ReviewReviews in endocrine & metabolic disorders2012
The role of vitamin D in the FGF23, klotho, and phosphate bone-kidney endocrine axis.
Review in Reviews in endocrine & metabolic disorders, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
65 citing papers in PubMed, 147 citations in OpenAlex.
- Low serum klotho concentration is associated with worse cognition, psychological components of frailty, dependence, and falls in nursing home residents.Scientific reports · 2021Trial
- Effect of Cholecalciferol therapy on serum FGFJournal of endocrinological investigation · 2018Trial
- Trial
- The interplay between vitamin D status and exerkine signaling: implications for exercise adaptation in athletes: narrative review.Journal of the International Society of Sports Nutrition · 2026Review
- The FGF23/α-Klotho Axis in Postmenopausal Osteoporosis: Associations with Bone Mineral Density and Diagnostic Discrimination.Journal of clinical medicine · 2026Article
- The Impact of Hyperphosphatemia on Mineral and Bone Metabolism: Implications for Bone and Vascular Health.International journal of molecular sciences · 2026Review
- Association between cannabis consumption and serum Klotho levels in middle-aged U.S. adults: NHANES cross-sectional analysis.Journal of cannabis research · 2026Article
- Calcimimetics and CaSR signaling in CKD-MBD: bone-immune-vascular crosstalk and therapeutic potential.Frontiers in immunology · 2026Review
- Current Controversies on Adequate Circulating Vitamin D Levels in CKD.International journal of molecular sciences · 2025Review
- Modeling the effects of radiation on the bone tumor microenvironment: opportunities for exploring combination therapies in microphysiologic systems.Cellular & molecular biology letters · 2025Review
- The relationship between serum α-Klotho with all-cause and cause-specific mortality.British journal of clinical pharmacology · 2024Article
- Influence of N- and/or P-restriction on bone metabolism in young goats.The British journal of nutrition · 2024Article
- A role for sirtuin 1 in FGF23 activation following β-glycerophosphate treatment.Pflugers Archiv : European journal of physiology · 2024Article
- Impact of deoxynivalenol in a calcium depletion and repletion nutritional strategy in piglets.Journal of animal science · 2024Article
- PKC regulates αKlotho gene expression in MDCK and NRK-52E cells.Pflugers Archiv : European journal of physiology · 2024Article
- Article
- Deterioration of Phosphate Homeostasis Is a Trigger for Cardiac Afterload - Clinical Importance of Fibroblast Growth Factor 23 for Accelerated Aging.Circulation reports · 2023Article
- Klotho's impact on diabetic nephropathy and its emerging connection to diabetic retinopathy.Frontiers in endocrinology · 2023Review
- Tissue-Wide Expression of Genes Related to Vitamin D Metabolism and FGF23 Signaling following Variable Phosphorus Intake in Pigs.Metabolites · 2022Article
- Autoimmune disease and interconnections with vitamin D.Endocrine connections · 2022Review
5 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
1,25-dihydroxyvitamin D (1,25D), through association with the nuclear vitamin D receptor (VDR), exerts control over a novel endocrine axis consisting of the bone-derived hormone FGF23, and the kidney-expressed klotho, CYP27B1, and CYP24A1 genes, which together prevent hyperphosphatemia/ectopic calcification and govern the levels of 1,25D to maintain bone mineral integrity while promoting optimal function of other vital tissues. When occupied by 1,25D, VDR interacts with RXR to form a heterodimer that binds to VDREs in the region of genes directly controlled by 1,25D (e.g., FGF23, klotho, Npt2c, CYP27B1 and CYP24A1). By recruiting complexes of comodulators, activated VDR initiates a series of events that induces or represses the transcription of genes encoding proteins such as: the osteocyte-derived hormone, FGF23; the renal anti-senescence factor and protein co-receptor for FGF23, klotho; other mediators of phosphate transport including Npt2a/c; and vitamin D hormone metabolic enzymes, CYP27B1 and CYP24A1. The mechanism whereby osteocytes are triggered to release FGF23 is yet to be fully defined, but 1,25D, phosphate, and leptin appear to play major roles. The kidney responds to FGF23 to elicit CYP24A1-catalyzed detoxification of the 1,25D hormone while also repressing both Npt2a/c to mediate phosphate elimination and CYP27B1 to limit de novo 1,25D synthesis. Comprehension of these skeletal and renal actions of 1,25D should facilitate the development of novel mimetics to prevent ectopic calcification, chronic renal and vascular disease, and promote healthful aging.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.