What is the protocol for a patient with severe osteoporosis who has failed 6 months of Evenity (romosozumab) therapy?

Management of Severe Osteoporosis After 6 Months of Evenity (Romosozumab) Failure

For a patient with severe osteoporosis who has failed 6 months of romosozumab therapy (defined as a new fracture occurring during treatment), you should immediately switch to either denosumab or a bisphosphonate (intravenous zoledronic acid or oral alendronate), with denosumab being preferred for its superior anti-fracture efficacy in very high-risk patients. 1

Defining Treatment Failure

Treatment failure after romosozumab is defined as:

• New fragility fracture occurring after ≥12 months of therapy (though you mention only 6 months, which represents incomplete treatment) 1
• Development of new vertebral compression fractures on imaging 1
• Continued bone loss despite therapy 1

Critical caveat: Romosozumab is FDA-approved for only 12 months of treatment, so 6 months represents an incomplete course. 2, 3 If the patient has experienced a fracture at 6 months, this represents true treatment failure requiring immediate intervention.

Immediate Next Steps

1. Complete Romosozumab Course vs. Switch Immediately

If fracture occurred at 6 months, switch immediately to an antiresorptive agent rather than completing the 12-month romosozumab course. 1 The American College of Rheumatology specifically recommends switching therapy when new fractures occur during treatment. 1

2. Sequential Therapy Selection

First-line option: Denosumab 60 mg subcutaneously every 6 months 1, 4

• Denosumab is conditionally recommended as the preferred sequential therapy after romosozumab failure in very high-risk patients 1
• Provides 61% hip fracture risk reduction and 68% vertebral fracture risk reduction 1
• Must be continued indefinitely without interruption due to severe rebound fracture risk 4, 5

Second-line option: Bisphosphonate therapy 1

• Intravenous zoledronic acid 5 mg annually if oral absorption or adherence is a concern 1
• Oral alendronate 70 mg weekly as alternative 1
• Bisphosphonates reduce hip fracture risk by 36% and vertebral fractures by 40-50% 1

Third-line option: Teriparatide (PTH analog) 1

• Consider only if both denosumab and bisphosphonates are contraindicated 1
• Must be followed by antiresorptive therapy after completion 1
• 76% reduction in clinical vertebral fractures at 17 months 1

Why Not Continue or Restart Romosozumab?

Romosozumab cannot be used beyond 12 months total due to:

• FDA approval limited to 12 months of therapy 2, 3
• Efficacy diminishes after 12 months 2
• Must be followed by antiresorptive therapy to prevent rapid bone loss 1

Critical Safety Considerations

Denosumab-Specific Warnings

If you choose denosumab, the patient must understand this is a lifelong commitment 4, 5:

• Discontinuation after >24 months causes severe rebound vertebral fractures 4
• If denosumab must be stopped, transition to bisphosphonate 6-7 months after last dose 1
• Requires at least 1 year of oral bisphosphonate or 1-2 years of IV bisphosphonate after stopping 1

Bisphosphonate-Specific Warnings

• Assess for atypical femoral fracture risk and osteonecrosis of jaw after 5 years 1
• Higher risk with longer treatment duration 1
• Can be discontinued after 5 years if fracture risk decreases, then reassess 1

Monitoring Protocol

Obtain baseline assessments before switching therapy:

• DXA scan of lumbar spine and hip to document current BMD 4, 6
• Vertebral fracture assessment (VFA) or lateral spine X-rays 6
• Serum calcium and vitamin D levels 6
• Renal function (creatinine clearance) before bisphosphonate use 1

Ongoing monitoring:

• Do NOT perform routine BMD monitoring during initial 5 years of bisphosphonate therapy 6
• Annual clinical assessment for new fractures 6
• Reassess fracture risk after 5 years of bisphosphonate therapy 1, 6

Adjunctive Measures

All patients require 1, 6:

• Calcium 1000-1200 mg daily 1, 6
• Vitamin D 600-800 IU daily 1, 6
• Weight-bearing and resistance exercises 1, 6
• Fall prevention counseling 1
• Smoking cessation and alcohol limitation 6

Common Pitfalls to Avoid

1. Never discontinue romosozumab without immediately starting antiresorptive therapy - this causes rapid bone loss and rebound fractures 1

2. Never interrupt denosumab therapy without a transition plan - rebound fractures occur within 6-9 months of discontinuation 1, 4

3. Do not assume 6 months of romosozumab is adequate - the standard course is 12 months, but fracture during treatment mandates switching 2, 3

4. Do not use teriparatide immediately after romosozumab - the DATA study showed problematic bone loss with this sequence; use antiresorptives instead 7