Effect of tyrosine kinase inhibitor sunitinib on tissue repair at tooth extraction sites.

BACKGROUND: Both zoledronic acid, a potent bisphosphonate, and the antiangiogenic drug sunitinib are included in anticancer protocols and have also been associated with jaw osteonecrosis. Our aim was to compare the effect of these drugs on tissue repair at tooth extraction sites. METHODS: Wistar rats were allocated into four groups: (1) sunitinib; (2) sunitinib/zoledronic acid; (3) zoledronic acid; (4) control group. The animals underwent tooth extractions and maxillae were macro- and microscopically analyzed. RESULTS: On macroscopic evaluation, the zoledronic acid group showed a significantly higher frequency of oral mucosal lesion; lesions in the sunitinib/zoledronic acid group were larger, albeit not significantly so. The sunitinib/zoledronic acid group had significantly less epithelium than the zoledronic acid and control group, but showed no significant difference compared to the sunitinib group. The sunitinib/zoledronic acid and zoledronic acid groups did not differ from each other, but had significantly less connective tissue and more non-vital bone and microbial colonies than sunitinib and control groups, whereas these latter two groups did not significantly differ from each other. Vital bone and inflammatory infiltrate did not significantly differ between groups. CONCLUSION: Sunitinib alone is not associated with non-vital bone, whereas the sunitinib/zoledronic acid combination and zoledronic acid alone are.

Interrelationship of clinical, radiographic and haematological features in patients under bisphosphonate therapy.

OBJECTIVES: To analyze the clinical, radiographic and haematological aspects of patients under bisphosphonate therapy. METHODS: A retrospective study was conducted where the records of patients taking bisphosphonates were analyzed considering the occurrence of bisphosphonate-related osteonecrosis of the jaw (BRONJ). Evaluation included panoramic and periapical radiographies, haematological examinations and clinical features. Radiographies were analyzed determining the presence or absence of bone sclerosis, osteolysis, persisting alveolar socket, narrowing of the mandibular canal, widening of the periodontal ligament space, periradicular radiolucency, sequestrum and thickening of the lamina dura. Laboratory tests consisted of complete blood count, fasting serum glucose, erythrocyte sedimentation rate (ESR) and serum levels of calcium, phosphorus, alkaline phosphatase, parathormone (PTH) and C-terminal telopeptide of collagen I (CTX). RESULTS: Alkaline phosphatase and ESR were significantly higher in the BRONJ group, whereas fasting serum glucose, CTX, PTH, calcium and phosphorus did not significantly differ. BRONJ showed association with smoking, tooth extraction, anaemia and leukocytosis. On radiographic analysis, persisting alveolar socket, osteolysis, bone sclerosis and narrowing of the mandibular canal were significantly more prevalent in the BRONJ group. Thickening of the lamina dura, periapical radiolucencies, widening of the periodontal ligament space and sequestrum did not significantly differ between the groups. CONCLUSIONS: BRONJ is a multifactorial disease with high morbidity, which requires experimental studies to clarify the role of the reported risk factors and clinical radiographic signs to improve its diagnosis.