Effects of exercise on muscle strength and characteristics in rheumatic diseases and sarcopenia: Protocol for the Care for Muscle (C4M) Study
6 affiliations
- 1Amsterdam University Medical Center, Department of Rehabilitation Medicine, Location VU University Medical Center, Amsterdam, The Netherlands
- 2Reade, Center for Rehabilitation and Rheumatology, Amsterdam, The Netherlands
- 3Amsterdam University Medical Center, Department of Rheumatology and Clinical Immunology, Location VU Medical Center, Amsterdam, The Netherlands
- 4Department of Human Movement Sciences, Faculty of Behavioural and Movement Sciences, Amsterdam Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
- 5Vrije Universiteit Amsterdam, Laboratory for Myology, Department of Human Movement Sciences, Faculty of Behavioral and Movement Sciences, Amsterdam Movement Sciences, Amsterdam, The Netherlands
- 6Amsterdam University of Applied Sciences, Center of Expertise Urban Vitality, Faculty of Health, Sport and Physical Activity, Amsterdam, The Netherlands
Abstract
Objective: Muscle weakness is prevalent in rheumatoid arthritis (RA), osteoarthritis (OA) and sarcopenia (SARC). Endurance exercises may improve mitochondrial function and oxidative capacity, while strength exercises are thought to stimulate myofibrillar protein synthesis. This study aims to compare the effects of strength and endurance exercise and explore the association between muscle characteristics and exercise outcomes in patients with RA, OA and SARC. We hypothesize that responses to endurance and strength exercises in patients with muscle weakness are influenced by intramuscular pathology including muscle morphology, mitochondrial function, and systemic inflammation, based on their disease pathology, potentially requiring personalized training schedules. Methods: This two-arm, parallel-group exploratory trial will enroll 69 patients (23 RA, 23 OA, 23 SARC), randomized to endurance (n = 35) or muscle strength exercises (n = 34), using minimization to balance disease type and gender. The 8-week intervention includes two supervised sessions per week using a controlled cable pulley device (Reforter™) and fitness equipment, plus one weekly home-based session. The primary outcome is isokinetic muscle strength (peak torque), measured with the Biodex system®. Secondary outcomes include muscle morphology, mitochondrial function, systemic inflammation and muscle endurance (by Biodex and 6 Minute Walk test). Muscle morphology will be assessed via 3D ultrasound imaging of the vastus lateralis. Mitochondrial function will be analyzed using high-resolution respirometry on muscle biopsies. Systemic inflammation will be measured using multiplex assays or ELISA on serum samples. Discussion: This study will explore differential responses to muscle endurance and muscle strength exercises in patients with RA, OA, and SARC, offering novel insights into the molecular mechanisms of muscle weakness. The findings may help identify potential mechanisms underlying variability in exercise response and provide effect size estimates to guide future confirmatory studies and more targeted exercise interventions. Trial registration: ClinicalTrials.gov NCT06480643 (date of registration28-06-24).
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BibTeX
@article{sobejana2026effects,
title = {{Effects of exercise on muscle strength and characteristics in rheumatic diseases and sarcopenia: Protocol for the Care for Muscle (C4M) Study}},
author = {Maia M. Sobejana and Rosa M. Korpershoek and Maarten M. Steinz and Conny J. van der Laken and Marike van der Leeden and Richard T. Jaspers and Bart Visser and Martin van der Esch and Carel G. M. Meskers and Mariëtte de Rooij},
journal = {PLOS One},
year = {2026},
month = sep,
doi = {10.1371/journal.pone.0356181},
url = {https://doi.org/10.1371/journal.pone.0356181},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Effects of exercise on muscle strength and characteristics in rheumatic diseases and sarcopenia: Protocol for the Care for Muscle (C4M) Study
AU - Maia M. Sobejana
AU - Rosa M. Korpershoek
AU - Maarten M. Steinz
AU - Conny J. van der Laken
AU - Marike van der Leeden
AU - Richard T. Jaspers
AU - Bart Visser
AU - Martin van der Esch
AU - Carel G. M. Meskers
AU - Mariëtte de Rooij
PY - 2026
DA - 2026/09/09
JO - PLOS One
DO - 10.1371/journal.pone.0356181
UR - https://doi.org/10.1371/journal.pone.0356181
AB - Objective: Muscle weakness is prevalent in rheumatoid arthritis (RA), osteoarthritis (OA) and sarcopenia (SARC). Endurance exercises may improve mitochondrial function and oxidative capacity, while strength exercises are thought to stimulate myofibrillar protein synthesis. This study aims to compare the effects of strength and endurance exercise and explore the association between muscle characteristics and exercise outcomes in patients with RA, OA and SARC. We hypothesize that responses to endurance and strength exercises in patients with muscle weakness are influenced by intramuscular pathology including muscle morphology, mitochondrial function, and systemic inflammation, based on their disease pathology, potentially requiring personalized training schedules. Methods: This two-arm, parallel-group exploratory trial will enroll 69 patients (23 RA, 23 OA, 23 SARC), randomized to endurance (n = 35) or muscle strength exercises (n = 34), using minimization to balance disease type and gender. The 8-week intervention includes two supervised sessions per week using a controlled cable pulley device (Reforter™) and fitness equipment, plus one weekly home-based session. The primary outcome is isokinetic muscle strength (peak torque), measured with the Biodex system®. Secondary outcomes include muscle morphology, mitochondrial function, systemic inflammation and muscle endurance (by Biodex and 6 Minute Walk test). Muscle morphology will be assessed via 3D ultrasound imaging of the vastus lateralis. Mitochondrial function will be analyzed using high-resolution respirometry on muscle biopsies. Systemic inflammation will be measured using multiplex assays or ELISA on serum samples. Discussion: This study will explore differential responses to muscle endurance and muscle strength exercises in patients with RA, OA, and SARC, offering novel insights into the molecular mechanisms of muscle weakness. The findings may help identify potential mechanisms underlying variability in exercise response and provide effect size estimates to guide future confirmatory studies and more targeted exercise interventions. Trial registration: ClinicalTrials.gov NCT06480643 (date of registration28-06-24).
SN - 1932-6203
ER -