Why is Fosamax (alendronate) not routinely prescribed for postmenopausal women with a history of osteoporosis?

Why Fosamax (Alendronate) IS Still Routinely Prescribed

Fosamax (alendronate) remains a first-line treatment for postmenopausal osteoporosis and is routinely prescribed—the premise of your question is incorrect. 1 The American College of Physicians strongly recommends bisphosphonates like alendronate as initial pharmacologic treatment to reduce fracture risk in postmenopausal women with osteoporosis, based on their favorable balance of benefits, harms, cost, and availability as generic formulations. 1

Why Alendronate Remains First-Line Therapy

Bisphosphonates have the most favorable risk-benefit profile among all osteoporosis medications. 1 The evidence supporting alendronate is robust:

• Vertebral fracture reduction: 45% relative risk reduction in both primary and secondary prevention settings 1, 2
• Hip fracture reduction: 53% relative risk reduction in secondary prevention (women with existing osteoporosis or prior fractures) 3
• Non-vertebral fracture reduction: 23% relative risk reduction in secondary prevention 3
• Cost advantage: Generic alendronate is substantially cheaper than alternatives like denosumab, romosozumab, or teriparatide 1

The Real Issue: Treatment Duration, Not Routine Use

The confusion likely stems from recommendations to STOP alendronate after 5 years in appropriate patients, not to avoid prescribing it initially. 1, 4 Here's the critical distinction:

Standard 5-Year Treatment Duration

• The American College of Physicians strongly recommends 5 years as the standard treatment duration for bisphosphonates 1, 4
• After 5 years, clinicians should reassess fracture risk and consider a drug holiday unless the patient has very high ongoing fracture risk 1, 4
• Extending treatment beyond 5 years reduces vertebral fractures but NOT other fracture types, while increasing risks of rare but serious adverse events 1, 4

Who Should Continue Beyond 5 Years

Patients with these high-risk features should continue treatment: 1, 4

• Previous hip or vertebral fractures during treatment
• Multiple non-spine fractures
• Hip BMD T-score ≤ -2.5 despite treatment
• Age >80 years
• Ongoing high-dose glucocorticoid use (≥7.5 mg prednisone daily)

Who Can Take a Drug Holiday After 5 Years

Patients without high-risk features can safely discontinue and be monitored: 1, 4

• No fractures during treatment
• Hip BMD T-score > -2.5 after treatment
• No ongoing glucocorticoid use
• Drug holidays of 3-5 years are supported by evidence 4

Rare But Serious Long-Term Risks (Why Duration Matters)

The risks that have generated concern are specifically associated with prolonged use BEYOND 5 years, not with standard-duration therapy: 1, 4

Atypical Femoral Fractures

• Incidence: 3.0-9.8 cases per 100,000 patient-years 1, 4
• Risk increases significantly after 5 years, escalating sharply beyond 8 years (from 1.78 to 113 per 100,000 person-years) 4
• Asian patients face up to 8 times higher risk than White patients 4
• Context: For every 1 atypical femoral fracture, alendronate prevents 162 osteoporotic fractures 4

Osteonecrosis of the Jaw

• Incidence: <1 case per 100,000 person-years with standard osteoporosis dosing 1, 4
• Risk increases with longer treatment duration 1
• Most consistent risk factor is recent dental surgery or tooth extraction 4
• Prevention: Complete dental work before initiating or continuing therapy 4, 5

Upper Gastrointestinal Events

• Esophageal ulceration can occur if dosing instructions are not followed 6, 7
• Prevention: Take with full glass of water (6-8 ounces), remain upright for at least 30 minutes, avoid food/drink during this period 4
• Contraindicated in patients with esophageal abnormalities or inability to stand/sit upright for 30 minutes 1, 6

Safety During Standard 5-Year Treatment

High to moderate certainty evidence shows alendronate results in no differences in serious adverse events or withdrawals due to adverse events during the standard 5-year treatment period. 1 The 2025 Cochrane review confirmed that alendronate may lead to little or no difference in gastrointestinal adverse events, with zero incidents of osteonecrosis of the jaw or atypical femoral fractures observed in primary prevention trials. 2

Clinical Algorithm for Alendronate Use

Initial Prescription (Year 0)

1. Confirm indication: T-score ≤ -2.5, or T-score -1.0 to -2.5 with FRAX showing ≥20% 10-year risk of major osteoporotic fracture or ≥3% hip fracture risk 1
2. Screen for contraindications: 5, 6
   • Creatinine clearance <35 mL/min (absolute contraindication)
   • Esophageal varices or portal hypertension (absolute contraindication)
   • Inability to stand/sit upright for 30 minutes
   • Hypocalcemia (correct before starting)
3. Complete dental examination and necessary dental work 4, 5
4. Ensure adequate calcium (1000-1200 mg/day) and vitamin D (800 IU/day) intake 1, 4, 5
5. Prescribe alendronate 70 mg once weekly 1, 6

Year 5 Reassessment

Assess for high-risk features: 1, 4

• Continue treatment if: previous hip/vertebral fractures, multiple non-spine fractures, hip T-score ≤ -2.5, age >80, ongoing glucocorticoids
• Consider drug holiday if: no fractures during treatment, hip T-score > -2.5, no high-risk features

During Drug Holiday (Years 5-10)

• Monitor clinically for new fractures 4
• Reassess fracture risk annually 4
• Restart alendronate if: new fracture occurs, fracture risk increases significantly, or BMD declines substantially 4

Common Pitfalls to Avoid

1. Do NOT automatically continue beyond 5 years without reassessing fracture risk - this exposes patients to unnecessary rare adverse events without proven additional benefit 1, 4

2. Do NOT perform routine BMD monitoring during the initial 5-year treatment - fracture reduction occurs even without BMD increases 1, 4

3. Do NOT switch to denosumab without specific indication - denosumab is second-line therapy reserved for patients with contraindications to bisphosphonates or renal impairment (CrCl <60 mL/min) 1, 5

4. NEVER discontinue denosumab without immediately starting bisphosphonate therapy within 6 months - rebound vertebral fractures can occur 4

5. Do NOT prescribe alendronate to patients with esophageal varices - risk of precipitating variceal hemorrhage from esophageal ulceration 5

Bottom Line

Alendronate IS routinely prescribed and remains the first-line treatment for postmenopausal osteoporosis. 1 What has changed is the recognition that treatment should be limited to 5 years in most patients, with continuation beyond that point reserved for those at very high ongoing fracture risk. 1, 4 This represents evidence-based optimization of treatment duration, not abandonment of the medication.