What are the recommended dosing, administration, monitoring, contraindications, and follow‑up for oral alendronate in post‑menopausal women or older men with osteoporosis (T‑score ≤ ‑2.5 or prior fragility fracture)?

Treatment Guidelines for Alendronate in Osteoporosis

Dosing and Administration

Alendronate 70 mg once weekly is the standard first-line oral bisphosphonate for postmenopausal women and older men with osteoporosis (T-score ≤ -2.5 or prior fragility fracture). 1, 2, 3

Specific Dosing Regimens

• Standard treatment: Alendronate 70 mg orally once weekly 1, 2, 3
• Alternative daily dosing: Alendronate 10 mg orally once daily (therapeutically equivalent to weekly dosing) 4
• Prevention dosing: Alendronate 35 mg once weekly or 5 mg daily for osteopenia with high fracture risk 2

Critical Administration Requirements

• Take on an empty stomach with 6-8 oz plain water only (no coffee, juice, or mineral water) first thing in the morning, at least 30 minutes before any food, beverage, or other medication 3, 4
• Remain fully upright (standing or sitting) for at least 30 minutes after taking the medication to prevent esophageal irritation and ensure proper drug delivery to the stomach 3, 4
• Do not lie down for at least 30 minutes after administration 4
• Patients unable to comply with these upright requirements should not receive oral alendronate and require alternative therapy 3

Mandatory Calcium and Vitamin D Supplementation

All patients on alendronate must receive calcium 1,000-1,200 mg daily and vitamin D 800-1,000 IU daily, as bisphosphonate efficacy is significantly reduced without adequate supplementation. 1, 2, 3, 5

• Target serum 25-hydroxyvitamin D level ≥20 ng/mL 2
• For documented vitamin D deficiency (<20 ng/mL), prescribe high-dose repletion: vitamin D₂ 50,000 IU weekly for 8-12 weeks followed by monthly dosing, or vitamin D₃ 2,000 IU daily for 12 weeks then 1,000-2,000 IU daily for maintenance 2
• Poor compliance with calcium and vitamin D supplementation is a major determinant of treatment failure and fracture occurrence during therapy 5

Contraindications

Absolute Contraindications

• Esophageal abnormalities that delay esophageal emptying (e.g., stricture, achalasia) 3, 4
• Inability to stand or sit upright for at least 30 minutes 3, 4
• Hypocalcemia (must be corrected before initiating therapy) 4
• Hypersensitivity to alendronate or any component 4

Relative Contraindications and Cautions

• Active upper gastrointestinal disease (esophagitis, gastritis, duodenitis, ulcers) requires careful risk-benefit assessment 4
• Severe renal impairment (creatinine clearance <35 mL/min) is not recommended due to lack of experience 4
• Dysphagia or swallowing difficulties warrant consideration of IV zoledronic acid instead 3

Baseline Evaluation and Monitoring

Pre-Treatment Assessment

• Serum calcium, phosphorus, 25-hydroxyvitamin D, alkaline phosphatase, parathyroid hormone, thyroid function, and renal function to detect secondary causes of osteoporosis (this panel has ~92% sensitivity for secondary causes) 2, 3
• Evaluate for secondary causes of bone loss: vitamin D deficiency, hypogonadism, glucocorticoid exposure, malabsorption disorders, hyperparathyroidism, hyperthyroidism, chronic alcohol or opioid misuse 2, 3
• Thoracic and lumbar spine radiographs or DXA with vertebral fracture assessment in patients reporting height loss to detect silent vertebral fractures 2

During Treatment Monitoring

• Do NOT monitor bone mineral density during the initial 5-year treatment period because bisphosphonates reduce fractures even when BMD does not increase or actually decreases, and routine monitoring provides no clinical benefit 1, 2, 3
• Monitor for clinical adverse events (gastrointestinal symptoms, musculoskeletal pain) at routine follow-up visits 4
• Assess treatment adherence at each visit, as poor compliance (≤50%) is a major determinant of inadequate response and fracture occurrence 5

Treatment Duration and Reassessment

Initial treatment duration is 5 years with alendronate, after which fracture risk must be reassessed to determine if continued therapy is warranted. 1, 2, 3

• After 5 years, patients at low fracture risk (no new fractures, stable or improved BMD, no high-risk features) may consider a drug holiday 2, 3
• Patients at continued high risk (T-score still ≤-2.5 at the hip, prior hip or vertebral fracture, multiple risk factors, or fracture during treatment) should continue therapy beyond 5 years 2, 3
• The risk of severe adverse effects (osteonecrosis of the jaw, atypical femoral fractures) increases with prolonged use, which is why treatment duration is limited and reassessment is required 2, 3

Efficacy Data

Alendronate reduces vertebral fractures by 47-56%, hip fractures by 50-53%, and nonvertebral fractures by 19-40% over 3-5 years in postmenopausal women with osteoporosis. 1, 6, 7

• In women with femoral neck T-score ≤-2.5, alendronate reduced clinical fractures by 36% (number needed to treat = 15) 7
• The relative risk reduction for fractures is constant across all age groups (55-85 years), without decline in older patients 6
• Absolute risk reduction increases with age due to higher baseline fracture risk: 65 fewer fractures per 10,000 patient-years in ages 55-65, increasing to 161 fewer fractures per 10,000 patient-years in ages 75-85 6
• In men with osteoporosis, alendronate increased lumbar spine BMD by 5.3% and reduced vertebral fractures, though data are more limited than in women 1, 4

Adverse Effects and Safety

High-certainty evidence from randomized trials shows bisphosphonates cause no difference in serious adverse events compared to placebo at 2-3 years. 1, 2

Common Adverse Effects (Generally Mild and Self-Limited)

• Upper gastrointestinal symptoms: dyspepsia (2.7-3.6%), abdominal pain (1.5-6.6%), acid regurgitation (1.1-4.2%), nausea (1.1-3.6%), constipation (0.8-3.1%) 4
• Musculoskeletal pain: bone, muscle, or joint pain (2.9-4.1%), muscle cramps (0.2-1.1%) 4
• Influenza-like symptoms, myalgias, arthralgias, and headaches are common but typically transient 2
• Mild, asymptomatic, transient decreases in serum calcium (18% of patients) and phosphate (10%) may occur but are clinically insignificant 4

Rare but Serious Adverse Effects

• Osteonecrosis of the jaw: extremely rare (1 case per treatment group in large trials) 1
• Atypical femoral fractures: rare (2-4 cases per 2000+ patients in large trials) 1
• Esophageal ulceration: rare but can occur, especially with non-compliance to upright positioning requirements 4
• One trial reported a statistically significant increase in gastrointestinal adverse events versus placebo, though pooled analyses show no overall difference 1

Cardiovascular Safety

• The 2025 USPSTF guideline notes that during year 1 of the ARCH trial, positively adjudicated serious cardiovascular adverse events were observed more often with romosozumab than with alendronate (2.5% vs. 1.9%), but this comparison is specific to romosozumab and does not indicate increased cardiovascular risk with alendronate itself 1

Lifestyle Modifications (Mandatory for All Patients)

All patients must implement weight-bearing exercise, resistance training, smoking cessation, alcohol limitation, fall prevention strategies, and maintain healthy body weight. 2, 3

• Weight-bearing aerobic activity (walking, jogging) for at least 30 minutes on ≥3 days per week 2
• Resistance and muscle-strengthening exercises to reduce fall risk 2
• Balance-training programs to further diminish fall likelihood, especially in older adults 2
• Smoking cessation (tobacco accelerates bone loss and increases fracture incidence) 1, 2, 3
• Limit alcohol to no more than 1-2 standard drinks per day 2, 3
• Maintain healthy body weight within recommended range 2, 3

Special Populations

Glucocorticoid-Induced Osteoporosis

• Alendronate 5 mg daily or 35 mg weekly is effective in patients receiving ≥7.5 mg/day prednisone or equivalent 4
• After 1 year, alendronate significantly increased lumbar spine BMD by 2.1-4.1% and prevented the BMD loss seen with placebo 4
• After 2 years, alendronate reduced new vertebral fractures by 93% (0.7% vs. 6.8% with placebo) 4

Men with Osteoporosis

• Alendronate 70 mg once weekly or 10 mg daily is effective in men with hypogonadal or idiopathic osteoporosis 1, 4
• At 1-2 years, alendronate increased lumbar spine BMD by 2.8-5.3%, femoral neck BMD by 1.9-2.6%, and reduced vertebral fractures 4
• Evidence is more limited than in postmenopausal women, with only 2 secondary prevention trials and 1 primary prevention trial available 1

Common Pitfalls and How to Avoid Them

• Failure to ensure upright positioning for 30 minutes: This is the most common cause of esophageal adverse events. Explicitly instruct patients to set a timer and remain standing or sitting upright 3, 4
• Taking with food, coffee, or other medications: This dramatically reduces absorption. Emphasize taking with plain water only, 30 minutes before anything else 4
• Inadequate calcium and vitamin D supplementation: Poor supplementation is a major determinant of treatment failure. Prescribe specific doses and verify compliance 2, 5
• Poor medication adherence: Compliance ≤50% significantly increases fracture risk during treatment. Address barriers to adherence at every visit 5
• Unnecessary BMD monitoring during treatment: This provides no clinical benefit and wastes resources. Reassess only after 5 years 1, 2, 3
• Continuing therapy indefinitely without reassessment: After 5 years, formally reassess fracture risk to determine if continued therapy is warranted, as prolonged use increases rare adverse effect risk 2, 3