Makindo Medical Notes

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

⚠️ Atypical femoral fractures have been reported with long-term bisphosphonate use. 💡 Ibandronic acid is a potent nitrogen-containing bisphosphonate used for osteoporosis and malignancy-related bone disease. It acts by inhibiting osteoclast-mediated bone resorption, thereby strengthening bone and lowering calcium in malignancy.

🧠 About

• Belongs to the bisphosphonate class of drugs that bind to hydroxyapatite in bone.
• Used both in osteoporosis and in oncology to control bone metastases and hypercalcaemia of malignancy.
• Has a higher binding affinity and longer skeletal half-life than alendronate or risedronate.
• Available as oral monthly and IV quarterly formulations for convenience and adherence.

⚙️ Mechanism of Action

• Bisphosphonates are synthetic analogues of pyrophosphate that strongly bind to bone surfaces undergoing resorption.
• Within osteoclasts, ibandronic acid inhibits farnesyl pyrophosphate synthase in the mevalonate pathway.
• This blocks prenylation of small GTP-binding proteins essential for osteoclast function and survival.
• Result → osteoclast apoptosis → reduced bone resorption → increased bone mineral density (BMD).

🎯 Indications and Typical Doses

• Postmenopausal osteoporosis: Ibandronic acid 150 mg orally once monthly, or 3 mg IV every 3 months (administer over 15–30 seconds).
• Bone metastases from breast cancer: Ibandronic acid 50 mg orally daily, or 6 mg IV every 3–4 weeks.
• Hypercalcaemia of malignancy: Ibandronic acid 2–4 mg as a single IV infusion (adjust to serum calcium).

⚠️ Administration

• Take on an empty stomach with a full glass of water (≥200 mL) after rising.
• Remain upright for ≥30 minutes and avoid eating or drinking (except water) during that time.
• Swallow tablets whole; do not chew or suck.
• Do not take at bedtime or before getting out of bed.
• Ensure adequate calcium and vitamin D intake.

🚫 Contraindications

• Oesophageal abnormalities (achalasia, strictures) or inability to remain upright for 30 minutes.
• Hypocalcaemia (must be corrected before therapy).
• Severe renal impairment (eGFR < 30 mL/min/1.73 m²).
• Known hypersensitivity to bisphosphonates.

⚠️ Cautions

• Assess renal function and calcium before each infusion.
• Dental check-up prior to long-term therapy due to risk of osteonecrosis of the jaw (ONJ).
• Reassess need for continuation after 5 years.
• Consider temporary discontinuation before major dental surgery or if atypical femoral fracture suspected.

💊 Interactions

• Reduced absorption with calcium, iron, magnesium, or antacids — separate by ≥30 minutes.
• Concurrent corticosteroids or chemotherapy may raise ONJ risk.
• See BNF for full list.

💥 Side Effects

• GI irritation: dyspepsia, nausea, abdominal pain, diarrhoea.
• Musculoskeletal pain, arthralgia, or transient flu-like reaction (esp. after IV dosing).
• Hypocalcaemia, hypophosphataemia.
• Headache, rash, urticaria.
• Rare: osteonecrosis of the jaw, atypical femoral fractures.

🩺 Monitoring

• Check calcium, phosphate, and renal function before each IV dose.
• Ensure ongoing calcium + vitamin D supplementation.
• Ask about jaw pain or thigh/groin discomfort (possible ONJ or atypical fracture).

💡 Teaching Tip

• Bisphosphonates act as “bone glue” — they embed in bone and disable osteoclasts as they resorb it.
• Explain to learners that all bisphosphonates share the same core mechanism, but ibandronate’s monthly schedule improves compliance.
• Mnemonic: I-BAND-your-bones — think of binding and strengthening.

📚 References

• BNF: Ibandronic Acid
• MHRA Drug Safety Update (2013): Long-term bisphosphonate therapy and atypical fractures
• NICE NG226: Osteoporosis — assessment and management (2023)
• Black DM et al., NEJM 2007;356:1809–1822 — Fracture risk reduction with Ibandronate.