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[Physiology](https://durgical.com/en/physiology/) · [Endocrine](https://durgical.com/en/physiology/#s-endocrine)

# Phosphate and FGF-23

- Regulation
- For completeness

Phosphate builds bone and stores energy. Bone cells make FGF-23, a hormone that tells the kidney to throw out extra phosphate.

Updated 2026-11-01

Also called: Phosphatonin, Klotho, NaPi-IIa

**See it in 3D:** [Kidneys](https://durgical.com/en/anatomy/kidney/) · [Parathyroid glands](https://durgical.com/en/anatomy/parathyroid-glands/) · [Femur](https://durgical.com/en/anatomy/femur/)

## Key points

- FGF-23 is made by osteocytes and needs the co-receptor α-Klotho in the kidney.
- FGF-23: ↓ NaPi-IIa/IIc in the proximal tubule (phosphaturia), ↓ 1α-hydroxylase and ↑ 24-hydroxylase (less calcitriol), ↓ PTH.
- PTH also causes phosphaturia but raises calcitriol; calcitriol raises phosphate absorption in the gut.
- High FGF-23 (X-linked hypophosphatemia, tumour-induced osteomalacia): low phosphate, inappropriately low calcitriol, rickets or osteomalacia.
- CKD: FGF-23 rises first, then calcitriol falls, phosphate rises and PTH rises (secondary hyperparathyroidism).
- Insulin and alkalosis shift phosphate into cells: refeeding after starvation can cause severe hypophosphatemia.

## What it is

Phosphate is needed for bone mineral, ATP, nucleic acids and membranes; about 85% of the body's phosphate is in bone. Its blood level is set mainly by the kidney, which reabsorbs most filtered phosphate in the proximal tubule. Two hormones make the kidney excrete phosphate: PTH and FGF-23, a hormone made by osteocytes. FGF-23 also lowers calcitriol, closing a loop between bone, kidney and gut. It rises early in chronic kidney disease.

## How it works, step by step

- Dietary phosphate is absorbed in the small intestine, partly through NaPi-IIb, which calcitriol upregulates.
- The kidney filters phosphate and the proximal tubule reabsorbs about 80–90% through NaPi-IIa and NaPi-IIc.
- A rise in phosphate load (and in calcitriol) stimulates osteocytes to secrete FGF-23.
- FGF-23 binds FGFR1–Klotho in the tubule: NaPi transporters are removed from the brush border and phosphate is lost in urine.
- It also suppresses renal calcitriol synthesis, which reduces gut phosphate absorption.
- In CKD fewer nephrons must excrete the load, so FGF-23 climbs; low calcitriol and phosphate retention then drive PTH up.

### Hormone axes and feedback

Calcium regulation (PTH, calcitriol, calcitonin) **Lesion** None (normal)

Tap a box to see the hormone, or choose a lesion to see the lab pattern.

- Stimulates (+)
- Inhibits / negative feedback (−)
- Level ↑
- Level ↓

Calcium–phosphate axis. Choose hypoparathyroidism: calcium falls and phosphate rises.

## Reference values

| Parameter | Value | Note |
| --- | --- | --- |
| Serum phosphate, adult | ≈ 2.5–4.5 mg/dL | ≈ 0.81–1.45 mmol/L |
| Serum phosphate, children | higher than adults | supports bone growth |
| Filtered phosphate reabsorbed | ≈ 80–90% | proximal tubule |
| Phosphate stored in bone | ≈ 85% | as hydroxyapatite |

Approximate values for a healthy adult at rest; each laboratory sets its own ranges.

## Hormones that set phosphate

| Hormone | Kidney phosphate | Calcitriol | Serum phosphate |
| --- | --- | --- | --- |
| [PTH](https://durgical.com/en/conditions/primary-hyperparathyroidism/) | Excretion ↑ | ↑ | ↓ |
| [FGF-23](https://durgical.com/en/conditions/rickets-and-osteomalacia/) | Excretion ↑ | ↓ | ↓ |
| Calcitriol | Small reabsorption ↑ | — | ↑ (gut absorption) |

## Clinical notes

- CKD–mineral and bone disorder: hyperphosphatemia, low calcitriol, high PTH and FGF-23, renal osteodystrophy and vascular calcification.
- Hyperphosphatemia binds calcium, lowering ionized calcium (tetany risk) and depositing calcium phosphate in tissues.
- Severe hypophosphatemia lowers ATP and 2,3-BPG: muscle weakness, respiratory failure, hemolysis and rhabdomyolysis.
- X-linked hypophosphatemia (PHEX mutation) is the most common inherited rickets; calcitriol is low despite low phosphate.

## Memory aid

FGF-23 is the bone's message to the kidney: «too much phosphate, open the drain and close the vitamin D tap».

## Test yourself

Think of the answer, then tap the question to see it.

## In X-linked hypophosphatemia, phosphate is low but calcitriol is not high. Why is that inappropriate, and what causes it?

Low phosphate normally stimulates 1α-hydroxylase. Excess FGF-23 suppresses that enzyme and activates 24-hydroxylase, so calcitriol stays low or normal.

## Why does FGF-23 rise before serum phosphate in early chronic kidney disease?

With fewer nephrons, each must excrete more phosphate. Osteocytes raise FGF-23, which increases excretion per nephron and keeps serum phosphate normal for a while.

## Why can refeeding a starved patient cause dangerous hypophosphatemia?

Carbohydrate raises insulin, which drives phosphate into cells for glycolysis and ATP synthesis, while total body phosphate is already depleted.

## How do PTH and FGF-23 differ in their effect on vitamin D?

Both cause phosphaturia, but PTH stimulates 1α-hydroxylase (more calcitriol) and FGF-23 suppresses it (less calcitriol).

[Add to my cards (4)](https://durgical.app/estudiar/?add=/en/physiology/phosphate-and-fgf-23/)

## See it in 3D

The structures of Durgical's 3D anatomy where it happens.

- [Kidneys](https://durgical.com/en/anatomy/kidney/)
- [Parathyroid glands](https://durgical.com/en/anatomy/parathyroid-glands/)
- [Femur](https://durgical.com/en/anatomy/femur/)

## Related topics

- [Calcium regulation: PTH, vitamin D and calcitonin](https://durgical.com/en/physiology/calcium-regulation-pth-vitamin-d-and-calcitonin/)
- [Bone remodeling](https://durgical.com/en/physiology/bone-remodeling/)
- [Renal handling of calcium, phosphate and magnesium](https://durgical.com/en/physiology/renal-handling-of-calcium-phosphate-and-magnesium/)
- [Physiology of acute and chronic kidney failure](https://durgical.com/en/physiology/physiology-of-acute-and-chronic-kidney-failure/)
- [Prolonged fasting and starvation](https://durgical.com/en/physiology/prolonged-fasting-and-starvation/)

## Related conditions

- [Chronic kidney disease](https://durgical.com/en/conditions/chronic-kidney-disease/)
- [Rickets and osteomalacia](https://durgical.com/en/conditions/rickets-and-osteomalacia/)
- [Hypocalcaemia](https://durgical.com/en/conditions/hypocalcaemia/)
- [Primary hyperparathyroidism](https://durgical.com/en/conditions/primary-hyperparathyroidism/)

## In Biochemistry

- [Calcium and phosphate](https://durgical.com/en/biochemistry/topics/calcium-and-phosphate/)
- [Vitamin D (calcitriol)](https://durgical.com/en/biochemistry/molecules/vitamin-d/)

[← All of physiology](https://durgical.com/en/physiology/)

Educational physiology content; not a diagnostic or treatment guide and no substitute for a health professional's advice. Values are approximate references. No doses are given.

Sources: [6.7 Calcium Homeostasis: Interactions of the Skeletal System and Other Organ Systems](https://openstax.org/books/anatomy-and-physiology-2e/pages/6-7-calcium-homeostasis-interactions-of-the-skeletal-system-and-other-organ-systems) (OpenStax (Rice University), 2022); [Phosphate in Blood: MedlinePlus Medical Test](https://medlineplus.gov/lab-tests/phosphate-in-blood/) (MedlinePlus, US National Library of Medicine, 2025); [Chronic Kidney Disease](https://www.ncbi.nlm.nih.gov/books/NBK535404/) (StatPearls (NCBI Bookshelf), 2024); [Rickets: MedlinePlus Medical Encyclopedia](https://medlineplus.gov/ency/article/000344.htm) (MedlinePlus, US National Library of Medicine, 2025); Hall JE. Guyton and Hall Textbook of Medical Physiology, 13th ed. (ch. 80). Reference book used to check facts; its text and figures are not reproduced (Elsevier, 2016).

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Representative model, for educational purposes only.

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License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/physiology/phosphate-and-fgf-23/