REVIEW article
Front. Endocrinol.
Sec. Renal Endocrinology
Research on Vitamin D Metabolic Regulation in the Pathogenesis of Related Diseases
Yumeng Ji 1,2
Ruru Bi 1,2
Lin Wang 1,2
1. Suzhou University, Suzhou, China
2. The Fourth Affiliated Hospital of Soochow University, Suzhou, China
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Abstract
Vitamin D is a group of fat-soluble vitamins that plays critical roles in calcium-phosphate homeostasis, bone health, and immune regulation. The metabolic pathway of vitamin D involves two key enzymatic steps: hepatic 25-hydroxylation to produce 25-hydroxyvitamin D [25(OH)D] and renal 1α-hydroxylation to generate the biologically active form 1,25-dihydroxyvitamin D [1,25(OH) ₂ D]. 25(OH)D serves as the gold standard biomarker for assessing vitamin D status due to its high circulating concentration, long half-life, and stable levels. This metabolic process is precisely regulated by parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), and negative feedback mechanisms mediated by the vitamin D receptor (VDR). Recent studies have demonstrated that CYP27B1, the gene encoding 1 α -hydroxylase, is also widely expressed in extrarenal tissues including prostate, breast, placenta, and macrophages, suggesting important roles for vitamin D in local paracrine and autocrine regulation. Dysregulation of vitamin D metabolism is closely associated with the pathogenesis of various diseases, including vitamin D-dependent rickets type 1A (VDDR-1A), chronic kidney disease-mineral and bone disorder (CKD-MBD), tumor-induced osteomalacia (TIO), granulomatous diseases, and CYP24A1 deficiency-related hypercalcemia. Notably, 24,25-dihydroxyvitamin D [24,25(OH) ₂ D], traditionally considered an inactive metabolic end-product, may possess independent biological functions, and its ratio to 1,25(OH)₂ D can serve as a novel biomarker for assessing vitamin D metabolic status. This review systematically examines the metabolic pathways and regulatory mechanisms of vitamin D, elucidates their associations with disease pathogenesis, and provides theoretical foundation for personalized clinical diagnosis and precision therapy. Future research should establish standardized multi-parameter detection protocols to advance the clinical application of vitamin D metabolomics in precision medicine.
Summary
Keywords
Chronic Kidney Disease, CYP24A1, CYP27B1, mineral and bone disorder, precision medicine, Vitamin D metabolism
Received
07 December 2025
Accepted
20 February 2026
Copyright
© 2026 Ji, Bi and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Lin Wang
Disclaimer
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