Genotoxic stress accelerates age-associated degenerative changes in intervertebral discs

Intervertebral disc degeneration (IDD) is the leading cause of debilitating spinal disorders such as chronic lower back pain. Aging is the greatest risk factor for IDD. Previously, we demonstrated IDD in a murine model of a progeroid syndrome caused by reduced expression of a key DNA repair enzyme. This led us to hypothesize that DNA damage promotes IDD. To test our hypothesis, we chronically exposed adult wild-type (Wt) and DNA repair-deficient Ercc1^?/Δ mice to the cancer therapeutic agent mechlorethamine (MEC) or ionization radiation (IR) to induce DNA damage and measured the impact on disc structure. Proteoglycan, a major structural matrix constituent of the disc, was reduced 3–5× in the discs of MEC- and IR-exposed animals compared to untreated controls. Expression of the protease ADAMTS4 and aggrecan proteolytic fragments was significantly increased. Additionally, new PG synthesis was reduced 2–3× in MEC- and IR-treated discs compared to untreated controls. Both cellular senescence and apoptosis were increased in discs of treated animals. The effects were more severe in the DNA repair-deficient Ercc1^?/Δ mice than in Wt littermates. Local irradiation of the vertebra in Wt mice elicited a similar reduction in PG. These data demonstrate that genotoxic stress drives degenerative changes associated with IDD.     

距骨骨折治疗方法的选择及疗效分析

目的：探讨距骨骨折治疗方法的选择并分析其疗效。方法：1998年10月至2009年10月,共治疗距骨骨折患者44例,其中38例获得随访,男28例,女10例;年龄19-65岁,平均33．5岁。采用石膏外固定10例、切开复位内固定22例、I期Blair胫-距-跟融合术6例。按Matti—Weber分型：I型3例,Ⅱ型15例,Ⅲ型16例,Ⅳ型4例。采用Hawkins评定标准通过疼痛、关节活动度、有无跛行等方面进行疗效评估。结果：38例患者的平均随访时间为4．8年（1～11年）。按Hawkins标准,石膏外固定10例中,优4例,良2例,可3例,差1例。切开复位内固定22例中,优2例,良6例。可6例,差8例。其中结果为差的8例,术后3～5年,均实行了Ⅱ期关节融合术,1例术后患肢短缩3em,跛行,患者拒绝进一步治疗,评价为差,余7例效果均为可。I期Blair胫-距-跟融合术6例中,良1例,可4例,差1例。随访期内发现距骨缺血性坏死12例,创伤性关节炎13例。结论：距骨骨折并发症多见且预后欠佳。骨折损伤程度与预后相关。距骨骨折移位小于2mm宜石膏外固定;手法复位后骨折移位大于2mm应切开复位内固定;骨折合并距骨体全脱位或者关节面不能修复的粉碎骨折宜采用Blair胫-距-跟融合术。     

椎弓根固定治疗不稳定胸腰椎骨折的临床疗效

目的评估椎弓根固定治疗不稳定胸腰椎骨折的临床疗效和安全性。方法1998～2001年,我们对31例T11～L2不稳定胸腰椎骨折患者,行椎弓根固定和横突间植骨治疗,其中男24例,女7例,平均年龄38岁。有或无神经症状的不稳定压缩骨折21例,爆裂性骨折伴不完全截瘫6例,爆裂性骨折伴完全截瘫4例。术前和术后均行X片和CT检查。术后通过平均2年的临床和放射学随访,观察脊柱的稳定性和植骨融合的情况。CT和X片评估标准包括脊柱后突角度、椎体前缘高度的压缩比例和椎管内占位的比例。结果所有椎弓根螺钉在术中的植入过程中都没有出现并发症。术后无1例患者出现内固定的失败或因疼痛原因需要行内固定取出,术后平均4个月出现骨折的愈合和放射学的稳定性。术前平均脊柱后突角度、椎体前缘高度的压缩比例、椎管内占位的比例分别为25°,42%,37%,术后1周平均为9°,10%、13%,术后2年平均为11°,13%、11%。结论后路椎弓根固定是治疗不稳定胸腰椎骨折的一种安全和有效的方法。即使在缺乏后方脊柱完整性的情况下,它仍能提供早期坚强固定,从而维持良好的三柱稳定性。     

全身振动对绝经后骨质疏松症患者细胞因子的影响

目的探讨全身振动对绝经后骨质疏松症患者细胞因子水平的影响。方法采用随机对照研究,70例入选的绝经后骨质疏松症志愿者随机分为振动组(n=35)和对照组(n=35)。两组受试者每日均服用钙尔奇D600mg。振动组:应用频率为30Hz的振动治疗仪,3次/周,10min/次,共12周振动干预;对照组仅服用相同剂量的钙尔奇D。观察两组患者干预前后腰椎骨密度(BMD)、疼痛程度和血清内IL-1β、TNF-α和IGF-1的变化。结果与干预前相比,振动组和对照组患者的腰椎BMD均有显著上升[(0.797±0.074)g/cm2vs.(0.734±0.071)g/cm2,(0.802±0.073)g/cm2vs.(0.740±0.064)g/cm2,均P<0.05],骨痛症状均有明显改善,但是振动组BMD的提高及骨痛的改善更为明显(与对照组相比,P<0.05);振动干预后患者血清内IL-1β和TNF-α显著降低[(15.9±4.4)ng/Lvs.(10.1±3.8)ng/L,(165.4±20.6)ng/Lvs.(82.5±18.6)ng/L,均P<0.05],IGF-1显著增高[(96.5±17.2)μg/Lvs.(178.3±22.5)μg/L,P<0.05];对照组实验前后三者均无显著变化。结论 30Hz全身振动具有防治绝经后骨质疏松症的作用,其机制可能与其下调IL-1β、TNF-α水平,上调IGF-1水平有关。     

老年髋部骨折合并肾功能衰竭透析患者的手术治疗

目的探讨老年髋部骨折合并肾功能衰竭透析患者的围手术期治疗方法及短期疗效。方法自2006-01—2012-01共收治11例65岁以上髋部骨折合并肾功能衰竭透析患者,3例股骨粗隆间骨折行闭合复位PFNA内固定术,8例股骨颈骨折均行骨水泥型人工股骨头置换术。总结此类患者围手术期治疗方法,并报道短期随访临床结果。结果 5例在院期间出现并发症。1例股骨颈骨折患者在术后12 d死亡,2例股骨粗隆间骨折内固定患者于术后7、9个月死于心血管意外,其余8例基本恢复术前的活动能力。术后6个月髋关节功能Harris评分：股骨粗隆间骨折平均61.7（49~74）分,股骨颈骨折平均82.6（69~92）分。术后6个月X线片显示3例股骨粗隆间骨折均愈合,至末次随访时7例股骨颈骨折患者X线片未发现股骨假体松动。结论老年髋部骨折合并肾功能衰竭透析患者的围手术期评估非常重要,合理的围手术期处理及合适的手术方式选择能明显提高此类患者围手术期的安全性及术后临床疗效。     

双能X线吸收与定量CT对比评价北京地区中老年女性与年龄相关的骨丢失

目的 采用双能X线吸收(DXA)和定量CT(QCT)对比评价北京地区中老年女性骨密度与年龄相关的骨丢失。方法 收集北京地区接受腰椎正位及髋部DXA检查(面积骨密度测量)的社区女性10 472名,接受腰椎QCT检查(体积骨密度测量)的女性562名。将接受两种检查的受检者分别按每10岁年龄段分组。计算各组别的平均骨密度,并计算峰值骨密度各组别的骨丢失率,分析骨密度与年龄间的相关性。结果 DXA测量北京地区女性腰椎、股骨颈及全髋部的峰值骨密度均在30~39岁年龄组,40岁以后各部位骨密度开始不同程度减低,至80~94岁组腰椎、股骨颈、全髋部累计骨丢失率分别为21.7%、31.4%和29.5%;QCT测量腰椎松质骨的峰值骨密度在20~29岁组,至80~97岁组累计骨丢失率达58.2%。累计骨丢失率从高到低依次为腰椎松质骨 >股骨颈 >全髋部 >腰椎正位。结论 腰椎QCT可较DXA更早、更准确地显示中老年女性的骨丢失情况,对增龄性骨丢失更敏感。     

微创椎间孔镜治疗伴有坐骨神经痛的腰椎间盘突出症

目的: 分析经皮穿刺经椎间孔入路内窥镜下选择性治疗伴有坐骨神经痛的腰椎间盘突出症的临床疗效. 方法: 对2011年6月至2012年1月接受经皮穿刺经椎间孔入路全内窥镜下治疗的46例腰椎间盘突出症患者进行回顾性分析,男28例,女18例;年龄11～77岁,平均(39.7±15.3)岁;其中L₅S₁ 20例,L_4,5 26例. 所有患者表现腰痛及下肢放射性坐骨神经痛,术前直腿抬高试验阳性. 术后即刻检查患者直腿抬高试验并记录手术时间、出血量、术中及术后并发症、住院时间、返回工作岗位时间,观察术前,术后1 d及术后3、6、12个月的视觉疼痛评分(visual analog scale,VAS),对术前和末次随访时JOA评分(Japanese orthopedic association score,JOA)及JOABPEQ评分(Japanese orthopedic back pain evaluation questionnaire,JOABPEQ)进行统计学分析以评价其临床疗效. 结果: 所有手术顺利完成,术后即刻直腿抬高试验转为阴性,平均手术时间(93.0±28.0) min,出血量(20.0±9.0) ml,术后住院时间(3.1±1.5) d,返回工作或恢复日常生活时间(11.6±4.2) d.平均随访时间(13.9±1.6)个月,术前,术后1 d,术后3、6、12个月的腰痛VAS评分分别为5.3±1.2,1.9±1.1,1.0±0.8,0.9±0.8,0.8±0.6;腿痛VAS评分分别为7.2±1.2,0.8±1.2,0.5±0.8,0.5±0.8,0.3±0.8;JOABPEQ评分5项指标(腰痛、腰部功能、行走能力、社会生活能力、心理状态)术前分别为27.0±30.6,37.3±27.4,38.5±26.6,33.0±13.7,55.4±19.0;末次随访时分别为83.6±24.8,89.4±15.7,87.0±17.9,58.4±14.6,79. 5±13.4.JOA评分术前及末次随访分别为9.1±2.6及27.3±1.7.各项评分术前术后差异均有统计学意义(P<0.05).结论: 经皮椎间孔入路镜下治疗伴有坐骨神经痛的腰椎间盘突出安全有效,能迅速缓解患者疼痛,治疗后患者能迅速恢复日常生活及工作.     

Accelerated aging of intervertebral discs in a mouse model of progeria

Intervertebral disc degeneration (IDD) is a common and debilitating disorder that results in reduced flexibility of the spine, pain, and reduced mobility. Risk factors for IDD include age, genetic predisposition, injury, and other environmental factors such as smoking. Loss of proteoglycans (PGs) contributes to IDD with advancing age. Currently there is a lack of a model for rapid investigation of disc aging and evaluation of therapeutic interventions. Here we examined progression of disc aging in a murine model of a human progeroid syndrome caused by deficiency of the DNA repair endonuclease, ERCC1–XPF (Ercc1^?/Δ mice). The ERCC1‐deficient mice showed loss of disc height and degenerative structural changes in their vertebral bodies similar to those reported for old rodents. Compared to their wild‐type littermates, Ercc1^?/Δ mice also exhibit other age‐related IDD characteristics, including premature loss of disc PG, reduced matrix PG synthesis, and enhanced apoptosis and cell senescence. Finally, the onset of age‐associated disc pathologies was further accelerated in Ercc1^?/Δ mice following chronic treatment with the chemotherapeutic agent mechlorethamine. These results demonstrate that Ercc1^?/Δ mice represent an accurate and rapid model of disc aging and provide novel evidence that DNA damage negatively impacts PG synthesis. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:1600–1607, 2010