Calcium homeostasis: PTH, vitamin D and calcitonin
One hormone, PTH, raises calcium yet lowers phosphate. Calcium homeostasis makes sense once you follow PTH, vitamin D and calcitonin across bone, kidney and gut.
Explain how PTH, 1,25-dihydroxyvitamin D and calcitonin regulate serum calcium and phosphate across bone, kidney and gut.
The short version
- PTH raises calcium through bone, the distal tubule and calcitriol, and lowers phosphate in the proximal tubule.
- Vitamin D goes skin, liver, kidney, and calcitriol raises calcium and phosphate absorption in the gut.
- Calcitonin comes from thyroid C cells when calcium is high and inhibits osteoclasts; its everyday role in humans is thought to be small.
- Total calcium is normal at about 8.8–10.4 mg/dL and moves about 0.8 mg/dL for each 1 g/dL change in albumin.
- Primary hyperparathyroidism is high calcium and low phosphate; kidney failure is low calcium and high phosphate.
The puzzle: calcium up, phosphate down
A woman has had two kidney stones, aching bones and constipation. Her calcium is 11.6 mg/dL and her phosphate is low, at 2.0 mg/dL. One hormone raised her calcium and dropped her phosphate.
How can one hormone push two minerals in opposite directions? Calcium homeostasis answers this by following three signals, PTH, vitamin D and calcitonin, across bone, kidney and gut.
Normal calcium and the albumin correction
Total serum calcium is normal from about 8.8 to 10.4 mg/dL. Below that is hypocalcaemia and above it is hypercalcaemia.[2]
A fraction of calcium is bound to albumin, so the total moves with albumin, by about 0.8 mg/dL for each 1 g/dL change in albumin. Normal albumin is taken as 4 g/dL.[2][8]
Because of this, a low total calcium with a low albumin may not be a true fall in calcium. The correction adds back the part of the shortfall that albumin explains, and it is a convention rather than an exact measurement.[8]
Calcium in mg/dL, albumin in g/dL; 4 g/dL is the normal albumin; 0.8 mg/dL per 1 g/dL.
- Measured calcium 8.2 mg/dL, albumin 2.8 g/dL, normal albumin 4
- 4 − 2.8 = 1.2 g/dL below normal
- 1.2 × 0.8 = 0.96, about 1 mg/dL to add
- 8.2 + 0.96 = 9.16 ≈ 9.2 mg/dL: inside 8.8–10.4, so normal
Calcium sensing and PTH release
The chief cells of the parathyroid glands sense calcium through the calcium-sensing receptor.[10] Low calcium releases PTH, and high calcium shuts it off.[1]
This is a feedback loop. When calcium falls, PTH rises and acts to bring it back up.[1] When calcium rises, the calcium-sensing receptor switches PTH release off, so the loop stops once calcium is restored.[1][10]
PTH then has three actions: on bone, on the kidney, and on vitamin D activation.
PTH in bone and kidney: calcium held in, phosphate thrown out
Bone. PTH acts on osteoblasts, which signal osteoclasts through RANK ligand. The osteoclasts then release calcium and phosphate.[2][9]
Kidney. PTH increases calcium reabsorption in the distal tubule and decreases phosphate reabsorption in the proximal tubule.[2][7]
Notice the bone step: PTH acts on osteoblasts, not directly on osteoclasts, which lack PTH receptors. That is why the signal has to pass through RANK ligand.[9]
That answers the puzzle: calcium is held in and phosphate is thrown out. The bone releases both minerals, but the kidney keeps only the calcium, so calcium rises while phosphate falls.
| Site | What PTH does | Effect |
|---|---|---|
| Bone | Osteoblasts signal osteoclasts via RANK ligand | Calcium and phosphate released |
| Distal tubule | Increases calcium reabsorption | Calcium retained |
| Proximal tubule | Decreases phosphate reabsorption | Phosphate lost in urine |
| Kidney, 1α-hydroxylase | Switches on the enzyme | More calcitriol |
Vitamin D: skin, liver, kidney and the gut
The third PTH action is vitamin D activation: PTH switches on 1α-hydroxylase in the kidney.[3]
- SkinUltraviolet B turns 7-dehydrocholesterol into vitamin D₃.
- LiverA hydroxyl group is added to make 25-hydroxyvitamin D, the storage form we measure.
- Kidney1α-hydroxylase makes 1,25-dihydroxyvitamin D, calcitriol, the active hormone.[3][4]
Calcitriol raises absorption of both calcium and phosphate from the gut.[1][3]
Two links matter for the exam. The 25-hydroxyvitamin D made in the liver is the storage form, so it is the one measured. The active hormone, calcitriol, is made in the kidney, and PTH is what switches that kidney step on.[3][4]
Calcitonin: released when calcium is high
Calcitonin comes from the thyroid's C cells. It is released when calcium is high, and it inhibits osteoclasts.[1][2] In humans its everyday role is thought to be small.[10]
So PTH raises calcium and lowers phosphate, while calcitriol raises both.
Reading the labs: four calcium and phosphate patterns
Use the contrast between PTH and calcitriol to read calcium homeostasis labs.[2][5][6]
| Condition | Calcium | Phosphate | PTH |
|---|---|---|---|
| Primary hyperparathyroidism | High | Low | High |
| Hypoparathyroidism | Low | High | Low |
| Kidney failure | Low | High | High |
| Vitamin D deficiency | Low or low-normal | Low | High |
In primary hyperparathyroidism, PTH is high (or inappropriately normal for the high calcium), so calcium is high and phosphate is low. In hypoparathyroidism, PTH is low, so calcium is low and phosphate is high.[2][5][6]
In vitamin D deficiency, calcium is low or low-normal and phosphate is low, with a high PTH.[2]
In kidney failure the kidney makes too little calcitriol and phosphate is retained, so calcium is low and phosphate high, with a high PTH.[2]
Practice question
Original · USMLE styleA 56-year-old woman comes to the clinic because of fatigue, constipation and one recent episode of nephrolithiasis. She takes no medications. Laboratory studies show:
| Calcium, total | 11.1 mg/dL (reference range 8.8 to 10.4) |
|---|---|
| Phosphate | 2.2 mg/dL (reference range 2.5 to 4.5) |
| Creatinine | 0.9 mg/dL (reference range 0.6 to 1.1) |
| 25-Hydroxyvitamin D | 34 ng/mL (reference range 30 to 100) |
| Parathyroid hormone (intact) | 138 pg/mL (reference range 15 to 65) |
Common questions
Why does PTH raise calcium but lower phosphate?
In bone, PTH releases both minerals. In the kidney it increases calcium reabsorption in the distal tubule and decreases phosphate reabsorption in the proximal tubule, so calcium is held in and phosphate is lost.
How do you correct calcium for albumin?
Total calcium changes by about 0.8 mg/dL for each 1 g/dL change in albumin. Add (4 − albumin) × 0.8 to the measured calcium.
What is the normal range for total serum calcium?
About 8.8 to 10.4 mg/dL. Below that is hypocalcaemia and above it is hypercalcaemia.
How is vitamin D activated?
Ultraviolet B turns 7-dehydrocholesterol in the skin into vitamin D₃, the liver makes 25-hydroxyvitamin D, and the kidney's 1α-hydroxylase makes calcitriol, the active hormone.
How does calcitonin affect calcium?
Thyroid C cells release calcitonin when calcium is high, and it inhibits osteoclasts. Its everyday role in humans is thought to be small.
Transcript
Read the full narration, by chapter618 words
0:00The case: high calcium, low phosphate, one hormone
A woman has had two kidney stones, aching bones and constipation. Her calcium is 11.6 milligrams per decilitre, and her phosphate is low, at 2.0. One hormone raised her calcium and dropped her phosphate. How can it push two minerals in opposite directions? Today: how PTH, vitamin D and calcitonin steer calcium and phosphate across bone, kidney and gut.
0:27Normal total calcium, hypo- and hypercalcaemia
Total serum calcium is normal from about 8.8 to 10.4 mg/dL. Below that is hypocalcaemia, above it is hypercalcaemia.
0:39Albumin and the corrected calcium
A fraction of calcium is bound to albumin, so the total moves with albumin, by about 0.8 mg/dL for each gram per decilitre. A measured calcium of 8.2 with an albumin of 2.8, against a normal four: add 1.2 times 0.8, which is about one, and the corrected calcium is about 9.2. Normal.
1:03Parathyroid chief cells and the calcium-sensing receptor
The chief cells of the parathyroid glands sense calcium through the calcium-sensing receptor. Low calcium releases PTH, and high calcium shuts it off. PTH has three actions.
1:17PTH in bone: osteoblasts, RANK ligand, osteoclasts
In bone, it acts on osteoblasts, which signal osteoclasts through RANK ligand, and osteoclasts release calcium and phosphate.
1:27PTH in the kidney: calcium in, phosphate out
In the kidney, PTH increases calcium reabsorption in the distal tubule, and decreases phosphate reabsorption in the proximal tubule. That is the answer to our puzzle: calcium held in, phosphate thrown out.
1:42Vitamin D: skin, liver, kidney, and calcitriol in the gut
The third action is vitamin D activation. PTH switches on one alpha hydroxylase in the kidney. Vitamin D starts in skin, where ultraviolet B turns seven dehydrocholesterol into vitamin D3. The liver adds a hydroxyl group to make 25-hydroxyvitamin D, the storage form we measure. The kidney's one alpha hydroxylase makes 1,25-dihydroxyvitamin D, calcitriol, the active hormone. Calcitriol raises absorption of both calcium and phosphate from the gut.
2:19Calcitonin and the summary of who raises and lowers what
Calcitonin, from the thyroid's C cells, is released when calcium is high, and it inhibits osteoclasts. In humans its everyday role is thought to be small. So PTH raises calcium and lowers phosphate. Calcitriol raises both.
2:37Reading the labs: four calcium and phosphate patterns
Use that to read the labs. Primary hyperparathyroidism: high calcium, low phosphate, high PTH. Hypoparathyroidism: low calcium, high phosphate, low PTH. Kidney failure: no calcitriol and retained phosphate, so low calcium, high phosphate, and a high PTH. Vitamin D deficiency: low or low-normal calcium, low phosphate, high PTH. When PTH is high, low phosphate points to primary hyperparathyroidism or vitamin D deficiency, and high phosphate points to the kidney.
3:17Your turn: a practice question
Your turn. A 56-year-old woman has fatigue, constipation and a recent kidney stone. Her calcium is 11.1 milligrams per decilitre, phosphate 2.2, creatinine normal, and 25-hydroxyvitamin D normal. Her PTH is 138 picograms per millilitre, and the reference range is 15 to 65. Which of the following best explains her low serum phosphate? A, decreased phosphate reabsorption in the proximal tubule. B, decreased calcitriol-mediated phosphate absorption in the gut. C, increased phosphate deposition in bone. D, increased phosphate reabsorption in the distal tubule. E, calcitonin-mediated phosphate excretion by the kidney. Pause here and decide.
4:13The answer, one option at a time
B is out: PTH increases calcitriol, and calcitriol raises phosphate absorption, which would push phosphate up. C is out: PTH drives bone resorption, which releases phosphate rather than depositing it. D is out: PTH acts on the distal tubule to retain calcium, not phosphate. E is out: calcitonin responds to high calcium, and its everyday role in humans is thought to be small. So the answer is A. Excess PTH lowers phosphate reabsorption in the proximal tubule, so phosphate is lost in the urine.
4:53Recap pocket card
Three things to keep. One: PTH raises calcium through bone, the distal tubule and calcitriol, and lowers phosphate in the proximal tubule. Two: vitamin D goes skin, liver, kidney, and calcitriol raises calcium and phosphate absorption in the gut. Three: primary hyperparathyroidism is high calcium and low phosphate; kidney failure is low calcium and high phosphate. Next, adrenal steroidogenesis.
Sources
Numbers in the text, e.g. [1], point here- OpenStax Anatomy and Physiology 2e, 17.5 The Parathyroid Glands. openstax.org/books/anatomy-and-physiology-2e/pages/17-5-the-parathyroid-glands
- MSD Manual Professional: Hypercalcemia; Hypocalcemia; Hyperparathyroidism. msdmanuals.com/professional
- Vitamin D and calcium-phosphate metabolism. europepmc.org/article/PMC/PMC13038531
- Consensus statement on vitamin D status, 2024. europepmc.org/article/PMC/PMC11405507
- Europe PMC PMC8789028 (albumin-adjusted calcium; PTH and renal calcium and phosphate handling). europepmc.org/article/PMC/PMC8789028
- Canadian primary hyperparathyroidism guideline, 2017. europepmc.org/article/PMC/PMC5206263
- JBMR 2022, primary hyperparathyroidism pathophysiology. europepmc.org/article/PMC/PMC10092691
- Europe PMC PMC11751745 (simplified Payne formula for albumin-adjusted calcium). europepmc.org/article/PMC/PMC11751745
- Europe PMC PMC13734714 (PTH, RANKL and OPG). europepmc.org/article/PMC/PMC13734714
- Wikipedia: Parathyroid hormone; Calcitonin (secondary)
Full claim-by-claim list: the lesson page.
The practice question is original and its patient is synthetic. Every fact is checked against the sources above in independent accuracy reviews. Always follow your local guidelines and your own laboratory’s ranges.
Image credits. Illustrations: Servier Medical Art (smart.servier.com), CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/), adapted (cropped, recoloured): woman, bone, posterior thyroid and parathyroids, calcium-sensing receptor, osteoblast, osteoclast, skin, liver, kidney, small intestine. Gray's Anatomy (1918) plate by Henry Vandyke Carter via Wikimedia Commons, public domain. Sun icon by Servier (via bioicons.com), CC BY 3.0 (https://creativecommons.org/licenses/by/3.0/). The nephron, diagrams, slips, cards and all handwriting are drawn in code (original). No AI-generated teaching images.
Corrections. None so far. Spotted an error? Email info@medservatory.com with the lesson code MS-S1-ENDO-007.
For exam study only, not medical advice. Read the medical disclaimer.
In this series
Playlist on YouTube- EP 01Hypothalamic-pituitary axes and feedback: primary, secondary, tertiary5:05
- EP 02Primary vs secondary endocrine disorders: paired hormone levels5:13
- EP 03Insulin secretion in the beta cell: from glucose to granule5:06
- EP 04Insulin vs glucagon signalling: receptors and effects5:19
- EP 05DKA vs HHS pathophysiology: why only one makes acid5:58
- EP 06Diabetes drugs by mechanism: where each class acts5:58
- EP 07Thyroid hormone synthesis, step by step5:14
- EP 08Calcium homeostasis: PTH, vitamin D and calcitonin5:28
- EP 09Adrenal steroidogenesis: zones, enzymes and the 17α-hydroxylase fork5:29
- EP 10Congenital adrenal hyperplasia: three enzymes, three patterns5:44
- EP 11Cushing syndrome: the dexamethasone suppression test and ACTH5:29
- EP 12Primary hyperaldosteronism: high aldosterone, low renin5:27
- EP 13SIADH vs diabetes insipidus: central vs nephrogenic DI5:44
- EP 14MEN1, MEN2A and MEN2B: match the gene to its tumours5:13