Should I prescribe Prolia (denosumab) to a patient who has been on alendronate for more than 5 years?

Should You Prescribe Prolia After 5+ Years of Alendronate?

No, you should not routinely switch to Prolia (denosumab) after 5 years of alendronate—instead, consider a drug holiday or continuation of alendronate based on fracture risk reassessment. 1, 2

Treatment Duration and Drug Holiday Considerations

After 5 years of alendronate therapy, the evidence supports reassessing rather than automatically switching agents:

• Standard treatment duration is 5 years for bisphosphonates like alendronate, after which you should reassess the patient's fracture risk profile rather than reflexively continuing or switching therapy 1, 2, 3

• Drug holidays are appropriate for many patients after 5 years, particularly those without hip or vertebral fractures during treatment and with hip BMD T-score > -2.5 2

• 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

Why Not Switch to Denosumab?

Switching to denosumab creates significant management challenges and risks:

• Denosumab discontinuation causes rebound vertebral fractures, occurring as early as 7 months (average 19 months) after the last dose, with multiple vertebral fractures being particularly concerning 4

• You cannot safely stop denosumab without immediately transitioning to bisphosphonates (within 6 months), creating a therapeutic trap 2, 4

• Denosumab is not recommended as adjuvant therapy in cancer patients, and guidelines explicitly state that switching between bisphosphonates offers no advantage 2

• While denosumab shows greater BMD increases than bisphosphonates (3.5% vs 2.6% for alendronate at the hip), this does not translate to superior fracture outcomes in patients already treated with bisphosphonates 1

Risk Stratification for Continuation vs. Drug Holiday

Continue alendronate beyond 5 years if the patient has: 2

• Previous hip or vertebral fractures during treatment
• Multiple non-spine fractures
• Hip BMD T-score ≤ -2.5 despite treatment
• Very high ongoing fracture risk (age >80, glucocorticoid use, multiple risk factors)

Consider drug holiday if the patient has: 2

• No fractures during the 5-year treatment period
• Hip BMD T-score > -2.5 after treatment
• Lower baseline fracture risk

Monitoring During Drug Holiday

• Do NOT perform routine BMD monitoring during the initial 5-year treatment period, as fracture reduction occurs even without BMD increases 1, 2, 3

• During a drug holiday, reassess regularly for new fractures, changes in fracture risk profile, and BMD changes (particularly femoral neck T-score) 2

• Resume bisphosphonate therapy if: a new fracture occurs, fracture risk increases significantly, or BMD remains low (femoral neck T-score ≤ -2.5) 2

Critical Pitfalls to Avoid

• Never discontinue denosumab without immediately starting bisphosphonate therapy within 6 months, as rebound vertebral fractures can occur 2, 4

• Do not automatically continue bisphosphonates beyond 5 years without reassessing fracture risk, as this exposes patients to unnecessary rare adverse events (atypical femoral fractures, osteonecrosis of the jaw) without proven additional benefit in low-risk individuals 2

• Ensure dental work is completed before initiating or continuing any bone-active therapy to reduce osteonecrosis of the jaw risk, which occurs at <1 case per 100,000 person-years with osteoporosis dosing but increases with dental procedures 2, 4

• Recognize that long-term alendronate (beyond 5 years) increases risk of atypical subtrochanteric femoral fractures (3.0 to 9.8 cases per 100,000 patient-years), often preceded by prodromal thigh pain 2, 5

Alternative Approach: If Continuing Treatment is Necessary

If you determine the patient requires continued antiresorptive therapy after 5 years:

• Continue alendronate rather than switching to denosumab, as real-world data shows no increased fracture risk in patients continuing versus discontinuing after 5 years 6

• Alendronate continuation avoids the rebound fracture risk inherent to denosumab and maintains therapeutic flexibility 2, 4

• If the patient has demonstrated poor response to alendronate (new fractures, declining BMD), then consider switching to denosumab, but counsel extensively about the inability to safely discontinue it later 7, 8