{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T08:42:21Z","timestamp":1771922541901,"version":"3.50.1"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T00:00:00Z","timestamp":1768867200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Osteoporosis imposes a substantial fracture burden, yet scalable and dynamic biomarkers for risk stratification remain limited. Serum creatinine\u2014routinely assayed and capturing intertwined muscle and renal signals\u2014has been little studied for incident osteoporosis or fractures.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In the UK Biobank, covariate-adjusted Cox models and restricted cubic splines assessed associations of baseline creatinine with incident osteoporosis and fractures. Creatinine was modeled categorically (six strata; G4 [70\u201380 \u03bcmol\/L] as reference) and continuously. The pre-defined analysis was stratified by sex and age (&amp;gt;65) as well as the three tertiles of the polygenic risk score for osteoporosis (PRS); the multiplicative interaction term examined the relationship between creatinine and PRS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Creatinine showed a U-shaped association with osteoporosis, with a nadir near 80 \u03bcmol\/L (overall P&amp;lt;0.001; nonlinearity P&amp;lt;0.001). In piecewise models, each 1-\u03bcmol\/L increase corresponded to a 2.0% lower osteoporosis risk within 25\u201380 \u03bcmol\/L (HR = 0.980, 95% CI 0.978\u20130.982) and a 1.1% higher risk within 80\u2013130 \u03bcmol\/L (HR = 1.011, 95% CI 1.006\u20131.017). For fractures, the dose\u2013response was J-shaped around the same nadir: risk decreased by 1.0% per \u03bcmol in 25\u201380 \u03bcmol\/L (HR = 0.990, 95% CI 0.988\u20130.992) and increased by 0.3% per \u03bcmol in 80\u2013130 \u03bcmol\/L (HR = 1.003, 95% CI 0.999\u20131.006). Sex-stratified patterns were directionally concordant. In PRS-stratified categorical analyses (vs G4), the low-creatinine stratum (G1) carried higher osteoporosis risk across tertiles (HRs 1.925, 1.811, and 1.592 for low, intermediate, and high PRS). Creatinine\u00d7PRS interactions were not significant (osteoporosis P = 0.132; fractures P = 0.210).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Baseline serum creatinine was significantly and nonlinearly associated with incident osteoporosis (U-shaped pattern) and fractures (J-shaped pattern), with the lowest risk observed at approximately 80 \u03bcmol\/L, and there was a notable sex difference (higher in males). These associations were independent of genetic susceptibility, suggesting that serum creatinine may serve as a low-cost adjunct marker for clinical risk stratification and surveillance of osteoporosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2025.1727636","type":"journal-article","created":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T05:28:04Z","timestamp":1768886884000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Serum creatinine, genetic susceptibility, and the risk of osteoporosis and fracture: a prospective cohort study from the UK Biobank"],"prefix":"10.3389","volume":"16","author":[{"given":"Weijie","family":"He","sequence":"first","affiliation":[{"name":"Dongguan Hospital of Guangzhou University of Chinese Medicine","place":["Dongguan, Guangdong, 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