{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T12:01:50Z","timestamp":1792670510519,"version":"4.5.0"},"reference-count":40,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,3,11]],"date-time":"2024-03-11T00:00:00Z","timestamp":1710115200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82273711"],"award-info":[{"award-number":["82273711"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010849","name":"Health and Family Planning Commission of Wuhan Municipality","doi-asserted-by":"publisher","award":["WY22B06"],"award-info":[{"award-number":["WY22B06"]}],"id":[{"id":"10.13039\/501100010849","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":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Systemic inflammation and frailty have been implicated in osteoporosis (OP) and fracture risks; however, existing evidence remains limited and inconclusive. This study aimed to assess the associations of systemic inflammation and frailty phenotype with incident OP and fracture and to evaluate the mediating role of frailty phenotype.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The present study analysed data from the UK Biobank, a comprehensive and representative dataset encompassing over 500\u00a0000 individuals from the general population. Baseline peripheral blood cell counts were employed to calculate the systemic inflammation markers, including neutrophil\u2010to\u2010lymphocyte ratio (NLR), platelet\u2010to\u2010lymphocyte ratio (PLR) and systemic immune\u2010inflammation index (SII). Frailty phenotype was assessed using five criteria, defined as frail (\u22653 items met), pre\u2010frail (1\u20132 items met) and non\u2010frail (0 items met). OP and fracture events were confirmed through participants' health\u2010related records. Multivariable linear and Cox regression models were utilized, along with mediation analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Increased systemic inflammation was associated with increased risks of OP and fracture. The corresponding hazard ratios and 95% confidence intervals (CIs) for OP risk per standard deviation increase in the log\u2010transformed NLR, PLR and SII were 1.113 (1.093\u20131.132), 1.098 (1.079\u20131.118) and 1.092 (1.073\u20131.111), and for fracture risk, they were 1.066 (1.051\u20131.082), 1.059 (1.044\u20131.075) and 1.073 (1.058\u20131.089), respectively. Compared with the non\u2010frail individuals, the pre\u2010frail and frail ones showed an elevated OP risk by 21.2% (95% CI: 16.5\u201326.2%) and 111.0% (95% CI: 98.1\u2013124.8%), respectively, and an elevated fracture risk by 6.1% (95% CI: 2.8\u20139.5%) and 38.2% (95% CI: 30.7\u201346.2%), respectively. The systemic inflammation level demonstrated a positive association with frailty, with\n                      <jats:italic>\u03b2<\/jats:italic>\n                      (95% CI) of 0.034 (0.031\u20130.037), 0.026 (0.023\u20130.029) and 0.008 (0.005\u20130.011) in response to per standard deviation increment in log\u2010transformed SII, NLR and PLR, respectively. The frailty phenotype mediated the association between systemic inflammation and OP\/fracture risk. Subgroup and sensitivity analyses confirmed the robustness of these findings.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Systemic inflammation and frailty phenotype are independently linked to increased risks of OP and fracture. The frailty phenotype partially mediates the association between systemic inflammation and osteoporotic traits. These results highlight the significance of interventions targeting systemic inflammation and frailty in OP and fracture prevention and management.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.13447","type":"journal-article","created":{"date-parts":[[2024,3,12]],"date-time":"2024-03-12T00:40:06Z","timestamp":1710204006000},"page":"897-906","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":78,"title":["Frailty phenotype as mediator between systemic inflammation and osteoporosis and fracture risks: A prospective study"],"prefix":"10.1002","volume":"15","author":[{"given":"Dongsheng","family":"Di","sequence":"first","affiliation":[{"name":"Key Laboratory of Environment and Health, Ministry of Education and Ministry of Environmental Protection, Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College Huazhong University of Science and Technology  Wuhan 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