss of skeletal muscle strength and mass, was formally recognized as a disease by its inclusion in the International Classification of Diseases in 2016. Sarcopenia typically affects older people, but younger individuals with chronic disease are also at risk. The risk of sarcopenia is high (with a prevalence of ≥25%) in individuals with rheumatoid arthritis (RA), and this rheumatoid sarcopenia is associated with increased likelihood of falls, fractures and physical disability, in addition to the burden of joint inflammation and damage. Chronic inflammation mediated by cytokines such as TNF, IL-6 and IFNγ contributes to aberrant muscle homeostasis (for instance, by exacerbating muscle protein breakdown), and results from transcriptomic studies have identified dysfunction of muscle stem cells and metabolism in RA. Progressive resistance exercise is an effective therapy for rheumatoid sarcopenia but it can be challenging or unsuitable for some individuals. The unmet need for anti-sarcopenia pharmacotherapies is great, both for people with RA and for otherwise healthy older adults.

Key points

  • Sarcopenia is a progressive and generalized skeletal muscle disorder that involves the accelerated loss of muscle strength and mass and affects approximately one in four people with rheumatoid arthritis (RA).

  • Disease-specific risk factors for rheumatoid sarcopenia include high disease activity, raised inflammatory markers, long disease duration, rheumatoid factor positivity, glucocorticoid use and joint damage.

  • Inflammatory cytokines can accelerate the development of sarcopenia through elevation of muscle proteolysis, disruption of muscle stem cell self-renewal and direct impairment of myofibre force.

  • Muscle strength is the key marker of sarcopenia; handgrip strength can be measured in RA and specific devices are available for individuals with severe hand arthritis.

  • Muscle mass in RA is most frequently measured with dual-energy X-ray absorptiometry, although newer techniques (ultrasonography, CT and MRI) are emerging, and panels of molecular biomarkers might prove useful in the future.

  • Exercise is currently the most effective intervention for improving strength and muscle mass in people with RA.

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Fig. 1: Overlapping syndromes of low muscle mass and their definitions.
Fig. 2: Proposed mechanisms for acceleration of sarcopenia by inflammatory cytokines in rheumatoid arthritis.

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Acknowledgements

J.D.I. and A.A.S. are National Institute for Health and Care Research (NIHR) Senior Investigators.

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Authors and Affiliations

  1. Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK

    Joshua L. Bennett, Arthur G. Pratt, Richard Dodds, Avan A. Sayer & John D. Isaacs

  2. NIHR Newcastle Biomedical Research Centre, Newcastle University, Newcastle upon Tyne, UK

    Joshua L. Bennett, Richard Dodds, Avan A. Sayer & John D. Isaacs

  3. Musculoskeletal Unit, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK

    Joshua L. Bennett, Arthur G. Pratt & John D. Isaacs

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J.L.B. researched data for and wrote the article. All authors contributed substantially to the discussion of content. J.L.B., A.G.P., A.A.S. and J.D.I. reviewed and edited the manuscript before submission.

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J.D.I. has received research funding from GSK, Janssen and Pfizer, and speaker and/or consultancy fees from AbbVie, BMS, Gilead, Roche and UCB. The remaining authors declare no competing interests.

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Nature Reviews Rheumatology thanks Michael Kjaer, Masahiro Tada, and Ricardo Xavier, who co-reviewed with Rafaela Cavalheiro do Espirito Santo, for their contribution to the peer review of this work.

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Glossary

Appendicular lean mass index

Appendicular lean mass divided by the square of the individual’s height.

Muscle quality

Used interchangeably to describe either muscle strength relative to muscle mass or muscle structure (such as the ratio of contractile muscle to fat within the tissue).

Primary sarcopenia

Gradual age-related deterioration in muscle health that leads to sarcopenia.

Rheumatoid cachexia

Abnormal body composition in the context of rheumatoid arthritis, with low muscle mass plus normal or increased fat mass.

Rheumatoid sarcopenia

Sarcopenia associated with rheumatoid arthritis.

Sarcopenia

A progressive and generalized skeletal muscle disorder that involves the accelerated loss of muscle strength and mass.

Sarcopenic obesity

Sarcopenia plus increased fat mass.

Secondary sarcopenia

Sarcopenia associated with disease.

Severe sarcopenia

Sarcopenia plus poor physical performance (such as slow gait speed).

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Bennett, J.L., Pratt, A.G., Dodds, R. et al. Rheumatoid sarcopenia: loss of skeletal muscle strength and mass in rheumatoid arthritis. Nat Rev Rheumatol 19, 239–251 (2023). https://doi.org/10.1038/s41584-023-00921-9

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