Generic Name

Alendronate

Mechanism

• Alendronate binds to hydroxyapatite in bone and is selectively taken up by osteoclasts during bone‑resorption events.
• Inside osteoclasts, it inhibits farnesyl diphosphate synthase, blocking the mevalonate pathway and preventing prenylation of small GTP‑binding proteins.
• This disruption impairs osteoclast function and apoptosis, leading to reduced bone resorption and increased bone mineral density (BMD).

Pharmacokinetics

• Absorption: Oral uptake is low (~0.6 % bioavailability after 10–13 h fasting). Food or dairy products reduce absorption by 20–30 %.
• Distribution: 80–90 % of the absorbed drug binds strongly to bone; bone half‑life >10 years, providing long‑term skeletal deposition.
• Metabolism: No significant hepatic metabolism; drug is largely unchanged in systemic circulation.
• Excretion: Primarily renal (75–80 % recovered unchanged in urine).
• Half‑life: Plasma half‑life 10 years.
• Renal impairment: Dose adjustment required for CrCl < 35 mL/min; not recommended in dialysis patients.

Indications

• Post‑menopausal osteoporosis (primary).
• Glucocorticoid‑induced osteoporosis in men and women.
• Osteoporosis due to estrogen deficiency, rheumatoid arthritis, or chronic steroid therapy.
• Paget disease of bone (some indications).
• Prevention of vertebral fractures in patients at high fracture risk (FRAX ≥ 20 %).

Contraindications

• Poor esophageal motility (achalasia, strictures, severe GERD).
• Hypocalcemia—ensure Ca₂⁺/vitamin D supplementation before therapy.
• Renal impairment (CrCl < 35 mL/min) or use on dialysis.
• Active or post‑dental procedures; patients must undergo a dental exam prior to therapy.
• Pregnant or lactating women—avoid due to teratogenic risk.

Dosing

*Use the daily dose for rapid onset (e.g., fracture prevention) and the weekly dose for chronic maintenance to improve adherence.*

Adverse Effects

Common
• Gastrointestinal irritation (esophagitis, dysphagia, reflux).
• Headache, neck/back pain.
• Flu‑like symptoms, muscle aches.

Serious
• Esophageal ulceration/perforation.
• Osteonecrosis of the jaw (especially after dental extraction).
• Atypical femoral fractures (subtrochanteric or midshaft).
• Hypocalcemia (particularly in patients with low dietary calcium or vitamin D deficiency).
• Severe GI bleeding or ulceration.

Monitoring

• Baseline labs: Serum calcium, magnesium, phosphate, vitamin D, eGFR.
• Repeat calcium after 2–4 weeks to confirm repletion.
• Bone turnover markers (e.g., serum CTX) every 6 months if continuation > 2 yr.
• Annual DEXA scans (every 6–12 mo) to assess BMD improvements.
• Dental assessment prior to initiation and annually thereafter.
• Renal function reassessment every 3–6 months; adjust dose or discontinue if CrCl < 35 mL/min.

Clinical Pearls

1. Dose‑Equivalence – 70 mg weekly ≈ 10 mg daily; choose weekly dosing to enhance patient adherence without compromising efficacy.
2. Ergonomic Swallow – If swallowing difficulties arise, use a lubricating jelly and encourage a firm bite to keep the tablet down; avoid fluids that contain calcium.
3. Kidney Safety – For patients with mild‑to‑moderate CKD, the 10 mg daily dose is acceptable; the 70 mg weekly dose is contraindicated in CrCl < 35 mL/min.
4. "Hydration Window" – Maintain upright posture for at least 30 min post‑dose; avoid lying down for an additional 15–20 min to minimize reflux risk.
5. High‑Risk Patients – Use FRAX to screen for fracture risk; patients ≥ 60 yr with ≥ 2 risk factors (e.g., prior fracture, glucocorticoid use) benefit most from therapy.
6. Monitoring For ONJ – Schedule dental prophylaxis before therapy; patients should inform dentists of alendronate use to avoid invasive procedures during active therapy.
7. Risk of Atypical Fractures – Educate patients to report any new, persistent groin or thigh pain; consider drug holiday after ≥ 5 years of therapy or endogenous risk factors.

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