Does Evenity Cause Osteonecrosis of the Jaw?
Yes, Evenity (romosozumab) can cause osteonecrosis of the jaw (ONJ), but the risk appears to be very low based on clinical trial data, with only one case reported across major trials involving over 5,900 patients. 1
Risk Profile from Clinical Trials
The FDA label for Evenity documents that across both pivotal trials, osteonecrosis of the jaw occurred in one patient during treatment with EVENITY 1. This translates to an extremely low incidence rate among the 5,914 postmenopausal women treated with romosozumab 210 mg monthly.
When compared to bisphosphonates in the ARCH trial, romosozumab followed by alendronate showed no increased risk for serious harms or withdrawal due to adverse effects compared with bisphosphonate alone at 12- to 36-month outcome assessment 2. The 2023 American College of Physicians guideline notes this with moderate to low certainty evidence 2.
Real-World Evidence
A recent real-world propensity-matched cohort study of 15,689 patients per group found no detectable excess short-term MRONJ risk with romosozumab compared with PTH analogs over the approved treatment window 3. During 1 year of follow-up, MRONJ occurred in 11 romosozumab-treated patients (0.070%) versus 12 PTH analog-treated patients (0.076%), with a hazard ratio of 0.89 (95% CI 0.39-2.01) 3.
Critical Caveat: Sequential Therapy Risk
The most important clinical consideration is that sequential antiresorptive therapy—particularly romosozumab followed by potent antiresorptives like denosumab or zoledronic acid—may substantially increase MRONJ risk. Recent preclinical studies demonstrate that sequential administration of romosozumab followed by denosumab or zoledronic acid severely impairs extraction socket healing and induces osteonecrotic lesions in mice 4, 5.
A 2026 observational study identified one MRONJ case in a patient with sequential exposure to denosumab, romosozumab, and subsequent intravenous zoledronic acid therapy, accompanied by local infection 6. This highlights that cumulative antiresorptive exposure may be the critical risk factor rather than romosozumab monotherapy alone.
Practical Clinical Management
Before Starting Romosozumab:
- Perform dental examination with preventive dentistry intervention before initiating therapy 1
- Complete any necessary invasive dental procedures and ensure complete mucosal healing before starting treatment
- Optimize oral hygiene and address periodontal disease
During Treatment:
- Advise patients to practice good oral hygiene and inform their dentist they are receiving Evenity before dental work 1
- Avoid unnecessary invasive oral surgery during therapy 7
- If invasive dental surgery is necessary, defer therapy until complete healing is confirmed 8
When Transitioning to Antiresorptives:
- Exercise heightened caution when transitioning from romosozumab to potent antiresorptives (denosumab or zoledronic acid)
- Consider the cumulative antiresorptive burden, particularly in patients with prior bisphosphonate or denosumab exposure 6
- Maintain vigilant dental surveillance during sequential therapy
Comparative Context
For perspective, bisphosphonates carry a 0.001% to 0.21% risk of ONJ in osteoporosis patients, with higher rates (0.21%) after >4 years of therapy 7. Denosumab and zoledronic acid show 1-2% incidence in cancer patients with bone metastases receiving higher doses 8. Romosozumab's risk profile appears comparable to or lower than standard osteoporosis therapies when used as monotherapy, but sequential therapy warrants particular caution.
The 2023 ACP guideline appropriately suggests romosozumab for females with primary osteoporosis at very high risk of fracture (conditional recommendation), acknowledging the overall favorable benefit-risk profile 2.