What is the recommended treatment with Fosamax (alendronate) for postmenopausal women and older adults with osteoporosis at high risk of fractures?

Fosamax (Alendronate) for Osteoporosis Treatment

Alendronate is the first-line pharmacologic treatment for postmenopausal women and older adults with osteoporosis at high risk of fractures, with a strong recommendation based on high-certainty evidence. 1, 2

Indications and Patient Selection

Initiate alendronate in the following populations:

• Postmenopausal women with T-score ≤ -2.5 on DEXA scan 1, 3
• Patients with T-score between -1.0 and -2.5 who have 10-year risk of major osteoporotic fracture ≥20% or hip fracture risk ≥3% by FRAX calculation 1
• Patients with history of low-trauma fracture, even without osteoporosis on DEXA 1
• Men with primary osteoporosis (conditional recommendation, low-certainty evidence) 1
• Men and women with glucocorticoid-induced osteoporosis receiving ≥7.5 mg prednisone equivalent daily 4

Dosing Regimens

Choose one of the following FDA-approved dosing schedules: 4

• 70 mg once weekly (most commonly prescribed for convenience) 2
• 10 mg once daily 2
• 35 mg once weekly for prevention in postmenopausal women 1
• 5 mg once daily for prevention 1

Administration Instructions to Prevent Esophageal Complications

Critical administration requirements to reduce upper GI adverse events: 4

• Take after overnight fast, first thing in the morning 4
• Swallow with full 8-ounce glass of plain water only (no coffee, juice, or other beverages) 4
• Remain upright (standing or sitting) for at least 30 minutes after taking the medication 1, 4
• Do not lie down for at least 30 minutes 1
• Do not eat or drink anything else for at least 30 minutes after administration 4

Contraindications

Do not prescribe alendronate in patients with: 1

• Abnormalities of the esophagus (stricture, achalasia) 1
• Inability to stand or sit upright for at least 30 minutes 1
• Hypocalcemia (must be corrected before initiating therapy) 1
• Hypersensitivity to alendronate 1

Essential Adjunctive Therapy

All patients must receive adequate supplementation: 3, 2

• Calcium: 1,000-1,200 mg daily 3, 2
• Vitamin D: 600-1,000 IU daily 3, 2

Efficacy Data

Alendronate reduces fracture risk with high-certainty evidence: 1

• Hip fractures: 6 fewer events per 1,000 patients 1
• Clinical vertebral fractures: 18 fewer events per 1,000 patients 1
• Any clinical fracture: 24 fewer events per 1,000 patients 1
• Radiographic vertebral fractures: 56 fewer events per 1,000 patients 1

The Fracture Intervention Trial demonstrated that 3 years of alendronate treatment reduces all clinically relevant fractures, including hip fractures, by approximately 50% for vertebral fractures and 30% for all clinical fractures. 5, 6

Treatment Duration and Drug Holidays

Initial treatment duration should be 5 years, followed by reassessment: 3, 2

• After 5 years of oral bisphosphonate therapy, reassess fracture risk 2
• Low-to-moderate risk patients: Consider drug holiday after 5 years 2
• High-risk patients: Continue treatment up to 10 years for oral bisphosphonates before reassessment 2
• During drug holiday, reassess fracture risk annually or biannually and evaluate for new fractures clinically 2

High-risk criteria warranting continued therapy beyond 5 years include: 2

• Age >74 years 2
• Recent fracture within 12 months 2
• Multiple prior osteoporotic fractures 2
• T-score ≤ -3.0 2
• Fractures despite ongoing bisphosphonate therapy 2

Safety Profile and Adverse Events

Common adverse events (generally well-tolerated): 4

• Upper GI symptoms: abdominal pain (6.6%), dyspepsia (3.6%), nausea (3.6%), acid regurgitation (2.0%) 4
• Musculoskeletal pain (4.1%) 4
• No statistically significant difference in serious adverse events compared to placebo in randomized controlled trials 4

Rare but serious adverse events (from observational studies, low-certainty evidence): 1

• Osteonecrosis of the jaw: 0.01% to 0.3% incidence, increased risk after 2-3 years of use (adjusted risk ratio 3.4) 1
• Atypical femoral fractures: increased risk after 8 years of use 1, 3

Important safety note: High-certainty evidence from randomized controlled trials showed no differences between alendronate and placebo in serious adverse events and withdrawals due to adverse events at 3 years. 1 The rare serious adverse events were identified primarily through observational studies with longer follow-up. 1

Rationale for First-Line Status

Alendronate is preferred as first-line therapy because: 1, 2

• Most favorable balance of benefits, harms, patient values, and cost among all osteoporosis medications 1
• Available as generic formulation, making it substantially more affordable than denosumab or anabolic agents 1, 3, 2
• High-certainty evidence for fracture reduction 1
• Long-term safety data up to 5 years from randomized controlled trials 4, 7

Second-Line Alternatives

If alendronate is contraindicated or not tolerated, consider: 1, 2

• Denosumab 60 mg subcutaneously every 6 months (conditional recommendation, moderate-certainty evidence for postmenopausal women) 1, 2
• Other bisphosphonates: risedronate or zoledronic acid 1, 2

Critical warning about denosumab: Never discontinue denosumab without immediately transitioning to bisphosphonate therapy, as discontinuation causes severe rebound bone loss and multiple vertebral fractures. 2

Very High-Risk Patients

For patients at very high fracture risk, consider anabolic agents before bisphosphonates: 2, 8

• Teriparatide or romosozumab may be used first-line in very high-risk patients 2, 8
• Mandatory sequential therapy: After completing anabolic therapy, patients must immediately transition to alendronate or another bisphosphonate to maintain bone density gains 2, 8

Common Pitfalls to Avoid

• Do not prescribe alendronate solution to patients at increased risk of aspiration 1
• Do not allow patients to lie down within 30 minutes of taking alendronate, as this significantly increases risk of esophageal ulceration 1, 4
• Do not continue bisphosphonates indefinitely without reassessment—evaluate need for drug holiday at 5 years in low-to-moderate risk patients 2
• Do not confuse bisphosphonate drug holidays with denosumab discontinuation—denosumab requires immediate transition to bisphosphonate, never a drug holiday 2
• Do not initiate alendronate in patients with uncorrected hypocalcemia 1