{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T18:10:00Z","timestamp":1780337400283,"version":"3.54.1"},"reference-count":40,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"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":["82172441"],"award-info":[{"award-number":["82172441"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Kunshan City Science and Technology Project","award":["KS2312"],"award-info":[{"award-number":["KS2312"]}]},{"name":"Kunshan City Science and Technology Project","award":["KSKFQYLWS2023019"],"award-info":[{"award-number":["KSKFQYLWS2023019"]}]},{"name":"Gusu Health Talent Plan Scientific Research Project","award":["GSWS2022105"],"award-info":[{"award-number":["GSWS2022105"]}]},{"name":"Suzhou Health Young Key Talent Program","award":["Qngg2024050"],"award-info":[{"award-number":["Qngg2024050"]}]},{"name":"Kunshan Health Talent Program\u2014Research Project","award":["X25-022-101539"],"award-info":[{"award-number":["X25-022-101539"]}]},{"name":"Jiangsu Provincial Health Commission Medical Research Project","award":["Z2024054"],"award-info":[{"award-number":["Z2024054"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>Osteoporotic fractures are frequent among older adults and are often accompanied by disturbances in endocrine and metabolic regulation. Parathyroid hormone (PTH) serves as a key regulator of bone remodeling, while elevated plasma homocysteine\u2014an established marker of vascular injury and skeletal fragility\u2014has been implicated in osteoporosis. Yet, the interaction between these two biochemical factors remains insufficiently characterized. This study investigated the link between circulating homocysteine and serum PTH concentrations among 2,190 hospitalized patients with osteoporotic fractures, emphasizing nonlinear associations and modifying influences. Fasting blood samples obtained at admission were used to measure plasma homocysteine and intact PTH levels. Multiple regression and spline-based modeling techniques were employed to estimate independent relationships and potential threshold effects, with subgroup analyses considering hypertension, renal function, and magnesium status. Homocysteine demonstrated an independent, positive correlation with PTH (P\u2009&lt;\u20090.001). A nonlinear dose\u2013response relationship was observed, wherein PTH increased progressively with homocysteine up to about 18 \u03bcmol\/L, followed by a sharper rise beyond this point, suggesting a statistically significant threshold. The relationship was more evident among patients with hypertension, impaired renal function, or low magnesium levels, indicating that vascular strain, renal stress, and mineral imbalance may heighten PTH activity. Elevated homocysteine levels may be associated with higher PTH concentrations in individuals with osteoporosis. However, the clinical relevance of homocysteine in metabolic assessment and risk stratification requires further validation.<\/jats:p>","DOI":"10.1371\/journal.pone.0349418","type":"journal-article","created":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T17:40:16Z","timestamp":1780335616000},"page":"e0349418","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Nonlinear relationship between circulating homocysteine and parathyroid hormone among patients with osteoporotic fractures: A cross-sectional study based on a hospital cohort"],"prefix":"10.1371","volume":"21","author":[{"given":"Jia-hao","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-hong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Da-wei","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0029-7874","authenticated-orcid":true,"given":"Ke","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0190-4971","authenticated-orcid":true,"given":"Yan-ming","family":"Hao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,6,1]]},"reference":[{"key":"pone.0349418.ref001","doi-asserted-by":"crossref","first-page":"882241","DOI":"10.3389\/fendo.2022.882241","article-title":"The 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Halawa","year":"2023","journal-title":"Ther Adv Chronic Dis"},{"issue":"6","key":"pone.0349418.ref038","first-page":"545","article-title":"The Bone-Vascular Axis: A Key Player in Chronic Kidney Disease Associated Vascular Calcification","volume":"10","author":"Y Shen","year":"2024","journal-title":"Kidney Dis (Basel)"},{"issue":"5","key":"pone.0349418.ref039","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1007\/s00394-024-03344-8","article-title":"Optimal folic acid dosage in lowering homocysteine: Precision Folic Acid Trial to lower homocysteine (PFAT-Hcy)","volume":"63","author":"X Huang","year":"2024","journal-title":"Eur J Nutr"},{"issue":"11","key":"pone.0349418.ref040","doi-asserted-by":"crossref","first-page":"1766","DOI":"10.1093\/ckj\/sfad112","article-title":"Can we reverse arterial stiffness by intervening on CKD-MBD biomarkers?","volume":"16","author":"MG Vervloet","year":"2023","journal-title":"Clin Kidney J"}],"container-title":["PLOS 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