What is the recommended duration of Alendronate (bisphosphonate) treatment before considering discontinuation or switching to an alternative medication, such as Risedronate (bisphosphonate) or Ibandronate (bisphosphonate)?

Duration of Alendronate Treatment

Alendronate should be continued for 5 years in most patients with osteoporosis, after which treatment should be stopped (drug holiday) unless the patient has very high fracture risk, such as previous hip or vertebral fractures, T-score ≤ -2.5 at the hip, or ongoing high-dose glucocorticoid use. 1, 2, 3, 4

Standard Treatment Duration

• The American College of Physicians strongly recommends 5 years as the standard treatment duration for alendronate therapy. 1, 2, 3
• The FDA label explicitly states that "patients at low-risk for fracture should be considered for drug discontinuation after 3 to 5 years of use," and emphasizes that "the optimal duration of use has not been determined" beyond clinical trial data of 4 years. 4
• Clinical trial evidence supporting alendronate's safety and efficacy extends up to 7 years, with continued BMD gains throughout this period, though fracture risk reduction is only proven for 4 years. 5, 6

Risk Stratification After 5 Years

Patients Who Should STOP (Drug Holiday)

Patients without high-risk features should discontinue alendronate after 5 years. 1, 2, 3 Specifically, those eligible for a drug holiday include:

• No previous hip or vertebral fractures during treatment 2, 7
• Hip BMD T-score > -2.5 after 5 years of treatment 2, 7
• No multiple non-spine fractures 7
• Not on ongoing high-dose glucocorticoids (≥7.5 mg prednisone daily) 7

The FLEX trial demonstrated that women who discontinued alendronate after 5 years had only a modest absolute increase in clinical vertebral fractures (5.3% vs 2.4%), but no significant difference in non-vertebral or hip fractures over the subsequent 5 years. 3, 8 This is critical because hip and non-vertebral fractures carry the highest morbidity and mortality burden.

Patients Who Should CONTINUE Beyond 5 Years

Continue alendronate beyond 5 years only in patients at very high fracture risk: 1, 2, 7, 3

• Previous hip or vertebral fractures (even while on treatment) 2, 7
• Hip BMD T-score ≤ -2.5 despite 5 years of treatment 2, 7
• Multiple non-spine fractures 7
• Ongoing high-dose glucocorticoid therapy (≥7.5 mg prednisone daily) 7
• Age >80 years with additional risk factors 3
• Significant bone loss (≥10% per year) despite bisphosphonate therapy 7

Evidence shows that continuing beyond 5 years reduces clinical vertebral fractures by 55% (RR 0.45) but does not reduce non-vertebral or hip fractures. 8 Since vertebral fractures have lower mortality impact than hip fractures, continuation is only justified in very high-risk patients.

Reassessment Before Discontinuation

Before stopping alendronate after 5 years, perform a comprehensive fracture risk reassessment: 2, 3

• Update FRAX score 2, 3
• Measure BMD with DXA, focusing on hip T-score 2, 7, 3
• Obtain vertebral fracture assessment (VFA) or spinal x-ray 3
• Review fracture history during treatment 7, 3
• Assess ongoing risk factors (glucocorticoid use, falls, comorbidities) 7, 3

Drug Holiday Duration and Monitoring

For patients who discontinue after 5 years, the drug holiday can safely last up to 5 years in low-to-moderate risk patients. 3 High-risk patients who still require a break should have shorter holidays of 1-2 years with close monitoring. 2, 3

During the drug holiday:

• Perform BMD with VFA or spinal x-ray every 1-2 years 3
• Do NOT perform routine BMD monitoring during the initial 5-year treatment period (fracture reduction occurs even without BMD increases) 7, 3
• Resume alendronate if: 7
  • New fracture occurs during the holiday
  • Femoral neck T-score drops to ≤ -2.5
  • Fracture risk increases significantly

The FLEX trial showed that BMD remained above pretreatment baseline levels even 5 years after discontinuation, and bone turnover markers remained somewhat suppressed, demonstrating persistent skeletal effects. 9, 8, 6 Real-world data from Denmark confirmed no increased fracture risk in patients discontinuing versus continuing alendronate after 5 years. 10

Switching to Alternative Agents

Do NOT routinely switch from alendronate to risedronate or ibandronate after 5 years—there is no evidence of benefit. 7 The SWOG S0307 trial found no efficacy differences among different bisphosphonates. 7

Consider switching to denosumab only in specific circumstances: 7

• Renal impairment (creatinine clearance <60 ml/min) 7
• Cancer-related bone disease (breast cancer, prostate cancer, multiple myeloma) 7
• Fractures despite adequate bisphosphonate treatment 7

Critical warning: If denosumab is ever started and then discontinued, bisphosphonate therapy MUST be initiated within 6 months to prevent rebound vertebral fractures. 7, 3 Never allow a denosumab drug holiday. 7

Long-Term Risks of Continued Treatment

Prolonged bisphosphonate use beyond 5 years increases risk of rare but serious adverse events: 1, 3

• Osteonecrosis of the jaw (ONJ): Incidence <1% with standard dosing, but increases with duration (11 cases with 5-year treatment vs 5 cases with 2-year treatment in SUCCESS A trial) 1, 7
• Atypical femoral fractures: 3.0-9.8 cases per 100,000 patient-years 7
• Chronic suppression of bone turnover with uncertain long-term skeletal consequences 1, 3

Special Considerations for Cancer Patients

In cancer patients receiving endocrine therapy (aromatase inhibitors, androgen deprivation therapy), bisphosphonates should be continued for the duration of endocrine treatment or up to 5 years, whichever is shorter. 1 The ESMO guidelines specifically recommend weekly oral alendronate or risedronate for up to 5 years in this population. 1

Common Pitfalls to Avoid

• Do NOT automatically continue bisphosphonates beyond 5 years without reassessing fracture risk—this exposes patients to unnecessary rare adverse events without proven benefit in low-risk individuals. 7
• Do NOT perform routine BMD monitoring during the initial 5-year treatment period—it does not predict fracture reduction and leads to unnecessary testing. 7, 3
• Ensure dental work is completed before initiating or continuing bisphosphonate therapy to reduce ONJ risk. 7
• Never discontinue denosumab without immediately starting bisphosphonate therapy within 6 months. 7, 3