Makindo Medical Notes

Related Subjects: |Calcium Physiology |Hypercalcaemia |Hypophosphataemia |Hyperphosphataemia |Bisphosphonates |Osteoporosis |Osteonecrosis of the jaw

Important: All major trials showing bisphosphonate benefits in osteoporosis ensured patients had adequate calcium & vitamin D. 💡 In UK practice, NICE recommends checking vitamin D and calcium status before starting therapy.

📖 About

• Bisphosphonates are first-line agents in osteoporosis prevention and treatment, usually combined with falls risk assessment, exercise, smoking cessation, and calcium/vitamin D optimisation.
• They are also used in metabolic bone disease (Paget’s), and in oncology for hypercalcaemia of malignancy and skeletal protection in metastatic disease.
• Reassess therapy duration at ~5 years to balance benefits against rare risks (e.g., atypical femoral fracture, osteonecrosis of the jaw).

🧩 Precise Indications

• Postmenopausal osteoporosis: Women with T-score ≤ –2.5, fragility fracture history, or high risk on FRAX/QFracture.
• Steroid-induced osteoporosis: Adults on ≥7.5 mg prednisolone equivalent for ≥3 months with additional risk factors. Alendronate or risedronate are NICE-recommended first choices.
• Paget’s disease of bone: Symptomatic disease or complications (bone pain, deformity, high turnover).
• Hypercalcaemia of malignancy / malignant bone disease: IV bisphosphonates reduce serum calcium and skeletal events (e.g. fractures, spinal cord compression).

⚙️ Mode of Action

• Bisphosphonates mimic pyrophosphate, binding strongly to hydroxyapatite in bone.
• Inhibit osteoclast recruitment, adhesion, and survival → ↓ bone resorption → ↑ bone mineral density.
• Nitrogen-containing bisphosphonates (e.g. alendronate, zoledronic acid) also inhibit the mevalonate pathway, impairing osteoclast function.

⏳ Duration of Therapy

• Standard initial course: 3–5 years in postmenopausal osteoporosis.
• Reassess at 5 years:
  • Low risk: consider a “drug holiday.”
  • High risk: continue or switch to alternative (denosumab, teriparatide).
• Review based on BMD, fracture history, age, and co-morbidity.

💊 Common UK Indications (with agents)

• Osteoporosis:
  • First-line: Alendronate (weekly PO), risedronate (weekly PO).
  • Alternative if intolerance: Ibandronate (monthly PO or IV), zoledronic acid (IV yearly infusion).
• Fracture risk reduction: Alendronate and risedronate reduce both vertebral and hip fractures; ibandronate primarily reduces vertebral risk.
• Paget’s disease: Zoledronic acid often preferred due to potency and convenience.
• Oncology: Zoledronic acid or pamidronate for malignant hypercalcaemia and prevention of skeletal events in metastatic bone disease.

🚫 Contraindications & Cautions

• Hypocalcaemia: must be corrected before therapy.
• Renal impairment: avoid if eGFR < 30 mL/min/1.73m² (dose adjust/avoid depending on agent).
• Oesophageal disease: oral agents contraindicated in achalasia, strictures, dysphagia.
• Vitamin D deficiency: treat before starting.
• Peptic ulcer disease: caution with oral therapy.
• Osteonecrosis of the jaw (ONJ): risk ↑ with IV therapy, especially in cancer. Complete major dental work before starting.
• Pregnancy and children: generally contraindicated.

💡 Administration Advice (Oral Bisphosphonates)

• Take first thing in the morning on an empty stomach with a full glass of water.
• Remain upright and avoid food/drink/other meds for at least 30 minutes (60 min for ibandronate).
• This minimises risk of oesophagitis and optimises absorptio