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However, current evidence on the determinants, particularly the modifiable factors of circulating FGF23 levels that increase independently of the kidney function, remains limited. In this study, we aimed to investigate the association between physical performance measures and circulating FGF23 levels in middle-aged and older adults with normal kidney function. This cross-sectional study assessed circulating FGF23 levels and physical performance parameters, including the handgrip strength, knee extension strength, maximal gait speed, the 30-second chair stand test (30s-CST), sit-and-reach test, and aerobic exercise capacity in 158 participants. Multiple regression analyses were performed to evaluate the independent associations between circulating FGF23 levels and physical performance measures after adjusting for potential confounders including age, sex, the presence of lifestyle-related disease, serum phosphate and phosphate-regulating hormone, estimated glomerular filtration rate, and urinary albumin-to-creatinine ratio. Higher circulating FGF23 levels were associated with lower handgrip strength, knee extension strength, maximal gait speed, 30s-CST score, and aerobic exercise capacity. These associations remained significant after adjusting for confounders, except for the association with handgrip strength and aerobic exercise capacity, which was attenuated when renal function variables were included. However, when all physical performance parameters were included in a model, knee extension strength and aerobic exercise capacity were identified as independent determinants of circulating FGF23 levels. Physical performance, particularly knee extension strength, and to a lesser extent aerobic exercise capacity, was independently or partially associated with circulating FGF23 levels in individuals with normal kidney function. Maintaining physical performance may help regulate circulating FGF23 levels, highlighting a potential role in preventing its elevation.<\/jats:p>","DOI":"10.1038\/s41598-025-17367-6","type":"journal-article","created":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T09:46:43Z","timestamp":1759398403000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Circulating fibroblast growth factor 23 and physical performance in middle-aged and older adults with normal kidney function"],"prefix":"10.1038","volume":"15","author":[{"given":"Keisei","family":"Kosaki","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shoya","family":"Mori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Matsui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chie","family":"Saito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Kuro-o","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunihiro","family":"Yamagata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seiji","family":"Maeda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,2]]},"reference":[{"key":"17367_CR1","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1038\/s41581-018-0078-3","volume":"15","author":"M Kuro-o","year":"2018","unstructured":"Kuro-o, M. 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