What are the recommended alendronate dosing regimens, administration guidelines, and contraindications for treating and preventing osteoporosis in post‑menopausal women, men, and glucocorticoid‑treated patients?

Alendronate Dosing for Osteoporosis

For postmenopausal osteoporosis treatment, prescribe alendronate 70 mg once weekly or 10 mg daily; for prevention, use 35 mg once weekly or 5 mg daily; and for glucocorticoid-induced osteoporosis, start with 5 mg daily (or 10 mg daily in postmenopausal women not on estrogen). 1

Standard Dosing Regimens

Treatment of Postmenopausal Osteoporosis

• 70 mg once weekly (preferred for convenience and compliance) 1, 2
• 10 mg once daily (therapeutically equivalent to weekly dosing) 1, 2
• Both regimens produce identical BMD increases (5.1–5.4% at lumbar spine over 12 months) and reduce vertebral fractures by 47–53% and hip fractures by 33–50% 3, 2
• Patient preference strongly favors weekly dosing: 84–86% of women prefer once-weekly over daily administration 4, 5

Prevention of Postmenopausal Osteoporosis

• 35 mg once weekly 3, 1
• 5 mg once daily 3, 1
• Use in women aged 40–60 years with osteopenia and risk factors 1

Treatment in Men with Osteoporosis

• 70 mg once weekly 1
• 10 mg once daily 1
• Produces 2.8% lumbar spine BMD increase at one year with weekly dosing 1

Glucocorticoid-Induced Osteoporosis

• 5 mg once daily for men and women receiving ≥7.5 mg/day prednisone equivalent 6, 1
• 10 mg once daily for postmenopausal women not receiving estrogen therapy (produces greater BMD gains: 4.1% vs 1.6% at lumbar spine compared to 5 mg) 1
• Oral bisphosphonates are first-line therapy over IV bisphosphonates, denosumab, or teriparatide 6

Administration Guidelines

Critical Instructions to Prevent Esophageal Injury

• Take first thing in the morning after overnight fast with plain water only (6–8 oz) 1
• Remain fully upright (sitting or standing) for at least 30 minutes after dosing 3, 1
• Do not lie down until after first food of the day 1
• Take at least 30 minutes before any food, beverage, or other medication 1

Concurrent Supplementation (Mandatory)

• Calcium: 1,000–1,200 mg daily 6, 3
• Vitamin D: 600–800 IU daily (target serum 25(OH)D ≥20–30 ng/mL) 6, 3
• For vitamin D deficiency (<30 ng/mL): ergocalciferol 50,000 IU weekly × 8 weeks, then recheck 3
• Never take calcium or vitamin D supplements simultaneously with alendronate—wait at least 30 minutes 1

Contraindications

Absolute Contraindications

• eGFR <35 mL/min/1.73 m² (drug accumulation risk, no safety data) 6, 3
• Esophageal abnormalities that delay esophageal emptying (stricture, achalasia) 3, 1
• Inability to stand or sit upright for ≥30 minutes 3, 1
• Hypocalcemia (must correct before initiating therapy) 3, 1
• Hypersensitivity to alendronate or any component 3, 1

Special Populations Requiring Caution

• Renal transplant recipients on chronic glucocorticoids: consult metabolic bone disease specialist to exclude renal osteodystrophy before starting bisphosphonates 3
• Active upper GI disease: history of peptic ulcer, gastritis, or esophagitis requires careful risk-benefit assessment 1

Treatment Duration and Monitoring

Standard Duration

• Treat for 5 years, then reassess fracture risk 3, 1
• Do not routinely monitor BMD during the initial 5-year period (patients benefit even without BMD increases) 3

After 5 Years of Therapy

• Low fracture risk: consider drug holiday after 3–5 years 3, 1
• High fracture risk (prior fracture, very low BMD, high FRAX score): continue therapy beyond 5 years 3
• Fracture protection persists up to 5 years after discontinuation 3

Treatment Failure and Switching

Criteria for Treatment Failure

• New osteoporotic fracture ≥12 months after starting alendronate 3
• Clinically significant BMD loss (greater than least significant change) after 1–2 years 3

Management of Treatment Failure

• Switch to alternative agent: IV bisphosphonate (zoledronic acid), denosumab, romosozumab, or parathyroid hormone analog (teriparatide, abaloparatide) 3
• Critical warning: Never switch directly from denosumab to teriparatide/abaloparatide (causes transient hip and spine BMD loss) 3
• Starting teriparatide after long-term bisphosphonate produces blunted but measurable anabolic response 3

Rare but Serious Adverse Effects

Medication-Related Osteonecrosis of the Jaw (MRONJ)

• Incidence: <1 to 28 cases per 100,000 person-years 3
• Risk increases after 2 years of therapy 3
• Preventive dental care recommended before starting therapy 3

Atypical Femoral Fractures

• Incidence: 3.0–9.8 cases per 100,000 patient-years 3
• Risk increases with duration beyond 5 years 3

Upper Gastrointestinal Events

• Abdominal pain, dyspepsia, acid regurgitation, esophageal ulceration reported 1, 7
• Once-weekly dosing shows trend toward fewer serious upper GI events compared to daily dosing 2
• No statistically significant difference in upper GI adverse events between alendronate and placebo in large trials 7

Common Pitfalls to Avoid

• Do not use in moderate-to-severe CKD (eGFR <35): risedronate is contraindicated at eGFR <30, but alendronate cutoff is <35 6, 3
• Do not start therapy with uncorrected hypocalcemia or vitamin D deficiency: check and correct before initiating 3
• Do not combine with calcium supplements at time of dosing: separates absorption by at least 30 minutes 1
• Do not prescribe to patients who cannot comply with upright positioning: esophageal injury risk is real 1
• Do not continue indefinitely without reassessment: reevaluate need after 3–5 years 3, 1