强直性脊柱炎炎性骨破坏和病理性骨化的信号转导机制

炎性骨破坏和病理性骨化是强直性脊柱炎的特征性病理表现,有多种细胞因子和信号通路参与其中。目前,肿瘤坏死因子α、白细胞介素是最广为人知的参与炎性破坏的细胞因子,与此同时,伴随着越来越多新的生物学标志物的出现,Wnt/β- catenin信号通路、BMP/TGF-β信号通路等在AS骨化中的作用也日益受到重视。细胞因子介导的炎症与病理性骨化信号通路之间关系的研究,可能从分子水平上揭示强直性脊柱炎从炎症到骨化过程的机制,并为TNF抑制剂的长期临床应用提供依据。     

强直性脊柱炎致病机制研究进展

强直性脊柱炎(AS)是一种慢性进行性脊柱关节病.骶髂关节炎症和关节骨化强直是AS典型病理变化的两个阶段,两者之间有一定相关性,但炎症的发生不是异位骨化的充分必要条件.AS异位骨化涉及BMP、Wnt、Notch和Hedgehog等多条信号通路,各信号通路之间相互联系、相互制约,形成一错综复杂的调节网络.该文就AS病理特征...     

MicroRNA在强直性脊柱炎成骨、破骨机制中的作用

炎性骨破坏和新骨形成是强直性脊柱炎(ankylosing spondylitis,AS)的典型病理改变,AS早期以炎症为主,晚期出现异位骨化和骨破坏,异位骨化和骨破坏两种矛盾的表现反映了强直性脊柱炎患者成骨与破骨过程之间的动态平衡被打破。其发病机制尚不完全清楚,目前研究认为,AS复杂的新骨形成机制与Wnt/β-catenin信号通路及BMP/Smads通路密切相关,而破骨细胞则在骨破坏过程中起重要作用,RANKL/RANK/OPG系统中的细胞因子是调控破骨细胞分化成熟的关键因子。Micro RNA可调节成骨细胞、软骨细胞和破骨细胞的分化与功能,是骨形成、骨吸收、骨重塑和修复过程中的关键调节因子。研究MicroRNA在强直性脊柱炎成骨、破骨机制中的作用,可为AS的诊断和治疗提供新的依据。     

中医药调控骨代谢防治强直性脊柱炎的研究进展

骨代谢紊乱在加剧强直性脊柱炎的病理进程中扮演了重要角色。强直性脊柱炎出现局部过度骨化的同时,存在全身骨量的流失,此外免疫及炎症反应也与骨代谢紊乱密切相关。通过检索国内外文献,对中医药维持强直性脊柱炎骨代谢平衡的分子学机制进行综述,认为中医药通过抑制强直性脊柱炎成骨相关的异位骨化,延缓强直性脊柱炎破骨相关的骨量流失,调节免疫及炎症反应维持强直性脊柱炎骨代谢平衡,发挥防治强直性脊柱炎的作用。     

强直性脊柱炎继发骨质疏松症的机制研究进展

强直性脊柱炎是临床的常见病、多发病，极易导致脊柱关节的进行性退变和脆性骨折的发生，给患者的身心健康和生活质量带来严重影响。骨质疏松症作为强直性脊柱炎的主要并发症，其本质还是机体内环境紊乱引起的骨代谢失衡，免疫紊乱、激素失调参与其发病的整个过程，细胞因子、激素和信号通路在强直性脊柱炎继发骨质疏松症中的作用极其重要。从分子生物学层面揭示强直性脊柱炎继发骨质疏松症的具体机制，可为临床强直性脊柱炎诊疗中积极配合抗骨质疏松治疗提供理论依据。     

强直性脊柱炎骨化临床研究进展

强直性脊柱炎（ankylosing spondylitis, AS)是脊柱关节病中最常见的疾病,早期以炎症为主,晚期可出现骨质疏松和骨化两种看似矛盾的表现,骨化的研究有助于AS的治疗。骨化是导致患者出现相关症状、功能障碍、甚至残疾的主要原因。骨化主要发生于脊柱,因为病变组织不易获取,且病程漫长,个体间差异大,目前研究进展缓慢。AS患者骨化平均每年改良的 Stoke强直性脊柱炎脊柱评分（modified Stoke’s AS spine score,mSASSS)进展1分,仅不到30%的患者出现较快进展。基线时炎症与骨化进展有关,主要是红细胞沉降率（erythrocyte sedimentation rate,ESR)、C-反应蛋白（C-reactive protein,CRP)、强直性脊柱炎疾病活动指数（ankylosing spondylitis disease activity score, ASDAS)等客观炎症指标,而与基于患者自我报告结果 (patient-reported outcome,PRO)的 Bath 强直性脊柱炎疾病活动指数（bath ankylosing spondylitis disease activity index, BASDAI) 关系不明确。此外,基线时已存在的骨化程度、磁共振成像（magnetic resonance imaging,MRI)骨髓脂肪沉积、吸烟等也是骨化预测因素。非甾体抗炎药和肿瘤坏死因子拮抗剂对延缓AS病理性成骨的作用尚不明确。     

强直性脊柱炎的骨密度探讨

目的 对与HLA-B27相关的脊椎及关节的免疫性、炎症性病变所伴有的骨质密度与骨矿含量变化进行研究,发现其骨量变化的规律。方法 用双能量骨密度仪(DEXA)测定16例确诊为强直性脊柱炎患者与20例正常对照组病例作比较。结果 早期强直性脊柱炎患者的脊椎及股骨近端骨密度值已有明显降低．晚期病例股骨颈骨密度仍低于对照组．但因晚期病例椎体周围软组织的骨化、矿化．使腰椎骨密度值反而增高。结论 ①强直性脊柱炎本身从早期开始即伴有骨量丢失．在治疗强直性脊柱炎同时应防止骨量丢失及畸形出现。②晚期患者因脊柱周围软组织骨化．使DEXA测量方法不能真实反映椎体骨量丢失,采用QCT方法更为可取。     

幼年型强直性脊柱炎5例诊治分析

幼年型强直性脊柱炎（Juvenile ankylosing spondylitis）不同于成人型强直性脊柱炎的脊柱椎间盘、纤维环韧带骨化融合和骶髂关节破坏,而主要表现为髋膝等外周大关节不对称性破坏所致的反复发作性肿痛,而腰背部及骶髂关节痛不明显。     

强直性脊柱炎异位骨化机制研究进展

强直性脊柱炎是一种发病机制不明的慢性炎性脊柱关节病,主要侵犯骶髂关节、脊柱关节等,严重者可发生脊柱、关节的畸形和强直。临床表现为炎性腰背痛,夜间及休息后加重,活动后减轻。该病发病率男性高于女性,且男性主要表现为中轴关节改变,而女性大多首发于外周关节。目前生物制剂肿瘤坏死因子抑制剂通过控制炎症,从而改善病情发展,被认为是最前沿的药物,但其在阻断新骨形成方面尚未经循证医学证实有效。本文着眼于新骨形成角度,从基因及细胞因子层面探讨强直性脊柱炎的病因。目前相关研究发现LRP5、ANTXR2、PTGER4、ANKH等基因的异常表达激活骨形成信号通路,在多种细胞因子及相关蛋白(如Noggin蛋白、DKK、转化生长因子-β、骨形态发生蛋白、碳酸酐酶1等)直接或间接作用下将骨形成信号传至靶细胞表面,进而传入细胞核,改变靶细胞正常生理代谢过程,导致过度骨形成,造成异位骨化。近年的临床影像学病例分析也提示了骨赘形成的分布特点,进而推断机械应力是促进其形成的外部因素。本文对强直性脊柱炎异位骨化方面进行了文献综述,以期待能进一步加深对本病的认识,为临床治疗研究提供新的思路。     

强直性脊柱炎合并颈椎无骨折脱位型脊髓损伤

目的 总结强直性脊柱炎合并颈椎无骨折脱位型脊髓损伤的临床特征、诊断和手术治疗。方法 1986～2004年，笔者手术治疗累及颈椎的强直性脊柱炎合并无骨折脱位型脊髓损伤27例。结果 本组27例中椎管内韧带骨化18例，脊髓损伤的原因依次为韧带骨化所致的椎管狭窄，椎间盘损伤和椎体后骨刺及椎间不稳定。术前均为不完全性损伤，非手术治疗不提高脊髓功能。术后脊髓ASIA分级平均改善1级。后路手术椎板切除率、出血量、手术时间、术后引流量明显高于不合并强直性脊柱炎的患者。前路手术可达到骨性融合。结论 强直性脊柱炎合并颈椎无骨折脱位型脊髓损伤一般为不完全性损伤，损伤的内因依次为椎管内韧带骨化所致的椎管狭窄、椎间盘损伤、椎间骨赘和椎间不稳定。适当的手术可改善脊髓功能。手术难度大，风险高。     

Ectopic ossification following total hip replacement in juvenile chronic arthritis

Of twenty-one patients with juvenile chronic arthritis (seventeen with juvenile rheumatoid arthritis and four with juvenile ankylosing spondylitis) who had total hip replacement before the age of thirty years, thirteen patients (62 per cent) showed different degrees of ectopic ossification: nine (53 per cent) of the seventeen with juvenile rheumatoid arthritis and all four of those with juvenile ankylosing spondylitis. Human leukocyte antigen B5 was found with an increased frequency in the patients with ectopic ossification. Functional capacity was not impaired regardless of the severity of the ectopic ossification. As in patients with adult-onset disease, ectopic ossification after total hip replacement occurred with a higher frequency in the patients with juvenile-onset ankylosing spondylitis than in those with juvenile-onset rheumatoid arthritis.     

Primary noncemented total hip arthroplasty in patients with ankylosing spondylitis: Clinical and radiographic results at an average follow-up period of 6 years

Twenty consecutive primary noncemented total hip arthroplasties performed on 12 men with ankylosing spondylitis were available to be studied clinically and radiographically at an average follow-up period of 75 months (range, 27–121 months). The average patient age at the time of surgery was 35 years (range, 23–53 years). Harris hip scores averaged 48.4 before surgery and 89.1 at the most recent follow-up examination. Significant improvements in pain, function, and range of motion were observed following total hip arthroplasty. No hip has required a surgical revision or reoperation. Heterotopic ossification was observed in 6 of 14 hips (43%) in the ankylosing spondylitis patients who had not had any perioperative prophylaxis for heterotopic bone formation. By contrast, 43 of 49 hips (88%) demonstrated heterotopic bone formation in a well-defined control group of 45 men with other diagnoses undergoing the same procedure by the same group of surgeons at the same institution. During the same period using the same implants. A thorough review of the literature and data from the institution does not support the notion that ankylosing spondylitis patients are necessarily predisposed to form heterotopic ossification. The use of routine perioperative prophylaxis for heterotopic ossification may not be warranted in all patients with ankylosing spondylitis undergoing routine primary noncemented total hip arthroplasty.     

强直性脊柱炎的早期诊断策略及其治疗决策

目的 探讨强直性脊柱炎的早期诊断策略及其治疗决策.方法 长时间记录一组(32例)强直性脊柱炎门诊患者的治疗效果.结果 随访2～20年,3例确诊2年后出现两髋关节症状,影像学示两髋关节轻度狭窄,1例20年后两骶髂关节近乎融合,其他患者病情始终平稳.结论 强直性脊柱炎的治疗重在早期发现,及时治疗,长期追踪,合理用药,否则将导致脊柱“竹节样”骨化、髋关节残疾等严重晚期症状.     

Short to long term outcomes of 154 cemented total hip arthroplasties in ankylosing spondylitis

BackgroundLong-term outcome of Total Hip arthroplasty (THA) in Ankylosing Spondylitis (AS) remains unreported. Literature suggests a higher overall failure rate in ankylosing spondylitis as compared to osteoarthritis. Concern has been expressed regarding joint survival, given that recipients are generally young. The results of cemented THA in patients with ankylosing spondylitis were studied to determine the utility of THA for these patients.MethodsConsecutive series of 96 patients (77 males (80%) and 19 females (20%)) with ankylosing spondylitis who underwent 154 cemented THAs at a tertiary referral orthopaedic centre between January 1990–September 2015 were retrospectively analyzed for clinical and radiological outcomes; 58 patients (60.4%) underwent bilateral surgery.ResultsMean age at surgery was 48 years. Average follow up was 12.8 (2.1–24.8) years. 95% of the patients had a good or excellent post-operative outcome.Out of the total 154 hips operated on, 11% (17 hips) developed post-operative complications. Overall, 15 hips (9.7%) required a revision of the procedure, with the most common indication being aseptic loosening of the acetabulum. Average time to revision was 8.5 years (2–15). Survivorship analysis revealed probability of survival of both components at the end of 10 years, with revision due to any reason as the end point to be 92% (with 95% confidence intervals).21 hips (14%) developed heterotopic ossification post-operatively, of which 4 patients (2%) had clinically significant ossification (Brooker III or IV).ConclusionThis is one of the largest series of patients with ankylosing spondylitis with long term follow up available. Cemented THA in patients with ankylosing spondylitis provided consistently good and predictable long term results, with low rate of complications and revisions.     

Total hip arthroplasty in ankylosing spondylitis: an analysis of 181 hips

The results of cemented total hip arthroplasty (THA) in patients with ankylosing spondylitis were studied to determine the utility of THA for these patients. A total of 103 patients with ankylosing spondylitis underwent 181 THAs; 72 patients (69.9%) had bilateral surgery. The mean follow-up was 10.3 years. The mean age of patients at surgery was 47 years. Before surgery, 42 hips (23.2%) were ankylosed. Revision surgery was carried out in 25 hips (13.8%). Heterotopic ossification was present in 21 hips (11.6%); however, no patients had functional impairment or reankylosis. At final follow-up examination, 173 hips (96%) had an excellent (low) pain score, and 53 hips had a normal or near-normal function score (29.2%). The probability of survival of the implant was 71% at 27 years. THA provides long-term improvement in hip function for patients with ankylosing spondylitis.     

Orthopaedic management of ankylosing spondylitis

Ankylosing spondylitis is an inflammatory disease of unknown etiology that affects an estimated 350,000 persons in the United States and 600,000 in Europe, primarily Caucasian males in the second through fourth decades of life. Worldwide, the prevalence is 0.9%. Genetic linkage to HLA-B27 has been established. Ankylosing spondylitis primarily affects the axial skeleton and is characterized by inflammation and fusion of the sacroiliac joints, spine, and hips. The resultant deformity leads to severe functional impairment in approximately 30% of patients. Orthopaedic management primarily involves correction of hip deformity through total hip arthroplasty and, less frequently, correction of spinal deformity with spine osteotomy. Closing wedge osteotomies have the lowest incidence of complications. Whether patients with ankylosing spondylitis are at increased risk for heterotopic ossification remains controversial, but comparison with age- and sex-matched counterparts suggests no dramatically higher risk. Because of the high rate of missed fractures and complications after minor trauma in patients with ankylosing spondylitis, plain radiographs are usually not sufficient for evaluation. Thorough patient assessment should include a comprehensive history, physical examination, and laboratory studies.     

Heterotopic bone formation following total hip arthroplasty in ankylosing spondylitis

Heterotopic ossification is a well-recognized complication of total hip arthroplasty. In a retrospective survey of 98 total hip arthroplasties in ankylosing spondylitis performed between 1970 and 1977, 39.8% showed some evidences of heterotopic ossification. Restriction of hip movements was noted in only two. Heterotopic ossification occurred within one year and was higher (64.6%) in patients with bilateral hip replacements if there was evidence of heterotopic bone formation in one hip. The complications were relatively high in hips with previous operations (55%); trochanteric bursitis (50%); and trochanteric detachment (63.3%). No correlation was found between high erythrocyte sedimentation rate and the incidence or extent of heterotopic bone formation.     

Bipolar hip arthroplasty in ankylosing spondylitis

Nineteen severely affected hips in 12 young patients with ankylosing spondylitis were treated with bipolar hip arthroplasty followed by a comprehensive postoperative rehabilitation programme. Additional operative procedures of adductor tenotomy, knee flexion release, supracondylar femoral osteotomy for genu valgum and tendo Achillis lengthening for equinus contracture were required in 13 limbs. After a mean follow-up of 45.8 months, results were good in all cases with respect to relief from pain, and there was significant improvement in posture and function. All the patients resumed employment. The average gain in sum total range of hip movements was 194 deg, and the mean preoperative Harris hip score of 27.8 improved to 82.6 after bipolar arthroplasty. Ectopic ossification did not develop in any case. Bipolar hip arthroplasty appears to be ideally suited for young patients with ankylosing spondylitis.     

Airway management in a man with ankylosing spondylitis

We report a case of difficult airway management in a 41-year-old man with ankylosing spondylitis who was scheduled for total left hip replacement surgery. After several failed attempts to achieve regional anesthesia, we converted to general anesthesia with orotracheal intubation using a fiberoptic bronchoscope. Ankylosing spondylitis leads to fibrosis, ossification, and ankylosis along the spinal column and sacroiliac articulations. Cervical column and atlantooccipital articulation mobility are reduced and in severe cases the cervical vertebrae become fixed in a flexed position. This portion of the spine is also the most susceptible to fracture, particularly in hyperextension, an event that could lead to damage to the cervical spinal cord during maneuvers to manage the airway. Patients with this condition may also have temporomandibular joint involvement, further complicating airway management. We report the case of a patient with ankylosing spondylitis with fixation along the entire spine. The airway was managed by intubation with a fiberoptic bronchoscope. Spontaneous ventilation was maintained during the maneuver, and sedation was achieved with perfusion of remifentanil as the only anesthetic agent following failure of intradural anesthesia.