When should alendronate (bisphosphonate) be stopped in a patient with a history of osteoporosis?

When to Stop Alendronate

Stop alendronate after 5 years of treatment in most patients, then reassess fracture risk to determine if a drug holiday is appropriate or if continuation is needed for those at very high ongoing risk. 1, 2

Standard Treatment Duration

• The American College of Physicians strongly recommends 5 years as the standard treatment duration for alendronate therapy. 1, 2
• Evidence shows that extending treatment beyond 5 years reduces vertebral fractures but does NOT reduce hip or other non-vertebral fractures, while increasing the risk of rare but serious adverse events. 1
• The FLEX trial demonstrated that women who discontinued alendronate after 5 years had only a modest increase in clinical vertebral fractures (5.3% vs 2.4%) but no difference in non-vertebral or hip fractures over the subsequent 5 years. 1, 3

Risk Stratification After 5 Years: Who Should Continue vs. Stop

High-Risk Patients Who Should Continue Beyond 5 Years:

• Previous hip or vertebral fractures during treatment 1
• Multiple non-spine fractures 1
• Hip BMD T-score ≤ -2.5 despite treatment 1
• Age >80 years 1
• Ongoing high-dose glucocorticoid use (≥7.5 mg prednisone daily) 1, 4
• Significant bone loss (≥10% per year) despite bisphosphonate therapy 1
• Fracture occurring after ≥18 months of adequate bisphosphonate treatment 1

Patients Eligible for Drug Holiday After 5 Years:

• No previous hip or vertebral fractures during treatment 1
• Hip BMD T-score > -2.5 after treatment 1
• No multiple non-spine fractures 1
• Age <80 years without other high-risk features 1

Increasing Risk of Serious Adverse Events with Prolonged Use

Atypical Femoral Fractures:

• Risk begins to increase significantly after 5 years of treatment, escalating sharply beyond 8 years. 1
• Incidence ranges from 3.0 to 9.8 cases per 100,000 patient-years, increasing with duration. 1, 4
• Asian patients face up to 8 times higher risk than White patients (595 vs 109 per 100,000 person-years). 1
• If an atypical femur fracture occurs, stopping bisphosphonates reduces contralateral fracture risk from 25%. 1

Osteonecrosis of the Jaw (ONJ):

• Incidence is very rare at <1 case per 100,000 person-years with osteoporosis dosing, but risk increases with duration beyond 5 years. 5, 1, 4
• The most consistent risk factor is recent dental surgery or tooth extraction. 5, 4
• Complete all dental work before continuing bisphosphonates beyond 5 years. 5, 1, 4

Monitoring During Drug Holiday

• Do NOT perform routine BMD monitoring during the initial 5-year treatment period. 1, 2
• During a drug holiday, reassess patients regularly for new fractures, changes in fracture risk profile, and BMD changes (particularly femoral neck T-score). 1
• Age and hip BMD at discontinuation predict clinical fractures during the subsequent 5 years; follow-up DXA measurements 1 year after discontinuation are NOT associated with fracture risk. 6
• Resume bisphosphonate therapy if a new fracture occurs during the holiday, fracture risk increases significantly, or BMD remains low (femoral neck T-score ≤ -2.5). 1

Duration of Drug Holiday

• Alendronate has a prolonged skeletal effect after discontinuation; BMD remains higher and bone turnover reduction persists compared to baseline values. 3
• Drug holidays of 3-5 years are supported by evidence for alendronate. 1
• High-risk patients should have shorter holidays (1-2 years maximum) and a lower threshold for restarting. 1

Essential Concurrent Measures

• Ensure adequate calcium (1000-1200 mg/day) and vitamin D (800 IU/day) supplementation throughout treatment and during drug holidays. 1, 2
• Vitamin D deficiency should be corrected prior to bisphosphonate initiation, as deficiency may attenuate efficacy and increase risk of bisphosphonate-related hypocalcemia. 5
• Proper alendronate administration is crucial: take with a full glass of water (6-8 ounces), remain upright for at least 30 minutes, and avoid food/drink during this period. 1, 4

Special Populations Requiring Earlier Discontinuation

• Discontinue alendronate in patients with creatinine clearance <35 mL/min; consider switching to denosumab for CrCl <60 mL/min. 1, 4
• Elderly patients with multiple comorbidities, polypharmacy, poor adherence, or gastrointestinal conditions may benefit from discontinuation after 5 years. 2

Critical Pitfall to Avoid

Never discontinue denosumab without immediately starting bisphosphonate therapy within 6 months, as denosumab discontinuation causes rebound vertebral fractures. This recommendation does NOT apply to alendronate, which has persistent skeletal effects after discontinuation. 1