Calcium and Bone Metabolism

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Calcium & Phosphate - Mineral Harmony

  • Normal Serum Calcium: 8.5-10.5 mg/dL (Total); 4.5-5.5 mg/dL (Ionized - active form).
  • Normal Serum Phosphate: 2.5-4.5 mg/dL.
  • Key Hormonal Regulators:
    • Parathyroid Hormone (PTH): ↑ Ca, ↓ PO₄ (acts on bone, kidney).
    • Vitamin D (Calcitriol): ↑ Ca, ↑ PO₄ (acts on gut, bone, kidney).
    • Calcitonin: ↓ Ca, ↓ PO₄ (minor role in humans).
  • Calcium-Phosphate Product: $Ca \times PO_4$ normally < 55 mg²/dL².
    • 📌 Mnemonic: "PTH Pushes The High (Ca), Flushes The Low (PO₄)".

Calcium Homeostasis Regulation

⭐ Ionized calcium is the physiologically active form and is affected by pH (acidosis ↑ ionized Ca, alkalosis ↓ ionized Ca).

Calcium's Captains - PTH & Vit D

Parathyroid Hormone (PTH):

  • Secreted by: Parathyroid chief cells (stimulus: ↓ Serum $Ca^{2+}$).
  • Key Actions:
    • Bone: ↑ Osteoclast activity → ↑ $Ca^{2+}$ & ↑ $PO_4^{3-}$ release.
    • Kidney: ↑ $Ca^{2+}$ reabsorption (DCT); ↓ $PO_4^{3-}$ reabsorption (PCT) → phosphaturia. 📌 PTH = Phosphate Trashing Hormone.
    • Kidney: Stimulates 1α-hydroxylase → ↑ active Vit D ($1,25(OH)_2D$).
  • Overall: ↑ Serum $Ca^{2+}$, ↓ Serum $PO_4^{3-}$.

Vitamin D (Calcitriol - $1,25(OH)_2D$):

  • Activation: Diet/Skin → Liver ($25(OH)D$) → Kidney ($1,25(OH)_2D$ by 1α-hydroxylase; stim: PTH, ↓$Ca^{2+}$, ↓$PO_4^{3-}$).
  • Key Actions:
    • Intestine: ↑ $Ca^{2+}$ & ↑ $PO_4^{3-}$ absorption (primary effect).
    • Bone: Promotes mineralization; high doses → resorption.
    • Kidney: ↑ $Ca^{2+}$ & ↑ $PO_4^{3-}$ reabsorption.
    • Parathyroid: ↓ PTH synthesis (feedback).
  • Overall: ↑ Serum $Ca^{2+}$, ↑ Serum $PO_4^{3-}$.

⭐ PTH primarily increases serum calcium and decreases serum phosphate (via phosphaturia), while active Vitamin D (calcitriol) increases both serum calcium and serum phosphate (via gut/kidney absorption).

PTH and Vitamin D Regulation of Calcium and Phosphate

Calcium Chaos - Ups & Downs Drama

Hypocalcemia (↓$Ca^{2+}$)

  • Causes: Hypoparathyroidism, Vit D deficiency, CKD, ↓Mg.
  • S/S: Tetany (Chvostek's, Trousseau's signs), paresthesia. 📌 CATS Go Numb (Convulsions, Arrhythmias, Tetany, Spasms). ECG: ↑QT interval.
  • Rx: Acute: IV $Ca^{2+}$ gluconate. Chronic: Oral $Ca^{2+}$ + Vit D.

Hypercalcemia (↑$Ca^{2+}$)

  • Causes:
    • PTH-dependent: Primary hyperparathyroidism.
    • PTH-independent: Malignancy (PTHrP), Vit D toxicity, Sarcoidosis. 📌 CHIMPANZEES.
  • S/S: "Stones (renal), Bones (pain), Groans (abd pain), Thrones (polyuria), Psych". ECG: ↓QT interval.
  • Rx: IV Saline, Furosemide (post-hydration), Bisphosphonates.

⭐ Malignancy & primary hyperparathyroidism: most common causes of hypercalcemia in adults.

Bone Structure Blues - When Bones Weaken

  • Osteoporosis: Reduced bone mass & microarchitectural deterioration, ↑fracture risk.
    • Risk Factors: Age, post-menopause, low Ca/Vit D, corticosteroids, smoking. 📌 ACCESS: Alcohol, Corticosteroid, Calcium low, Estrogen low, Smoking, Sedentary.
    • Diagnosis: DEXA scan T-score ≤ -2.5.
    • Clinical: Fragility fractures (vertebral, hip, Colles'). Often silent.
    • Management: Calcium, Vit D, bisphosphonates, exercise. DEXA Scan T-Score Interpretation
  • Osteomalacia & Rickets: Defective bone mineralization; soft bones.
    • Rickets (children): Epiphyseal plate widening, bowing legs, rachitic rosary.
    • Osteomalacia (adults): Bone pain, muscle weakness, waddling gait.
    • Causes: Severe Vit D deficiency (common), renal phosphate wasting, malabsorption.
    • Labs: ↓Ca²⁺, ↓PO₄³⁻ (or normal Ca²⁺ due to ↑PTH), ↑ALP, ↑PTH. $25(OH)D$ levels low.

    ⭐ Looser's zones (pseudofractures) on X-ray are characteristic of osteomalacia.

High-Yield Points - ⚡ Biggest Takeaways

  • Primary hyperparathyroidism: Commonest outpatient hypercalcemia; stones, bones, groans.
  • Vitamin D deficiency: Causes rickets/osteomalacia; ↓Ca, ↓PO4, ↑PTH, ↑ALP.
  • Paget's disease of bone: ↑ALP, normal Ca/PO4; risk of osteosarcoma, deafness.
  • Osteoporosis: Diagnosed by DEXA (T-score ≤ -2.5); bisphosphonates are first-line.
  • Hypercalcemia of malignancy: Often due to PTHrP or lytic bone metastases.
  • Hypoparathyroidism: Presents with ↓Ca, ↑PO4, ↓PTH; Chvostek's & Trousseau's signs.

Practice Questions: Calcium and Bone Metabolism

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Parathyroid hormone (PTH) exerts its effect on calcium metabolism by acting on receptors present on the–

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Flashcards: Calcium and Bone Metabolism

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One clinical feature of Cushing syndrome is _____, which is a result of decreased osteoblast activity

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One clinical feature of Cushing syndrome is _____, which is a result of decreased osteoblast activity

osteoporosis

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