{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T04:56:14Z","timestamp":1790916974074,"version":"4.1.0"},"reference-count":24,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["K08AR082457"],"award-info":[{"award-number":["K08AR082457"]}],"id":[{"id":"10.13039\/100000069","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":[[2026,10]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n Cachexia is a multifactorial muscle wasting syndrome and is responsible for 20%\u201340% of cancer\u2010related deaths, yet no FDA\u2010approved therapies exist. Preclinical studies suggest that metastatic bone disease may contribute to muscle wasting, but this relationship has not been evaluated in clinical populations. This study evaluated whether metastatic bone disease at diagnosis is associated with longitudinal skeletal muscle loss and whether metastatic bone disease and longitudinal skeletal muscle loss are associated with overall survival in patients with kidney cancer.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n A total of 293 patients (66.9% male, 33.1% female, median age 60\u2009years) were retrospectively identified with either localised kidney cancer, extraosseous metastatic disease, or osseous metastatic disease at diagnosis. Clinical and demographic variables and treatments were recorded. Body composition was quantified over time for a subset by body mass index (BMI) (\n N<\/jats:italic>\n \u2009=\u2009221) and CT analysis at the L3 vertebral level (\n N<\/jats:italic>\n \u2009=\u200999). Longitudinal changes were analysed using linear regression, and overall survival was assessed with Kaplan\u2013Meier and multivariable Cox proportional hazards models.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Patients with osseous metastatic disease had a reduction in BMI over time compared with those with localised or extraosseous metastatic disease (median of \u22123.6% per year, compared with +0.7% and \u22122.6% respectively,\n p<\/jats:italic>\n \u2009<\u20090.01). Skeletal muscle loss was greatest for those with osseous metastasis (\u22127.5% per year, compared with \u22120.8% and \u22121.2% respectively,\n p<\/jats:italic>\n \u2009<\u20090.01). Multivariable linear regression demonstrated osseous metastasis at diagnosis was strongly associated with muscle loss (\n \u03b2<\/jats:italic>\n coefficient of \u221220.9 [95% confidence interval (CI): \u221235.56 to \u22126.27]). In multivariable Cox regression analysis, osseous metastasis at diagnosis was associated with an increased risk of death (HR 15.8; 95% CI: 2.00 to 124.95;\n p<\/jats:italic>\n \u2009<\u20090.01), as was longitudinal skeletal muscle loss (HR 1.02 for each 1% loss per year; 95% CI: 1.01 to 1.04;\n p<\/jats:italic>\n \u2009<\u20090.01).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n This study provides the first clinical evidence that metastatic bone disease is strongly associated with skeletal muscle loss and reduced survival in kidney cancer patients. These findings extend prior preclinical observations into the clinical setting and support further investigation into the possibility that tumour\u2013bone\u2013muscle interactions drive systemic muscle wasting. Importantly, the observation that severe muscle loss is strongly associated with mortality in kidney cancer highlights the need to consider cachexia as a modifiable determinant of outcomes, not just a byproduct of advanced disease.<\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/jcsm.70400","type":"journal-article","created":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T04:45:08Z","timestamp":1790916308000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Metastatic Bone Disease Is Associated With Longitudinal Muscle Loss and Reduced Survival in Kidney Cancer"],"prefix":"10.1002","volume":"17","author":[{"given":"Jon\u2010Luc","family":"Poirier","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery Indiana University School of Medicine Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel T.","family":"Jines","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery Indiana University School of Medicine Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Libbie M.","family":"Silverman","sequence":"additional","affiliation":[{"name":"Department of Surgery Indiana University School of Medicine Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anuradha Valiya","family":"Kambrath","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery Indiana University School of Medicine Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L. Daniel","family":"Wurtz","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery Indiana University School of Medicine Indianapolis Indiana USA"},{"name":"Simon Comprehensive Cancer Center Indiana University School of Medicine Indianapolis Indiana USA"},{"name":"Indiana Center for Musculoskeletal Health Indiana University School of Medicine Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa A.","family":"Zimmers","sequence":"additional","affiliation":[{"name":"Department of Cell, Developmental & Cancer Biology Oregon Health & Science University Portland Oregon USA"},{"name":"Knight Cancer Institute Oregon Health & Science University Portland Oregon USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2639-4290","authenticated-orcid":false,"given":"Christopher D.","family":"Collier","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery Indiana University School of Medicine Indianapolis Indiana USA"},{"name":"Simon Comprehensive Cancer Center Indiana University School of Medicine Indianapolis Indiana USA"},{"name":"Indiana Center for Musculoskeletal Health Indiana University School of Medicine Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,1]]},"reference":[{"issue":"1","key":"e_1_2_9_2_1","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1002\/jcsm.12402","article-title":"Orphan Disease Status of Cancer Cachexia in the USA and in the European Union: A Systematic Review","volume":"10","author":"Anker M. S.","year":"2019","journal-title":"Journal of Cachexia, Sarcopenia and Muscle"},{"issue":"1","key":"e_1_2_9_3_1","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/s41574-018-0123-0","article-title":"Inter\u2010Tissue Communication in Cancer Cachexia","volume":"15","author":"Argiles J. M.","year":"2018","journal-title":"Nature Reviews. Endocrinology"},{"issue":"5","key":"e_1_2_9_4_1","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1038\/s41568-020-0251-4","article-title":"Understanding Cachexia in the Context of Metastatic Progression","volume":"20","author":"Biswas A. K.","year":"2020","journal-title":"Nature Reviews. Cancer"},{"issue":"24","key":"e_1_2_9_5_1","doi-asserted-by":"crossref","first-page":"2291","DOI":"10.1056\/NEJMoa2409515","article-title":"Ponsegromab for the Treatment of Cancer Cachexia","volume":"391","author":"Groarke J. D.","year":"2024","journal-title":"New England Journal of Medicine"},{"issue":"7","key":"e_1_2_9_6_1","doi-asserted-by":"crossref","first-page":"482","DOI":"10.21037\/atm.2020.03.55","article-title":"Incidence of Patients With Bone Metastases at Diagnosis of Solid Tumors in Adults: A Large Population\u2010Based Study","volume":"8","author":"Huang J. F.","year":"2020","journal-title":"Annals of Translational Medicine"},{"issue":"9","key":"e_1_2_9_7_1","doi-asserted-by":"crossref","first-page":"2471","DOI":"10.1016\/j.cell.2021.03.011","article-title":"The Bone Microenvironment Invigorates Metastatic Seeds for Further Dissemination","volume":"184","author":"Zhang W.","year":"2021","journal-title":"Cell"},{"issue":"11","key":"e_1_2_9_8_1","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1038\/nm.3961","article-title":"Excess TGF\u2010beta Mediates Muscle Weakness Associated With Bone Metastases in Mice","volume":"21","author":"Waning D. L.","year":"2015","journal-title":"Nature Medicine"},{"issue":"1","key":"e_1_2_9_9_1","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1186\/s12943-016-0565-8","article-title":"Choosing the Right Cell Line for Renal Cell cancer Research","volume":"15","author":"Brodaczewska K. K.","year":"2016","journal-title":"Molecular Cancer"},{"issue":"6","key":"e_1_2_9_10_1","doi-asserted-by":"crossref","DOI":"10.3390\/cancers12061605","article-title":"The Combination of Low Skeletal Muscle Mass and High Tumor Interleukin\u20106 Associates With Decreased Survival in Clear Cell Renal Cell Carcinoma","volume":"12","author":"Kays J. K.","year":"2020","journal-title":"Cancers (Basel)"},{"issue":"1","key":"e_1_2_9_11_1","first-page":"12","article-title":"Cancer Statistics, 2024","volume":"74","author":"Siegel R. L.","year":"2024","journal-title":"CA: A Cancer Journal for Clinicians"},{"issue":"3","key":"e_1_2_9_12_1","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1007\/s11914-024-00872-4","article-title":"The Impact of Non\u2010Bone Metastatic Cancer on Musculoskeletal Health","volume":"22","author":"Galiana\u2010Melendez F.","year":"2024","journal-title":"Current Osteoporosis Reports"},{"key":"e_1_2_9_13_1","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.ejca.2018.10.023","article-title":"Prognosis of Renal Cell Carcinoma With Bone Metastases: Experience From a Large Cancer Centre","volume":"107","author":"Ruatta F.","year":"2019","journal-title":"European Journal of Cancer"},{"issue":"3","key":"e_1_2_9_14_1","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1002\/ijc.35181","article-title":"New Players in the Landscape of Renal Cell Carcinoma Bone Metastasis and Therapeutic Opportunities","volume":"156","author":"Cesana B.","year":"2025","journal-title":"International Journal of Cancer"},{"issue":"8","key":"e_1_2_9_15_1","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1002\/bco2.405","article-title":"Muscle Matters: Skeletal Muscle Index and Body Mass Index Impact on Complications and Survival in Renal Cancer","volume":"5","author":"Hillers A. H.","year":"2024","journal-title":"BJUI Compass."},{"issue":"10","key":"e_1_2_9_16_1","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1158\/1055-9965.EPI-24-0306","article-title":"Radiodensities of Skeletal Muscle and Visceral Adipose Tissues Are Prognostic Factors in Clear\u2010Cell Renal Cell Carcinoma","volume":"33","author":"Bradshaw P. T.","year":"2024","journal-title":"Cancer Epidemiology, Biomarkers & Prevention"},{"issue":"23","key":"e_1_2_9_17_1","doi-asserted-by":"crossref","first-page":"5180","DOI":"10.1158\/1078-0432.CCR-22-1389","article-title":"Associations Between Pretreatment Body Composition Features and Clinical Outcomes Among Patients With Metastatic Clear Cell Renal Cell Carcinoma Treated With Immune Checkpoint Blockade","volume":"28","author":"Ged Y.","year":"2022","journal-title":"Clinical Cancer Research: An Official Journal of the American Association for Cancer Research"},{"issue":"1","key":"e_1_2_9_18_1","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.juro.2015.08.071","article-title":"Prognostic Significance of Sarcopenia in Patients With Metastatic Renal Cell Carcinoma","volume":"195","author":"Fukushima H.","year":"2016","journal-title":"Journal of Urology"},{"issue":"1","key":"e_1_2_9_19_1","doi-asserted-by":"crossref","first-page":"7587","DOI":"10.1038\/s41598-017-07955-6","article-title":"Early Skeletal Muscle Loss During Target Therapy Is a Prognostic Biomarker in Metastatic Renal Cell Carcinoma Patients","volume":"7","author":"Gu W.","year":"2017","journal-title":"Scientific Reports"},{"issue":"8","key":"e_1_2_9_20_1","doi-asserted-by":"crossref","first-page":"1543","DOI":"10.1158\/2159-8290.CD-25-0293","article-title":"Cancer\u2010Associated Cachexia: Bridging Clinical Findings With Mechanistic Insights in Human Studies","volume":"15","author":"Koh K.","year":"2025","journal-title":"Cancer Discovery"},{"issue":"6","key":"e_1_2_9_21_1","doi-asserted-by":"crossref","first-page":"e429","DOI":"10.1016\/j.clgc.2023.05.006","article-title":"Relationship Between Pretreatment Body Composition and Clinical Outcomes in Patients With Metastatic Renal Cell Carcinoma Receiving First\u2010Line Ipilimumab Plus Nivolumab","volume":"21","author":"McManus H. D.","year":"2023","journal-title":"Clinical Genitourinary Cancer"},{"issue":"9","key":"e_1_2_9_22_1","doi-asserted-by":"crossref","DOI":"10.3390\/jcm14093140","article-title":"Early Changes in Volumetric Body Composition Parameters Predict Survival Outcomes in Patients With Metastatic Renal Cell Carcinoma Treated With Targeted Therapy","volume":"14","author":"Aktepe O. H.","year":"2025","journal-title":"Journal of Clinical Medicine"},{"key":"e_1_2_9_23_1","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1038\/s41591-023-02232-8","article-title":"Body Composition and Lung cancer\u2010Associated cachexia in TRACERx","volume":"29","author":"Al\u2010Sawaf O.","year":"2023","journal-title":"Nature Medicine"},{"issue":"1","key":"e_1_2_9_24_1","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1056\/NEJMoa2502760","article-title":"Structured Exercise After Adjuvant Chemotherapy for Colon Cancer","volume":"393","author":"Courneya K. S.","year":"2025","journal-title":"New England Journal of Medicine"},{"issue":"6","key":"e_1_2_9_25_1","doi-asserted-by":"crossref","first-page":"2259","DOI":"10.1002\/jcsm.12899","article-title":"Ethical Guidelines for Publishing in the Journal of Cachexia, Sarcopenia and Muscle: Update 2021","volume":"12","author":"Haehling S.","year":"2021","journal-title":"Journal of Cachexia, Sarcopenia and Muscle"}],"container-title":["Journal of Cachexia, Sarcopenia and Muscle"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcsm.70400","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcsm.70400","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcsm.70400","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T04:45:17Z","timestamp":1790916317000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcsm.70400"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10]]},"references-count":24,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.1002\/jcsm.70400"],"URL":"https:\/\/doi.org\/10.1002\/jcsm.70400","archive":["Portico"],"relation":{},"ISSN":["2190-5991","2190-6009"],"issn-type":[{"value":"2190-5991","type":"print"},{"value":"2190-6009","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10]]},"assertion":[{"value":"2025-10-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70400"}}