{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T09:13:21Z","timestamp":1787735601474,"version":"build-2784847793"},"reference-count":40,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,7,9]],"date-time":"2025-07-09T00:00:00Z","timestamp":1752019200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Muscle mass declines after menopause and is a key risk factor for frailty, falls and poor physical function as women age. The deuterated creatine (D<jats:sub>3<\/jats:sub>Cr) dilution method provides a direct assessment of muscle mass, but its accuracy in Asian women has not been evaluated. Our aim was to develop a new D<jats:sub>3<\/jats:sub>Cr algorithm incorporating anthropomorphic variables that can estimate fat\u2010free muscle mass, using magnetic resonance imaging (MRI) as the reference standard.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The Integrated Women's Health Programme (IWHP) enrolled 1201 healthy community\u2010dwelling women, aged 45\u201369\u2009years at baseline, who attended gynaecological clinics from 2014 to 2016. Between February 2021 and July 2023, 894 participants were recontacted, and 451 of the respondents agreed to ingest 30\u2009mg of D<jats:sub>3<\/jats:sub>Cr and had available MRI measurements of fat\u2010free thigh and erector spinae volumes. Urinary levels of creatine, creatinine and D<jats:sub>3<\/jats:sub>\u2010creatinine levels were measured by tandem mass spectrometry 4\u2009days after ingestion of D<jats:sub>3<\/jats:sub>Cr. Muscle mass was estimated using the two D<jats:sub>3<\/jats:sub>Cr algorithms (D<jats:sub>3<\/jats:sub>Cr<jats:sub>original<\/jats:sub> and D<jats:sub>3<\/jats:sub>Cr<jats:sub>modified<\/jats:sub>) in current use and a newly developed algorithm (D<jats:sub>3<\/jats:sub>Cr<jats:sub>Ht\u2010Wt<\/jats:sub>) incorporating anthropometric variables that estimate fat\u2010free muscle volumes. Pearson's correlation analyses were used to compare the performances of the D<jats:sub>3<\/jats:sub>Cr algorithms with MRI. Bland\u2013Altman analysis was used to ascertain agreement between D<jats:sub>3<\/jats:sub>Cr<jats:sub>Ht\u2010Wt<\/jats:sub> and MRI.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Participants (<jats:italic>n<\/jats:italic>\u2009=\u2009451, mean age 62.6\u2009\u00b1\u20095.9) were randomly divided into training (<jats:italic>n<\/jats:italic>\u2009=\u2009367) and validation (<jats:italic>n<\/jats:italic>\u2009=\u200984) cohorts. In the training cohort, stepwise multivariable regression modelling indicated that age (<jats:italic>\u03b2<\/jats:italic>\u2009=\u2009\u22120.011, <jats:italic>p<\/jats:italic>\u2009=\u20090.076) and ethnicity (<jats:italic>\u03b2<\/jats:italic>\u2009=\u20090.154, <jats:italic>p<\/jats:italic>\u2009=\u20090.317 [Indian]; <jats:italic>\u03b2<\/jats:italic>\u2009=\u2009\u22120.012, <jats:italic>p<\/jats:italic>\u2009=\u20090.942 [Malay] compared to Chinese) were not associated with fat\u2010free muscle volumes. In the final model, D<jats:sub>3<\/jats:sub>Cr\u2010determined creatine pool size (<jats:italic>\u03b2<\/jats:italic>\u2009=\u20090.032, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001), body weight (<jats:italic>\u03b2<\/jats:italic>\u2009=\u20090.030, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001) and height (<jats:italic>\u03b2<\/jats:italic>\u2009=\u20094.336, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001) were independently associated with fat\u2010free muscle volumes and were incorporated into a new algorithm (D<jats:sub>3<\/jats:sub>Cr<jats:sub>Ht\u2010Wt<\/jats:sub>). In a separate validation cohort, muscle volumes estimated using the D<jats:sub>3<\/jats:sub>Cr<jats:sub>Ht\u2010Wt<\/jats:sub> algorithm (<jats:italic>R<\/jats:italic>\u2009=\u20090.813) had a higher correlation with MRI\u2010measured fat\u2010free muscle volumes than both D<jats:sub>3<\/jats:sub>Cr<jats:sub>original<\/jats:sub> (<jats:italic>R<\/jats:italic>\u2009=\u20090.672) and D<jats:sub>3<\/jats:sub>Cr<jats:sub>modified<\/jats:sub> (<jats:italic>R<\/jats:italic>\u2009=\u20090.692) algorithms. Bland\u2013Altman analysis indicated a low bias of 0.112\u2009L and limits of agreement of \u22120.969\u2009L to +1.190\u2009L.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Muscle volumes estimated with the D<jats:sub>3<\/jats:sub>Cr<jats:sub>Ht\u2010Wt<\/jats:sub> algorithm had high correlation and agreement with MRI\u2010measured fat\u2010free muscle volumes. The convenience of the D<jats:sub>3<\/jats:sub>Cr method for participants suggests its potential to be a clinically relevant method for assessing fat\u2010free muscle volumes in sarcopenia studies.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.13872","type":"journal-article","created":{"date-parts":[[2025,7,9]],"date-time":"2025-07-09T14:19:18Z","timestamp":1752070758000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Novel Algorithm to Estimate Fat\u2010Free Muscle Volumes in Women Using the Urinary Deuterated\u2010Creatine Dilution Method"],"prefix":"10.1002","volume":"16","author":[{"given":"Darren\u00a0Yuen\u00a0Zhang","family":"Tan","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Yong Loo Lin School of Medicine National University of Singapore  Singapore Republic of 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