When should alendronate be stopped before initiating Evenity (romosozumab)?

When to Stop Alendronate Before Starting Evenity

Stop alendronate immediately and transition directly to Evenity (romosozumab) without any washout period or drug holiday. The clinical trial data and FDA labeling demonstrate that patients can safely and effectively switch from alendronate to romosozumab without an intervening gap 1, 2.

Evidence-Based Rationale

The pivotal ARCH trial, which forms the basis of FDA approval, enrolled patients who were either treatment-naïve or had prior bisphosphonate exposure and initiated romosozumab directly 2. The study design involved:

• Immediate transition: Patients switched from alendronate to romosozumab without a specified washout period
• Superior outcomes: Romosozumab followed by alendronate reduced vertebral fractures by 48%, clinical fractures by 27%, and hip fractures by 38% compared to alendronate alone over 24 months 1, 2

Critical Sequencing Principle

Treatment sequence matters significantly for efficacy. Starting romosozumab BEFORE long-term bisphosphonate use produces substantially better bone mineral density (BMD) gains than the reverse sequence 3:

• Romosozumab-first approach: Total hip BMD increased 6.0-6.2% and lumbar spine BMD increased 13.1-13.7% in the first year 3
• After prior bisphosphonate use: Total hip BMD increased only 2.9% and lumbar spine 9.8% when romosozumab followed alendronate 3
• Responder rates: 69% achieved ≥6% BMD gains at the hip with romosozumab-first versus only 15% with the reverse sequence 3

Practical Implementation

For patients currently on alendronate who qualify for Evenity:

1. Discontinue alendronate at the next scheduled dose
2. Initiate romosozumab 210 mg subcutaneously monthly (two 105 mg injections) without delay
3. Continue for exactly 12 months (the FDA-approved duration) 1
4. Transition back to alendronate 70 mg weekly after completing the 12-month romosozumab course to maintain gains 1, 4

Important Clinical Considerations

Cardiovascular screening is mandatory before switching. During the first year of romosozumab treatment in ARCH, serious cardiovascular events occurred in 2.5% of romosozumab patients versus 1.9% on alendronate 2. Romosozumab carries a boxed warning for myocardial infarction and stroke risk 1.

Sequential therapy is non-negotiable. After completing 12 months of romosozumab, patients MUST transition to an antiresorptive agent (alendronate or denosumab) to preserve BMD gains 5, 4. Without sequential antiresorptive therapy, the anabolic benefits will be lost.

Avoid the reverse sequence when possible. If a patient has been on alendronate for years and now qualifies for romosozumab due to very high fracture risk, the switch is still appropriate, but recognize that prior bisphosphonate exposure blunts the BMD response to romosozumab 3, 6. The anti-fracture efficacy appears preserved despite reduced BMD gains 6.

Common Pitfalls to Avoid

• Do not create a treatment gap: There is no need for a "washout period" between stopping alendronate and starting romosozumab
• Do not extend romosozumab beyond 12 months: The FDA approval limits treatment to 12 monthly doses 1
• Do not skip the sequential alendronate: Failing to follow romosozumab with an antiresorptive results in rapid bone loss 5