ArticleThe Journal of clinical investigation2016
CYP24 inhibition as a therapeutic target in FGF23-mediated renal phosphate wasting disorders.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 35 papers, 1 of them a synthesis that pooled it.
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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
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 62 citations in OpenAlex.
- Genetic Variants Associated with Circulating Fibroblast Growth Factor 23.Journal of the American Society of Nephrology : JASN · 2018Pooled it
- Safety and efficacy of ferric citrate in patients with nondialysis-dependent chronic kidney disease.PloS one · 2017Trial
- Trial
- Treatment with Minicircle DNA Expressing a FGF23 Fragment in a Clinically relevant Mouse Model of X-Linked Hypophosphatemic Rickets.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Review
- Biochemical evaluation of X-linked hypophosphatemia and tumor-induced osteomalacia: insights into diagnosis and management.Frontiers in endocrinology · 2025Review
- Emerging Role of Gallium-68 DOTANOC PET/CT Guided Radiofrequency Ablation in the Treatment of Tumor-induced Osteomalacia.JCEM case reports · 2024Article
- Phosphate Homeostasis and Disorders of Phosphate Metabolism.Current pediatric reviews · 2024Review
- X-linked hypophosphatemia, fibroblast growth factor 23 signaling, and craniosynostosis.Experimental biology and medicine (Maywood, N.J.) · 2023Review
- Skeletal and extraskeletal disorders of biomineralization.Nature reviews. Endocrinology · 2022Review
- Codelivery of 1α,25-Dihydroxyvitamin DMolecular pharmaceutics · 2022Article
- The Role of Alterations in Alpha-Klotho and FGF-23 in Kidney Transplantation and Kidney Donation.Frontiers in medicine · 2022Review
- Identification of a Novel Missense Mutation of theFrontiers in genetics · 2022Article
- The Role of DMP1 in CKD-MBD.Current osteoporosis reports · 2021Review
- X-linked hypophosphatemic rickets caused by a de novo PHEX gene variation in a family.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2021Article
- The Causes of Hypo- and Hyperphosphatemia in Humans.Calcified tissue international · 2021Review
- Congenital Conditions of Hypophosphatemia Expressed in Adults.Calcified tissue international · 2021Review
- Congenital Conditions of Hypophosphatemia Expressed in Adults.Calcified tissue international · 2021Review
- Probing the Scope and Mechanisms of Calcitriol Actions Using Genetically Modified Mouse Models.JBMR plus · 2021Article
- Consensus Recommendations for the Diagnosis and Management of X-Linked Hypophosphatemia in Belgium.Frontiers in endocrinology · 2021Review
Corrections and comments
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- Erratum issued
Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
CYP24A1 (hereafter referred to as CYP24) enzymatic activity is pivotal in the inactivation of vitamin D metabolites. Basal renal and extrarenal CYP24 is usually low but is highly induced by its substrate 1,25-dihydroxyvitamin D. Unbalanced high and/or long-lasting CYP24 expression has been proposed to underlie diseases like chronic kidney disease, cancers, and psoriasis that otherwise should favorably respond to supplemental vitamin D. Using genetically modified mice, we have shown that renal phosphate wasting hypophosphatemic states arising from high levels of fibroblast growth factor 23 (FGF23) are also associated with increased renal Cyp24 expression, suggesting that elevated CYP24 activity is pivotal to the pathophysiology of these disorders. We therefore crossed 2 mouse strains, each with distinct etiology for high levels of circulating FGF23, onto a Cyp24-null background. Specifically, we evaluated Cyp24 deficiency in Hyp mice, the murine homolog of X-linked dominant hypophosphatemic rickets, and transgenic mice that overexpress a mutant FGF23 (FGF23R176Q) that is associated with the autosomal dominant form of hypophosphatemic rickets. Loss of Cyp24 in these murine models of human disease resulted in near-complete recovery of rachitic/osteomalacic bony abnormalities in the absence of any improvement in the serum biochemical profile. Moreover, treatment of Hyp and FGF23R1760-transgenic mice with the CYP24 inhibitor CTA102 also ameliorated their rachitic bones. Our results link CYP24 activity to the pathophysiology of FGF23-dependent renal phosphate wasting states and implicate pharmacologic CYP24 inhibition as a therapeutic adjunct for their treatment.
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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.