Sharma, Chakrabhavi Gundurao Dileep, Hamlet, Stephen, Pectu, Eugene, Christopher, Philippa, and Ivanovski, Saso (2016) Inflammation and suppressed angiogenesis in zoledronic acid-induced osteonecrosis of the jaws. In: [Presented at the 94th General Session & Exhibition of the IADR/3rd Meeting of the IADR Asia Pacific Region. 0391. From: 94th General Session & Exhibition of the IADR/3rd Meeting of the IADR Asia Pacific Region, 22-25 June 2016, Seoul, Korea.

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Abstract

Objectives: Over the past few decades, bisphosphonates (BPs) have become the primary class of drugs prescribed for the management of bone pathologies associated with excessive bone resorption such as osteoporosis, Paget’s disease, and primary and secondary bone malignancies. Although BPs are effective treatment agents for these conditions, their use has also been associated with significant side effect such asbisphosphonate related osteonecrosis of the jaws, viz BRONJ. Our study utilized Zoledronic acid (ZA), the most potent drug among the BPs and most common drug implicated in the BRONJ pathogenesis to develop a BRONJ rat model that involved extraction of maxillary molars.

Methods: Sprague-Dawley rats(n=28) were divided into four groups out of which two test groups were injected ZA (intraperitoneally, once weekly) for three weeks, followedby maxillary teeth extraction (first two molars) and a contralateral soft tissue defectwithout any exposure of bone. ZA was continued for two or four more weeks and therats sacrificed at either end of two or four weeks healing. Gross examination, micro-CT evaluation and histological assessment were used to confirm the BRONJ lesion. Histomorphometrical analysis was used to quantify total necrosis and inflammatory infiltrate and compared to that of controls. Further, total vascularity was quantifi ed andcompared to that of corresponding controls at boh time points to assess the effects of ZA on healing defect.

Results : BRONJ lesion was confirmed in all of the rats administered ZA (100%), on gross examination, micro-CT evaluation and histological assessment following surgical bone exposure and not with soft tissue defect alone. Histologically, significantly highernecrosis (25048± 3489 sq μm vs 4076 ± 3489 sq μm, p〈0.0001) and excessiveinfl ammation (22945 ± 2481 vs 2794 ± 252.3 sq μm, p< 0.0001) were evident in BRONJ lesions. In contrast, total vascularity was significantly suppressed in ZA group (0.1749 ±0.01324 μm vs 0.2792 ± 0.02233, p=0.0011).

Conclusions : This in vivo study successfully established a BRONJ rat model that confirmed the critical role of ZA-induced local anti-angiogenesis in etiopathogenesis of BRONJ. This model can be a valuable tool to conduct further interventional studies toprevent the localized effect of ZA in the development of BRONJ.

Item ID:	70993
Item Type:	Conference Item (Poster)
Keywords:	Hydrogel; Bisphosphonates; VEGF; Zoledronic acid; Angiogenesis
Related URLs:	Organisation
Date Deposited:	29 Nov 2021 00:55
FoR Codes:	32 BIOMEDICAL AND CLINICAL SCIENCES > 3203 Dentistry > 320399 Dentistry not elsewhere classified @ 50% 32 BIOMEDICAL AND CLINICAL SCIENCES > 3203 Dentistry > 320303 Dental therapeutics, pharmacology and toxicology @ 50%
SEO Codes:	20 HEALTH > 2001 Clinical health > 200102 Efficacy of medications @ 100%
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