What is the comparative efficacy of Forteo (teriparatide) vs Evenity (romosozumab) in treating osteoporosis?

Comparative Efficacy of Forteo vs Evenity in Osteoporosis

For patients with primary osteoporosis at very high risk of fracture, both Evenity (romosozumab) and Forteo (teriparatide) are appropriate anabolic options with conditional recommendations, though Evenity demonstrates superior vertebral fracture reduction (75% relative risk reduction) compared to placebo in head-to-head data, while direct comparative trials between these two agents remain limited. 1, 2

Guideline-Based Treatment Positioning

Both agents are reserved for very high-risk patients, not first-line therapy:

• The American College of Physicians (2023) recommends bisphosphonates as first-line treatment (strong recommendation, high-certainty evidence) for primary osteoporosis 1
• Romosozumab (Evenity) or teriparatide (Forteo) should be used only for females with primary osteoporosis at very high risk of fracture (conditional recommendation, low-certainty evidence for teriparatide) 1
• Very high risk typically includes: prior vertebral fracture, multiple fractures, T-score ≤-3.0, or fracture on osteoporosis therapy 1

Fracture Efficacy Data

Evenity (Romosozumab)

Vertebral fracture reduction is superior with Evenity:

• 75% relative risk reduction in new vertebral fractures at 24 months when followed by denosumab (0.6% vs 2.5% absolute risk) 2
• 73% relative risk reduction at 12 months (0.5% vs 1.8% absolute risk) 2
• Significantly reduced clinical fractures at 12 months, though 88% were nonvertebral fractures 2
• Nonvertebral fracture reduction was NOT statistically significant at either 12 or 24 months 2

Forteo (Teriparatide)

Teriparatide reduces vertebral and nonvertebral fractures:

• Effective in reducing fracture risk in postmenopausal women, men with osteoporosis, and glucocorticoid-induced osteoporosis over 11-21 months 3
• Benefits on vertebral fracture prevention and BMD persist after treatment cessation 3
• However, teriparatide carries low-certainty evidence per ACP guidelines and may increase risk for serious adverse events and withdrawal due to adverse events 1

Bone Mineral Density Gains

Evenity produces greater BMD increases:

• 12.7% increase at lumbar spine, 5.8% at total hip, 5.2% at femoral neck at 12 months compared to placebo 2
• BMD continued to increase through 24 months when transitioned to denosumab 2
• Normal bone architecture and quality on histology with no woven bone or mineralization defects 2

Teriparatide also improves BMD effectively:

• Improves BMD and bone structure, strength, and quality on histomorphometric studies 3
• Specific percentage gains not detailed in available evidence but established as effective 3, 4

Sequential Therapy Considerations

Critical: Both agents MUST be followed by antiresorptive therapy:

• Patients initially treated with anabolic agents must be offered an antiresorptive agent after discontinuation to preserve gains and prevent serious risk of rebound and multiple vertebral fractures 1, 5
• After Evenity discontinuation, BMD returns to approximately baseline within 12 months without follow-on antiresorptive therapy 2
• Transition to bisphosphonates or denosumab is mandatory 1, 5

Real-world sequential data:

• Romosozumab following teriparatide (daily or weekly) showed +7.9% spine BMD and +2.4% total hip BMD at 12 months, with 2.2% new fracture incidence 6
• This sequential approach was more effective in primary osteoporosis than secondary osteoporosis 6

Safety Profile Differences

Evenity cardiovascular concerns:

• Moderate-to-low certainty evidence: romosozumab followed by alendronate probably did not increase risk for serious harms at 12-36 months 1
• Real-world data showed cardiovascular events in 2.3% of patients with secondary osteoporosis (0.6% fatal) 6

Forteo adverse effects:

• May increase risk for serious adverse events and probably increases withdrawal due to adverse events 1
• Associated with hypercalcemia (OR 12.9), gastrointestinal symptoms (OR 3.26), headache (OR 1.46), and hypercalciuria (OR 2.44) 1
• No osteosarcoma cases linked to teriparatide in postmarketing surveillance 1

Treatment Duration

Both agents have limited treatment windows:

• Evenity: 12 months maximum duration 2
• Forteo: 11-21 months typical treatment period 3
• Must transition to antiresorptive therapy immediately after completion 1, 5

Clinical Decision Algorithm

Use Evenity when:

• Patient at very high risk prioritizes maximal vertebral fracture reduction (75% RRR) 2
• No significant cardiovascular disease history 6
• Can afford higher cost (no generic available) 1

Use Forteo when:

• Patient has cardiovascular contraindications to Evenity 6
• Fresh vertebral fracture requiring accelerated healing (teriparatide may be superior for acute fracture healing) 7
• Patient has glucocorticoid-induced osteoporosis (established indication) 3

Avoid both agents when:

• Patient not at very high fracture risk—use bisphosphonates instead 1
• Patient cannot commit to mandatory follow-on antiresorptive therapy 1, 5
• Cost is prohibitive and bisphosphonates remain untried 1

Common Pitfalls

• Never discontinue anabolic therapy without immediately starting antiresorptive therapy—this causes rapid BMD loss and rebound vertebral fractures 1, 5
• Do not use these agents as first-line therapy when bisphosphonates are appropriate and less expensive 1
• Do not assume nonvertebral fracture protection is equivalent between agents—Evenity did not show statistical significance for nonvertebral fractures 2
• Ensure calcium (1000-1200 mg daily) and vitamin D (800-1000 IU daily) supplementation with either agent 5, 2