Lesclous Philippe, Abi Najm Semaan, Carrel Jean-Pierre, Baroukh Brigitte, Lombardi Tommaso, Willi Jean-Pierre, Rizzoli René, Saffar Jean-Louis, Samson Jacky
Laboratoire Réparation et Remodelages Oro-Faciaux, EA2496, Université Paris Descartes, Faculté de Chirurgie Dentaire, France.
Bone. 2009 Nov;45(5):843-52. doi: 10.1016/j.bone.2009.07.011. Epub 2009 Jul 22.
Osteonecrosis of the jaw (ONJ) can be associated with nitrogen-containing bisphosphonates (NBPs) therapy. Various mechanisms of NBP-associated ONJ have been proposed and there is currently no consensus of the underlying pathogenesis. The detailed medical and dental histories of 30 ONJ patients treated with NBPs for malignant diseases (24) or osteoporosis (6) were analyzed. The necrotic bone was resected and analyzed histologically after demineralization. In 10 patients the perinecrotic bone was also resected and processed without demineralization. Alveolar bone samples from 5 healthy patients were used as controls. In 14 ONJ patients, serial technetium-99m-methylene diphosphonate scintigraphic scans were also available and confronted to the other data. Strong radionuclide uptake was detected in some patients several months before clinical diagnosis of ONJ. The medullary spaces of the necrotic bone were filled with bacterial aggregates. In the perinecrotic bone, the bacteria-free bone marrow characteristically showed an inflammatory reaction. The number of medullary inflammatory cells taken as an index of inflammation allowed us to discriminate two inflammation grades in the ONJ samples. Low-grade inflammation, characterized by marrow fibrosis and low inflammatory cells infiltration, increased numbers of TRAP(+) mono- and multineacleated cells was seen in patients with bone exposure<2 cm(2). High-grade inflammation, associated with larger lesions, showed amounts of tartrate-resistant acid phosphatase(+)/calcitonin receptor(-) mono- and multinucleated cells, osteocyte apoptosis, hypervascularization and high inflammatory cell infiltration. The clinical extent of ONJ was statistically linked to the numbers of inflammatory cell. Taken together these data suggest that bone necrosis precedes clinical onset and is an inflammation-associated process. We hypothesize that from an initial focus, bone damage spreads centrifugally, both deeper into the jaw and towards the mucosa before the oral bone exposure and the clinical diagnosis of ONJ.
颌骨坏死（ONJ）可能与含氮双膦酸盐（NBP）治疗有关。已经提出了NBP相关ONJ的各种机制，目前对于潜在的发病机制尚无共识。分析了30例因恶性疾病（24例）或骨质疏松症（6例）接受NBP治疗的ONJ患者的详细医学和牙科病史。切除坏死骨并在脱矿后进行组织学分析。在10例患者中，还切除了坏死骨周围的骨组织并在未脱矿的情况下进行处理。将5例健康患者的牙槽骨样本用作对照。在14例ONJ患者中，还可获得系列锝-99m-亚甲基二膦酸盐闪烁扫描图像，并与其他数据进行对照。在一些患者中，在ONJ临床诊断前数月检测到强烈的放射性核素摄取。坏死骨的骨髓腔中充满了细菌聚集体。在坏死骨周围的骨组织中，无细菌的骨髓表现出特征性的炎症反应。以骨髓炎症细胞数量作为炎症指标，使我们能够在ONJ样本中区分两种炎症等级。低度炎症的特征是骨髓纤维化和低炎症细胞浸润，在骨暴露面积<2 cm²的患者中可见TRAP（+）单核和多核细胞数量增加。高度炎症与较大的病变相关，表现为抗酒石酸酸性磷酸酶（+）/降钙素受体（-）单核和多核细胞数量增加、骨细胞凋亡、血管增生和高炎症细胞浸润。ONJ的临床范围与炎症细胞数量在统计学上相关。综合这些数据表明，骨坏死先于临床发病，是一个与炎症相关的过程。我们假设，从最初的病灶开始，骨损伤呈离心性扩散，在口腔骨暴露和ONJ临床诊断之前，既向颌骨深部扩散，也向黏膜方向扩散。
