Drugs Affecting Calcium

These drugs aim to mimic/antagonize the endogenous hormone PTH to maintain calcium homeostasis.

– The regulation of calcium is especially important as calcium phosphate is a large component of bones:

– In osteoporosis, bone turnover increases so that bone resorption is greater than bone formation, due to increased activity of osteoclasts.

 

Drugs which increase plasma calcium

Teriparatide

This is a recombinant version of parathyroid hormone which is a full PTH agonist

– Intermittent exposure results in net bone formation –> used to treat osteoporosis

Side effects

• Hypercalcemia

• Osteosarcoma

Calcipotriol

This is a synthetic form of active vitamin D made by the kidney (1,25-DHCC).

– Vitamin D usually acts to increase calcium reabsorption from the kidney and small intestine.

– In reality, this drug actually has few effects on Calcium homeostasis

– Instead it is used as a topical cream to treat skin disorders like psoriasis.

Calcium/cholecalciferol

This is a combination of calcium salt and vitamin D3.

– Used to increase serum Ca2+ in hypocalcaemia and Vitamin D deficiency

– Used to treat calcium deficiencies in the elderly and osteoporosis.

Drugs which increase plasma calcium

Bisphosphonates

e.g. Alendronate + Etidronate (- dronate)

These are analogues of pyrophosphate (P-O-P) that bind directly to hydroxyapatite (inorganic salts) and stop the resorption of bone by osteoclasts.

– They are first line drugs both in the prevention and treatment of osteoporosis and hypercalcemia

Side effects

• Corrosive oesophagitis if patients do not take the drug with water and remain upright for 30 minutes

• Atypical stress fractures (especially of the proximal femoral shaft)

Calcitonin

This is released by the parafollicular C-cells of the thyroid gland

– Interacts with osteoclasts to stop reabsorption of calcium from bone

– It reduces hypercalcemia due to Paget disease and hyperparathyroidism

– It is used as a marker of Medullary Carcinoma: a thyroid cancer that presents with localized amyloidosis due to polymerization of pro-calcitonin into b-sheets.

Denosumab

This is a monoclonal antibody which blocks the action of RANK ligand

– RANK ligand usually ligand binds to RANK receptor and promotes osteoclast activity

– This therefore reduces osteoclast activity –> treats osteoporosis

– Used in post-menopausal women who are intolerant to other drugs or have renal failure.

Cinacalcet

The parathyroid gland senses calcium via protein CaSR

– This drug activates CaSR which reduces the serum PTH

– Acts to decreased plasma Ca2+ to treat hyperparathyroidism.

N.B. It is important to remember that several drugs indirectly affect Calcium homeostasis too:

– Thiazide diuretics –> reduce renal calcium excretion

– Loop diuretics –> increase renal calcium excretion

– Glucocorticoids increase bone resorption and stop absorption in intestine –> net decrease in calcium

– Oestrogens impair action of PTH –> used in the treatment of osteoporosis

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