Systematic review examines large-animal BRONJ models
Bottom line
A new systematic review in Archives of Oral Biology maps out how researchers have induced advanced bisphosphonate-related osteonecrosis of the jaw, or BRONJ, in non-rodent mammals using zoledronate plus dental trauma. The review focuses on experimental parameters such as species choice, zoledronate dosing, and surgical triggers needed to reproduce preclinical stage 2 disease more reliably. That matters because most prior preclinical work has leaned heavily on rodent models, while large-animal models, including sheep and minipigs, may better reflect jaw anatomy, bone remodeling, and oral wound-healing patterns relevant to clinically significant disease. (edoc.unibas.ch)
Why it matters: For veterinary professionals, the paper is less about immediate practice change and more about translational relevance. Zoledronate and other bisphosphonates are used in both human and veterinary medicine, and jaw osteonecrosis risk is closely linked to invasive dental procedures and underlying oral inflammation. The AAOMS 2022 update notes that tooth extraction is a major precipitating event and that stage 2 disease often requires antibiotics for symptom control, with surgery considered when conservative care fails. Better non-rodent models could improve prevention and treatment research, while also sharpening awareness around dental planning in animal patients receiving antiresorptives. (aaoms.org)
What to watch: Watch for whether this review helps standardize large-animal MRONJ study designs, especially around species selection and extraction-based induction protocols. (edoc.unibas.ch)
Key facts
- Study type
- Systematic review
- Journal
- Archives of Oral Biology
- Focus
- Preclinical stage 2 bisphosphonate-related osteonecrosis of the jaw in non-rodent mammals
- Drug
- Zoledronate
- Model trigger
- Dental trauma
- Species mentioned
- Sheep and minipigs
- Research aim
- Identify species selection, dosing regimens, and surgical triggers
- Why it matters
- Large-animal models may better reflect jaw anatomy, bone remodeling, and oral wound healing
A new systematic review in Archives of Oral Biology takes on a practical preclinical problem: how to reliably reproduce stage 2 bisphosphonate-related osteonecrosis of the jaw in non-rodent mammals using zoledronate. The authors set out to identify the experimental ingredients, including animal species, dosing regimens, and dental trauma protocols, that are most likely to generate advanced jaw lesions suitable for translational research.
That question sits at the intersection of oral surgery, oncology support, and comparative medicine. In human medicine, the condition is now more broadly framed as medication-related osteonecrosis of the jaw, or MRONJ, reflecting that agents beyond bisphosphonates can be involved. Still, zoledronate remains one of the best-known high-risk antiresorptives, particularly in oncology settings. The American Association of Oral and Maxillofacial Surgeons’ 2022 position paper says MRONJ risk in cancer patients exposed to zoledronate is higher than in comparable placebo-treated populations, and it highlights tooth extraction and preexisting inflammatory dental disease as major risk factors. (pubmed.ncbi.nlm.nih.gov)
The review’s emphasis on non-rodent mammals is notable because much of the mechanistic literature has come from rodent work, where zoledronate monotherapy and combination protocols can produce MRONJ-like lesions but don’t fully solve the question of clinical fidelity. A 2019 rodent systematic review found both zoledronic acid alone and zoledronic acid combined with chemotherapy and/or dexamethasone were significant risk factors for lesion development in those models. But large-animal systems may offer a better approximation of oral biomechanics, extraction healing, and jawbone architecture. (onlinelibrary.wiley.com)
Existing non-rodent evidence helps explain why researchers are pushing in that direction. In sheep, investigators previously reported that zoledronate treatment after tooth extraction led to BP-ONJ-like lesions, while osteopenic control animals healed uneventfully. The veterinary literature cited in a 2024 feline case series also points to a 2012 minipig large-animal model and a 2023 pig study suggesting chronic periodontal infection, rather than iatrogenic interference alone, may be an important trigger in MRONJ development. Taken together, that supports the idea that species choice and local oral disease conditions may be just as important as drug exposure alone. (edoc.unibas.ch)
There’s also a veterinary backdrop here. Although the new review is preclinical and not a companion-animal clinical study, MRONJ is no longer just a human concern. A 2024 retrospective case series described 20 cats with medication-related osteonecrosis of the jaw, all treated with alendronate for idiopathic hypercalcemia; 85% had prior dental extractions at the lesion site, and 95% required surgery to control disease. The same paper cites earlier reports of MRONJ after long-term bisphosphonate treatment in a cat and zoledronate-associated osteonecrosis of the jaw in a dog with appendicular osteosarcoma. (frontiersin.org)
Expert consensus from human oral surgery underscores why stage 2 modeling matters. In the AAOMS staging framework, stage 2 disease is symptomatic and can be difficult to manage conservatively; patients may need antibiotics for symptom control, and operative treatment may be appropriate when local wound care is inadequate or disease progresses. That makes a reproducible stage 2 animal model especially valuable for testing interventions before lesions advance further. (aaoms.org)
Why it matters: For veterinary professionals, this review is a reminder that antiresorptive therapy and dentistry can intersect in consequential ways. Even if BRONJ or MRONJ remains uncommon in veterinary patients, the signal across species is consistent: extractions, periodontal disease, and potent bisphosphonates can create the conditions for jaw osteonecrosis. More standardized non-rodent models could improve translational research on prevention, surgical timing, antimicrobial strategies, and wound-healing support. In practice, it also reinforces the value of thorough oral assessment before and during bisphosphonate treatment, especially for patients with cancer, chronic dental disease, or a history of extractions. (aaoms.org)
What to watch: The next step is whether investigators adopt a more uniform large-animal protocol, likely centered on zoledronate exposure plus extraction or chronic oral inflammation, and whether that leads to intervention studies with clearer timelines and more clinically relevant endpoints. (edoc.unibas.ch)