FGF23 (Fibroblast Growth Factor 23)
Evidence: B/D — Meaningful Human EvidenceEndocrine / Calcium-Bone Axis Signaling
Evidence Snapshot
What this grade covers
B applies to FGF23's genetic-disease mechanism (via PHEX/XLH) and its biomarker/mortality-association evidence. No direct human administration evidence exists for native FGF23 — a structural absence, not a research gap, since administering FGF23 has no plausible therapeutic rationale; this component of the grade is not merely weak but not applicable. Burosumab's target-inhibition evidence never raises this grade.
Regulatory Context
Native FGF23 is an endogenous hormone with no approved product of its own; there is no rational therapeutic case for administering FGF23. Burosumab (Crysvita) is an FDA-approved monoclonal antibody that blocks FGF23, indicated for X-linked hypophosphatemia (XLH) and FGF23-related hypophosphatemia in tumor-induced osteomalacia (TIO) — a separate, firewalled target-inhibition context.
Research Takeaway
FGF23 is an osteocyte/osteoblast-derived endocrine hormone that reduces renal phosphate reabsorption and suppresses renal synthesis of active vitamin D (1,25-dihydroxyvitamin D), signaling through FGFR1 in complex with the co-receptor Klotho.
See all 5 evidence claims →Quick Summary
FGF23 is a bone-derived hormone that tells the kidneys to get rid of excess phosphate. FGF23 excess is generally the problem in phosphate-wasting diseases like XLH — the approved treatment (burosumab) works by blocking FGF23, not adding more of it.
Mechanism & Research Overview
FGF23 is a bone-derived hormone that tells the kidneys to get rid of excess phosphate. FGF23 excess is generally the problem in phosphate-wasting diseases like XLH — the approved treatment (burosumab) works by blocking FGF23, not adding more of it.
Evidence Claims
Individual scientific statements drawn from the sources cited below, each shown with the specific evidence boundary that statement does not establish.
Supported
FGF23 is an osteocyte/osteoblast-derived endocrine hormone that reduces renal phosphate reabsorption and suppresses renal synthesis of active vitamin D (1,25-dihydroxyvitamin D), signaling through FGFR1 in complex with the co-receptor Klotho.
Sources: CRYSVITA (burosumab-twza) injection — FDA Prescribing Information
Supported
Loss-of-function mutations in the PHEX gene cause X-linked hypophosphatemia (XLH); PHEX itself is a distinct gene from FGF23.
Supported
In XLH, FGF23 activity is pathologically excessive, driving the disease's characteristic renal phosphate wasting; this FGF23-mediated mechanism, not PHEX itself, directly drives phosphate loss.
Does not establish
Evidence boundary: Do not imply the 1995 PHEX gene-discovery paper itself studied FGF23.
Sources: CRYSVITA (burosumab-twza) injection — FDA Prescribing Information
Supported
In a prospective cohort of patients initiating hemodialysis, higher FGF23 levels were independently associated with increased mortality.
Does not establish
Evidence boundary: This is an observational association, not evidence that FGF23 itself is a therapeutic target or that modulating it changes outcomes.
Sources: Fibroblast Growth Factor 23 and Mortality among Patients Undergoing Hemodialysis
Supported
Burosumab, a monoclonal antibody that binds and inhibits FGF23, is FDA-approved for X-linked hypophosphatemia and for FGF23-related hypophosphatemia in tumor-induced osteomalacia.
Does not establish
Evidence boundary: This is evidence about the antibody, not evidence that administering FGF23 itself would be therapeutic — the drug's mechanism is inhibition, the opposite of replacement.
Sources: CRYSVITA (burosumab-twza) injection — FDA Prescribing Information
Safety & Evidence Limitations
Considerations reported in the sources cited on this page — not a complete list of every possible risk, and not medical advice.
Safety Consideration
The Gutiérrez 2008 mortality association in hemodialysis patients is observational; it does not establish that FGF23 itself causes death or that lowering FGF23 improves survival.Safety Consideration
Burosumab's efficacy in blocking FGF23 must not be inverted into a claim that FGF23 administration would be therapeutic; the mechanisms are opposite.
Research Areas Being Studied
Research areas discussed on this page reflect the Endocrine / Calcium-Bone Axis Signaling category and the sources cited below.
Findings Reported in Studies
Educational summary only — reported in cited studies, not a claim of proven benefit.
- Fibroblast Growth Factor 23 and Mortality among Patients Undergoing Hemodialysis (2008):
- A gene (PEX) with homologies to endopeptidases is mutated in patients with X-linked hypophosphatemic rickets (1995):
Study Tables by Evidence Type
Human Studies & Clinical Data
| Title | Year | Population / Model | Dose / Duration / Finding | Safety Notes | Source |
|---|---|---|---|---|---|
| Fibroblast Growth Factor 23 and Mortality among Patients Undergoing Hemodialysis | 2008 | Prospective cohort of 10,044 patients initiating hemodialysis; nested case-control sample of 200 for FGF23 analysis | Higher FGF23 levels were independently associated with increased mortality in patients initiating hemodialysis. Observational association; does not establish that FGF23 itself is a therapeutic target or that modulating it changes outcomes. | ||
| A gene (PEX) with homologies to endopeptidases is mutated in patients with X-linked hypophosphatemic rickets | 1995 | Primary gene-discovery paper: loss-of-function mutations in PHEX (formerly PEX) cause X-linked hypophosphatemia (XLH). PHEX itself is a distinct gene from FGF23; this paper establishes the genetic cause of XLH, not a mutation in FGF23 itself. In XLH, FGF23 activity subsequently becomes pathologically excessive as a downstream consequence (see Crysvita label mechanism context), driving renal phosphate wasting. |
Animal / Cell / Preclinical Data
No Animal / Cell / Preclinical Data Listed Yet
This section will be updated as sources are added.
Regulatory Documents & Official Trial Registries
| Title | Year | Population / Model | Dose / Duration / Finding | Safety Notes | Source |
|---|---|---|---|---|---|
| CRYSVITA (burosumab-twza) injection — FDA Prescribing Information | Burosumab-twza is a human IgG1 anti-FGF23 monoclonal antibody that binds FGF23's N-terminal domain, blocking its interaction with the FGFR1/Klotho co-receptor complex and restoring renal phosphate reabsorption. FDA-approved for X-linked hypophosphatemia (XLH, ages 6mo+) and, per the current label, FGF23-related hypophosphatemia in tumor-induced osteomalacia (TIO) associated with non-resectable/non-localizable phosphaturic mesenchymal tumors (ages 2y+). This is TARGET_INHIBITION_CONTEXT: evidence about the antibody blocking FGF23, never evidence that administering FGF23 itself would be therapeutic. The label's mechanism-of-action background also establishes that in XLH, FGF23 activity is pathologically excessive, driving renal phosphate wasting. | No source link available |
Anecdotal Reported Patterns — Not Medical Advice
Anecdotal Reported Patterns — Not Medical Advice
Reported dosing patterns are included for educational context only. They are self-reported, unverified, not medical advice, and not instructions for human use. Community-submitted patterns are not yet available in this Phase 1 prototype; this section is a placeholder reserved for moderated, aggregated community data.
Lab Markers to Discuss With a Clinician
Educational topics only — not self-monitoring instructions.
FAQ
Disclaimer
Educational information only. This page summarizes published research and official regulatory information about FGF23 and does not provide medical advice, an individualized treatment recommendation, or dosing instructions.
Educational use only. This content is provided for informational and research-summary purposes only. It is not medical advice, not a treatment recommendation, not a dosing guide, and not a substitute for care from a licensed medical professional. Nothing here is intended to diagnose, treat, cure, prevent, or mitigate disease. Reported dosing patterns, when shown elsewhere on the site, must be labeled either as Study / Trial Dosing or Anecdotal Reported Patterns — Not Medical Advice. Community reports are self-reported, unverified, and not scientific proof.
Community-reported experiences, once enabled, must be displayed only as moderated, anonymized, or aggregated data. They are anecdotal, self-reported, unverified, and should never be presented as proof of safety, efficacy, or expected results.
Content status: Published. Last updated .
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