{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T04:50:24Z","timestamp":1791521424466,"version":"4.3.4"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T00:00:00Z","timestamp":1791504000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Muscle mass and bone mineral density decrease with aging, although following different patterns among males and females. Growth differentiation factor 15 (GDF-15) is a stress-induced cytokine and has emerged as a key biomarker for inflammation, tissue injury, and metabolic stress. We tested the association between GDF-15 and specific bone and muscle parameters in a large cohort of community-dwelling subjects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The SardiNIA survey included 4,842 subjects (2,795 females). All underwent a detailed medical visit and laboratory testing. Peripheral quantitative computed tomography at the tibia was performed to evaluate volumetric bone mineral density and bone microstructure as well as muscle mass.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Multivariate regression analysis showed that GDF-15 was negatively associated with cortical bone density (Beta \u22120.042,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&amp;lt;\u20090.001) in females. In males, total bone density and trabecular bone density at 4% site and cortical bone area at 38% site were negatively associated with GDF-15 levels (respectively, Beta \u22120.016,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.027, Beta \u22120.014,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.039, and Beta \u22120.022,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.002). Multivariate regression analysis for muscle parameters showed that GDF-15 was negatively associated with muscle density (Beta \u22120.002 in females and males,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&amp;lt;\u20090.001 for all) and muscle area (Beta \u22120.338,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.003, Beta \u22120.744,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&amp;lt;\u20090.001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Higher circulating GDF-15 levels were independently associated with lower volumetricBMD and poorer muscle parameters in both women and men. These findings support the potential role of GDF-15 as a biomarker of age-related musculoskeletal decline, although longitudinal studies are needed to determine whether GDF-15 contributes to the development of these changes or simply reflects the underlying biological processes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1920342","type":"journal-article","created":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T04:26:24Z","timestamp":1791519984000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Association of Serum GDF-15 with Bone and Muscle Parameters in Community-Dwelling Individuals"],"prefix":"10.3389","volume":"13","author":[{"given":"Nicia I.","family":"Profili","sequence":"first","affiliation":[{"name":"Department of Medicine, Surgery, and Pharmacy, University of Sassari","place":["Sassari, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sokratis","family":"Makrogiannis","sequence":"additional","affiliation":[{"name":"Division of Physics, Engineering, Mathematics, and Computer Science, Delaware State University","place":["Dover, DE, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Castelli","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery, and Pharmacy, University of Sassari","place":["Sassari, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Benelli","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery, and Pharmacy, University of Sassari","place":["Sassari, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Orr\u00f9","sequence":"additional","affiliation":[{"name":"Institute for Genetic and Biomedical Research, National Research Council","place":["Monserrato, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Marongiu","sequence":"additional","affiliation":[{"name":"Institute for Genetic and Biomedical Research, National Research Council","place":["Monserrato, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edoardo","family":"Fiorillo","sequence":"additional","affiliation":[{"name":"Institute for Genetic and Biomedical Research, National Research Council","place":["Monserrato, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Cucca","sequence":"additional","affiliation":[{"name":"Institute for Genetic and Biomedical Research, National Research Council","place":["Monserrato, Italy"]},{"name":"Department of Biomedical Science, University of Sassari","place":["Sassari, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro P.","family":"Delitala","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery, and Pharmacy, University of Sassari","place":["Sassari, Italy"]},{"name":"Institute for Genetic and Biomedical Research, National Research Council","place":["Monserrato, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2447","DOI":"10.1007\/s00198-018-4653-z","article-title":"Osteoporosis and osteopenia in the distal forearm predict all-cause mortality independent of grip strength: 22-year follow-up in the population-based Tromso study","volume":"29","author":"Hauger","year":"2018","journal-title":"Osteoporos Int"},{"key":"B2","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1007\/s00198-018-4704-5","article-title":"European guidance for the diagnosis and management of osteoporosis in postmenopausal women","volume":"30","author":"Kanis","year":"2019","journal-title":"Osteoporos Int"},{"key":"B3","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1007\/s00198-002-1322-y","article-title":"Aging bone in men and women: beyond changes in bone mineral density","volume":"14","author":"Russo","year":"2003","journal-title":"Osteoporos Int"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1603879","DOI":"10.3389\/fmed.2025.1603879","article-title":"The correlation between sarcopenia and osteoporosis in the elderly: a systematic review and meta-analysis","volume":"12","author":"Jin","year":"2025","journal-title":"Front Med (Lausanne)"},{"key":"B5","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1038\/s41574-018-0059-4","article-title":"Inflammaging: a new immune-metabolic viewpoint for age-related diseases","volume":"14","author":"Franceschi","year":"2018","journal-title":"Nat Rev Endocrinol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"654","DOI":"10.1016\/j.molcel.2016.01.028","article-title":"The mitochondrial basis of aging","volume":"61","author":"Sun","year":"2016","journal-title":"Mol Cell"},{"key":"B7","doi-asserted-by":"publisher","first-page":"101569","DOI":"10.1016\/j.arr.2022.101569","article-title":"GDF15, an emerging key player in human aging","volume":"75","author":"Conte","year":"2022","journal-title":"Ageing Res Rev"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1418","DOI":"10.1002\/jcsm.12823","article-title":"Changes in systemic GDF15 across the adult lifespan and their impact on maximal muscle power: the Copenhagen Sarcopenia Study","volume":"12","author":"Alcazar","year":"2021","journal-title":"J Cachexia Sarcopenia Muscle"},{"key":"B9","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1111\/ggi.12724","article-title":"Secreted growth differentiation factor 15 as a potential biomarker for mitochondrial dysfunctions in aging and age-related disorders","author":"Fujita","year":"2016","journal-title":"Geriatr Gerontol Int"},{"key":"B10","doi-asserted-by":"publisher","first-page":"11073","DOI":"10.3390\/ijms262211073","article-title":"The effect of thyroid function on GDF15 levels","volume":"26","author":"Profili","year":"2025","journal-title":"Int J Mol Sci"},{"key":"B11","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1016\/j.cmet.2019.12.004","article-title":"GDF15 induces anorexia through nausea and emesis","volume":"31","author":"Borner","year":"2020","journal-title":"Cell Metab"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1333","DOI":"10.1038\/nm1677","article-title":"Tumor-induced anorexia and weight loss are mediated by the TGF-beta superfamily cytokine MIC-1","volume":"13","author":"Johnen","year":"2007","journal-title":"Nat Med"},{"key":"B13","doi-asserted-by":"publisher","first-page":"112124","DOI":"10.1016\/j.mad.2025.112124","article-title":"Circulating mitokines GDF-15 and FGF21 are associated with frailty, sarcopenia, and malnutrition in older adults: evidence from the FRASNET study","volume":"228","author":"Damanti","year":"2025","journal-title":"Mech Ageing Dev"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1549","DOI":"10.1002\/jcsm.13513","article-title":"GDF-15 is associated with sarcopenia and frailty in acutely admitted older medical patients","volume":"15","author":"Kamper","year":"2024","journal-title":"J Cachexia Sarcopenia Muscle"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1404047","DOI":"10.3389\/fendo.2024.1404047","article-title":"Different roles of circulating and intramuscular GDF15 as markers of skeletal muscle health","volume":"15","author":"Chiariello","year":"2024","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B16","doi-asserted-by":"publisher","first-page":"938","DOI":"10.1002\/jbmr.1538","article-title":"Positive regulation of osteoclastic differentiation by growth differentiation factor 15 upregulated in osteocytic cells under hypoxia","volume":"27","author":"Hinoi","year":"2012","journal-title":"J Bone Miner Res"},{"key":"B17","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1677\/JME-07-0048","article-title":"Vitamin K2 induces phosphorylation of protein kinase A and expression of novel target genes in osteoblastic cells","volume":"39","author":"Ichikawa","year":"2007","journal-title":"J Mol Endocrinol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1016\/j.amjms.2023.05.002","article-title":"The association of growth differentiation factor-15 levels and osteoporosis in patients with thalassemia","volume":"366","author":"Teawtrakul","year":"2023","journal-title":"Am J Med Sci"},{"key":"B19","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1093\/jbmr\/zjad011","article-title":"Large-scale circulating proteome association study (CPAS) meta-analysis identifies circulating proteins and pathways predicting incident hip fractures","volume":"39","author":"Austin","year":"2024","journal-title":"J Bone Miner Res"},{"key":"B20","doi-asserted-by":"publisher","first-page":"764","DOI":"10.3390\/jcm8060764","article-title":"Role of adipokines in the association between thyroid hormone and components of the metabolic syndrome","volume":"8","author":"Delitala","year":"2019","journal-title":"J Clin Med"},{"key":"B21","doi-asserted-by":"publisher","first-page":"035011","DOI":"10.1088\/1361-6579\/aaafb5","article-title":"Automated skeletal tissue quantification in the lower leg using peripheral quantitative computed tomography","volume":"39","author":"Makrogiannis","year":"2018","journal-title":"Physiol Meas"},{"key":"B22","doi-asserted-by":"publisher","first-page":"5591","DOI":"10.3390\/ijms23105591","article-title":"Osteosarcopenia: a narrative review on clinical studies","volume":"23","author":"Polito","year":"2022","journal-title":"Int J Mol Sci"},{"key":"B23","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1016\/j.jocd.2009.06.004","article-title":"Beyond FRAX: it\u2019s time to consider \u201csarco-osteopenia\u201d","volume":"12","author":"Binkley","year":"2009","journal-title":"J Clin Densitom"},{"key":"B24","doi-asserted-by":"publisher","first-page":"e22547","DOI":"10.1016\/j.heliyon.2023.e22547","article-title":"Advances in the research on myokine-driven regulation of bone metabolism","volume":"10","author":"Shao","year":"2024","journal-title":"Heliyon"},{"key":"B25","doi-asserted-by":"publisher","first-page":"eadk9811","DOI":"10.1126\/scitranslmed.adk9811","article-title":"Muscle-bone cross-talk through the FNIP1-TFEB-IGF2 axis is associated with bone metabolism in human and mouse","volume":"16","author":"Mao","year":"2024","journal-title":"Sci Transl Med"},{"key":"B26","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.abb.2014.05.003","article-title":"Osteoblast and osteocyte: games without frontiers","volume":"561","author":"Capulli","year":"2014","journal-title":"Arch Biochem Biophys"},{"key":"B27","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1002\/jbmr.320","article-title":"The amazing osteocyte","volume":"26","author":"Bonewald","year":"2011","journal-title":"J Bone Miner Res"},{"key":"B28","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1016\/j.freeradbiomed.2020.01.007","article-title":"Older adults with frailty syndrome present an altered platelet function and an increased level of circulating oxidative stress and mitochondrial dysfunction biomarker GDF-15","volume":"149","author":"Arauna","year":"2020","journal-title":"Free Radic Biol Med"},{"key":"B29","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1007\/s12020-023-03377-9","article-title":"Growth differentiation factor 15 (GDF-15) in endocrinology","volume":"81","author":"Iglesias","year":"2023","journal-title":"Endocrine"},{"key":"B30","doi-asserted-by":"publisher","first-page":"915","DOI":"10.3389\/fimmu.2020.00915","article-title":"GDF15 plasma level is inversely associated with level of physical activity and correlates with markers of inflammation and muscle weakness","volume":"11","author":"Conte","year":"2020","journal-title":"Front Immunol"},{"key":"B31","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1007\/s00223-021-00912-6","article-title":"Associations between plasma growth and differentiation factor-15 with aging phenotypes in muscle, adipose tissue, and bone","volume":"110","author":"Lee","year":"2022","journal-title":"Calcif Tissue Int"},{"key":"B32","doi-asserted-by":"publisher","first-page":"714","DOI":"10.1080\/09513590.2020.1764929","article-title":"Relationship between GDF15 level and bone metabolism in postmenopausal Chinese women","volume":"36","author":"Li","year":"2020","journal-title":"Gynecol Endocrinol"},{"key":"B33","doi-asserted-by":"publisher","first-page":"e511","DOI":"10.3324\/haematol.2015.124511","article-title":"Growth differentiation factor 15 (GDF15) promotes osteoclast differentiation and inhibits osteoblast differentiation and high serum GDF15 levels are associated with multiple myeloma bone disease","volume":"100","author":"Westhrin","year":"2015","journal-title":"Haematologica"},{"key":"B34","doi-asserted-by":"publisher","first-page":"948176","DOI":"10.3389\/fendo.2022.948176","article-title":"Growth differentiation factor-15 as a modulator of bone and muscle metabolism","volume":"13","author":"Hong","year":"2022","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B35","doi-asserted-by":"publisher","first-page":"e70124","DOI":"10.14814\/phy2.70124","article-title":"Health implications of racial differences in serum growth differentiation factor levels among men with obesity","volume":"12","author":"Bathina","year":"2024","journal-title":"Physiol Rep"},{"key":"B36","doi-asserted-by":"publisher","first-page":"101114","DOI":"10.1016\/j.ijcha.2022.101114","article-title":"Association between serum GDF-15, myostatin, and sarcopenia in cardiovascular surgery patients","volume":"42","author":"Nishikawa","year":"2022","journal-title":"Int J Cardiol Heart Vasc"},{"key":"B37","doi-asserted-by":"publisher","first-page":"e0178123","DOI":"10.1371\/journal.pone.0178123","article-title":"New diagnostic index for sarcopenia in patients with cardiovascular diseases","volume":"12","author":"Harada","year":"2017","journal-title":"PLoS One"},{"key":"B38","doi-asserted-by":"publisher","first-page":"897097","DOI":"10.3389\/fnut.2022.897097","article-title":"Growth differentiation factor-15 as a biomarker for sarcopenia in patients with chronic obstructive pulmonary disease","volume":"9","author":"Deng","year":"2022","journal-title":"Front Nutr"},{"key":"B39","doi-asserted-by":"publisher","first-page":"1955","DOI":"10.1007\/s11357-025-01946-6","article-title":"GDF-15 plasma levels are elevated in mobility-limited older adults with frailty and sarcopenia-results from the BIOFRAIL study","volume":"48","author":"Hansen","year":"2026","journal-title":"Geroscience"},{"key":"B40","doi-asserted-by":"publisher","first-page":"S2","DOI":"10.1007\/s00198-002-1340-9","article-title":"Reduced bone formation and increased bone resorption: rational targets for the treatment of osteoporosis","author":"Seeman","year":"2003","journal-title":"Osteoporos Int"},{"key":"B41","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1016\/j.bone.2013.02.006","article-title":"Relationship of adiposity to bone volumetric density and microstructure in men and women across the adult lifespan","volume":"55","author":"Ng","year":"2013","journal-title":"Bone"},{"key":"B42","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1016\/j.jocd.2011.05.010","article-title":"Official positions for FRAX\u00ae clinical regarding falls and frailty: can falls and frailty be used in FRAX\u00ae? From joint official positions development conference of the International Society for Clinical Densitometry and International Osteoporosis Foundation on FRAX\u00ae","volume":"14","author":"Masud","year":"2011","journal-title":"J Clin Densitom"},{"key":"B43","doi-asserted-by":"publisher","first-page":"626","DOI":"10.1038\/nri.2016.90","article-title":"Sex differences in immune responses","volume":"16","author":"Klein","year":"2016","journal-title":"Nat Rev Immunol"},{"key":"B44","doi-asserted-by":"publisher","first-page":"1566","DOI":"10.1002\/1873-3468.13498","article-title":"Mitochondrial dysfunction and cell senescence: deciphering a complex relationship","volume":"593","author":"Chapman","year":"2019","journal-title":"FEBS Lett"},{"key":"B45","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1186\/s12967-023-04369-z","article-title":"Mitochondrial dysfunction: roles in skeletal muscle atrophy","volume":"21","author":"Chen","year":"2023","journal-title":"J Transl Med"},{"key":"B46","doi-asserted-by":"publisher","first-page":"1089","DOI":"10.1002\/jcsm.12563","article-title":"Satellite cell-specific ablation of CDON impairs integrin activation, FGF signalling, and muscle regeneration","volume":"11","author":"Bae","year":"2020","journal-title":"J Cachexia Sarcopenia Muscle"},{"key":"B47","doi-asserted-by":"publisher","first-page":"e12943","DOI":"10.1111\/acel.12943","article-title":"mTORC1 underlies age-related muscle fiber damage and loss by inducing oxidative stress and catabolism","volume":"18","author":"Tang","year":"2019","journal-title":"Aging Cell"},{"key":"B48","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1002\/jcsm.12192","article-title":"Anorexia of ageing: a key component in the pathogenesis of both sarcopenia and cachexia","volume":"8","author":"Morley","year":"2017","journal-title":"J Cachexia Sarcopenia Muscle"}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1920342\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T04:26:25Z","timestamp":1791519985000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1920342\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,9]]},"references-count":48,"alternative-id":["10.3389\/fmed.2026.1920342"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2026.1920342","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,9]]},"article-number":"1920342"}}