Novel Algorithm to Estimate Fat‐Free Muscle Volumes in Women Using the Urinary Deuterated‐Creatine Dilution Method
ABSTRACT Background Muscle mass declines after menopause and is a key risk factor for frailty, falls and poor physical function as women age. The deuterated creatine (D3Cr) dilution method provides a direct assessment of muscle mass, but its accuracy in Asian women has not been evaluated. Our aim wa...
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| Published in | Journal of cachexia, sarcopenia and muscle Vol. 16; no. 4; pp. e13872 - n/a |
|---|---|
| Main Authors | , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Germany
John Wiley & Sons, Inc
01.08.2025
John Wiley and Sons Inc Wiley |
| Subjects | |
| Online Access | Get full text |
| ISSN | 2190-5991 2190-6009 2190-6009 |
| DOI | 10.1002/jcsm.13872 |
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| Abstract | ABSTRACT
Background
Muscle mass declines after menopause and is a key risk factor for frailty, falls and poor physical function as women age. The deuterated creatine (D3Cr) 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 D3Cr algorithm incorporating anthropomorphic variables that can estimate fat‐free muscle mass, using magnetic resonance imaging (MRI) as the reference standard.
Methods
The Integrated Women's Health Programme (IWHP) enrolled 1201 healthy community‐dwelling women, aged 45–69 years 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 mg of D3Cr and had available MRI measurements of fat‐free thigh and erector spinae volumes. Urinary levels of creatine, creatinine and D3‐creatinine levels were measured by tandem mass spectrometry 4 days after ingestion of D3Cr. Muscle mass was estimated using the two D3Cr algorithms (D3Croriginal and D3Crmodified) in current use and a newly developed algorithm (D3CrHt‐Wt) incorporating anthropometric variables that estimate fat‐free muscle volumes. Pearson's correlation analyses were used to compare the performances of the D3Cr algorithms with MRI. Bland–Altman analysis was used to ascertain agreement between D3CrHt‐Wt and MRI.
Results
Participants (n = 451, mean age 62.6 ± 5.9) were randomly divided into training (n = 367) and validation (n = 84) cohorts. In the training cohort, stepwise multivariable regression modelling indicated that age (β = −0.011, p = 0.076) and ethnicity (β = 0.154, p = 0.317 [Indian]; β = −0.012, p = 0.942 [Malay] compared to Chinese) were not associated with fat‐free muscle volumes. In the final model, D3Cr‐determined creatine pool size (β = 0.032, p < 0.001), body weight (β = 0.030, p < 0.001) and height (β = 4.336, p < 0.001) were independently associated with fat‐free muscle volumes and were incorporated into a new algorithm (D3CrHt‐Wt). In a separate validation cohort, muscle volumes estimated using the D3CrHt‐Wt algorithm (R = 0.813) had a higher correlation with MRI‐measured fat‐free muscle volumes than both D3Croriginal (R = 0.672) and D3Crmodified (R = 0.692) algorithms. Bland–Altman analysis indicated a low bias of 0.112 L and limits of agreement of −0.969 L to +1.190 L.
Conclusions
Muscle volumes estimated with the D3CrHt‐Wt algorithm had high correlation and agreement with MRI‐measured fat‐free muscle volumes. The convenience of the D3Cr method for participants suggests its potential to be a clinically relevant method for assessing fat‐free muscle volumes in sarcopenia studies. |
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| AbstractList | Muscle mass declines after menopause and is a key risk factor for frailty, falls and poor physical function as women age. The deuterated creatine (D3Cr) 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 D3Cr algorithm incorporating anthropomorphic variables that can estimate fat-free muscle mass, using magnetic resonance imaging (MRI) as the reference standard.BACKGROUNDMuscle mass declines after menopause and is a key risk factor for frailty, falls and poor physical function as women age. The deuterated creatine (D3Cr) 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 D3Cr algorithm incorporating anthropomorphic variables that can estimate fat-free muscle mass, using magnetic resonance imaging (MRI) as the reference standard.The Integrated Women's Health Programme (IWHP) enrolled 1201 healthy community-dwelling women, aged 45-69 years 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 mg of D3Cr and had available MRI measurements of fat-free thigh and erector spinae volumes. Urinary levels of creatine, creatinine and D3-creatinine levels were measured by tandem mass spectrometry 4 days after ingestion of D3Cr. Muscle mass was estimated using the two D3Cr algorithms (D3Croriginal and D3Crmodified) in current use and a newly developed algorithm (D3CrHt-Wt) incorporating anthropometric variables that estimate fat-free muscle volumes. Pearson's correlation analyses were used to compare the performances of the D3Cr algorithms with MRI. Bland-Altman analysis was used to ascertain agreement between D3CrHt-Wt and MRI.METHODSThe Integrated Women's Health Programme (IWHP) enrolled 1201 healthy community-dwelling women, aged 45-69 years 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 mg of D3Cr and had available MRI measurements of fat-free thigh and erector spinae volumes. Urinary levels of creatine, creatinine and D3-creatinine levels were measured by tandem mass spectrometry 4 days after ingestion of D3Cr. Muscle mass was estimated using the two D3Cr algorithms (D3Croriginal and D3Crmodified) in current use and a newly developed algorithm (D3CrHt-Wt) incorporating anthropometric variables that estimate fat-free muscle volumes. Pearson's correlation analyses were used to compare the performances of the D3Cr algorithms with MRI. Bland-Altman analysis was used to ascertain agreement between D3CrHt-Wt and MRI.Participants (n = 451, mean age 62.6 ± 5.9) were randomly divided into training (n = 367) and validation (n = 84) cohorts. In the training cohort, stepwise multivariable regression modelling indicated that age (β = -0.011, p = 0.076) and ethnicity (β = 0.154, p = 0.317 [Indian]; β = -0.012, p = 0.942 [Malay] compared to Chinese) were not associated with fat-free muscle volumes. In the final model, D3Cr-determined creatine pool size (β = 0.032, p < 0.001), body weight (β = 0.030, p < 0.001) and height (β = 4.336, p < 0.001) were independently associated with fat-free muscle volumes and were incorporated into a new algorithm (D3CrHt-Wt). In a separate validation cohort, muscle volumes estimated using the D3CrHt-Wt algorithm (R = 0.813) had a higher correlation with MRI-measured fat-free muscle volumes than both D3Croriginal (R = 0.672) and D3Crmodified (R = 0.692) algorithms. Bland-Altman analysis indicated a low bias of 0.112 L and limits of agreement of -0.969 L to +1.190 L.RESULTSParticipants (n = 451, mean age 62.6 ± 5.9) were randomly divided into training (n = 367) and validation (n = 84) cohorts. In the training cohort, stepwise multivariable regression modelling indicated that age (β = -0.011, p = 0.076) and ethnicity (β = 0.154, p = 0.317 [Indian]; β = -0.012, p = 0.942 [Malay] compared to Chinese) were not associated with fat-free muscle volumes. In the final model, D3Cr-determined creatine pool size (β = 0.032, p < 0.001), body weight (β = 0.030, p < 0.001) and height (β = 4.336, p < 0.001) were independently associated with fat-free muscle volumes and were incorporated into a new algorithm (D3CrHt-Wt). In a separate validation cohort, muscle volumes estimated using the D3CrHt-Wt algorithm (R = 0.813) had a higher correlation with MRI-measured fat-free muscle volumes than both D3Croriginal (R = 0.672) and D3Crmodified (R = 0.692) algorithms. Bland-Altman analysis indicated a low bias of 0.112 L and limits of agreement of -0.969 L to +1.190 L.Muscle volumes estimated with the D3CrHt-Wt algorithm had high correlation and agreement with MRI-measured fat-free muscle volumes. The convenience of the D3Cr method for participants suggests its potential to be a clinically relevant method for assessing fat-free muscle volumes in sarcopenia studies.CONCLUSIONSMuscle volumes estimated with the D3CrHt-Wt algorithm had high correlation and agreement with MRI-measured fat-free muscle volumes. The convenience of the D3Cr method for participants suggests its potential to be a clinically relevant method for assessing fat-free muscle volumes in sarcopenia studies. ABSTRACT Background Muscle mass declines after menopause and is a key risk factor for frailty, falls and poor physical function as women age. The deuterated creatine (D3Cr) 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 D3Cr algorithm incorporating anthropomorphic variables that can estimate fat‐free muscle mass, using magnetic resonance imaging (MRI) as the reference standard. Methods The Integrated Women's Health Programme (IWHP) enrolled 1201 healthy community‐dwelling women, aged 45–69 years 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 mg of D3Cr and had available MRI measurements of fat‐free thigh and erector spinae volumes. Urinary levels of creatine, creatinine and D3‐creatinine levels were measured by tandem mass spectrometry 4 days after ingestion of D3Cr. Muscle mass was estimated using the two D3Cr algorithms (D3Croriginal and D3Crmodified) in current use and a newly developed algorithm (D3CrHt‐Wt) incorporating anthropometric variables that estimate fat‐free muscle volumes. Pearson's correlation analyses were used to compare the performances of the D3Cr algorithms with MRI. Bland–Altman analysis was used to ascertain agreement between D3CrHt‐Wt and MRI. Results Participants (n = 451, mean age 62.6 ± 5.9) were randomly divided into training (n = 367) and validation (n = 84) cohorts. In the training cohort, stepwise multivariable regression modelling indicated that age (β = −0.011, p = 0.076) and ethnicity (β = 0.154, p = 0.317 [Indian]; β = −0.012, p = 0.942 [Malay] compared to Chinese) were not associated with fat‐free muscle volumes. In the final model, D3Cr‐determined creatine pool size (β = 0.032, p < 0.001), body weight (β = 0.030, p < 0.001) and height (β = 4.336, p < 0.001) were independently associated with fat‐free muscle volumes and were incorporated into a new algorithm (D3CrHt‐Wt). In a separate validation cohort, muscle volumes estimated using the D3CrHt‐Wt algorithm (R = 0.813) had a higher correlation with MRI‐measured fat‐free muscle volumes than both D3Croriginal (R = 0.672) and D3Crmodified (R = 0.692) algorithms. Bland–Altman analysis indicated a low bias of 0.112 L and limits of agreement of −0.969 L to +1.190 L. Conclusions Muscle volumes estimated with the D3CrHt‐Wt algorithm had high correlation and agreement with MRI‐measured fat‐free muscle volumes. The convenience of the D3Cr method for participants suggests its potential to be a clinically relevant method for assessing fat‐free muscle volumes in sarcopenia studies. ABSTRACT Background Muscle mass declines after menopause and is a key risk factor for frailty, falls and poor physical function as women age. The deuterated creatine (D3Cr) 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 D3Cr algorithm incorporating anthropomorphic variables that can estimate fat‐free muscle mass, using magnetic resonance imaging (MRI) as the reference standard. Methods The Integrated Women's Health Programme (IWHP) enrolled 1201 healthy community‐dwelling women, aged 45–69 years 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 mg of D3Cr and had available MRI measurements of fat‐free thigh and erector spinae volumes. Urinary levels of creatine, creatinine and D3‐creatinine levels were measured by tandem mass spectrometry 4 days after ingestion of D3Cr. Muscle mass was estimated using the two D3Cr algorithms (D3Croriginal and D3Crmodified) in current use and a newly developed algorithm (D3CrHt‐Wt) incorporating anthropometric variables that estimate fat‐free muscle volumes. Pearson's correlation analyses were used to compare the performances of the D3Cr algorithms with MRI. Bland–Altman analysis was used to ascertain agreement between D3CrHt‐Wt and MRI. Results Participants (n = 451, mean age 62.6 ± 5.9) were randomly divided into training (n = 367) and validation (n = 84) cohorts. In the training cohort, stepwise multivariable regression modelling indicated that age (β = −0.011, p = 0.076) and ethnicity (β = 0.154, p = 0.317 [Indian]; β = −0.012, p = 0.942 [Malay] compared to Chinese) were not associated with fat‐free muscle volumes. In the final model, D3Cr‐determined creatine pool size (β = 0.032, p < 0.001), body weight (β = 0.030, p < 0.001) and height (β = 4.336, p < 0.001) were independently associated with fat‐free muscle volumes and were incorporated into a new algorithm (D3CrHt‐Wt). In a separate validation cohort, muscle volumes estimated using the D3CrHt‐Wt algorithm (R = 0.813) had a higher correlation with MRI‐measured fat‐free muscle volumes than both D3Croriginal (R = 0.672) and D3Crmodified (R = 0.692) algorithms. Bland–Altman analysis indicated a low bias of 0.112 L and limits of agreement of −0.969 L to +1.190 L. Conclusions Muscle volumes estimated with the D3CrHt‐Wt algorithm had high correlation and agreement with MRI‐measured fat‐free muscle volumes. The convenience of the D3Cr method for participants suggests its potential to be a clinically relevant method for assessing fat‐free muscle volumes in sarcopenia studies. 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 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 Cr algorithm incorporating anthropomorphic variables that can estimate fat-free muscle mass, using magnetic resonance imaging (MRI) as the reference standard. The Integrated Women's Health Programme (IWHP) enrolled 1201 healthy community-dwelling women, aged 45-69 years 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 mg of D Cr and had available MRI measurements of fat-free thigh and erector spinae volumes. Urinary levels of creatine, creatinine and D -creatinine levels were measured by tandem mass spectrometry 4 days after ingestion of D Cr. Muscle mass was estimated using the two D Cr algorithms (D Cr and D Cr ) in current use and a newly developed algorithm (D Cr ) incorporating anthropometric variables that estimate fat-free muscle volumes. Pearson's correlation analyses were used to compare the performances of the D Cr algorithms with MRI. Bland-Altman analysis was used to ascertain agreement between D Cr and MRI. Participants (n = 451, mean age 62.6 ± 5.9) were randomly divided into training (n = 367) and validation (n = 84) cohorts. In the training cohort, stepwise multivariable regression modelling indicated that age (β = -0.011, p = 0.076) and ethnicity (β = 0.154, p = 0.317 [Indian]; β = -0.012, p = 0.942 [Malay] compared to Chinese) were not associated with fat-free muscle volumes. In the final model, D Cr-determined creatine pool size (β = 0.032, p < 0.001), body weight (β = 0.030, p < 0.001) and height (β = 4.336, p < 0.001) were independently associated with fat-free muscle volumes and were incorporated into a new algorithm (D Cr ). In a separate validation cohort, muscle volumes estimated using the D Cr algorithm (R = 0.813) had a higher correlation with MRI-measured fat-free muscle volumes than both D Cr (R = 0.672) and D Cr (R = 0.692) algorithms. Bland-Altman analysis indicated a low bias of 0.112 L and limits of agreement of -0.969 L to +1.190 L. Muscle volumes estimated with the D Cr algorithm had high correlation and agreement with MRI-measured fat-free muscle volumes. The convenience of the D Cr method for participants suggests its potential to be a clinically relevant method for assessing fat-free muscle volumes in sarcopenia studies. |
| Author | Shen, Liang Cauley, Jane Yong, Eu‐Leong Cheong, Wei Fun Tan, Darren Yuen Zhang Ji, Shanshan Cazenave‐Gassiot, Amaury |
| AuthorAffiliation | 5 Biostatistics Unit, Yong Loo Lin School of Medicine National University of Singapore Singapore Republic of Singapore 4 Department of Epidemiology, Graduate School of Public Health University of Pittsburgh Pittsburgh Pennsylvania USA 1 Department of Obstetrics and Gynecology, Yong Loo Lin School of Medicine National University of Singapore Singapore Republic of Singapore 3 Department of Biochemistry, Yong Loo Lin School of Medicine National University of Singapore Singapore Republic of Singapore 2 Singapore Lipidomics Incubator, Life Sciences Institute National University of Singapore Singapore Republic of Singapore |
| AuthorAffiliation_xml | – name: 1 Department of Obstetrics and Gynecology, Yong Loo Lin School of Medicine National University of Singapore Singapore Republic of Singapore – name: 4 Department of Epidemiology, Graduate School of Public Health University of Pittsburgh Pittsburgh Pennsylvania USA – name: 5 Biostatistics Unit, Yong Loo Lin School of Medicine National University of Singapore Singapore Republic of Singapore – name: 2 Singapore Lipidomics Incubator, Life Sciences Institute National University of Singapore Singapore Republic of Singapore – name: 3 Department of Biochemistry, Yong Loo Lin School of Medicine National University of Singapore Singapore Republic of Singapore |
| Author_xml | – sequence: 1 givenname: Darren Yuen Zhang surname: Tan fullname: Tan, Darren Yuen Zhang organization: National University of Singapore – sequence: 2 givenname: Wei Fun surname: Cheong fullname: Cheong, Wei Fun organization: National University of Singapore – sequence: 3 givenname: Shanshan surname: Ji fullname: Ji, Shanshan organization: National University of Singapore – sequence: 4 givenname: Amaury surname: Cazenave‐Gassiot fullname: Cazenave‐Gassiot, Amaury organization: National University of Singapore – sequence: 5 givenname: Jane surname: Cauley fullname: Cauley, Jane organization: University of Pittsburgh – sequence: 6 givenname: Liang surname: Shen fullname: Shen, Liang organization: National University of Singapore – sequence: 7 givenname: Eu‐Leong orcidid: 0000-0001-6511-770X surname: Yong fullname: Yong, Eu‐Leong email: obgyel@nus.edu.sg organization: National University of Singapore |
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| Copyright | 2025 The Author(s). published by Wiley Periodicals LLC. 2025 The Author(s). Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC. 2025. This work is published under http://creativecommons.org/licenses/by/4.0/ (the "License"). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. |
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| Keywords | muscle mass body composition creatinine MRI creatine sarcopenia |
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| License | Attribution 2025 The Author(s). Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
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| Notes | This study was funded by a Singapore National Medical Research Council grant (Numbers: CSASI20nov‐0006, MOH‐000670‐01). Darren Yuen Zhang Tan and Wei Fun Cheong are co–first authors. Funding ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Funding: This study was funded by a Singapore National Medical Research Council grant (Numbers: CSASI20nov‐0006, MOH‐000670‐01). |
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| Publisher | John Wiley & Sons, Inc John Wiley and Sons Inc Wiley |
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| Snippet | ABSTRACT
Background
Muscle mass declines after menopause and is a key risk factor for frailty, falls and poor physical function as women age. The deuterated... 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 Cr)... ABSTRACT Background Muscle mass declines after menopause and is a key risk factor for frailty, falls and poor physical function as women age. The deuterated... Muscle mass declines after menopause and is a key risk factor for frailty, falls and poor physical function as women age. The deuterated creatine (D3Cr)... |
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| SubjectTerms | Aged Algorithms body composition Chromatography creatine Creatine - urine Creatinine Deuterium Ethnicity Female Humans Magnetic Resonance Imaging Middle age Middle Aged Mortality MRI muscle mass Muscle, Skeletal - diagnostic imaging Musculoskeletal system Original Quality control Quality standards Sarcopenia Urine Womens health |
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| Title | Novel Algorithm to Estimate Fat‐Free Muscle Volumes in Women Using the Urinary Deuterated‐Creatine Dilution Method |
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