Paulo Siri, Laranjo Mafalda, Paula Anabela, Abrantes Ana Margarida, Martins João, Marto Carlos Miguel, Coelho Ana, Casalta-Lopes João, Carvalho Lina, Carrilho Eunice, Serra Arménio, Botelho Maria Filomena, Marques Ferreira Manuel
Institute of Endodontics, Faculty of Medicine, University of Coimbra, 3000-075 Coimbra, Portugal.
Coimbra Institute for Clinical and Biomedical Research (iCBR) Area of Environment, Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal.
Materials (Basel). 2020 Apr 22;13(8):1955. doi: 10.3390/ma13081955.
Bisphosphonate-associated osteonecrosis of the jaw (BRONJ), a post-surgical non-healing wound condition, is one of the most common side effects in patients treated with nitrogen-containing bisphosphonates. Its physiopathology has been related with suppression of bone turnover, of soft tissue healing and infection. Biphasic calcium phosphates (BCP) are used as a drug delivery vehicle and as a bone substitute in surgical wounds. Due to their capacity to adsorb zoledronate, it was hypothesized these compounds might have a protective effect on the soft tissues in BRONJ wounds. To address this hypothesis, a reproducible in vivo model of BRONJ in Wistar rats was used. This model directly relates chronic bisphosphonate administration with the development of osteonecrosis of the jaw after tooth extraction. BCP granules were placed in the alveolus immediately after tooth extraction in the test group. The animals were evaluated through nuclear medicine, radiology, macroscopic observation, and histologic analysis. Encouragingly, calcium phosphate ceramics were able to limit zoledronate toxicity in vivo and to favor healing, which was evidenced by medical imaging (nuclear medicine and radiology), macroscopically, and through histology. The studied therapeutic option presented itself as a potential solution to prevent the development of maxillary osteonecrosis.
双膦酸盐相关颌骨坏死（BRONJ）是一种术后伤口不愈合的病症，是接受含氮双膦酸盐治疗的患者中最常见的副作用之一。其病理生理学与骨转换抑制、软组织愈合及感染有关。双相磷酸钙（BCP）用作药物递送载体及手术伤口中的骨替代物。鉴于其吸附唑来膦酸盐的能力，推测这些化合物可能对BRONJ伤口中的软组织具有保护作用。为验证这一假设，采用了一种可重现的Wistar大鼠BRONJ体内模型。该模型直接将慢性双膦酸盐给药与拔牙后颌骨坏死的发生联系起来。在试验组中，拔牙后立即将BCP颗粒置于牙槽窝内。通过核医学、放射学、宏观观察及组织学分析对动物进行评估。令人鼓舞的是，磷酸钙陶瓷能够在体内限制唑来膦酸盐的毒性并促进愈合，这在医学成像（核医学和放射学）、宏观及组织学方面均得到了证实。所研究的治疗方案显示出作为预防上颌骨坏死发生的潜在解决方案的可能性。
