FGF-23 (Fibroblast Growth Factor 23)
What is FGF-23?
FGF-23, or fibroblast growth factor 23, is a hormone-like protein that plays a critical role in phosphate and vitamin D metabolism. It is primarily produced by bone cells (osteocytes and osteoblasts) and acts mainly on the kidneys to regulate:
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Phosphate excretion in urine
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Vitamin D activation
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Calcium-phosphate balance
FGF-23 is part of a feedback system that helps maintain normal blood phosphate levels. When phosphate levels rise, FGF-23 secretion increases to help eliminate excess phosphate through the urine and reduce vitamin D activation.
Why is FGF-23 Measured?
Testing FGF-23 levels is especially useful in diagnosing and monitoring disorders involving abnormal phosphate metabolism, bone health, or kidney function.
FGF-23 is most commonly used to evaluate:
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Hypophosphatemia (low phosphate levels)
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Chronic kidney disease–mineral and bone disorder (CKD-MBD)
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Hereditary or acquired rickets/osteomalacia
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Rare phosphate-wasting disorders
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Tumor-induced osteomalacia (TIO)
By measuring FGF-23, healthcare providers can determine whether phosphate loss is due to overproduction of this hormone or other factors.
How FGF-23 Works in the Body
FGF-23 reduces blood phosphate by:
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Decreasing phosphate reabsorption in the kidneys — promoting phosphate excretion in urine.
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Inhibiting 1α-hydroxylase, an enzyme needed to activate vitamin D (which normally helps absorb calcium and phosphate from the gut).
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Suppressing PTH (parathyroid hormone) under certain conditions.
In essence, FGF-23 works as a phosphate-lowering hormone. When levels are too high or too low, the result is disruption of mineral homeostasis, which can negatively affect bone health, kidney function, and cardiovascular risk.
What Conditions Are Associated With Abnormal FGF-23 Levels?
Elevated FGF-23 Levels
High FGF-23 levels are seen in conditions that involve excess phosphate loss, disrupted bone remodeling, or impaired kidney function.
Common causes include:
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Chronic Kidney Disease (CKD)
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FGF-23 rises early in CKD to compensate for reduced phosphate excretion.
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Very high FGF-23 is associated with vascular calcification, left ventricular hypertrophy, and poor cardiovascular outcomes.
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Tumor-Induced Osteomalacia (TIO)
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Rare tumors (usually benign) produce excess FGF-23, causing bone pain, muscle weakness, and fractures.
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X-linked Hypophosphatemia (XLH) or Autosomal Dominant Hypophosphatemic Rickets (ADHR)
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Genetic disorders where FGF-23 is inappropriately elevated, leading to chronic phosphate wasting and defective bone mineralization.
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Oncogenic or genetic causes of phosphate wasting
Low FGF-23 Levels
Less commonly, low FGF-23 levels may be associated with:
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Hyperphosphatemia (high phosphate) due to inadequate renal excretion
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Familial tumoral calcinosis (a rare condition marked by soft tissue calcifications and hyperphosphatemia)
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Low phosphate excretion despite high phosphate levels, often due to impaired FGF-23 production or function
Symptoms of FGF-23–Related Disorders
High or dysregulated FGF-23 levels may contribute to symptoms such as:
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Bone pain
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Muscle weakness
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Fatigue
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Recurrent fractures
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Short stature (in genetic conditions)
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Joint stiffness or deformities (in rickets or osteomalacia)
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Abnormal lab findings: low phosphate, low/normal vitamin D, high ALP
In CKD patients, elevated FGF-23 may correlate with:
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Anemia
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Increased cardiovascular risk
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Poorer outcomes in dialysis patients
How Is the FGF-23 Test Performed?
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Sample type: Blood (usually serum or plasma)
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Special considerations:
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Some labs measure intact FGF-23, while others measure C-terminal fragments. Be sure to interpret results in the context of the assay used.
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FGF-23 levels may fluctuate based on kidney function, iron status, and time of day.
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Reference Ranges
Reference ranges vary depending on the testing method (intact vs. C-terminal assay) and laboratory. Typical intact FGF-23 levels in healthy individuals are approximately:
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<100 RU/mL (for intact assay)
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Some labs use pg/mL with normal ranges typically <50 pg/mL
Elevated values must always be interpreted alongside:
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Serum phosphate
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Vitamin D
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Parathyroid hormone (PTH)
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Creatinine/eGFR (to assess kidney function)
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Alkaline phosphatase (ALP) and bone markers (for bone health)
Clinical Applications and Monitoring
In CKD
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Monitoring FGF-23 can help track phosphate retention and mineral-bone disorder progression.
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It may serve as an early marker of disordered phosphate handling—often rising before phosphate and PTH.
In Rare Bone or Tumor Disorders
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Helps confirm a diagnosis of hereditary hypophosphatemic rickets or tumor-induced osteomalacia
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Used to guide imaging and treatment decisions
In Phosphate Disorders
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Differentiates between renal phosphate wasting and other causes of hypophosphatemia
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Helps determine if the body is inappropriately excreting phosphate
Summary
FGF-23 is a key regulator of phosphate balance and vitamin D metabolism, with rising clinical importance in conditions like chronic kidney disease, osteomalacia, rickets, and rare phosphate-wasting disorders. Abnormal levels may lead to significant complications in bone health, cardiovascular function, and mineral metabolism. Measuring FGF-23 provides valuable insight when investigating unexplained hypophosphatemia, bone pain, or CKD-related mineral disturbances.
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