Calcium, phosphate and bone: physiology and disorders

How the body keeps calcium and phosphate in balance, how bone is constantly rebuilt, and what goes wrong in osteoporosis, rickets and kidney disease.

Updated Nov 12, 2026

Blood calcium and phosphate are held in a narrow range by parathyroid hormone, vitamin D, FGF23 and calcitonin acting on gut, bone and kidney. Bone is renewed throughout life by osteoclasts that remove it and osteoblasts that rebuild it. This page brings the axis, its disorders and the treatment strategy together; the drugs have their own pages.

Calcium and phosphate handling

Most body calcium and phosphate sit in bone mineral; the small fraction in blood is what nerves, muscle and clotting depend on. Balance is the sum of three flows: absorption in the gut, exchange with bone and excretion by the kidney. Healthy kidneys remove extra phosphate in the urine and convert vitamin D to calcitriol, the active hormone.

The hormonal axis

PTH: released when blood calcium falls (sensed by the calcium-sensing receptor). It frees calcium from bone, increases calcium reabsorption and phosphate loss in the kidney, and stimulates calcitriol production.
Vitamin D: made in skin or eaten, then hydroxylated in liver and kidney to calcitriol, which increases gut absorption of calcium and phosphate.
FGF23: a bone-derived hormone that promotes phosphate excretion and lowers calcitriol.
Calcitonin: from thyroid C cells; it inhibits osteoclasts and is used as a drug in hypercalcaemia and, less often, osteoporosis.

Bone remodelling

Bone is removed and rebuilt in small units throughout life. Osteoblast-lineage cells express RANKL, which binds RANK on osteoclast precursors and drives their formation and activity; osteoprotegerin is a decoy that restrains it. After resorption, osteoblasts lay down new matrix that then mineralises. Osteocytes buried in bone make sclerostin, a brake on formation. Each modern osteoporosis drug targets one of these steps: bisphosphonates poison osteoclasts, denosumab blocks RANKL, romosozumab blocks sclerostin, and PTH-receptor agonists given intermittently stimulate formation.

Disorders of minerals and bone

Hypercalcaemia: mostly primary hyperparathyroidism or cancer; also excess vitamin D, thiazides, lithium, immobility, sarcoidosis and tuberculosis.
Rickets and osteomalacia: soft bone from lack of vitamin D, calcium or phosphate (rickets in growing children, osteomalacia in adults); causes include little sun, poor diet, malabsorption, liver or kidney disease and inherited phosphate wasting.
Osteoporosis: low bone mass and poor structure with fractures of hip, spine and wrist, often silent until a fracture. Risk rises with age, menopause, low body weight, smoking, alcohol and long-term glucocorticoids.
Paget disease of bone: focal, disordered remodelling with enlarged, weak bone, bone pain and deformity; bisphosphonates are standard treatment.
CKD-mineral bone disorder: low calcitriol and phosphate retention raise PTH and FGF23, weaken bone and calcify vessels, increasing fracture, heart attack and stroke risk.

Treating hypercalcaemia

Treatment combines lowering calcium with correcting the cause. Intravenous fluids are the most important first step, since high calcium causes dehydration. Calcitonin and bisphosphonates slow bone breakdown; glucocorticoids help when the cause is vitamin D excess, because they reduce activation of vitamin D; loop diuretics such as furosemide promote calcium loss in the urine; dialysis is reserved for kidney failure. Primary hyperparathyroidism is often cured by removing the abnormal gland.

Integrated osteoporosis treatment

All patients need enough calcium, vitamin D and protein, exercise and fall prevention. Antiresorptives (bisphosphonates, denosumab, raloxifene) slow loss; anabolic agents (teriparatide, abaloparatide, romosozumab) build new bone and are kept for severe disease or multiple fractures. Order matters: an anabolic course followed by an antiresorptive keeps or adds to the gain, and denosumab after romosozumab maintains density. Stopping denosumab can raise the risk of spinal fractures months to years later, so it is not stopped without a follow-on plan. Because bisphosphonates persist in bone, the need to continue them is reassessed after some years.

CKD-MBD care: limit dietary phosphate, phosphate binders with meals, active vitamin D, calcimimetics to lower PTH, and parathyroidectomy when PTH stays high.

Test yourself

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

Why does chronic kidney disease raise parathyroid hormone?

The failing kidney makes less calcitriol and retains phosphate, so calcium falls and PTH rises; FGF23 also climbs.

What is the first and most important step in treating severe hypercalcaemia?

Intravenous fluids to correct dehydration; drugs that block bone resorption and treatment of the cause follow.

Which signal drives osteoclast formation, and which drug blocks it?

RANKL binding to RANK on osteoclast precursors; denosumab is an antibody against RANKL.

Why is denosumab not simply stopped without a plan?

Stopping it can raise the risk of spinal fractures months to years later, so a follow-on antiresorptive is usually planned.

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Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: Mineral & Bone Disorder in Chronic Kidney Disease (National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), 2026); Osteoporosis: Diagnosis, Treatment, and Steps to Take (National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), 2026); Hypercalcemia: MedlinePlus Medical Encyclopedia (MedlinePlus (U.S. National Library of Medicine), 2026); Denosumab Injection: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026).

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