Calcitonin

1. Introduction

• Calcitonin is a peptide hormone naturally produced by the parafollicular C cells of the thyroid gland in humans and by the ultimobranchial body in some animals.

• Plays a role in calcium and phosphate homeostasis, acting to lower serum calcium levels.

• Pharmacological calcitonin is derived from salmon, eel, or synthetic sources, with salmon calcitonin being most potent and commonly used clinically due to higher receptor affinity and longer half-life.

• Administered intranasally or by subcutaneous/intramuscular injection for therapeutic purposes.

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2. Mechanism of Action

• Binds to calcitonin receptors on osteoclasts, inhibiting their resorptive activity → reduced bone breakdown.

• Decreases osteoclast recruitment and motility, limiting bone resorption.

• In the kidney, reduces tubular reabsorption of calcium and phosphate, promoting urinary excretion.

• Net effect: lowered plasma calcium and phosphate concentrations.

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3. Pharmacological Preparations

• Salmon calcitonin – highest potency and longer duration.

• Synthetic human calcitonin – lower potency, less commonly used.

• Forms:

  • Injectable (subcutaneous, intramuscular).

  • Intranasal spray.

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4. Pharmacokinetics

• Absorption:

  • Injectable: rapid systemic absorption.

  • Nasal: moderate absorption; reduced bioavailability (~25%–30%) compared to injection.

• Distribution: widely distributed; does not cross the blood–brain barrier significantly.

• Metabolism: degraded by proteolytic enzymes in the kidney and blood.

• Elimination half-life: ~10–15 minutes for human calcitonin; salmon calcitonin longer (~40–50 minutes).

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5. Therapeutic Indications

A. Bone Disorders

• Paget’s disease of bone – reduces abnormal bone turnover.

• Postmenopausal osteoporosis – decreases bone resorption; modest increase in bone mineral density; alternative for those intolerant to other osteoporosis drugs.

• Glucocorticoid-induced osteoporosis – option when other agents are unsuitable.

B. Hypercalcemia

• Acute hypercalcemia – rapid but short-term reduction in serum calcium; often used in emergency settings alongside other agents (e.g., bisphosphonates).

C. Other

• Pain relief in acute vertebral compression fractures (osteoporotic).

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6. Contraindications

• Known hypersensitivity to calcitonin or any formulation component (especially salmon protein for salmon calcitonin).

• Caution in patients with hypocalcemia.

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7. Adverse Effects

Common

• Nasal route: rhinitis, nasal irritation, epistaxis.

• Injection route: nausea, vomiting, flushing, local injection site reaction.

Serious

• Hypocalcemia (rare but possible).

• Hypersensitivity and anaphylactic reactions (especially with salmon-derived preparations).

• Long-term use: small increased risk of certain malignancies noted in some studies (reason for caution in chronic use).

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8. Drug Interactions

• Lithium: calcitonin may decrease serum lithium concentrations by increasing renal clearance.

• No major CYP450-mediated interactions due to peptide nature.

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9. Monitoring

• Serum calcium and phosphate during therapy, especially in hypercalcemia treatment.

• Nasal mucosa for irritation with long-term intranasal use.

• Periodic reassessment of need for therapy due to malignancy risk with prolonged use.

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10. Advantages and Limitations

Advantages

• Rapid onset of calcium-lowering action in acute hypercalcemia.

• Useful in patients intolerant to first-line osteoporosis drugs.

• Additional analgesic benefit in certain bone conditions.

Limitations

• Modest efficacy in fracture prevention compared to bisphosphonates or denosumab.

• Short duration of calcium-lowering effect; tachyphylaxis can occur within 48 hours to a few days in hypercalcemia treatment.

• Risk of malignancy with long-term use warrants caution and periodic review.