{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T22:44:33Z","timestamp":1787957073408,"version":"build-2784847793"},"reference-count":25,"publisher":"Wiley","issue":"19","license":[{"start":{"date-parts":[[2024,8,31]],"date-time":"2024-08-31T00:00:00Z","timestamp":1725062400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,8,31]],"date-time":"2024-08-31T00:00:00Z","timestamp":1725062400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>\n                      Duchenne muscular dystrophy (DMD) results in a progressive loss of functional skeletal muscle mass (MM) and replacement with fibrofatty tissue. Accurate evaluation of MM in DMD patients has not previously been available. Our objective was to measure MM using the D\n                      <jats:sub>3<\/jats:sub>\n                      creatine (D\n                      <jats:sub>3<\/jats:sub>\n                      Cr) dilution method and determine its relationship with strength and functional capacity in patients with DMD over a wide range of ages. Subjects were recruited for participation in a 12\u00a0month, longitudinal, observational study. Here, we report the baseline data. A 20\u00a0mg dose of D\n                      <jats:sub>3<\/jats:sub>\n                      Cr dissolved in water was ingested by 92 patients with DMD (ages 4\u201325\u00a0years) followed later with a fasting urine sample. Enrichment of D\n                      <jats:sub>3<\/jats:sub>\n                      creatinine was determined by liquid chromatography\u2010mass spectrometry analysis. The North Star Ambulatory Assessment (NSAA) total score was determined for ambulatory participants, and the Performance of Upper Limb (PUL 2.0) total score and grip strength for all participants. We observed a significant age\u2010associated increase in body weight along with a substantial decrease in MM\/body weight (%MM). MM and %MM were associated with PUL score (\n                      <jats:italic>r<\/jats:italic>\n                      \u00a0=\u00a00.517,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.0001 and\n                      <jats:italic>r<\/jats:italic>\n                      \u00a0=\u00a00.764,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.0001 respectively). The age\u2010associated decrease in MM and %MM was strongly associated with ambulatory status. We observed very little overlap in %MM between ambulant and non\u2010ambulant subjects, suggesting a threshold of 18\u201322% associated with loss of ambulation. MM is substantially diminished with advancing age and is highly related to clinically meaningful functional status. The D\n                      <jats:sub>3<\/jats:sub>\n                      Cr dilution method may provide a biomarker of disease progression and therapeutic efficacy in patients with DMD or other neuromuscular disorders.\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp16293-gra-0001-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>\n                            The non\u2010invasive D\n                            <jats:sub>3<\/jats:sub>\n                            creatine dilution method provides novel data on whole body functional muscle mass (MM) in a wide range of ages in patients with DMD and reveals profoundly low functional MM in older non\u2010ambulant patients.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>The difference in %MM between ambulant and non\u2010ambulant subjects suggests a threshold for loss of ambulatory ability between 18 and 22% MM.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>The data suggest that as functional MM declines with age, maintaining a lower body weight may help to conserve ambulatory ability.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1113\/jp287069","type":"journal-article","created":{"date-parts":[[2024,8,31]],"date-time":"2024-08-31T15:34:09Z","timestamp":1725118449000},"page":"4929-4939","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Reductions in functional muscle mass and ability to ambulate in Duchenne muscular dystrophy from ages 4 to 24 years"],"prefix":"10.1113","volume":"602","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6757-1471","authenticated-orcid":false,"given":"William J.","family":"Evans","sequence":"first","affiliation":[{"name":"Department Nutritional Sciences and Toxicology University of California  Berkeley California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2327-0834","authenticated-orcid":false,"given":"Marc","family":"Hellerstein","sequence":"additional","affiliation":[{"name":"Department Nutritional Sciences and Toxicology University of California  Berkeley California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russell J.","family":"Butterfield","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Utah  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0073-9377","authenticated-orcid":false,"given":"Edward","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Duke University Medical Center  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8455-0637","authenticated-orcid":false,"given":"Michela","family":"Guglieri","sequence":"additional","affiliation":[{"name":"John Walton Muscular Dystrophy Research Centre Newcastle University and Newcastle Hospitals NHS Foundation Trust  Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie","family":"Katz","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Duke University Medical Center  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brittany","family":"Nave","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Duke University Medical Center  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"Branigan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Utah  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Thera","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Duke University Medical Center  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kalista L.","family":"Vordos","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Utah  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Behar","sequence":"additional","affiliation":[{"name":"John Walton Muscular Dystrophy Research Centre Newcastle University and Newcastle Hospitals NHS Foundation Trust  Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianela","family":"Schiava","sequence":"additional","affiliation":[{"name":"John Walton Muscular Dystrophy Research Centre Newcastle University and Newcastle Hospitals NHS Foundation Trust  Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8078-7744","authenticated-orcid":false,"given":"Meredith K.","family":"James","sequence":"additional","affiliation":[{"name":"John Walton Muscular Dystrophy Research Centre Newcastle University and Newcastle Hospitals NHS Foundation Trust  Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5098-8932","authenticated-orcid":false,"given":"Tyler","family":"Field","sequence":"additional","affiliation":[{"name":"Department Nutritional Sciences and Toxicology University of California  Berkeley California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hussein","family":"Mohammed","sequence":"additional","affiliation":[{"name":"Department Nutritional Sciences and Toxicology University of California  Berkeley California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9138-9610","authenticated-orcid":false,"given":"Mahalakshmi","family":"Shankaran","sequence":"additional","affiliation":[{"name":"Department Nutritional Sciences and Toxicology University of California  Berkeley California 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