Balıkesir Üniversitesi Tıp Fakültesi Ortopedi ve Travmatoloji Anabilim Dalı, 10145 Balıkesir, Türkiye.
Jt Dis Relat Surg. 2022;33(1):193-202. doi: 10.52312/jdrs.2022.537. Epub 2022 Mar 28.
In this experimental study, we aimed to investigate the specific value of receptor activator of nuclear factor kappa-Β ligand (RANKL) plasma level in osteomyelitis to show the bone destruction and to determine its correlation with classical markers of infection in mice model of osteomyelitis.
Sixty Balb/c female mice (30 to 40 g weight, 3.5 to 4 month-old) were divided into two groups: Controls (n=15) and study group (n=45). All mice underwent tibial decortication and received an injection of sclerosing agent into the intramedullary cavity. The next process was proceeded in two steps to observe the detectability of osteomyelitis-induced bone destruction (step 1) and treatment response (step 2) using the variables examined in our study. In step 1, the study group received 1 mL solution containing Staphylococcus aureus (S. aureus) bacteria (2X108 per mL) into the intramedullary cavity. Five mice from each group were sacrificed every seven days for three weeks and tibia and blood samples were obtained. In step 2, the remaining 30 infected mice were further divided into two groups to investigate the possible value of RANKL plasma level as a marker of treatment response. Fifteen of these mice received teicoplanin 20 mg/kg for four weeks, while the rest did not receive antibiotics. Eight mice from each group were sacrificed at the end of the second week and the remaining 14 mice were sacrificed at the end of four weeks. Complete blood count, procalcitonin level, C-reactive protein (CRP), and RANKL concentrations were measured from blood samples of each sacrificed mouse.
Median RANKL concentration of the control subjects was significantly higher than recipients of intervention at the first and third weeks in step 1 where bone destruction of osteomyelitis was examined. No significant changes occurred in groups receiving and not receiving antimicrobial treatment in terms of RANKL, CRP, and procalcitonin levels throughout four weeks in step 2. The RANKL concentration was significantly correlated with colony growth in subjects allocated to the S. aureus inoculation group (r=-0.547, p=0.035).
The RANKL levels in mice with S. aureus osteomyelitis are not correlated with colony growth or other markers of inflammation and not useful for monitoring the response to antimicrobial treatment during osteomyelitis.
在这项实验研究中，我们旨在探讨核因子κB 受体激活配体（RANKL）血浆水平在骨髓炎中的特定价值，以显示骨破坏，并确定其与骨髓炎小鼠模型中感染的经典标志物的相关性。
60 只 Balb/c 雌性小鼠（体重 30 至 40 克，3.5 至 4 月龄）分为两组：对照组（n=15）和研究组（n=45）。所有小鼠均接受胫骨皮质切除术，并向髓腔内注射硬化剂。接下来的过程分为两步进行，以使用我们研究中检查的变量观察骨髓炎诱导的骨破坏的可检测性（步骤 1）和治疗反应（步骤 2）。在步骤 1 中，研究组将 1 毫升含有金黄色葡萄球菌（S. aureus）细菌（每毫升 2X108）的溶液注入髓腔内。每组各有 5 只小鼠每 7 天处死一次，持续 3 周，并获得胫骨和血液样本。在步骤 2 中，其余 30 只感染的小鼠进一步分为两组，以研究 RANKL 血浆水平作为治疗反应标志物的可能价值。其中 15 只小鼠接受替考拉宁 20mg/kg 治疗 4 周，而其余小鼠未接受抗生素治疗。每组各有 8 只小鼠在第二周结束时处死，其余 14 只小鼠在第四周结束时处死。从每组处死的小鼠的血液样本中测量全血细胞计数、降钙素原水平、C 反应蛋白（CRP）和 RANKL 浓度。
在步骤 1 中检查骨髓炎骨破坏时，对照组的 RANKL 浓度中位数明显高于干预组的第 1 周和第 3 周。在步骤 2 中，接受和不接受抗菌治疗的两组在整个 4 周内，RANKL、CRP 和降钙素原水平均无显著变化。在分配给金黄色葡萄球菌接种组的受试者中，RANKL 浓度与菌落生长呈显著相关（r=-0.547，p=0.035）。
金黄色葡萄球菌骨髓炎小鼠的 RANKL 水平与菌落生长或其他炎症标志物均不相关，不能用于监测骨髓炎抗菌治疗的反应。
