Particulate endocytosis mediates biological responses of human mesenchymal stem cells to titanium wear debris.

Continual loading and articulation cycles undergone by metallic (e.g., titanium) alloy arthroplasty prostheses lead to liberation of a large number of metallic debris particulates, which have long been implicated as a primary cause of periprosthetic osteolysis and postarthroplasty aseptic implant loosening. Long-term stability of total joint replacement prostheses relies on proper integration between implant biomaterial and osseous tissue, and factors that interfere with this integration are likely to cause osteolysis. Because multipotent mesenchymal stem cells (MSCs) located adjacent to the implant have an osteoprogenitor function and are critical contributors to osseous tissue integrity, when their functions or activities are compromised, osteolysis will most likely occur. To date, it is not certain or sufficiently confirmed whether MSCs endocytose titanium particles, and if so, whether particulate endocytosis has any effect on cellular responses to wear debris. This study seeks to clarify the phenomenon of titanium endocytosis by human MSCs (hMSCs), and investigates the influence of endocytosis on their activities. hMSCs incubated with commercially pure titanium particles exhibited internalized particles, as observed by scanning electron microscopy and confocal laser scanning microscopy, with time-dependent reduction in the number of extracellular particles. Particulate endocytosis was associated with reduced rates of cellular proliferation and cell-substrate adhesion, suppressed osteogenic differentiation, and increased rate of apoptosis. These cellular effects of exposure to titanium particles were reduced when endocytosis was inhibited by treatment with cytochalasin D, and no significant effect was seen when hMSCs were treated only with conditioned medium obtained from particulate-treated cells. These findings strongly suggest that the biological responses of hMSCs to wear debris are triggered primarily by the direct endocytosis of titanium particulates, and not mediated by secreted soluble factors. In this manner, therapeutical approaches that suppress particle endocytosis could reduce the bioreactivity of hMSCs to particulates, and enhance long-term orthopedic implant prognosis by minimizing wear-debris periprosthethic osteolysis.     

降钙素防治骨质疏松模型兔的人工假体无菌性松动的实验研究

[目的]探讨降钙素对已行人工假体植入骨质疏松模型免的假体无菌性松动防治作用的实验研究。[方法]将30只假体植入模型的骨质疏松症兔随机分成实验组和对照组，各15只。实验组给予鲑鱼降钙素治疗（6U／kg，肌注，隔日1次），而对照组给予等量的生理盐水肌注，持续治疗半年。两组均分别于术前、术后4、8、12和24周检测假体周围感应区（ROI）骨密度（BMD）；于术前及术后4、12、24周行血清骨代谢指标检测：骨特异性碱性磷酸酶（BALP）、骨钙素（BGP）、抗酒石酸酸性磷酸酶-5b（TRAP-5b）；所有动物于术后24周处死，分别行假体拔出实验与扭转实验测定和假体周围骨组织形态计量学分析。[结果]术后24周，实验组假体周围局部感兴趣区BMD增加近5％，而对照组假体周围局部感兴趣区BMD下降了6％，两组比较有显著性差异（P〈0．01）；骨代谢指标中，术后24周实验组的BALP、BGP稍有下降，但组内无显著性差异（P〉0．05），而TRAP-5b有明显下降（P〈0．05），这些指标与对照组比较差异显著（P〈0．05或P〈0．01）；生物力学检测显示，实验组的假体拔出实验较对照组提高了约50％，扭转实验提高近1倍，且两组比较差异显著（P〈0．01）；骨组织形态计量学显示，实验组中反映骨吸收的Oc．No／Tb．Pm、ES／BS明显减少；反映骨量和微结构的％Tb．Ar、Tb．N明显增多，而Tb．Sp明显变窄：反映骨形成与骨矿化的OS／BS、MAR、BFR／TV及％L．Pm也均明显增多；这些指标与对照组比较差异显著（P〈0．01或P〈0．05）。[结论]鲑鱼降钙素能明显减少人工假体周围骨量的丢失和抑制骨溶解；并加快假体周围的骨形成，提高骨密度，促进生理性骨矿化；还能改善骨质量，促进骨微结构改变，提高骨的生物力学特性并增加假体四周的支撑力。其对骨质疏松症兔的假体松动有明显的预防和治疗作用。这对临床预防和治疗人工关节的无菌性松动有很好的指导意义。     

钛颗粒负荷对切应力作用下骨髓间质干细胞F-actin表达和DNA含量的影响

假体磨损碎屑颗粒是引起假体一骨界面无菌性炎症和骨溶解而致全关节置换术失败的主要原因之一。磨屑颗粒所诱发的骨溶解须有周围骨组织中成骨细胞分泌足够的骨基质以弥补丢失的骨量，而成骨细胞正常的数量和质量有赖于其来源骨髓祖细胞—骨髓问质干细胞的正常增殖分化能力的维持。为了探讨磨屑钛颗粒对大鼠骨髓间质干细胞(Rat MSCs，rMSCs)产生细胞毒性的可能细胞分子机制，选用健康3月龄SD雄性大鼠，采用Percoll等密度梯度离心法分离获取rMSCs，经体外传代纯化培养后，与不同直径、不同负荷浓度、不同负荷作用时间的钛颗粒悬液共孵育，再采用精准的流室系统对钛颗粒负荷的rMSCs施加一定的流体剪切应力(Fluid shear stress，FSS)后立刻固定细胞，经免疫荧光抗体染色，结合激光共聚焦显微镜技术和图像分析软件定性定量分析rMSCs F—actin表达和DNA含量的变化情况。同时设置相应的未经钛颗粒孵育的rMSCs细胞为对照组细胞。结果显示，切应力作用可上调rMSCs胞内F—actin的表达。亚微(Submieron)直径(0．9μm)的钛颗粒负荷对rMSCs F—actin表达和DNA含量的抑制作用最为显著，并伴有凋亡小体出现；直径为2．7μm的钛颗粒负荷产生的抑制作用略为减弱，而较大直径(6．9μm)的抑制效应最弱。相同条件下，钛颗粒负荷对F—actin的抑制效应有一定的时间和浓度依赖性：以0．1wt％浓度对F—actin表达和DNA含量的抑制效应最为明显，亦有凋亡小体的出现；随着浓度的降低，抑制作用亦减弱，以0．01wt％浓度最弱；随着作用时间的延长，F—actin表达和DNA含量逐渐降低，至实验中的32h达到最低值。提示：磨屑颗粒对rMSCs活力的抑制作用是假体无菌性松动的可能分子机制，对其具体细胞分子机制进行深入研究，必将有助于有效防治假体松动药物的研发应用以及人工关节材料的优化设计，从而为全关节置换术患者真正带来福音。     

Risk Factor Analysis of Facet Fusion Following Cervical Lateral Mass Screw Fixation with a Minimum 1-Year Follow-up: Assessment of Maximal Insertional Screw Torque and Incidence of Loosening

Posterior stabilization is a common surgical procedure, which aims for rigid stabilization by facet fusion. Facet non-union has a potential risk of the screw loosening and malalignment. Although some authors have reported the influencing factors about screw loosening in the lumbar spine, there are few reports about the risk factor contributing to the facet non-union in the cervical spine. In all, 22 patients (78 facets and 122 screws) with degenerative cervical kyphosis or spondylolisthesis who underwent decompression and lateral mass screw (LMS) fixation were analyzed. Age, gender, smoking, bone mineral density (BMD), the degree of facet decortication with bone packing, and screw loosening were investigated as risk factors contributing to the facet non-union at each segmental fused level. Facet fusion rate was 85.9% (67/78 facets) and the incidence of loosening was 4.9% (6/122 screws, 4 patients). Insufficient facet decortication with bone packing is a significant risk factor of facet non-union (p <0.05, odds ratio: 26.5). All six loosened screws were associated with bony non-union of the facet and were located in the uppermost or lowermost vertebrae. Comparing loosened screws and stable screws, the average maximal insertional screw torque (MIT) was 9.8 cNm and 39.5 cNm, respectively (p <0.05). Additionally, the length of the stable screws was significantly longer versus the loosened screws (p <0.05). Lower MIT and shorter screw length located near the ends of the lateral mass may predict loosening, which can lead to facet non-union. Sufficient facet decortication with bone packing is one of the important factors contributing to the facet fusion.     

Utility and Prognostic Ability of a Diagnostic Injection Before Revision Total Knee Arthroplasty

BackgroundDiagnostic injections are commonly utilized in the workup of painful total knee arthroplasties (TKA), particularly when the diagnosis remains unclear. However, current literature provides limited evidence regarding the utility and prognostic capability of anesthetic injections in this scenario. This study sought to establish the role of diagnostic injections in predicting successful revision TKA.MethodsA retrospective review was conducted on 144 consecutive aseptic revision TKAs receiving diagnostic anesthetic injections. Instability (57.6%) and aseptic loosening (33.3%) comprised most revision etiologies. Patient-reported percentage pain relief after the injection was statistically correlated with KOOS JR, Knee Society Score, UCLA Activity Level, and satisfaction scores.ResultsAbout 74.3% (107/144) of revision TKAs reported >50% pain relief after injection. There were no differences in pain relief based on revision indication (P = .841). Improvement from preoperative activity level was greater in the >50% pain relief group (P = .024). Four-month patient satisfaction did not differ between patients who reported >50% and ≤50% pain relief (67% vs. 66%, P = .130). About 64% of patients who reported >50% pain relief were satisfied at minimum 1-year follow-up, compared with only 47% of those who reported ≤50% pain relief after diagnostic injection (P < .001).ConclusionStudy results show that patients reporting >50% pain relief after diagnostic injection have improvements in activity level and maintain greater satisfaction at minimum 1-year than those reporting ≤50% pain relief. Expectations for improvement after revision TKA should be tempered if diagnostic anesthetic injection yields minimal subjective pain relief.     

Alignment in Medial Fixed-Bearing Unicompartmental Knee Arthroplasty: The Limb Has a Leg Up on the Component

BackgroundTo assess how implant alignment affects unicompartmental knee arthroplasty (UKA) outcome, we compared tibial component alignment of well-functioning UKAs against 2 groups of failed UKAs, revised for progression of lateral compartment arthritis (“Progression”) and aseptic loosening (“Loosening”).MethodsWe identified 37 revisions for Progression and 61 revisions for Loosening from our prospective institutional database of 3351 medial fixed-bearing UKAs performed since 2000. Revision cohorts were matched on age, gender, body mass index, and postoperative range of motion with “Successful” unrevised UKAs with minimum 10-year follow-up and Knee Society Score ≥70. Tibial component coronal (TCA) and sagittal (TSA) plane alignment was measured on postoperative radiographs. Limb alignment was quantified by hip-knee-ankle (HKA) angle on long-leg radiographs. In addition to directly comparing groups, a multivariate logistic regression examined how limb and component alignments were associated with UKA revision.ResultsIn the Progression group, component alignment was similar to the matched successes (TCA 3.6° ± 3.5° varus vs 5.1° ± 3.5° varus, P = .07; TSA 8.4° ± 4.4° vs 8.8° ± 3.6°, P = .67), whereas HKA angle was significantly more valgus (0.3° ± 3.6° valgus vs 4.4° ± 2.6° varus, P < .001). Loosening group component alignment was also similar to the matched successes (TCA 6.1° ± 3.7° varus vs 5.9° ± 3.1° varus, P = .72; TSA 8.4° ± 4.6° vs 8.1° ± 3.9°, P = .68), and HKA was significantly more varus (6.1° ± 3.1° varus vs 4.0° ± 2.7° varus, P < .001). Using a multivariate logistic regression, HKA angle was the most significant factor associated with revision (P < .001).ConclusionIn this population of revised UKAs and long-term successes, limb alignment was a more important determinant of outcome than tibial component alignment.Level of EvidenceLevel III case-control study.     

股骨头钻孔骨移植髋关节外支撑治疗股骨头无菌坏死

探讨股骨头钻孔管移植髋关节外支撑治疗股骨头无菌坏死的疗效。方法 :股骨头钻孔去除坏死骨加上腓骨骨移植 ,髋关节外支撑架固定。结果 :治疗成人股骨头坏死1 1例 ,男 8例 ,女 3例 ;平均年龄 40岁 ,平均病史 2年 ;本组Ⅰ～Ⅲ期 8例 ,Ⅲ～Ⅳ期 3例 ;随访2年 ,优良率 86 6 %。结论 :本术式优点是 :注重彻底清除坏死骨 ,髋关节外植骨 ,早期负重。     

青壮年股骨颈骨折患者行闭合复位内固定手术后发生股骨头无菌性缺血坏死影响因素分析

目的探讨青壮年股骨颈骨折患者经闭合复位内固定手术治疗后发生股骨头无菌性缺血坏死的影响因素。方法回顾性分析自2015年1月至2020年1月北部战区总医院骨科收治的经闭合复位内固定手术治疗的62例青壮年股骨颈骨折患者临床资料,包括年龄、性别、体质量指数、骨折侧、Garden分型、损伤至手术前时间、术前是否牵引、内固定是否取出、股骨头后倾角度、是否有股骨颈皮质粉碎、术后负重活动时间、复位质量等,并分析上述指标对术后发生股骨头无菌性缺血坏死的影响。结果青壮年患者发生术后股骨头无菌性缺血坏死与Garden分型、内固定是否取出、股骨头后倾角度、股骨颈皮质粉碎情况、复位质量相关(P<0.05)。多因素Logistic分析显示,内固定是否取出、复位质量、股骨头后倾角度与术后发生股骨头无菌性缺血坏死关系密切(P<0.05)。结论青壮年股骨颈骨折闭合复位内固定术后发生股骨头坏死的影响因素较多,其中,内固定是否取出、复位质量、股骨头后倾角度与术后发生股骨头坏死密切关系。