Which medication has a maximum 12-month duration of therapy due to decreased effectiveness after 1 year of use: Abaloparatide, Calcitonin, Raloxifene, or Romosozumab?

Romosozumab Has a Maximum 12-Month Duration of Therapy Due to Decreased Effectiveness After 1 Year of Use

Among abaloparatide, calcitonin, raloxifene, and romosozumab, romosozumab is the only medication that has a maximum 12-month duration of therapy due to decreased effectiveness after 1 year of use. 1

Evidence Supporting Limited Duration of Romosozumab

The 2023 American College of Physicians clinical guideline for osteoporosis treatment specifically states that "use of romosozumab should be limited to 12 monthly doses because the anabolic effect wanes after 12 monthly doses." 1 This limitation is unique to romosozumab among the medications listed in the question.

The recommendation is based on clinical evidence showing that:

• Romosozumab's bone-forming anabolic effect diminishes after 12 months of use
• The drug is specifically designed and approved for a 12-month treatment course
• After 12 months, patients must transition to an antiresorptive agent to maintain benefits

Mechanism and Treatment Sequence

Romosozumab works by:

• Inhibiting sclerostin, a protein that regulates bone formation
• Simultaneously increasing bone formation and decreasing bone resorption
• Providing rapid increases in bone mineral density (BMD) during the first 12 months

After the 12-month treatment period:

• Patients must transition to an antiresorptive agent (typically a bisphosphonate or denosumab)
• This sequential therapy approach is necessary to maintain the BMD gains achieved 1

Comparison with Other Medications in the Question

1. Abaloparatide:

   • Does not have a mandatory 12-month limitation
   • While it has precautions related to osteosarcoma risk with long-term use, it does not have a specific effectiveness limitation at 12 months 2

2. Raloxifene:

   • Can be used long-term without a specific duration limitation
   • Does not demonstrate waning effectiveness after 12 months 1

3. Calcitonin:

   • No specific 12-month limitation on duration of use
   • Can be used for longer periods, though effectiveness may be less than other options

Clinical Implications and Sequential Therapy

When using romosozumab:

• Treatment should be planned for exactly 12 monthly doses
• Transition to an antiresorptive agent must be arranged before completing romosozumab
• Research shows that attempting a second course of romosozumab after a treatment gap results in different BMD responses compared to the initial treatment 3

The American College of Rheumatology guideline for glucocorticoid-induced osteoporosis also confirms that "ROM is used for 12 months only" and requires sequential therapy with bisphosphonates or denosumab afterward 1.

Safety Considerations

Beyond the effectiveness limitation, romosozumab has important safety considerations:

• Increased risk for cardiovascular events compared with alendronate (hazard ratio 1.9) 1
• FDA safety warnings recommend avoiding use in patients with high risk for major cardiovascular events 1
• The high cost ($5,574 annually) compared to bisphosphonates ($39-$2,700) makes it less cost-effective for long-term use 4

In conclusion, romosozumab is the only medication among those listed that has a mandatory 12-month duration limitation due to decreased effectiveness after one year of use, requiring transition to another therapy to maintain benefits.