What is the comparison between teriparatide (recombinant human parathyroid hormone) and romosuzumab (monoclonal antibody) for osteoporosis treatment?

Teriparatide vs Romosozumab for Osteoporosis Treatment

For postmenopausal women with primary osteoporosis at very high fracture risk, both romosozumab and teriparatide are reasonable options with comparable fracture prevention efficacy, though romosozumab offers superior cost-effectiveness ($5,574 vs $22,156 annually) while teriparatide provides the advantage of self-administration and avoids cardiovascular concerns. 1, 2

Efficacy Comparison

Fracture Prevention

• Direct head-to-head comparison: A 2024 population-based cohort study of 49,104 patients found no significant differences between romosozumab and teriparatide for nonvertebral fracture prevention (weighted HR 0.95% CI 0.81-1.12) or hip fracture prevention (weighted HR 0.99,95% CI 0.76-1.29) 2

• Teriparatide efficacy: Reduces any clinical fractures by 27 fewer events per 1000 patients and radiographic vertebral fractures by 69 fewer events per 1000 patients (high certainty evidence), though evidence for hip fracture reduction is low certainty 3

• Romosozumab efficacy: Reduces clinical vertebral fractures by 4 fewer events per 1000 patients, radiographic vertebral fractures by 13 fewer events per 1000 patients, and any clinical fractures by 9 fewer events per 1000 patients compared to placebo (moderate certainty) 1

• Sequential therapy advantage: Romosozumab followed by alendronate reduces hip fractures by 12 fewer events per 1000 patients, clinical vertebral fractures by 13 fewer events per 1000 patients, and any clinical fracture by 33 fewer events per 1000 patients compared to bisphosphonate alone (moderate certainty) 1

Safety Profile

Cardiovascular Risk

• Romosozumab: Increased cardiovascular events compared to alendronate (HR 1.9,95% CI 1.1-3.1), making it contraindicated in patients with recent myocardial infarction or stroke 1

• Teriparatide: No increased cardiovascular risk; the 2024 comparative study found comparable MACE rates between drugs (weighted HR 0.90,95% CI 0.68-1.19) 2

Other Adverse Events

• Teriparatide: May increase serious adverse events and probably increases withdrawal due to adverse events; causes hypercalcemia more frequently than other agents 1, 4

• Romosozumab: May result in no differences in serious adverse events (moderate certainty) or withdrawals due to adverse events (low certainty) compared to placebo 1

Treatment Duration and Sequential Therapy

Critical Requirement for Both Agents

• Both drugs MUST be followed by antiresorptive therapy (bisphosphonates or denosumab) after discontinuation to preserve bone density gains and prevent rebound vertebral fractures 1, 3, 5

Duration Limits

• Teriparatide: Maximum 24 months of treatment due to osteosarcoma risk in animal models 3, 6

• Romosozumab: Strictly limited to 12 monthly doses as anabolic effect wanes after this period 5

Cost Considerations

Direct Costs

• Teriparatide: Most expensive osteoporosis treatment at $22,156 average annual cost per Medicare beneficiary 1

• Romosozumab: $5,574 average annual cost per Medicare beneficiary—substantially less expensive than teriparatide 1

Administration Costs

• Teriparatide: Can be self-administered by subcutaneous injection, reducing overall treatment costs 1

• Romosozumab: Often requires clinician administration, adding to total treatment costs 1

Clinical Decision Algorithm

Choose Romosozumab When:

• Patient has no history of myocardial infarction or stroke within the past year 1
• Cost is a significant concern (approximately 4-fold less expensive than teriparatide) 1
• Patient prefers shorter treatment duration (12 months vs 24 months) 5
• Sequential therapy data shows superior fracture reduction when followed by bisphosphonate 1

Choose Teriparatide When:

• Patient has recent cardiovascular events or significant cardiovascular disease 1, 4
• Patient prefers self-administration at home 1
• Patient has history of malignancy (romosozumab may be preferred, but teriparatide contraindicated with osteosarcoma risk factors) 4
• Longer treatment duration acceptable (24 months) 3

Common Pitfalls to Avoid:

• Never discontinue either agent without transitioning to antiresorptive therapy—this results in rapid bone loss and increased fracture risk 1, 5
• Do not use teriparatide for more than 24 months due to theoretical osteosarcoma risk 3, 6
• Do not use romosozumab beyond 12 months as anabolic effects diminish 5
• Ensure adequate calcium (≤1500 mg daily) and vitamin D (≤1000 IU daily) supplementation during treatment 1
• Monitor serum calcium after 1 month of teriparatide treatment 6

Target Population

Both agents are indicated specifically for postmenopausal women (mean age >74 years) with primary osteoporosis at very high fracture risk, defined as: 1, 3

• Recent fracture
• History of multiple clinical osteoporotic fractures
• Multiple risk factors for fracture
• Failure of other available osteoporosis therapy