{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T01:21:13Z","timestamp":1790990473236,"version":"4.1.0"},"reference-count":52,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,4,21]],"date-time":"2025-04-21T00:00:00Z","timestamp":1745193600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,4,21]],"date-time":"2025-04-21T00:00:00Z","timestamp":1745193600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Aging Clin Exp Res"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Musculoskeletal disease, which has a complicated relationship with frailty, is a common clinical problem among elderly individuals.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Aims<\/jats:title>\n            <jats:p>This study evaluated the potential causal relationships between osteosarcopenia, osteoarthritis and frailty by Mendelian Randomization (MR) analysis.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>This study employed a two-sample MR approach to investigate the causal relationships among osteosarcopenia, osteoarthritis and frailty. Published summary statistics were used to obtain instrumental variables at the genome-wide significance level.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Among the age groups with osteoporosis, high total bone mineral density (TBMD) (45\u201460, OR\u2009=\u20090.966, 95% CI 0.940\u20130.993, <jats:italic>P<\/jats:italic>\u2009=\u20090.013) and TBMD (over 60, OR\u2009=\u20090.974, 95% CI 0.954\u20130.994, <jats:italic>P<\/jats:italic>\u2009=\u20090.011) reduced the risk of frailty. Similarly, high forearm BMD (FA-BMD), high ultradistal forearm BMD (UFA-BMD), and high Heel-BMD at different sites also reduced the risk of frailty (OR\u2009=\u20090.966, 95% CI 0.936\u20130.996, <jats:italic>P<\/jats:italic>\u2009=\u20090.028; OR\u2009=\u20090.975, 95% CI 0.953\u20130.997, <jats:italic>P<\/jats:italic>\u2009=\u20090.029; OR\u2009=\u20090.981, 95% CI 0.967\u20130.995, <jats:italic>P<\/jats:italic>\u2009=\u20090.008). Among the characteristics related to sarcopenia, grip strength in the left hand, grip strength in the right hand, appendicular lean mass, and walking pace were all protective factors for frailty (OR\u2009=\u20090.788, 95% CI 0.721\u20130.862, <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001; OR\u2009=\u20090.800, 95% CI 0.737\u20130.869, <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001; OR\u2009=\u20090.955, 95% CI 0.937\u20130.974, <jats:italic>P<\/jats:italic>\u2009=\u20090.000; OR\u2009=\u20090.480, 95% CI 0.388\u20130.593, <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001), with low grip strength in those over 60 years of age significantly positively correlated with frailty (OR\u2009=\u20091.168, 95% CI 1.059\u20131.289, <jats:italic>P<\/jats:italic>\u2009=\u20090.002). The MR results of osteoarthritis and frailty revealed a causal relationship between specific joint sites and frailty, including KOA (OR\u2009=\u20091.086, 95% CI 1.017\u20131.160, <jats:italic>P<\/jats:italic>\u2009=\u20090.014), HOA (OR\u2009=\u20091.028, 95% CI 1.007\u20131.049, <jats:italic>P<\/jats:italic>\u2009=\u20090.009), and KOA\/HOA (OR\u2009=\u20091.082, 95% CI 1.053\u20131.113, <jats:italic>P<\/jats:italic>\u2009=\u20090.000), increasing the risk of frailty.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>Osteosarcopenia, osteoarthritis and frailty exhibit significant causal effects, rendering them risk factors for frailty. Therefore, in clinical practice, patients with osteosarcopenia and osteoarthritis should be required to undergo relevant interventions to reduce the risk of frailty.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s40520-025-03012-9","type":"journal-article","created":{"date-parts":[[2025,4,21]],"date-time":"2025-04-21T05:47:16Z","timestamp":1745214436000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Osteosarcopenia, osteoarthritis and frailty: a two-sample Mendelian randomization study"],"prefix":"10.1007","volume":"37","author":[{"given":"Jili","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaolin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanqin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Qin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,21]]},"reference":[{"issue":"1","key":"3012_CR1","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1093\/ageing\/afaa219","volume":"50","author":"R O\u2019Caoimh","year":"2021","unstructured":"O\u2019Caoimh R et al (2021) Prevalence of frailty in 62 countries across the world: a systematic review and meta-analysis of population-level studies. Age Ageing 50(1):96\u2013104","journal-title":"Age Ageing"},{"issue":"3","key":"3012_CR2","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1111\/jgs.15214","volume":"66","author":"L Ma","year":"2018","unstructured":"Ma L et al (2018) Prevalence of frailty and associated factors in the Community-Dwelling population of China. J Am Geriatr Soc 66(3):559\u2013564","journal-title":"J Am Geriatr Soc"},{"issue":"5","key":"3012_CR3","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1007\/s12603-019-1179-9","volume":"23","author":"B He","year":"2019","unstructured":"He B et al (2019) Prevalence and risk factors for frailty among Community-Dwelling older people in China: A systematic review and Meta-Analysis. J Nutr Health Aging 23(5):442\u2013450","journal-title":"J Nutr Health Aging"},{"issue":"1","key":"3012_CR4","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1093\/gerona\/glx098","volume":"73","author":"C Wu","year":"2017","unstructured":"Wu C et al (2017) Prevalence and correlates of frailty among Community-Dwelling Chinese older adults: the China health and retirement longitudinal study. J Gerontol Biol Sci Med Sci 73(1):102\u2013108","journal-title":"J Gerontol Biol Sci Med Sci"},{"key":"3012_CR5","doi-asserted-by":"publisher","first-page":"2249","DOI":"10.2147\/CIA.S225149","volume":"14","author":"YD Liang","year":"2019","unstructured":"Liang YD et al (2019) Identification of frailty and its risk factors in elderly hospitalized patients from different wards: A Cross-Sectional study in China. Clin Interv Aging 14:2249\u20132259","journal-title":"Clin Interv Aging"},{"key":"3012_CR6","doi-asserted-by":"crossref","unstructured":"Serra-Prat M et al (2022) Development and validation of the electronic screening index of frailty. Age Ageing, 51(7)","DOI":"10.1093\/ageing\/afac161"},{"issue":"3","key":"3012_CR7","doi-asserted-by":"publisher","first-page":"M146","DOI":"10.1093\/gerona\/56.3.M146","volume":"56","author":"LP Fried","year":"2001","unstructured":"Fried LP et al (2001) Frailty in older adults: evidence for a phenotype. J Gerontol Biol Sci Med Sci 56(3):M146\u2013M156","journal-title":"J Gerontol Biol Sci Med Sci"},{"issue":"3","key":"3012_CR8","doi-asserted-by":"publisher","first-page":"897","DOI":"10.1002\/jcsm.13447","volume":"15","author":"D Di","year":"2024","unstructured":"Di D et al (2024) Frailty phenotype as mediator between systemic inflammation and osteoporosis and fracture risks: A prospective study. J Cachexia Sarcopenia Muscle 15(3):897\u2013906","journal-title":"J Cachexia Sarcopenia Muscle"},{"issue":"10","key":"3012_CR9","doi-asserted-by":"publisher","first-page":"2781","DOI":"10.1007\/s00198-017-4151-8","volume":"28","author":"HP Hirschfeld","year":"2017","unstructured":"Hirschfeld HP, Kinsella R, Duque G (2017) Osteosarcopenia: where bone, muscle, and fat collide. Osteoporos Int 28(10):2781\u20132790","journal-title":"Osteoporos Int"},{"issue":"1","key":"3012_CR10","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1002\/jcsm.13392","volume":"15","author":"S Chen","year":"2024","unstructured":"Chen S et al (2024) Global epidemiological features and impact of osteosarcopenia: A comprehensive meta-analysis and systematic review. J Cachexia Sarcopenia Muscle 15(1):8\u201320","journal-title":"J Cachexia Sarcopenia Muscle"},{"key":"3012_CR11","doi-asserted-by":"publisher","first-page":"1287972","DOI":"10.3389\/fendo.2023.1287972","volume":"14","author":"Z Zhao","year":"2023","unstructured":"Zhao Z et al (2023) Mechanism and physical activities in bone-skeletal muscle crosstalk. Front Endocrinol (Lausanne) 14:1287972","journal-title":"Front Endocrinol (Lausanne)"},{"issue":"3","key":"3012_CR12","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1002\/agm2.12080","volume":"2","author":"B Kirk","year":"2019","unstructured":"Kirk B, Saedi AA, Duque G (2019) Osteosarcopenia: A case of geroscience. Aging Med (Milton) 2(3):147\u2013156","journal-title":"Aging Med (Milton)"},{"issue":"12","key":"3012_CR13","doi-asserted-by":"publisher","first-page":"2793","DOI":"10.1007\/s00198-015-3194-y","volume":"26","author":"HA Bischoff-Ferrari","year":"2015","unstructured":"Bischoff-Ferrari HA et al (2015) Comparative performance of current definitions of sarcopenia against the prospective incidence of falls among community-dwelling seniors age 65 and older. Osteoporos Int 26(12):2793\u20132802","journal-title":"Osteoporos Int"},{"issue":"9","key":"3012_CR14","doi-asserted-by":"publisher","first-page":"1199","DOI":"10.1093\/gerona\/glx245","volume":"73","author":"LA Schaap","year":"2018","unstructured":"Schaap LA et al (2018) Associations of sarcopenia definitions, and their components, with the incidence of recurrent falling and fractures: the longitudinal aging study Amsterdam. J Gerontol Biol Sci Med Sci 73(9):1199\u20131204","journal-title":"J Gerontol Biol Sci Med Sci"},{"key":"3012_CR15","doi-asserted-by":"publisher","first-page":"255","DOI":"10.3389\/fendo.2019.00255","volume":"10","author":"EA Greco","year":"2019","unstructured":"Greco EA, Pietschmann P, Migliaccio S (2019) Osteoporosis and sarcopenia increase frailty syndrome in the elderly. Front Endocrinol (Lausanne) 10:255","journal-title":"Front Endocrinol (Lausanne)"},{"issue":"1","key":"3012_CR16","doi-asserted-by":"publisher","first-page":"19714","DOI":"10.1038\/s41598-023-46558-2","volume":"13","author":"SH Joo","year":"2023","unstructured":"Joo SH et al (2023) Knee osteoarthritis with a high grade of Kellgren-Lawrence score is associated with a worse frailty status, KNHANES 2010\u20132013. Sci Rep 13(1):19714","journal-title":"Sci Rep"},{"issue":"2","key":"3012_CR17","first-page":"274","volume":"91","author":"F Salaffi","year":"2020","unstructured":"Salaffi F, Farah S, Di Carlo M (2020) Frailty syndrome in rheumatoid arthritis and symptomatic osteoarthritis: an emerging concept in rheumatology. Acta Biomed 91(2):274\u2013296","journal-title":"Acta Biomed"},{"issue":"6","key":"3012_CR18","doi-asserted-by":"publisher","first-page":"1519","DOI":"10.1007\/s40520-020-01667-0","volume":"33","author":"F Salaffi","year":"2021","unstructured":"Salaffi F et al (2021) Frailty prevalence according to the survey of health, ageing and retirement in Europe-Frailty instrument (SHARE-FI) definition, and its variables associated, in patients with symptomatic knee osteoarthritis: findings from a cross-sectional study. Aging Clin Exp Res 33(6):1519\u20131527","journal-title":"Aging Clin Exp Res"},{"issue":"12","key":"3012_CR19","first-page":"1482","volume":"93","author":"AV Naumov","year":"2021","unstructured":"Naumov AV et al (2021) [The prevalence of osteoarthritis and its association with geriatric syndromes in people over 65: data from the Russian epidemiological study EVKALIPT]. Ter Arkh 93(12):1482\u20131490","journal-title":"Ter Arkh"},{"key":"3012_CR20","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/j.mad.2019.03.003","volume":"180","author":"MS O\u2019Brien","year":"2019","unstructured":"O\u2019Brien MS, McDougall JJ (2019) Age and frailty as risk factors for the development of osteoarthritis. Mech Ageing Dev 180:21\u201328","journal-title":"Mech Ageing Dev"},{"issue":"5","key":"3012_CR21","doi-asserted-by":"publisher","first-page":"2333","DOI":"10.1177\/0962280215597579","volume":"26","author":"S Burgess","year":"2017","unstructured":"Burgess S, Small DS, Thompson SG (2017) A review of instrumental variable estimators for Mendelian randomization. Stat Methods Med Res 26(5):2333\u20132355","journal-title":"Stat Methods Med Res"},{"issue":"1","key":"3012_CR22","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1016\/j.ajhg.2017.12.005","volume":"102","author":"C Medina-Gomez","year":"2018","unstructured":"Medina-Gomez C et al (2018) Life-Course Genome-wide association study Meta-analysis of total body BMD and assessment of Age-Specific effects. Am J Hum Genet 102(1):88\u2013102","journal-title":"Am J Hum Genet"},{"issue":"7571","key":"3012_CR23","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1038\/nature14878","volume":"526","author":"HF Zheng","year":"2015","unstructured":"Zheng HF et al (2015) Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture. Nature 526(7571):112\u2013117","journal-title":"Nature"},{"issue":"1","key":"3012_CR24","doi-asserted-by":"publisher","first-page":"4093","DOI":"10.1038\/s41467-020-17315-0","volume":"11","author":"I Surakka","year":"2020","unstructured":"Surakka I et al (2020) MEPE loss-of-function variant associates with decreased bone mineral density and increased fracture risk. Nat Commun 11(1):4093","journal-title":"Nat Commun"},{"issue":"7","key":"3012_CR25","doi-asserted-by":"publisher","first-page":"906","DOI":"10.1038\/s41588-018-0144-6","volume":"50","author":"PR Loh","year":"2018","unstructured":"Loh PR et al (2018) Mixed-model association for biobank-scale datasets. Nat Genet 50(7):906\u2013908","journal-title":"Nat Genet"},{"issue":"1","key":"3012_CR26","doi-asserted-by":"publisher","first-page":"654","DOI":"10.1038\/s41467-021-20918-w","volume":"12","author":"G Jones","year":"2021","unstructured":"Jones G et al (2021) Genome-wide meta-analysis of muscle weakness identifies 15 susceptibility loci in older men and women. Nat Commun 12(1):654","journal-title":"Nat Commun"},{"issue":"3","key":"3012_CR27","doi-asserted-by":"publisher","first-page":"e1001779","DOI":"10.1371\/journal.pmed.1001779","volume":"12","author":"C Sudlow","year":"2015","unstructured":"Sudlow C et al (2015) UK biobank: an open access resource for identifying the causes of a wide range of complex diseases of middle and old age. PLoS Med 12(3):e1001779","journal-title":"PLoS Med"},{"issue":"1","key":"3012_CR28","doi-asserted-by":"publisher","first-page":"608","DOI":"10.1038\/s42003-020-01334-0","volume":"3","author":"YF Pei","year":"2020","unstructured":"Pei YF et al (2020) The genetic architecture of appendicular lean mass characterized by association analysis in the UK biobank study. Commun Biol 3(1):608","journal-title":"Commun Biol"},{"issue":"2","key":"3012_CR29","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1038\/s41588-018-0327-1","volume":"51","author":"I Tachmazidou","year":"2019","unstructured":"Tachmazidou I et al (2019) Identification of new therapeutic targets for osteoarthritis through genome-wide analyses of UK biobank data. Nat Genet 51(2):230\u2013236","journal-title":"Nat Genet"},{"issue":"22","key":"3012_CR30","doi-asserted-by":"publisher","first-page":"4851","DOI":"10.1093\/bioinformatics\/btz469","volume":"35","author":"MA Kamat","year":"2019","unstructured":"Kamat MA et al (2019) PhenoScanner V2: an expanded tool for searching human genotype-phenotype associations. Bioinformatics 35(22):4851\u20134853","journal-title":"Bioinformatics"},{"issue":"3","key":"3012_CR31","doi-asserted-by":"publisher","first-page":"740","DOI":"10.1093\/ije\/dyq151","volume":"40","author":"BL Pierce","year":"2011","unstructured":"Pierce BL, Ahsan H, Vanderweele TJ (2011) Power and instrument strength requirements for Mendelian randomization studies using multiple genetic variants. Int J Epidemiol 40(3):740\u2013752","journal-title":"Int J Epidemiol"},{"key":"3012_CR32","doi-asserted-by":"publisher","first-page":"2338","DOI":"10.1016\/j.csbj.2022.05.015","volume":"20","author":"FJ Boehm","year":"2022","unstructured":"Boehm FJ, Zhou X (2022) Statistical methods for Mendelian randomization in genome-wide association studies: A review. Comput Struct Biotechnol J 20:2338\u20132351","journal-title":"Comput Struct Biotechnol J"},{"issue":"5","key":"3012_CR33","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1007\/s10654-017-0255-x","volume":"32","author":"S Burgess","year":"2017","unstructured":"Burgess S, Thompson SG (2017) Interpreting findings from Mendelian randomization using the MR-Egger method. Eur J Epidemiol 32(5):377\u2013389","journal-title":"Eur J Epidemiol"},{"issue":"3","key":"3012_CR34","doi-asserted-by":"publisher","first-page":"728","DOI":"10.1093\/ije\/dyy258","volume":"48","author":"J Bowden","year":"2019","unstructured":"Bowden J et al (2019) Improving the accuracy of two-sample summary-data Mendelian randomization: moving beyond the NOME assumption. Int J Epidemiol 48(3):728\u2013742","journal-title":"Int J Epidemiol"},{"issue":"2","key":"3012_CR35","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1093\/ije\/dyv080","volume":"44","author":"J Bowden","year":"2015","unstructured":"Bowden J, Davey Smith G, Burgess S (2015) Mendelian randomization with invalid instruments: effect Estimation and bias detection through Egger regression. Int J Epidemiol 44(2):512\u2013525","journal-title":"Int J Epidemiol"},{"key":"3012_CR36","unstructured":"Lianfu M (2018) China guideline for diagnosis and treatment of senile osteoporosis. Chinese Journal of Osteoporosis, 2018. 24(12): pp. 1541\u20131567"},{"issue":"3","key":"3012_CR37","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1016\/j.jocd.2006.03.010","volume":"9","author":"AM Kenny","year":"2006","unstructured":"Kenny AM et al (2006) Association between level of frailty and bone mineral density in community-dwelling men. J Clin Densitom 9(3):309\u2013314","journal-title":"J Clin Densitom"},{"issue":"4","key":"3012_CR38","first-page":"635","volume":"46","author":"MJ Cook","year":"2017","unstructured":"Cook MJ et al (2017) Frailty and bone health in European men. Age Ageing 46(4):635\u2013641","journal-title":"Age Ageing"},{"issue":"1","key":"3012_CR39","doi-asserted-by":"publisher","first-page":"e0296867","DOI":"10.1371\/journal.pone.0296867","volume":"19","author":"JX Shen","year":"2024","unstructured":"Shen JX et al (2024) Exploring causality between bone mineral density and frailty: A bidirectional Mendelian randomization study. PLoS ONE 19(1):e0296867","journal-title":"PLoS ONE"},{"issue":"2","key":"3012_CR40","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1111\/ajag.13253","volume":"43","author":"TN Nguyen","year":"2024","unstructured":"Nguyen TN et al (2024) Factors associated with frailty in geriatric patients with and without sarcopenia in Vietnam. Australas J Ageing 43(2):281\u2013287","journal-title":"Australas J Ageing"},{"key":"3012_CR41","doi-asserted-by":"crossref","unstructured":"Seko T et al (2024) The contributions of knee extension strength and hand grip strength to factors relevant to physical frailty: the Tanno-Sobetsu study, vol 9. Geriatrics (Basel), 1","DOI":"10.3390\/geriatrics9010009"},{"issue":"7","key":"3012_CR42","doi-asserted-by":"publisher","first-page":"1439","DOI":"10.2105\/AJPH.2014.302540","volume":"105","author":"J Song","year":"2015","unstructured":"Song J et al (2015) Sedentary behavior as a risk factor for physical frailty independent of moderate activity: results from the osteoarthritis initiative. Am J Public Health 105(7):1439\u20131445","journal-title":"Am J Public Health"},{"issue":"3","key":"3012_CR43","first-page":"414","volume":"18","author":"N Veronese","year":"2017","unstructured":"Veronese N et al (2017) Pain increases the risk of developing frailty in older adults with osteoarthritis. Pain Med 18(3):414\u2013427","journal-title":"Pain Med"},{"issue":"11","key":"3012_CR44","doi-asserted-by":"publisher","first-page":"2146","DOI":"10.1093\/pm\/pnx296","volume":"19","author":"SM Bindawas","year":"2018","unstructured":"Bindawas SM, Vennu V, Stubbs B (2018) Longitudinal relationship between knee pain status and incident frailty: data from the osteoarthritis initiative. Pain Med 19(11):2146\u20132153","journal-title":"Pain Med"},{"issue":"4","key":"3012_CR45","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1002\/art.1780400419","volume":"40","author":"TD Spector","year":"1997","unstructured":"Spector TD et al (1997) Low-level increases in serum C-reactive protein are present in early osteoarthritis of the knee and predict progressive disease. Arthritis Rheum 40(4):723\u2013727","journal-title":"Arthritis Rheum"},{"issue":"7","key":"3012_CR46","doi-asserted-by":"publisher","first-page":"2037","DOI":"10.1002\/art.24598","volume":"60","author":"G Livshits","year":"2009","unstructured":"Livshits G et al (2009) Interleukin-6 is a significant predictor of radiographic knee osteoarthritis: the Chingford study. Arthritis Rheum 60(7):2037\u20132045","journal-title":"Arthritis Rheum"},{"issue":"9B","key":"3012_CR47","doi-asserted-by":"publisher","first-page":"3103","DOI":"10.1111\/j.1582-4934.2009.00733.x","volume":"13","author":"RE Hubbard","year":"2009","unstructured":"Hubbard RE et al (2009) Inflammation and frailty measures in older people. J Cell Mol Med 13(9B):3103\u20133109","journal-title":"J Cell Mol Med"},{"issue":"9","key":"3012_CR48","doi-asserted-by":"publisher","first-page":"1679","DOI":"10.1111\/j.1532-5415.2011.03570.x","volume":"59","author":"S Giovannini","year":"2011","unstructured":"Giovannini S et al (2011) Interleukin-6, C-reactive protein, and tumor necrosis factor-alpha as predictors of mortality in frail, community-living elderly individuals. J Am Geriatr Soc 59(9):1679\u20131685","journal-title":"J Am Geriatr Soc"},{"key":"3012_CR49","doi-asserted-by":"publisher","first-page":"155638","DOI":"10.1016\/j.metabol.2023.155638","volume":"145","author":"E Gielen","year":"2023","unstructured":"Gielen E et al (2023) Sarcopenia, osteoporosis and frailty. Metabolism 145:155638","journal-title":"Metabolism"},{"key":"3012_CR50","doi-asserted-by":"publisher","first-page":"1045","DOI":"10.3389\/fphys.2017.01045","volume":"8","author":"S Dalle","year":"2017","unstructured":"Dalle S, Rossmeislova L, Koppo K (2017) The role of inflammation in Age-Related sarcopenia. Front Physiol 8:1045","journal-title":"Front Physiol"},{"issue":"2","key":"3012_CR51","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1089\/gtmb.2015.0170","volume":"20","author":"Y Mao","year":"2016","unstructured":"Mao Y et al (2016) Association of Irisin and CRP levels with the radiographic severity of knee osteoarthritis. Genet Test Mol Biomarkers 20(2):86\u201389","journal-title":"Genet Test Mol Biomarkers"},{"key":"3012_CR52","doi-asserted-by":"publisher","first-page":"115884","DOI":"10.1016\/j.biopha.2023.115884","volume":"169","author":"G Liu","year":"2023","unstructured":"Liu G et al (2023) Insights into the Notch signaling pathway in degenerative musculoskeletal disorders: mechanisms and perspectives. Biomed Pharmacother 169:115884","journal-title":"Biomed Pharmacother"}],"container-title":["Aging Clinical and Experimental Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40520-025-03012-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s40520-025-03012-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40520-025-03012-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,21]],"date-time":"2025-04-21T07:02:16Z","timestamp":1745218936000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s40520-025-03012-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,21]]},"references-count":52,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["3012"],"URL":"https:\/\/doi.org\/10.1007\/s40520-025-03012-9","relation":{},"ISSN":["1720-8319"],"issn-type":[{"value":"1720-8319","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,21]]},"assertion":[{"value":"7 January 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 March 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 April 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The MR analysis in this study utilized data solely from previously reported summary statistics. This research did not require patient consent or ethical approval.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"132"}}