Calcium homeostasis is maintained by the interplay of PTH, calcitonin, and vitamin D, each of which can be targeted pharmacologically.
Parathyroid Hormone (PTH)/ Parathormone
Physiology:
Secreted by parathyroid chief cells in response to low calcium.
Increases serum calcium by:
Stimulating osteoclast activity via osteoblast signaling.
Increasing renal calcium reabsorption.
Activating vitamin D to enhance intestinal calcium absorption.
Pharmacology:
1) PTH Analogues:
Teriparatide (PTH 1–34):
Uses: Osteoporosis (stimulates bone formation).
Adverse Effects: Hypercalcemia, potential osteosarcoma (animal studies).
2) PTH Inhibitors:
Calcimimetics (e.g., Cinacalcet):
Uses: Secondary hyperparathyroidism in CKD, parathyroid carcinoma.
Mechanism: Increases calcium receptor sensitivity, reducing PTH secretion.
Calcitonin
Physiology:
Secreted by thyroid parafollicular (C) cells in response to high calcium.
Lowers calcium by inhibiting osteoclast-mediated bone resorption and reducing renal calcium reabsorption.
Pharmacology:
Salmon Calcitonin:
Uses: Hypercalcemia, Paget’s disease, osteoporosis (less common).
Adverse Effects: Hypersensitivity, nausea, flushing.
Vitamin D
Physiology:
Obtained as cholecalciferol (D3) from skin or ergocalciferol (D2) from diet.
Hydroxylated in liver (25-OH D) and kidney (1,25-(OH)2 D or calcitriol).
Enhances calcium and phosphate absorption and promotes bone mineralization.
Pharmacology:
1) Vitamin D Analogues:
Calcitriol (active form):
Uses: Hypocalcemia, osteoporosis, rickets, osteomalacia.
Adverse Effects: Hypercalcemia, hypercalciuria.
2) Synthetic Analogues (e.g., Paricalcitol, Alfacalcidol):
Uses: Secondary hyperparathyroidism in CKD.
Mechanism: Similar to calcitriol, with variations in potency and kinetics.
Clinical Applications
Osteoporosis: Treated with teriparatide or calcitriol.
Hypercalcemia: Managed with calcitonin.
Hypocalcemia/Rickets: Corrected with vitamin D analogues.
Secondary Hyperparathyroidism: Controlled with calcimimetics or synthetic vitamin D analogues.
Side Effects
Teriparatide: Hypercalcemia, leg cramps, nausea.
Salmon Calcitonin: Nausea, flushing, allergic reactions.
Calcitriol: Hypercalcemia, hypercalciuria, kidney stones.