Center for Regenerative Medicine, Fukuoka Dental College, Fukuoka, Japan; Department of Oral Rehabilitation, Fukuoka Dental College, Fukuoka, Japan.
Center for Regenerative Medicine, Fukuoka Dental College, Fukuoka, Japan; Department of Oral Rehabilitation, Fukuoka Dental College, Fukuoka, Japan.
Bone. 2021 Feb;143:115611. doi: 10.1016/j.bone.2020.115611. Epub 2020 Aug 21.
Antiresorptive agent-related osteonecrosis of the jaw (ARONJ) and infectious osteomyelitis of the jaw (OMJ) in antiresorptive-naïve patients are different disease entities. Although osteoclast inhibition is at the center of the pathogenesis of ARONJ, the role of osteoclast inhibition in infectious OMJ is unknown. The objective of this study was to determine the effect of bisphosphonate osteoclast inhibition in infectious OMJ.
Osteomyelitis was induced in mice by S. aureus inoculation. The establishment of OMJ was verified by the culture of bone marrow samples obtained from the mandible. Infected animals received either zoledronic acid (ZA) or saline starting at week-2. Treated animals along with non-infected animals underwent tooth extractions at week-4 post-infection. Healing was assessed every week using in vivo micro-computed tomography and intraoral photos. Animals were euthanized at week-8 and cervical lymph nodes were assessed for lymphatic and blood vessels.
Tooth extraction wounds did not heal in animals with OMJ. These wounds were characterized by incomplete soft tissue coverage, sporadic bone fill in the sockets, and inflammatory cell accumulation in the connective tissue at 4 weeks after tooth extractions. Conversely, the majority of tooth extraction wounds in the infected animals treated with ZA had improved healing with better bone fill than even non-infected control animals. Consistently, atrophic lymphatic vessels were noted in the draining lymph nodes in animals with OMJ. However, infected animals treated with ZA had lymphatic vessels that were unaltered and showed a similar appearance to those in non-infected control animals.
ZA treatment promoted wound healing in the jaw with infectious osteomyelitis. Clearly, antiresorptive therapy is contraindicated in patients with ARONJ. However, our finding suggests that osteoclast inhibition is potentially an effectual remedy for infectious OMJ in antiresorptive-naïve patients.
抗吸收剂相关的颌骨坏死（ARONJ）和抗吸收剂初治患者的颌骨骨髓炎（OMJ）是不同的疾病实体。虽然破骨细胞抑制是 ARONJ 发病机制的核心，但破骨细胞抑制在感染性 OMJ 中的作用尚不清楚。本研究的目的是确定双膦酸盐破骨细胞抑制在感染性 OMJ 中的作用。
通过金黄色葡萄球菌接种诱导小鼠骨髓炎。通过培养下颌骨骨髓样本来验证 OMJ 的建立。感染动物在第 2 周开始接受唑来膦酸（ZA）或生理盐水治疗。治疗动物和未感染动物在感染后第 4 周进行拔牙。每周通过体内 micro-CT 和口腔内照片评估愈合情况。动物在第 8 周被安乐死，颈淋巴结评估淋巴管和血管。
OMJ 动物的拔牙伤口未愈合。这些伤口的特点是软组织覆盖不完全，牙槽窝内骨填充稀疏，拔牙后 4 周结缔组织中炎症细胞积聚。相反，在接受 ZA 治疗的感染动物中，大多数拔牙伤口愈合情况改善，骨填充情况优于未感染的对照组动物。一致地，在 OMJ 动物的引流淋巴结中观察到萎缩的淋巴管。然而，接受 ZA 治疗的感染动物的淋巴管未改变，外观与未感染的对照组动物相似。
ZA 治疗促进了感染性颌骨骨髓炎的伤口愈合。显然，抗吸收治疗在 ARONJ 患者中是禁忌的。然而，我们的发现表明，破骨细胞抑制可能是抗吸收剂初治患者感染性 OMJ 的有效治疗方法。
