Evenity (Romosozumab) is the True Anabolic Agent for Bone Growth
Evenity (romosozumab) is the anabolic agent for bone growth, while Reclast (zoledronic acid) is an antiresorptive bisphosphonate that prevents bone breakdown but does not build new bone. 1, 2
Understanding the Fundamental Difference
- Romosozumab is a sclerostin inhibitor that uniquely increases bone formation while simultaneously decreasing bone resorption, making it a true dual-action anabolic agent 1, 3
- Zoledronic acid (Reclast) is a bisphosphonate that only prevents bone breakdown through antiresorptive mechanisms—it does not stimulate new bone formation 1
- Romosozumab works by blocking sclerostin, which permits Wnt signaling to activate osteoblasts and build new bone tissue 4, 5
When to Use Romosozumab (Evenity)
The American College of Physicians recommends romosozumab as first-line treatment for postmenopausal women at very high risk for fracture, defined as: 1, 2
- Age >74 years
- Multiple prior osteoporotic fractures
- T-score ≤-3.0
- High FRAX scores (≥20% for major osteoporotic fracture or ≥3% for hip fracture)
- Recent hip fracture
- Failed bisphosphonate therapy
Efficacy Data for Romosozumab
- Reduces new vertebral fractures by 73% at 12 months compared to placebo 6
- Reduces clinical vertebral fractures by 4 per 1000 patients and radiographic vertebral fractures by 13 per 1000 patients (moderate certainty evidence) 1
- When followed by alendronate, reduces hip fractures by 12 per 1000 patients, clinical vertebral fractures by 13 per 1000, and any clinical fracture by 33 per 1000 compared to bisphosphonate alone 1
- Increases lumbar spine BMD by 12.7%, total hip by 5.8%, and femoral neck by 5.2% at 12 months 6
When to Use Zoledronic Acid (Reclast)
Bisphosphonates like zoledronic acid are first-line for standard osteoporosis (not very high risk) and serve as mandatory sequential therapy after completing romosozumab 1, 2
- Use as initial treatment for postmenopausal women with osteoporosis who do not meet very high-risk criteria 1, 2
- Mandatory transition to bisphosphonates or denosumab after completing 12 months of romosozumab to preserve bone gains 1, 2
- Zoledronic acid may reduce clinical vertebral fractures at 3 years but evidence is very uncertain for hip fractures 1
Critical Safety Considerations
Romosozumab Cardiovascular Risk
The FDA warns against using romosozumab in patients with myocardial infarction or stroke within the preceding year due to increased cardiovascular risk 1
- Romosozumab increased cardiovascular events compared to alendronate (hazard ratio 1.9, CI 1.1-3.1) 1
- Avoid in patients with high cardiovascular risk or documented coronary heart disease 1
Treatment Duration Limits
- Romosozumab must be limited to exactly 12 monthly doses because the anabolic effect wanes after 12 months 1
- Patients must transition to antiresorptive therapy (bisphosphonate or denosumab) immediately after completing romosozumab to prevent rebound bone loss 1, 2
Other Romosozumab Precautions
- Correct hypocalcemia before initiating treatment 6, 3
- Ensure adequate calcium (1000-1200 mg daily) and vitamin D (800-1000 IU daily) supplementation 1, 2
Treatment Algorithm
For very high-risk patients: 2
- Start romosozumab 210 mg subcutaneously monthly for 12 months (if no cardiovascular contraindications)
- Immediately transition to zoledronic acid or denosumab to maintain gains
For standard osteoporosis (not very high risk): 1, 2
- Start bisphosphonate (zoledronic acid or oral alendronate/risedronate)
- Reassess after 3-5 years for drug holiday consideration
For patients with cardiovascular disease: 1
- Avoid romosozumab entirely
- Use bisphosphonates as first-line regardless of fracture risk