Nitrogen‐containing bisphosphonate therapy: assessment of the alveolar bone structure in rats – a blind randomized controlled trial

Abstract

This study aimed to assess the effect of zoledronic acid exposure on structures of the alveolar bone of rats. The sample was composed of 42 male Wistar rats. Animals in the T1 and T2 groups received weekly doses of 0.2 mg/kg intraperitoneal zoledronic acid for 3 weeks, while animals in the T3 group received the same treatment for 8 weeks. The control groups C1, C2 and C3 received equivalent doses of saline. The first upper molars of Wistar rats in the C2, T2, C3 and T3 groups were extracted. Cone-beam computerized tomography scans were performed, and the image density was analysed by grey levels. The presence and type of inflammatory infiltrate, vascularization and bone necrosis were assigned by histological qualitative scores. Histomorphometric analysis of bone density was performed in the groups without extraction. No significant differences were found in the bone grey density estimated by grey-level value and histomorphometric analysis between the C1 and T1 groups (P > 0.05). The grey levels in the T3 group were lower (P < 0.05) than in the C3 group, corresponding to the bone defect. Histological assessments showed the presence of bone necrosis in the T3 group and lower levels of bone remodelling in the test groups (T2 and T3) compared to the control groups (C2 and C3). The results of qualitative analyses did not differ significantly between the groups (P > 0.05). Zoledronic acid-exposed animals showed maxillary changes including reduced grey levels, the presence of bone necrosis and a higher prevalence of inflammatory signs.

Dental extraction following zoledronate, induces osteonecrosis in rat´s jaw

“…We also observed that the experimental group exhibit evident delayed reepithelialization at the fourth week, in contrast with other BRONJ models which showed the same condition but during a longer period of time. ( 2 , 9 , 22 , 23 )…”

“…The standardized radiological parameters for all study groups were 60-70kV with an exposure time of 0.24 seconds. X-ray images were analyzed according to Pacheco using the IMAGE J software® ( 9 ). All images were converted into an 8-bit data (256 grey levels) generating a scale (0-255) for each image.…”

“…In this condition, the bone tissue in jaws often fails to heal following minor trauma, although it can also occur spontaneously ( 5 - 8 ). The most commonly reported symptoms of this condition are bone exposure, pain, bone sequestration, fistulas that extend from mucous membranes to the surface of the skin, edema, paraesthesia and susceptibility to pathological bone fractures ( 9 ). However, in 90% of cases, it is caused by dental treatment of some kind.…”

Nitrogen‐containing bisphosphonate therapy—Part II: Assessment of alveolar bone tissue inflammatory response in rats—A blind randomized controlled trial

“…Studies in animals have also clarified the relationship between bisphosphonates use and changes in alveolar bone tissue . Factors such as stagnation of osteoclastic activity and angiogenesis, which are fundamental to bone repair, have been observed …”

“…8 Studies in animals have also clarified the relationship between bisphosphonates use and changes in alveolar bone tissue. 9 Factors such as stagnation of osteoclastic activity and angiogenesis, which are fundamental to bone repair, have been observed. 10,11 This study aimed to analyse the inflammatory response of alveolar bone after pulp injury in rats submitted to two different regimens of zoledronic acid therapy.…”