What is the next treatment step for a patient with osteoporosis who has been taking Fosamax (alendronate) for 5 years?

Next Treatment Step After 5 Years of Fosamax

After 5 years of alendronate (Fosamax) therapy, you should reassess the patient's fracture risk and strongly consider a drug holiday rather than automatically continuing or switching therapy, unless the patient remains at very high fracture risk. 1, 2

Risk Stratification to Guide Decision-Making

The critical first step is determining whether this patient falls into a high-risk category that warrants continued treatment versus a lower-risk profile that supports a drug holiday:

High-Risk Features Requiring Treatment Continuation 2, 3

• Previous hip or vertebral fracture (either before treatment or during the 5-year treatment period)
• Current femoral neck T-score ≤ -2.5 despite 5 years of treatment
• Age >80 years
• Multiple non-spine fractures
• Ongoing high-dose glucocorticoid use (≥7.5 mg prednisone daily)
• Significant bone loss (≥10% per year) despite bisphosphonate therapy

Lower-Risk Features Supporting Drug Holiday 2, 3

• No fractures experienced before or during the 5-year treatment period
• Hip BMD T-score > -2.5 after treatment
• No new high-risk factors developed during treatment

Treatment Options Based on Risk Category

For High-Risk Patients: Continue Treatment

Continue alendronate for up to 10 years total if the patient has experienced previous hip or vertebral fractures or maintains a T-score ≤ -2.5 at the femoral neck. 2, 4 The FLEX trial demonstrated that women who continued alendronate beyond 5 years had reduced clinical vertebral fractures (2.4% vs 5.3%) compared to those who discontinued, though no difference was seen in non-vertebral or hip fractures. 2, 5

Alternative: Switch to denosumab only in specific circumstances: 2, 6

• Renal impairment with creatinine clearance <60 mL/min
• Cancer-related bone disease (breast cancer, prostate cancer, multiple myeloma)
• Documented treatment failure (new fracture after ≥18 months of bisphosphonate therapy)

Critical Warning About Denosumab: If denosumab is ever started and then discontinued, you must initiate bisphosphonate therapy within 6 months to prevent rebound vertebral fractures—this is non-negotiable. 2, 3

For Lower-Risk Patients: Implement Drug Holiday

Discontinue alendronate and monitor for patients without high-risk features. 1, 2, 3 The evidence supports drug holidays of:

• 3-5 years for alendronate (the longest supported duration) 7, 3
• Residual fracture protection persists due to alendronate's accumulation in bone and continued release for months to years after discontinuation 4, 5

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 However, during a drug holiday: 2, 3

• Reassess fracture risk regularly (annually is reasonable)
• Monitor for new fractures clinically
• Check BMD at femoral neck after 2-3 years of drug holiday
• Resume bisphosphonate therapy if:
  • New fracture occurs
  • Femoral neck T-score drops to ≤ -2.5
  • New high-risk factors emerge

Critical Pitfalls to Avoid

Dental screening is mandatory: Complete all necessary dental work before continuing bisphosphonates or starting denosumab, as osteonecrosis of the jaw risk increases with longer treatment duration (11 cases with 5-year treatment vs 5 cases with 2-year treatment in one trial). 2

Ensure adequate supplementation: Verify the patient is taking calcium 1000-1200 mg/day and vitamin D 800 IU/day throughout treatment and during drug holidays. 2, 6 Failure to maintain adequate supplementation reduces treatment efficacy and increases fracture risk.

Recognize atypical fracture risk: The risk of atypical femoral fractures increases significantly after 5 years (from 1.78 to 113 per 100,000 person-years with >8 years exposure), though 162 osteoporotic fractures are prevented for every one atypical fracture. 2 Asian patients face up to 8 times higher risk than White patients. 2

Never automatically switch to anabolic therapy: Anabolic agents (teriparatide, romosozumab) are reserved only for patients at very high fracture risk with features like multiple vertebral fractures or fractures occurring despite adequate bisphosphonate treatment. 2 For most patients completing 5 years of alendronate, either continuing the same medication (if high-risk) or taking a drug holiday (if lower-risk) is more appropriate than switching agents.

The Bottom Line Algorithm

1. Assess current fracture risk using the criteria above
2. High-risk patients: Continue alendronate up to 10 years total OR switch to denosumab only if renal impairment or cancer-related bone disease exists
3. Lower-risk patients: Implement 3-5 year drug holiday with periodic reassessment
4. All patients: Ensure dental clearance and adequate calcium/vitamin D supplementation
5. Resume treatment if new fracture, declining BMD, or increased fracture risk develops during holiday

The evidence strongly supports that most patients do not require automatic continuation or switching after 5 years—individualized risk assessment should drive the decision. 1, 2, 5