ArticleBone2021
Age and sex effects on FGF23-mediated response to mild phosphate challenge.
Article in Bone, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.
- FGF23 level in poultry chicken, a systematic review and meta-analysis.Frontiers in physiology · 2023Pooled it
- BoneJBMR plus · 2026Article
- Fibroblast growth factor 23: Regulation, signalling and systemic links between bone, metabolism and inflammation.Molecular metabolism · 2026Review
- Steroid hormones and nephrolithiasis: regulation of urine components metabolism and inflammation.Biology of sex differences · 2026Review
- Age: A Moderating Effect on Cerebrospinal Fluid Fibroblast Growth Factor 21 and Cognitive Function.Brain and behavior · 2025Article
- Baseline fibroblast growth factor 23 predicts incident heart failure and cardiovascular mortality in patients with chronic kidney disease: A 3-year follow-up study.International journal of cardiology. Heart & vasculature · 2025Article
- Association Between Dietary Intake of Phosphorus and Measures of Obesity in the Jackson Heart Study.The Journal of nutrition · 2024Article
- Phosphate in Cardiovascular Disease: From New Insights Into Molecular Mechanisms to Clinical Implications.Arteriosclerosis, thrombosis, and vascular biology · 2024Review
- Insights and implications of sexual dimorphism in osteoporosis.Bone research · 2024Review
- The basics of phosphate metabolism.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2024Review
- Open Genes-a new comprehensive database of human genes associated with aging and longevity.Nucleic acids research · 2024Article
- New concepts in regulation and function of the FGF23.Clinical and experimental medicine · 2023Review
- Dietary phosphorus consumption alters T cell populations, cytokine production, and bone volume in mice.JCI insight · 2023Article
- Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundDuring aging, there is a normal and mild loss in kidney function that leads to abnormalities of the kidney-bone metabolic axis. In the setting of increased phosphorus intake, hyperphosphatemia can occur despite increased concentrations of the phosphaturic hormone FGF23. This is likely from decreased expression of the FGF23 co-receptor Klotho (KL) with age; however, the roles of age and sex in the homeostatic responses to mild phosphate challenges remain unclear.
methodsMale and female 16-week and 78-week mice were placed on either normal grain-based chow or casein (higher bioavailable phosphate) diets for 8 weeks. Gene expression, serum biochemistries, micro-computed tomography, and skeletal mechanics were used to assess the impact of mild phosphate challenge on multiple organ systems. Cell culture of differentiated osteoblast/osteocytes was used to test mechanisms driving key outcomes.
resultsAging female mice responded to phosphate challenge by significantly elevating serum intact FGF23 (iFGF23) versus control diet; males did not show this response. Male mice, regardless of age, exhibited higher kidney KL mRNA with similar phosphate levels across both sexes. However, males and females had similar blood phosphate, calcium, and creatinine levels irrespective of age, suggesting that female mice upregulated FGF23 to maintain blood phosphorus, and compromised renal function could not explain the increased serum iFGF23. The 17β-estradiol levels were not different between groups, and in vivo bone steroid receptor (estrogen receptor 1 [Esr1], estrogen receptor 2 [Esr2], androgen receptor [Ar]) expression was not different by age, sex, or diet. Trabecular bone volume was higher in males but decreased with both age and phosphate challenge in both sexes. Cortical porosity increased with age in males but not females. In vitro studies demonstrated that 17β-estradiol treatment upregulated FGF23 and Esr2 mRNAs in a dose-dependent manner.
conclusionsOur study demonstrates that aging female mice upregulate FGF23 to a greater degree during a mild phosphate challenge to maintain blood phosphorus versus young female and young/old male mice, potentially due to direct estradiol effects on osteocytes. Thus, the control of phosphate intake during aging could have modifiable outcomes for FGF23-related phenotypes.
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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.