What are the risks of taking Fosamax (alendronate) for a healthy 65-year-old postmenopausal woman with osteopenia?

Risks of Fosamax (Alendronate) in a Healthy 65-Year-Old with Osteopenia

For a healthy 65-year-old woman with osteopenia, the American College of Physicians recommends an individualized approach to starting bisphosphonate therapy, as the benefits must be carefully weighed against potential harms and costs based on baseline fracture risk 1.

Key Context: Osteopenia vs. Osteoporosis

The critical distinction here is that osteopenia (T-score between -1.0 and -2.5) represents lower fracture risk than osteoporosis (T-score ≤ -2.5), and Fosamax is FDA-approved for treatment of osteoporosis and prevention of osteoporosis in postmenopausal women, but evidence for treating osteopenia specifically is limited 2, 1.

Low-quality evidence from post-hoc analysis suggests that risedronate (a similar bisphosphonate) may reduce fracture risk in women with advanced osteopenia near the osteoporosis threshold (T-score approaching -2.5), with a 73% relative risk reduction 1. However, women with mild osteopenia (T-score between -1.0 and -1.5) will benefit substantially less than those with severe osteopenia 1.

Common Gastrointestinal Risks

The most frequent adverse effects involve the upper gastrointestinal tract:

• Abdominal pain occurs in 3.7-6.6% of patients (compared to 3.0-4.8% with placebo) 2
• Dyspepsia affects 2.7-3.6% of patients 2
• Acid regurgitation, nausea, and constipation are reported in 1-4% of patients 2
• Esophageal ulceration is a serious concern, particularly in patients who don't follow proper administration instructions (taking with full glass of water, remaining upright for 30 minutes, avoiding food/drink during this period) 3, 2

The FDA label notes that in large clinical trials, no statistically significant differences in upper GI adverse events were found between alendronate and placebo, though post-marketing surveillance has reported esophageal complications 2, 4.

Rare but Serious Long-Term Risks

Osteonecrosis of the Jaw (ONJ)

• Incidence is very rare at <1 case per 100,000 person-years with osteoporosis dosing 3, 5
• The most consistent risk factor is recent dental surgery or tooth extraction 3
• Risk increases with cumulative exposure beyond 5 years 3
• Complete necessary dental work before initiating therapy to minimize this risk 3, 5

Atypical Femoral Fractures

• Incidence ranges from 3.0 to 9.8 cases per 100,000 patient-years 3, 5
• Risk begins to increase significantly after 5 years of treatment and escalates sharply beyond 8 years 3
• Asian patients face up to 8 times higher risk (595 vs 109 per 100,000 person-years in White patients) 3
• Despite this risk, an estimated 162 osteoporosis-related fractures are prevented for every one atypical femoral fracture associated with treatment 3

Atrial Fibrillation

• Some trials have shown association with bisphosphonates, though insufficient evidence exists to establish clear causality 1, 3
• The USPSTF analysis found no clear evidence of association 3

Treatment Duration Considerations

The optimal duration has not been definitively established, but the American College of Physicians strongly recommends 5 years as the standard treatment duration 3, 2:

• All patients should have the need for continued therapy re-evaluated periodically 2
• Patients at low risk for fracture should be considered for drug discontinuation after 3 to 5 years 2
• Evidence shows that increasing duration beyond 5 years probably reduces vertebral fractures but not other fractures, while increasing long-term harm risk 3

Risk-Benefit Analysis for Osteopenia

For a healthy 65-year-old with osteopenia, the decision hinges on several factors:

Factors favoring treatment:

• T-score approaching -2.5 (severe osteopenia) 1
• Additional risk factors: low body weight (<70 kg), prior fracture history, family history of fractures, smoking, decreased physical activity 1
• FRAX score indicating high 10-year fracture risk 3

Factors favoring observation:

• T-score between -1.0 and -1.5 (mild osteopenia) 1
• Age 65 without additional risk factors 1
• No prior fractures 1

Common Pitfalls to Avoid

• Do not automatically start bisphosphonates for all women with osteopenia at age 65 - the evidence supports individualized assessment based on fracture risk profile 1
• Do not continue treatment beyond 5 years without reassessing fracture risk, as this exposes patients to unnecessary rare adverse events without proven additional benefit in low-risk individuals 3, 2
• Ensure proper administration technique to minimize esophageal complications: full glass of water, remain upright 30 minutes, no food/drink during this period 3, 2
• Ensure adequate calcium (1000-1200 mg/day) and vitamin D (800 IU/day) intake throughout treatment 3, 5
• Correct vitamin D deficiency prior to initiating therapy, as deficiency may attenuate efficacy and increase risk of hypocalcemia 3