When is it appropriate to stop alendronate (bisphosphonate) in a patient with osteoporosis?

When to Stop Alendronate in Osteoporosis

After 5 years of alendronate treatment, most patients should stop therapy and begin a drug holiday unless they have very high-risk features including previous hip or vertebral fractures during treatment, T-score ≤ -2.5 at the hip, age >80 years, or ongoing glucocorticoid use. 1, 2

Standard Treatment Duration

• The American College of Physicians strongly recommends 5 years as the standard treatment duration for alendronate therapy. 1, 2
• This recommendation is based on evidence showing that extending treatment beyond 5 years reduces vertebral fractures but NOT hip or non-vertebral fractures, while increasing the risk of rare but serious adverse events including osteonecrosis of the jaw and atypical femoral fractures. 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 for Continuation vs. Drug Holiday

High-risk patients who should continue beyond 5 years: 1

• Previous hip or vertebral fractures occurring during treatment
• Multiple non-spine fractures
• Hip BMD T-score ≤ -2.5 despite treatment
• Age >80 years
• Ongoing glucocorticoid use (≥7.5 mg prednisone daily)
• Significant bone loss (≥10% per year) despite therapy

Low-to-moderate risk patients eligible for drug holiday: 1

• No fractures during treatment
• Hip BMD T-score > -2.5 after treatment
• Age <80 years
• No ongoing glucocorticoid use

Duration of Drug Holiday

• Drug holidays for oral alendronate can safely last 3-5 years in appropriate patients. 1
• During the drug holiday, BMD remains higher and bone turnover markers remain lower than pretreatment baseline levels, demonstrating persistent skeletal effects of alendronate. 4, 3
• The rate of bone loss during the holiday resumes at the background rate without accelerated loss or marked increase in bone turnover. 4

Monitoring During Drug Holiday

• Do NOT perform routine BMD monitoring during the initial 5-year treatment period. 1, 2
• During the drug holiday, reassess patients regularly for new fractures clinically, changes in fracture risk profile, and consider BMD measurement (particularly femoral neck T-score). 1
• Resume bisphosphonate therapy if: 1
  • A new fracture occurs during the holiday
  • Fracture risk increases significantly (new risk factors emerge)
  • BMD declines substantially (femoral neck T-score ≤ -2.5)

Critical Safety Considerations

Increasing risks with prolonged use beyond 5 years: 1, 5

• Osteonecrosis of the jaw incidence: <1 case per 100,000 person-years with standard dosing, but risk increases with duration beyond 5 years
• Atypical femoral fractures: 3.0-9.8 cases per 100,000 patient-years, with risk beginning to increase significantly after 5 years and escalating sharply beyond 8 years
• Asian patients face up to 8 times higher risk for atypical femoral fractures than White patients

Before stopping alendronate: 1

• Complete any necessary dental work before initiating or continuing therapy, as osteonecrosis of the jaw risk increases with cumulative exposure
• Ensure adequate calcium (1000-1200 mg/day) and vitamin D (800 IU/day) supplementation continues during and after the drug holiday

Special Populations

Elderly patients with multiple comorbidities: 2

• The American Geriatrics Society recommends considering drug holidays after 5 years in elderly patients with polypharmacy, as fracture protection persists for up to 5 years after stopping
• Patients with poor adherence due to stringent dosing requirements or gastrointestinal conditions like hiatal hernia may benefit from discontinuation

Patients with renal impairment: 5

• Alendronate is not recommended for patients with creatinine clearance <35 mL/min
• Consider switching to denosumab for patients with CrCl <60 mL/min rather than continuing alendronate 1

Critical Pitfall to Avoid

Never discontinue denosumab without immediately starting bisphosphonate therapy within 6 months, as denosumab discontinuation causes rebound vertebral fractures—this is NOT the same as alendronate, which can be safely stopped for drug holidays. 1