The nitrogen containing BP, Zoledronic acid, is one of the most commonly implicated drugs in BRONJ cases due to its higher potency and multimodal effect on bone remodeling and oral mucosa. 20-22
ZA induced BRONJ models are known to show classical BRONJ lesions with macroscopic features of bone necrosis, soft tissue inflammation and sequestration in various animal models, ranging from rats to large animal models like sheep. 16,17,23 However, the exposure of bone to the oral environment, either through a tooth extraction, artificially induced periodontitis, or repeated trauma is a pre-requisite for the initiation of BRONJ lesion in animal models. 24-27
The use of SD rats to develop a BRONJ model by mimicking human dosage and regimen was reported by Sonis et al (2009) whereby it was used in addition to dexamethasone (DX) as a co-medication, consistent with the regime used in the …show more content…
An interesting observation reported was that the maxillary ulcerations were higher in frequency than mandibular lesions (80% vs 60%) when three cycles of ZA was administered along with DX. Effects of BP on bone vascularity was studied and quantified, but no statistically significant difference between the groups was evident. PAS staining to detect the presence of actinomyces, a group of microbes most commonly associated with BRONJ lesions, failed to confirm their presence. TUNEL staining confirmed the apoptotic cells in the bone tissue confirming the necrotic nature of the lesions. The study was able to demonstrate the induction of BRONJ with drugs (ZA+DX), although there were issues with the dosage of both drugs, with DX being relatively high and ZA being too low to replicate the clinically used regimen. Also, the extraction of all molars instead of single tooth extraction may be considered to be “excessive” as compared to other animal
ZA induced BRONJ models are known to show classical BRONJ lesions with macroscopic features of bone necrosis, soft tissue inflammation and sequestration in various animal models, ranging from rats to large animal models like sheep. 16,17,23 However, the exposure of bone to the oral environment, either through a tooth extraction, artificially induced periodontitis, or repeated trauma is a pre-requisite for the initiation of BRONJ lesion in animal models. 24-27
The use of SD rats to develop a BRONJ model by mimicking human dosage and regimen was reported by Sonis et al (2009) whereby it was used in addition to dexamethasone (DX) as a co-medication, consistent with the regime used in the …show more content…
An interesting observation reported was that the maxillary ulcerations were higher in frequency than mandibular lesions (80% vs 60%) when three cycles of ZA was administered along with DX. Effects of BP on bone vascularity was studied and quantified, but no statistically significant difference between the groups was evident. PAS staining to detect the presence of actinomyces, a group of microbes most commonly associated with BRONJ lesions, failed to confirm their presence. TUNEL staining confirmed the apoptotic cells in the bone tissue confirming the necrotic nature of the lesions. The study was able to demonstrate the induction of BRONJ with drugs (ZA+DX), although there were issues with the dosage of both drugs, with DX being relatively high and ZA being too low to replicate the clinically used regimen. Also, the extraction of all molars instead of single tooth extraction may be considered to be “excessive” as compared to other animal