APANK-Study: Application of autogenous platelet-rich fibrin membranes in the treatment of antiresorptive-associated necrosis of the jaw - a multicenter observational study

焦磷酸(双膦)的合成类似物，核因子Kappa b配体的单抗受体激活剂(RANKL)-抗体或抗血管生成抗体用于进展性乳腺癌和前列腺癌或多发性骨髓瘤的治疗。自马克思等人第一次描述以来。2003年，药物相关性颌骨坏死(MRONJ)是抗吸收治疗的严重并发症，可导致部分或全部颌骨丧失。符合指南的治疗包括手术切除坏死骨以及实现无张力和唾液紧密的伤口闭合。尽管符合所有标准，但手术治疗与术后伤口愈合障碍和治疗失败的比率显著相关。它可能会导致早期伤口裂开并露出骨头，或者可能在治疗进行后几周或几个月发生延迟并发症。并发症的病理生理机制尚不完全清楚，似乎影响创面愈合的各种因素(胶原合成、胶原交联、血管生成、成纤维细胞增殖)。在MRONJ的手术治疗中，由于富含生长因子和基质成分的自体产品，如富含血小板的纤维蛋白(PRF)膜，可作为一种添加剂应用于MRONJ。这项多中心研究的目的是观察应用自体PRF膜是否能减少术后创面愈合并发症。预计每个中心将包括23名患者(n=46)，总持续时间为12个月。主要结果是临床成功(6周后伤口完全愈合，无骨外露)，这将通过两种不同的伤口愈合评分来确定。假说是，在治疗MRONJ时额外应用PRF膜会在头六周内导致更好的伤口愈合。这项先导性研究旨在为随后进行随机对照干预研究奠定基础，该研究将证明PRF膜在治疗药物相关性颌骨坏死方面的有效性。

Synthetic analoga of pyrophosphat (bisphosphonates), monoclonal Receptor Activator of Nuclear Factor Kappa b Ligand (RANKL)-antibodies or anti-angiogenetic antibodies are used in the therapy of progressed breast and prostate cancer, or multiple myeloma. Since the first description by Marx et al. in 2003, medication-related osteonecrosis of the jaw (MRONJ) is a severe complication of the antiresorptive therapy, which can lead to partial or complete loss of parts of the jaw. The guideline-compatible therapy consists in the surgical removal of the necrotic bone as well as the achievement of a tension-free and saliva-tight wound closure. Despite compliance with all criteria, surgical therapy is associated with a significant rate of postoperative wound healing disorders and therapy failure. It may result in early wound dehiscence with exposed bone or delayed complications may occur weeks or months after the therapy has been carried out. The pathophysiology of complications is not fully understood, it seems than various factors of wound healing are affected (collagen synthesis, collagen crosslinking, angiogenesis, proliferation of fibroblasts). The additional application of autogenous products, such as the platelet rich fibrin (PRF) membrane, could appear useful as an additive agent in the surgical therapy of MRONJ, as it contains a high concentration of growth factors and matrix components.The aim of the proposed multicenter study is to observe the reduction of post-surgical wound healing complication by application of autogenous PRF-membranes. It is envisaged to include 23 patients per center (n = 46) for a total duration of 12 months. The primary outcome is clinical success (completed wound healing without bone exposure after 6 weeks), which will be determined using two different wound healing scores. The hypothesis is that the additional application of PRF-membranes in the treatment of MRONJ leads to better wound healing within the first six weeks. This pilot study is supposed to gain the prerequisites to subsequently conduct a randomized controlled intervention study that will proof the effectiveness of PRF-membranes in the treatment of medication-related osteonecrosis of the jaw.