{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T10:03:05Z","timestamp":1784887385243,"version":"3.55.0"},"reference-count":38,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T00:00:00Z","timestamp":1781481600000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R61NS119639"],"award-info":[{"award-number":["R61NS119639"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Duchenne Muscular Dystrophy (DMD) is characterized by progressive muscle wasting leading to early loss of motor function. Functional tests monitor disease progression and serve as clinical trial endpoints but are influenced by maturation in younger patients, high intra\u2010patient variability and patient motivation. Clinical milestones, instead, have been used to identify modifiers of disease progression but are rarely used as primary endpoints since clinical trials are usually too short to capture them. Blood biomarkers, that can reflect disease progression and objectively evaluate treatment responses, offer a valuable alternative.<\/jats:p>\n                    <jats:p>In this study, we investigated whether longitudinal observations of biomarkers myostatin and creatine\/creatinine ratio (Cr\/Crn) are associated with functional tests, such as 6\u2010min walk test, North Star Ambulatory Assessment (NSAA), 10\u2010m walk\u2010run test velocity (10MWT), Performance of Upper Limb (PUL2.0) and disease milestones like loss of ambulation, overhead reach and hand\u2010to\u2010mouth function.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We used longitudinal data from an observational study on 74 DMD patients followed between 2009 and 2022 with annual visits to the LUMC outpatient clinic, linked to 408 serum samples. Associations between log2\u2010biomarkers, functional tests and clinical milestones were assessed using linear mixed models and time\u2010dependent Cox models. A post\u2010hoc sample size calculation was performed to evaluate whether the biomarkers' lower intra\u2010patient variability (NSAA SD: 0.79, 10MWT SD: 0.88, log2\u2010myostatin and log2\u2010Cr\/Crn SDs: 0.57) may improve future clinical trials design.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Lower Cr\/Crn and higher myostatin levels were associated with better functional performance and a less rapid decline in ambulation, given fixed treatment and BMI. Children with one\u2010unit higher log2\u2010myostatin levels had, on average, 4.73 points higher NSAA and 3.40 points higher PUL2.0 (\n                      <jats:italic>p<\/jats:italic>\n                      \u2010values &lt;\u20090.001) and were 42% less likely to lose ambulation over the following year. Conversely, children with one\u2010unit lower log2\u2010ratio levels had, on average, 11.40 points higher NSAA and 7.18 points higher PUL2.0 (p\u2010values &lt;\u20090.001) and were 3.67 times more likely to remain ambulant. We proved that incorporating log2\u2010myostatin and log2\u2010Cr\/Crn as endpoints could reduce the required sample size for clinical trials by more than half without compromising statistical power. For instance, to detect a yearly drop of 3 points in the NSAA with 80% power, recruitment requires almost 80 participants in a 1:1 randomized trial, compared to a little more than 50 patients for the respective value of log2\u2010myostatin or log2\u2010Cr\/Crn.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings support the potential of myostatin and Cr\/Crn as monitoring biomarkers to enhance trial design and endpoints in clinical and interventional trials for DMD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.70320","type":"journal-article","created":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T03:54:57Z","timestamp":1781582097000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Creatine\/Creatinine Ratio and Myostatin as Biomarkers to Monitor Muscle Function in Duchenne Muscular Dystrophy Patients"],"prefix":"10.1002","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-9993-9346","authenticated-orcid":false,"given":"Chiara","family":"Degan","sequence":"first","affiliation":[{"name":"Department of Biomedical Data Sciences Leiden University Medical Center  the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3466-5401","authenticated-orcid":false,"given":"Roula","family":"Tsonaka","sequence":"additional","affiliation":[{"name":"Department of Biomedical Data Sciences Leiden University Medical Center  the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon I.","family":"de Vries","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Leiden University Medical Center  the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0609-4752","authenticated-orcid":false,"given":"Nadine A.","family":"Ikelaar","sequence":"additional","affiliation":[{"name":"Department of Neurology Leiden University Medical Center  the Netherlands"},{"name":"Duchenne Center  the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0797-5711","authenticated-orcid":false,"given":"Menno","family":"van der Holst","sequence":"additional","affiliation":[{"name":"Duchenne Center  the Netherlands"},{"name":"Department of Orthopedics, Rehabilitation and Physiotherapy Leiden University Medical Center  the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5772-7177","authenticated-orcid":false,"given":"Hermien E.","family":"Kan","sequence":"additional","affiliation":[{"name":"Duchenne Center  the Netherlands"},{"name":"Department of Radiology Leiden University Medical Center  the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5892-5143","authenticated-orcid":false,"given":"Erik H.","family":"Niks","sequence":"additional","affiliation":[{"name":"Department of Neurology Leiden University Medical Center  the Netherlands"},{"name":"Duchenne Center  the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2783-688X","authenticated-orcid":false,"given":"Pietro","family":"Spitali","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Leiden University Medical Center  the Netherlands"},{"name":"Duchenne Center  the 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