Is romosozumab (Romosozumab) a treatment option for patients with primary hyperparathyroidism (PHPT) at high risk of fractures due to bone loss?

Romosozumab for Primary Hyperparathyroidism with High Fracture Risk

Romosozumab is not recommended for patients with primary hyperparathyroidism (PHPT) at high risk of fractures due to bone loss, as there is no evidence supporting its use in this specific condition and it may pose cardiovascular risks that could be particularly concerning in PHPT patients. 1

Current Evidence and Recommendations

Romosozumab (Evenity) is a sclerostin inhibitor with a dual mechanism of action that both increases bone formation and decreases bone resorption. However, its use has several important limitations:

• Romosozumab has only been studied and approved for postmenopausal women with osteoporosis at high risk for fracture 1, 2
• No clinical trials have evaluated romosozumab specifically in patients with primary hyperparathyroidism
• Romosozumab increases risk for cardiovascular events compared with alendronate (hazard ratio 1.9) 1
• Primary hyperparathyroidism itself is associated with increased cardiovascular risk, making the cardiovascular safety profile of romosozumab particularly concerning

Treatment Approach for PHPT with Bone Loss

For patients with PHPT and high fracture risk, the following approach is recommended:

1. First-line treatment: Parathyroidectomy

   • Definitive treatment for PHPT that addresses the underlying cause of bone loss
   • Leads to improvements in bone mineral density after successful surgery

2. If surgery is not possible or declined:

   • Oral bisphosphonates should be considered as first-line pharmacologic therapy
     • Strong evidence for fracture reduction in various high-risk populations 1
     • Established safety profile with long-term use
   • Denosumab may be considered as an alternative for patients who cannot tolerate bisphosphonates 3
     • Particularly useful in patients with renal impairment (common in PHPT)

Specific Concerns with Romosozumab in PHPT

Several factors make romosozumab particularly problematic for PHPT patients:

• Calcium metabolism concerns: Romosozumab can cause hypocalcemia 4, which could complicate calcium management in PHPT patients who may experience hypocalcemia after parathyroidectomy
• Cardiovascular risk: PHPT patients often have increased cardiovascular risk, and romosozumab has shown increased cardiovascular events (myocardial infarction, stroke, and death) 1
• Limited duration: Romosozumab is only approved for 12 months of use, requiring transition to another therapy afterward 3
• Lack of evidence: No studies have evaluated romosozumab in PHPT patients, while bisphosphonates have established efficacy in this population

Monitoring and Management

For PHPT patients with high fracture risk:

• Optimize calcium intake (1,000-1,200 mg/day) and vitamin D (600-800 IU/day) 3
• Regular BMD testing every 1-2 years to assess bone health 3
• Consider vertebral fracture assessment to identify subclinical vertebral fractures
• Address modifiable risk factors: smoking cessation, limiting alcohol, weight-bearing exercise 3

Important Considerations

• Romosozumab requires sequential therapy with an antiresorptive agent after completion to prevent bone loss 1, 3
• The high cost of romosozumab ($5,574 annually) compared to bisphosphonates ($39-$2,700) makes it less cost-effective 1
• Real-world data shows romosozumab is most effective in treatment-naïve patients with primary osteoporosis, not secondary causes of bone loss like PHPT 5

In conclusion, while romosozumab is effective for postmenopausal osteoporosis, its use in PHPT is not supported by evidence and carries potentially significant risks. Parathyroidectomy remains the definitive treatment for PHPT with bone loss, with bisphosphonates as the preferred pharmacologic option when surgery is not possible.