Makindo Medical Notes

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

⚠️ Atypical femoral fractures are rare but have been reported with prolonged bisphosphonate use. 💡 Always reassess therapy duration after 5 years to weigh benefits versus risks. 🦴 Risedronate is a potent oral bisphosphonate that reduces bone resorption by inhibiting osteoclasts, thereby preventing fragility fractures in osteoporosis.

🧠 About

• Risedronate is a nitrogen-containing bisphosphonate used to strengthen bone and reduce fracture risk.
• Acts as an antiresorptive agent in conditions with high bone turnover — especially postmenopausal and glucocorticoid-induced osteoporosis.
• Reduces both vertebral and non-vertebral fractures, including the hip, when taken correctly.
• Best used as part of a comprehensive plan with fall prevention, exercise, and adequate calcium/vitamin D intake.

⚙️ Mechanism of Action

• Bisphosphonates bind to hydroxyapatite in bone, where they are ingested by osteoclasts during bone resorption.
• Within osteoclasts, risedronate inhibits the enzyme farnesyl pyrophosphate synthase in the mevalonate pathway.
• This blocks prenylation of small GTPase signalling proteins, leading to osteoclast apoptosis and decreased bone resorption.
• Result: improved bone mass and microarchitecture with reduced fracture risk.

🎯 Indications & Dosing

• Treatment of postmenopausal osteoporosis: 5 mg once daily or 35 mg once weekly to reduce vertebral and hip fracture risk.
• Prevention of corticosteroid-induced osteoporosis: 5 mg once daily (in postmenopausal women or men at high risk).
• Paget’s disease of bone: 30 mg once daily for 2 months (off-label in some settings).

⚠️ Administration Guidance

• Take on an empty stomach with a full glass of water (≥200 mL) immediately after rising in the morning.
• Do not lie down or eat/drink anything (except water) for 30 minutes after ingestion to prevent oesophageal irritation.
• Swallow tablets whole — do not chew or suck.
• Never take at bedtime or before getting up in the morning.
• Ensure adequate dietary calcium and vitamin D; supplement if needed.

🚫 Contraindications

• Oesophageal disorders (achalasia, strictures) or inability to remain upright for ≥30 minutes.
• Hypocalcaemia — correct before starting treatment.
• Severe renal impairment (eGFR <30 mL/min/1.73m²).

⚠️ Cautions

• Assess renal function before treatment initiation.
• Dental check-up recommended before starting long-term bisphosphonate therapy (risk of ONJ).
• Re-evaluate the need for continuation after 5 years.
• Discontinue temporarily before major dental or maxillofacial surgery.

💊 Interactions

• Absorption markedly reduced by food, calcium, iron, magnesium, or antacids — avoid taking within 30 minutes of these substances.
• Concurrent corticosteroids increase risk of osteonecrosis of the jaw.
• See BNF for detailed interaction data.

💥 Side Effects

• GI upset — nausea, dyspepsia, abdominal pain, or diarrhoea.
• Musculoskeletal pain or arthralgia.
• Headache, fatigue.
• Rare: oesophagitis, gastritis, osteonecrosis of the jaw, atypical femoral fractures with prolonged use.

🩺 Monitoring

• Check calcium, vitamin D, and renal function before initiation.
• Review therapy annually; consider “drug holiday” after 5 years in low-risk patients.
• Ask about thigh or groin pain (may precede atypical femur fracture).

💡 Teaching Tip

• Bisphosphonates act as “bone stabilisers” — imagine them sticking like cement to bone surfaces where osteoclasts normally resorb.
• They do not form new bone; they slow down bone loss so osteoblasts can catch up.
• Explain to learners how the nitrogen group (in risedronate, alendronate) increases potency by inhibiting the mevalonate pathway.
• Mnemonic: “RISE your bone density with Risedronate.”

📚 References

• BNF: Risedronate Sodium
• MHRA Drug Safety Update (2013): Atypical femoral fractures and ONJ with long-term bisphosphonate therapy
• NICE NG226: Osteoporosis: assessment and management (2023)
• Black DM et al. NEJM 2006;355:205–215 — Bisphosphonate efficacy and safety.