{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T18:08:39Z","timestamp":1788977319263,"version":"build-2803163510"},"reference-count":59,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100020068","name":"Topconsortium voor Kennis en Innovatie","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100020068","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This two-arm, parallel-group exploratory trial will enroll 69 patients (23 RA, 23 OA, 23 SARC), randomized to endurance (n\u2009=\u200935) or muscle strength exercises (n\u2009=\u200934), 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\u2122) and fitness equipment, plus one weekly home-based session. The primary outcome is isokinetic muscle strength (peak torque), measured with the Biodex system\n                      <jats:bold>\u00ae<\/jats:bold>\n                      . 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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>\n                      ClinicalTrials.gov\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT06480643\" xlink:type=\"simple\">NCT06480643<\/jats:ext-link>\n                      (date of registration28-06-24).\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0356181","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T17:34:12Z","timestamp":1788975252000},"page":"e0356181","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effects of exercise on muscle strength and characteristics in rheumatic diseases and sarcopenia: Protocol for the Care for Muscle (C4M) Study"],"prefix":"10.1371","volume":"21","author":[{"given":"Maia M.","family":"Sobejana","sequence":"first","affiliation":[{"name":"Amsterdam University Medical Center","place":["Amsterdam, The Netherlands"],"department":["Department of Rehabilitation Medicine"]},{"name":"Reade, Center for Rehabilitation and Rheumatology","place":["Amsterdam, The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-3147-8000","authenticated-orcid":true,"given":"Rosa M.","family":"Korpershoek","sequence":"additional","affiliation":[{"name":"Amsterdam University Medical Center","place":["Amsterdam, The Netherlands"],"department":["Department of Rehabilitation Medicine"]},{"name":"Reade, Center for Rehabilitation and Rheumatology","place":["Amsterdam, The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maarten M.","family":"Steinz","sequence":"additional","affiliation":[{"name":"Amsterdam University Medical Center","place":["Amsterdam, The Netherlands"],"department":["Department of Rheumatology and Clinical Immunology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Conny J.","family":"van der Laken","sequence":"additional","affiliation":[{"name":"Amsterdam University Medical Center","place":["Amsterdam, The Netherlands"],"department":["Department of Rheumatology and Clinical Immunology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marike","family":"van der Leeden","sequence":"additional","affiliation":[{"name":"Amsterdam University Medical Center","place":["Amsterdam, The Netherlands"],"department":["Department of Rehabilitation Medicine"]},{"name":"Amsterdam Movement Sciences, Vrije Universiteit Amsterdam","place":["Amsterdam, the Netherlands"],"department":["Department of Human Movement Sciences, Faculty of Behavioural and Movement Sciences"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6951-0952","authenticated-orcid":true,"given":"Richard T.","family":"Jaspers","sequence":"additional","affiliation":[{"name":"Vrije Universiteit Amsterdam, Laboratory for Myology","place":["Amsterdam, The Netherlands"],"department":["Department of Human Movement Sciences, Faculty of Behavioral and Movement Sciences, Amsterdam Movement Sciences"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8559-9715","authenticated-orcid":true,"given":"Bart","family":"Visser","sequence":"additional","affiliation":[{"name":"Amsterdam Movement Sciences, Vrije Universiteit Amsterdam","place":["Amsterdam, the Netherlands"],"department":["Department of Human Movement Sciences, Faculty of Behavioural and Movement Sciences"]},{"name":"Amsterdam University of Applied Sciences, Center of Expertise Urban Vitality","place":["Amsterdam, The Netherlands"],"department":["Faculty of Health, Sport and Physical Activity"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"van der Esch","sequence":"additional","affiliation":[{"name":"Reade, Center for Rehabilitation and Rheumatology","place":["Amsterdam, The Netherlands"]},{"name":"Amsterdam University of Applied Sciences, Center of Expertise Urban Vitality","place":["Amsterdam, The Netherlands"],"department":["Faculty of Health, Sport and Physical Activity"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carel G. 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