What is the best next treatment step for a patient with osteoporosis who has responded to romosozumab?

Management of Osteoporosis After Romosozumab Treatment

Recommendation

The most appropriate approach for B.H.'s continued treatment of osteoporosis is to change to alendronate 70 mg by mouth once weekly. 1

Rationale for Switching to Alendronate

Romosozumab is an anabolic agent that should only be used for a limited duration of 12 months, after which sequential therapy with an antiresorptive agent is required to maintain bone mineral density gains and prevent fracture risk:

• B.H. has already completed the maximum recommended 12-month course of romosozumab 1
• Sequential therapy with an antiresorptive agent is mandatory after romosozumab to prevent rebound bone loss and vertebral fractures 1
• Oral bisphosphonates, specifically alendronate, are strongly recommended as the first-line antiresorptive agent following romosozumab 1
• The patient has shown a positive response to romosozumab with improvement in hip BMD from -3.2 to -2.6, indicating she will likely benefit from continued treatment with an antiresorptive agent

Evidence Supporting Sequential Therapy

The American College of Rheumatology (ACR) guidelines explicitly state that "sequential OP treatment is recommended to prevent rebound bone loss and vertebral fractures after discontinuation of romosozumab" 1. This recommendation is based on high-quality evidence showing:

• Without sequential therapy after romosozumab, there is significant risk of rapid bone loss and increased fracture risk 1
• The FRAME trial demonstrated that transitioning from romosozumab to an antiresorptive agent (denosumab) maintained fracture reduction benefits at 24 months 2
• The ARCH trial showed that romosozumab followed by alendronate reduced all clinical fractures compared to alendronate alone 1

Why Not Continue Romosozumab?

Continuing romosozumab beyond 12 months is not appropriate because:

• Romosozumab is only approved for a maximum treatment duration of 12 months 1
• Clinical trials have not established safety and efficacy beyond 12 months of continuous use 3
• The patient has already received the full recommended course (1 year)

Why Not Vitamin D and Calcium Alone?

While calcium and vitamin D supplementation is important, it is insufficient as the sole therapy for this patient:

• B.H. is at very high risk for fracture with a T-score of -2.6 at the hip and -2.7 at the lumbar spine 4
• Calcium and vitamin D alone would not provide adequate protection against fractures in this high-risk patient 1
• These supplements should be continued alongside the antiresorptive therapy, not as a replacement 4

Why Not Add Abaloparatide?

Adding abaloparatide is not appropriate because:

• Using another anabolic agent immediately after romosozumab is not supported by guidelines 1
• Sequential use of two anabolic agents is not a recommended treatment strategy 1
• The patient has already received bone-forming therapy and now requires an antiresorptive to maintain gains 1

Treatment Algorithm Based on Risk Stratification

For patients who have completed romosozumab therapy:

1. Assess current fracture risk:

   • B.H. remains at high risk with T-scores of -2.6 (hip) and -2.7 (spine)

2. Select appropriate sequential therapy:

   • For patients who have completed romosozumab and remain at high risk: transition to an oral bisphosphonate (alendronate 70 mg weekly) 1
   • For patients with contraindications to oral bisphosphonates: consider denosumab 1

3. Duration of sequential therapy:

   • Continue bisphosphonate therapy for at least 3-5 years 4
   • Reassess fracture risk periodically with BMD testing every 1-3 years 4

Implementation Considerations

• Ensure proper administration of alendronate: taken with a full glass of water on an empty stomach, remaining upright for 30-60 minutes after administration 4
• Continue calcium (1000-1200 mg daily) and vitamin D (800-1000 IU daily) supplementation 4
• Encourage weight-bearing exercise as tolerated 4
• Monitor for potential adverse effects of bisphosphonates, including gastrointestinal symptoms, atypical femoral fractures, and osteonecrosis of the jaw 1
• Consider generic formulations to reduce cost 1, 4

By transitioning B.H. to alendronate after her successful course of romosozumab, we can maintain the BMD gains achieved and provide continued protection against fractures in this high-risk patient.