Calcium and Bone Metabolism

Calcium homeostasis is tightly regulated by the interplay of parathyroid hormone (PTH), vitamin D (calcitriol), and calcitonin. Normal serum calcium is 2.1–2.6 mmol/L; approximately 45% is protein-bound (mainly albumin), 10% is complexed, and 45% is free ionised (the biologically active form). Corrected calcium = measured total calcium + 0.02 × (40 − albumin in g/L).

Parathyroid hormone (PTH): released by chief cells of the parathyroid glands in response to low ionised calcium. Actions: (1) stimulates osteoclast-mediated bone resorption, releasing Ca²⁺ and PO₄³⁻; (2) increases renal calcium reabsorption and phosphate excretion; (3) stimulates renal 1α-hydroxylase → converts 25-OH-D to calcitriol (1,25-OH₂-D — active vitamin D). Calcitriol increases gut calcium and phosphate absorption. Net result: PTH raises serum calcium. High phosphate suppresses calcitriol by inhibiting 1α-hydroxylase.

Vitamin D deficiency is highly prevalent in New Zealand, particularly in Māori and Pacific peoples (darker skin produces less vitamin D at the latitudes of NZ, especially in winter in the South Island). Vitamin D3 (cholecalciferol) is synthesised in skin by UVB irradiation. It is hydroxylated in the liver to 25-OH-D (measured to assess vitamin D status) and then by the kidney to calcitriol (1,25-OH₂-D, active form). Deficiency (25-OH-D < 50 nmol/L) causes rickets in children (growth plate failure) and osteomalacia in adults (bone pain, proximal myopathy, fracture risk). Secondary hyperparathyroidism develops as PTH rises to compensate for low intestinal calcium absorption.

Primary hyperparathyroidism (PHPT): autonomous PTH secretion, most commonly from a solitary parathyroid adenoma. Most patients are asymptomatic with incidental hypercalcaemia discovered on routine biochemistry. Classical features (when present): "bones, stones, groans, and psychic moans" — osteoporosis/fractures, nephrolithiasis, abdominal pain/constipation, depression/cognitive impairment. Lab findings: elevated PTH (or inappropriately normal for the level of calcium), elevated serum calcium, low phosphate, elevated urinary calcium. Surgery (parathyroidectomy) is indicated for symptomatic patients or those meeting asymptomatic criteria (calcium > 0.25 mmol/L above upper limit of normal, eGFR < 60, T-score ≤ −2.5, or age < 50).

Hypocalcaemia: most common post-thyroidectomy (hypoparathyroidism from inadvertent removal or damage to parathyroid glands) or post-parathyroidectomy. Symptoms: perioral tingling, carpopedal spasm, tetany, seizures. Signs: Chvostek's sign (tapping over the facial nerve causes facial muscle twitching) and Trousseau's sign (blood pressure cuff inflated above systolic for 3 minutes causes carpal spasm). Treatment: IV calcium gluconate for acute severe hypocalcaemia; oral calcium + calcitriol for maintenance.

Osteoporosis is characterised by reduced bone mineral density and microarchitectural deterioration, predisposing to fragility fractures. The FRAX tool calculates 10-year fracture probability incorporating age, sex, BMI, prior fracture, parental hip fracture, smoking, alcohol, glucocorticoids, and BMD (if available). Management: fall and fracture prevention (balance training, home hazard modification, NZ Green Prescription), calcium (1200 mg/day dietary), vitamin D supplementation (800–1000 IU/day), bisphosphonates (alendronate — inhibit osteoclast farnesyl pyrophosphate synthase), or denosumab (anti-RANKL monoclonal antibody). Paget's disease of bone is characterised by focal accelerated, disordered bone remodelling with increased osteoclast and compensatory osteoblast activity. Affected bone is expanded, vascular, and structurally weak. Treatment: bisphosphonates (zoledronic acid).