Makindo Medical Notes

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

Important: All major clinical trials showing the benefits of bisphosphonates in osteoporosis ensured that patients were concurrently receiving adequate oral calcium and vitamin D.

About: Always consult the latest BNF or equivalent guidelines for specific prescribing advice.

• Bisphosphonate therapy is one component of a comprehensive osteoporosis management plan, which includes falls assessment, lifestyle modifications (e.g., exercise, smoking cessation), and ensuring sufficient calcium/vitamin D intake.
• Atypical femoral fractures are rare but have been reported with prolonged (5+ years) bisphosphonate use. Periodically reassess the balance of risks and benefits, typically at the 5-year mark.

Precise Indications

• Postmenopausal Osteoporosis: Usually initiated in women with a T-score ≤ –2.5 or those with a significant fracture history or high fracture risk (e.g., based on FRAX or QFracture tools).
• Steroid-Induced Osteoporosis: Patients on chronic glucocorticoid therapy (e.g., ≥ 7.5 mg prednisone/day for ≥ 3 months) often warrant bisphosphonate prophylaxis, especially if they have additional risk factors (e.g., low BMD, older age).
• Paget’s Disease of Bone: To control excessive bone turnover and relieve pain or when bone expansion compromises function.
• Hypercalcaemia of Malignancy & Malignant Bone Disease: Reduces serum calcium levels and cancer-related skeletal events (e.g., fractures, bone pain).

Mode of Action

• Structurally, bisphosphonates replace the typical P–O–P bond of pyrophosphate with a P–C–P bond, which resists hydrolysis and binds strongly to bone mineral.
• Inhibits osteoclast activity, reducing bone resorption and increasing bone mineral density. This directly affects fracture risk reduction.
• Additional effects on the mevalonate pathway may also contribute to their antiresorptive properties.

Duration of Therapy

• Initial Course: Typically 3–5 years of continuous treatment for postmenopausal osteoporosis.
• Reassessment at 5 Years:
  • Low Risk (no new fractures, stable BMD): Bisphosphonate “drug holiday” may be considered to minimize atypical fracture risk.
  • Ongoing High Risk (new fractures, low BMD, other risk factors): Continue treatment longer or switch to an alternative therapy (e.g., denosumab, teriparatide), guided by specialist advice.
• Individualization: The decision to continue, stop, or switch therapy after 5 years depends on fracture history, BMD changes, and overall patient risk profile.

Indications (Detailed)

• Osteoporosis:
  • Postmenopausal: Alendronate, risedronate, ibandronate, zoledronic acid.
  • Steroid-induced: Often alendronate or risedronate if the patient is at high fracture risk or has a T-score < –1.5 (local protocols may vary).
• Fracture Risk Reduction:
  • Vertebral fractures: etidronate, alendronate, risedronate, ibandronate.
  • Hip fractures: alendronate, risedronate, ibandronate.
• Hypercalcaemia & Malignant Bone Disease: E.g., multiple myeloma, metastatic bone disease from breast cancer.
• Paget’s Disease: To reduce pain and control excessive osteoclastic activity.

Contraindications & Cautions

• Hypocalcaemia: Correct before initiating treatment.
• Severe Renal Impairment: (CKD stages 4–5) Typically avoid bisphosphonates or use with caution if eGFR < 30 mL/min/1.73m².
• Oesophageal Disorders: (e.g., strictures, achalasia) Oral bisphosphonates can cause oesophagitis; take upright with a full glass of water.
• Vitamin D Deficiency: Must be corrected prior to bisphosphonate therapy.
• Peptic Ulcer Disease: Use cautiously; consider an alternative if severe.
• Osteonecrosis of the Jaw (ONJ): Rare but more common with high-dose IV bisphosphonates in cancer patients. Complete any necessary dental procedures before starting therapy.
• Pregnancy & Pediatrics: Generally contraindicated.