Introduction
Fosamax (alendronate sodium) is a bisphosphonate medication primarily used for the treatment and prevention of osteoporosis. It was the first bisphosphonate approved by the FDA for osteoporosis management and remains a cornerstone therapy for bone disorders characterized by increased bone resorption.
Mechanism of Action
Alendronate works by inhibiting osteoclast-mediated bone resorption. As a bisphosphonate, it binds to hydroxyapatite crystals in bone tissue, particularly at sites of active bone remodeling. Once incorporated into bone, alendronate is internalized by osteoclasts during resorption, where it inhibits farnesyl pyrophosphate synthase in the mevalonate pathway. This disruption of the cholesterol biosynthesis pathway prevents prenylation of GTP-binding proteins essential for osteoclast function, ultimately leading to osteoclast apoptosis and reduced bone turnover.
Indications
- Treatment of osteoporosis in postmenopausal women
- Treatment to increase bone mass in men with osteoporosis
- Treatment of glucocorticoid-induced osteoporosis in men and women
- Treatment of Paget's disease of bone
- Prevention of osteoporosis in postmenopausal women
Dosage and Administration
Standard dosing:- Osteoporosis treatment: 10 mg daily or 70 mg once weekly
- Osteoporosis prevention: 5 mg daily or 35 mg once weekly
- Paget's disease: 40 mg daily for 6 months
- Take with plain water only (6-8 oz) at least 30 minutes before first food, beverage, or medication
- Remain upright (sitting or standing) for at least 30 minutes after administration
- Do not crush, chew, or suck tablets
- Avoid lying down for at least 30 minutes after dose
- Renal impairment: Not recommended if CrCl <35 mL/min
- Hepatic impairment: No dosage adjustment needed
- Geriatric: No dosage adjustment needed
Pharmacokinetics
Absorption: Oral bioavailability is approximately 0.6-0.7% when taken fasting. Food, coffee, orange juice, and other beverages significantly reduce absorption. Distribution: Approximately 78% of absorbed drug binds to bone, with the remainder excreted unchanged in urine. Plasma protein binding is approximately 78%. Metabolism: No hepatic metabolism; not metabolized by cytochrome P450 enzymes. Elimination: Half-life in plasma is approximately 0.5-1 hour, but the terminal half-life from bone exceeds 10 years. Renal excretion of unabsorbed drug is rapid.Contraindications
- Hypersensitivity to alendronate or any component of the formulation
- Abnormalities of the esophagus that delay emptying (stricture, achalasia)
- Inability to stand or sit upright for at least 30 minutes
- Hypocalcemia
- Severe renal impairment (CrCl <35 mL/min)
Warnings and Precautions
Esophageal reactions: Risk of esophageal ulceration, erosion, and stricture. Discontinue use if new or worsening dysphagia, odynophagia, or retrosternal pain develops. Osteonecrosis of the jaw: Rare but serious complication, particularly after dental procedures. Complete preventive dentistry before starting therapy when possible. Atypical femoral fractures: Low-energy subtrochanteric and diaphyseal fractures reported with long-term use. Hypocalcemia: Must be corrected before initiating therapy. Renal impairment: Use caution in patients with CrCl 35-60 mL/min. Musculoskeletal pain: Severe bone, joint, and/or muscle pain may occur.Drug Interactions
- Calcium supplements, antacids, and mineral supplements: Significantly reduce absorption (administer at least 30 minutes apart)
- Aspirin and NSAIDs: Increased risk of gastrointestinal irritation
- Proton pump inhibitors: May reduce efficacy due to altered gastric pH
- Intravenous bisphosphonates: Additive effects on bone metabolism
Adverse Effects
Common (>10%): Abdominal pain, dyspepsia, constipation, diarrhea, musculoskeletal pain Less common (1-10%): Nausea, esophageal ulcer, headache, acid regurgitation Rare (<1%): Osteonecrosis of the jaw, atypical femoral fractures, hypocalcemia, uveitis, scleritis Post-marketing reports: Severe skin reactions, esophagitis, esophageal strictureMonitoring Parameters
- Bone mineral density (baseline and every 1-2 years)
- Serum calcium and 25-hydroxyvitamin D levels (baseline and periodically)
- Renal function (baseline and annually)
- Height measurement (annually)
- Signs/symptoms of esophageal irritation
- Dental examination (regularly, especially before invasive procedures)
- Assessment of musculoskeletal pain
Patient Education
- Take first thing in the morning with plain water only
- Remain upright for at least 30 minutes after dose
- Do not eat, drink, or take other medications for at least 30 minutes
- Report any difficulty swallowing, pain when swallowing, or new chest pain
- Report any thigh or groin pain
- Maintain adequate calcium (1200-1500 mg/day) and vitamin D (800-1000 IU/day) intake
- Practice weight-bearing exercise as appropriate
- Inform dentist of alendronate use before any dental procedures
- Do not stop medication without consulting healthcare provider
References
1. FDA Prescribing Information: Fosamax (alendronate sodium) 2. Rosen CJ. Postmenopausal osteoporosis. N Engl J Med. 2005;353(6):595-603 3. Black DM, et al. Fracture risk reduction with alendronate in women with osteoporosis. J Clin Endocrinol Metab. 2000;85(11):4118-4124 4. Bone HG, et al. Ten years' experience with alendronate for osteoporosis in postmenopausal women. N Engl J Med. 2004;350(12):1189-1199 5. Watts NB, et al. Insights from the Fracture Intervention Trial. Endocr Pract. 2000;6(2):127-133 6. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the diagnosis and treatment of postmenopausal osteoporosis. Endocr Pract. 2016;22(Suppl 4):1-42