KCHECK

Indications

• Osteoporosis
• Paget's disease of bone
• Hypercalcemia

Dosage

Children: Refer to BNF for Children for specific dosing information.

Adults: The usual adult dose for osteoporosis is 100 IU (1 spray) intranasally once daily. For Paget's disease, the recommended dose is 100 IU subcutaneously every other day until the desired response is achieved, then may be adjusted.

Mechanism of action

Calcitonin exerts its effects primarily through binding to calcitonin receptors on osteoclasts, leading to a decrease in osteoclast activity and subsequent reduction in bone resorption. It also promotes the synthesis of proteoglycans and collagen type II in articular cartilage, enhancing cartilage health. The activation of the cAMP signaling pathway is a key component of its mechanism, resulting in increased metabolic activity and synthesis of cartilage components.

Pharmacodynamics

Calcitonin's pharmacodynamics involve its role in calcium and bone metabolism. By inhibiting osteoclast activity, it decreases the rate of bone resorption, thereby lowering serum calcium levels. In addition to its systemic effects, calcitonin has local effects on cartilage, enhancing the synthesis of important extracellular matrix components, which can help alleviate symptoms of osteoarthritis and promote joint health.

Pharmacokinetics

Calcitonin is typically administered subcutaneously or intranasally. It has a short half-life, requiring frequent dosing for sustained effects. The bioavailability of intranasal calcitonin is approximately 3-5%. The drug is primarily metabolized in the kidneys and is excreted unchanged in the urine. The onset of action occurs within a few hours, with peak effects seen within 12-24 hours.

Adverse effects

• Nausea
• Vomiting
• Flushing
• Hypocalcemia
• Injection site reactions

Precautions

• Use with caution in patients with renal impairment
• Monitor calcium levels in patients receiving long-term therapy

Pregnancy

Calcitonin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

It is not known whether calcitonin is excreted in human milk. Caution should be exercised when administering calcitonin to nursing women.

Storage

Store in a refrigerator (2°C to 8°C). Do not freeze. Protect from light.

Formulations

• Injection solution
• Nasal spray

Mechanism of action

Calcitonin has been demonstrated to have chondroprotective effects under pre-clinical settings. It is debated whether this effect is mediated through subchondral-bone, directly on cartilage or both in combination. We investigated possible direct effects of salmon calcitonin on proteoglycans and collagen-type-II synthesis in osteoarthritic (OA) cartilage. Human OA cartilage explants were cultured with salmon calcitonin (100 pM-100 nM). Direct effects of calcitonin on articular cartilage were evaluated by 1) measurement of proteoglycan synthesis by incorporation of radioactive labeled 35SO4 (5 uCi) 2) quantification of collagen-type-II formation by pro-peptides of collagen type II (PIINP) ELISA, 3) QPCR expression of the calcitonin receptor in OA chondrocytes using four individual primer pairs, 4) activation of the cAMP signaling pathway by EIA and, 5) investigations of metabolic activity by AlamarBlue. QPCR analysis and subsequent sequencing confirmed expression of the calcitonin receptor in human chondrocytes. All doses of salmon calcitonin significantly elevated cAMP levels (P < 0.01 and P < 0.001). Calcitonin significantly and concentration-dependently [100 pM-100 nM] induced proteoglycan synthesis measured by radioactive 35SO4 incorporation, with a 96% maximal induction at 10 nM (P < 0.001) corresponding to an 80% induction of 100 ng/ml IGF, (P < 0.05). In alignment with calcitonin treatments (100 pM-100 nM) resulted in 35% (P < 0.01) increased PIINP levels. Calcitonin treatment increased proteoglycan and collagen synthesis in human OA cartilage. In addition to its well-established effect on subchondral bone, calcitonin may prove beneficial to the management of joint diseases through direct effects on chondrocytes. Caclitonin directly inhibits osteoclastic bone resorption. Another way calcitonin plays a role in calcium homeostasis is by decreasing tubular reabsorption and promoting renal excretion of calcium. The mechanism for analgesia is unknown, but it is thought to be from decreased prostaglandins and stimulation of beta-endorphins.