Week 13 – Drugs affecting Calcium & Bone

 Main minerals in bone are calcium and phosphates

 Hormones involved in calcium homeostasis
- Vit D
- Parathyroid hormone (PTH)
- Oestrogens
- Growth hormone
- Steroids
- Calcitonin
- Various cytokines

 Bone remodeling via demineralisation & mineralization

- Old bone resorbed by osteoclast cells and new bone deposited by osteoblasts
 ↑ [Ca2+] = ↑ bone mineralisation
 ↓[Ca2+] = ↑ bone demineralisation

Parathyroid Glands
 Not subject to control from pituitary gland but respond directly to blood calcium levels
 ↑ [Ca2+] ECF= ↓PTH
 ↓[Ca2+] ECF= ↑PTH
 Calcitonin: ↑ [Ca2+] ECF = calcitonin release from thyroid and PT gland
- Decreases bone resorption and renal reabsorption of CA
- Considered natural antagonists of PTH and vitamin D

 Ageing associated with decrease calcium absorption  continued bone loss

 Calcium supplements do not replace dietary calcium
 Fraction absorbed is relatively low and depends on
- Daily calcium intake
- Intestinal transit time
- Age
- Oestrogen levels in females
- Parathyroid hormone
- Vitamin D

Indications
 Calcium deficiency, osteo, acute hypocalcaemia
Contraindications
 Hypercalcaemia, hypercalciuria, digoxin toxicity

Adverse effects:
- Belching
- Flatulence
- Abdominal distension
- Constipation
- Hypercalcaemia
- Alkalosis
Vitamin D
 Mode of action: regulates calcium homeostasis and bone metabolism
 Promotes bone mineralization
 Increasing intestinal absorption and renal reabsorption of calcium and phosphorous
 Forms available:
o Cholecalciferol (vit D3) – more effective
o Ergocalciferol (vit D2)
o Calcitriol
 Indications:
- Prevent vit D deficiency due to inadequate sunlight or diet
 Contraindications:
- Renal impairment
 Calcitriol – active metabolite of vitamin D – rapid onsent

Bisphosphonates
o Alendronate
o Clodronate
o Eitdronate
o Pamidronate
o Risedronate
o Tiludronate
o Zoledronic acid
 Synthetic analogue of pyrophosphate
 Decrease bone resorption by inhibiting osteoclasts, ATP enzymes
 Indications:
- 1st line treatment in postmenopausal osteoporosis
- Paget’s disease
- Hypocalcaemia of malignancy

Adverse effects
 Oesophagitis: oesophagel erosions, ulcers, gastritis, glossitis – must be taken with water before food
 Osteonecrosis of jaw

Denosumab
 Monoclonal antibody injection
 Decrease bone destruction and increase bone mass/strength
 Mode: anti-receptor activator of nuclear factor K B ligand antibody
 Indications: post menopausal osteo