目的新骨形成和骨吸收是强直性脊柱炎(AS)的2个主要组织病理学特征。研究已经表明,碳酸酐酶阻断剂可以抑制骨吸收,本实验室也发现碳酸酐酶1(CA1)在AS滑膜中高表达,并可以促进碳酸钙沉淀导致新骨形成。醋甲唑胺是一种抗碳酸酐酶的药物,本文探索醋甲唑胺治疗AS的有效性和安全性。方法 2名处于AS活动期患者(分别称为S和L)每天口服甲醋唑胺片2次,25mg/次,共3个月。每个月进行常规血检、尿检、血生化检测和CT检查。同时根据AS疾病的活动指标(BASDAI)和AS功能性指标(BASFI)进行临床观察。2名患者均经历过非类固醇抗炎药(NSAIDs)和缓解病情抗风湿药(DMARDs)治疗,但无明显疗效。结果经过3个月的治疗之后,2名AS患者在疲劳度、晨僵和全身关节疼痛度方面均明显好转。患者S的BASDAI从5.4降到4.4,患者L的BASDA1从2.4降到2。患者L的BASFI从1.2降到0.2。患者S的红细胞沉积率(ESR)明显降低,而患者L的ESR没有发生变化,仍然处于正常范围。患者S的IgM从2.32g/L明显下降到1.86g/L,尤其是治疗1个月时IgM的水平显著性下降。患者L的IgM没有发生明显的改变,仍然保持在正常的范围内。虽然患者S在治疗第1个月时IgG和IgA有所降低,但是这2名患者的IgG和IgA总体水平上升。患者S的钙浓度从3.05mmol/L降到2.39mmol/L。CT结果表明,治疗后被侵蚀的骶髂关节的关节面变得清晰,炎症区域、钙化沉积面积开始缩小。患者用药后没有表现明显不良反应,虽然患者S和L的尿液中的蛋白质含量有所升高,但是仍处于正常的范围。结论醋甲唑胺对AS有一定治疗,无明显不良反应。醋甲唑胺可能通过抑制CA1活性来抑制AS新骨形成和骨吸收过程。
Objectives Increased bone resorption and new bone information are two characteristics of ankylosing spondylitis (AS). Much evidence has shown that carbonic anhydrase inhibitors can restrain bone resorption. We had detected increased expression of carbonic anhydrase I (CA1) in synovium of patients with AS. Other studies reported that CA1 stimulates CaCO3 precipitation, an essential step for new bone formation. The current study aimed to evaluate the effectiveness and safety of methazolamide, an anti-carbonic anhydrase drug, for treating patients with AS. Methods This study was designed to examine the effi cacy and safety of 12 weeks of oral methazolamide. Two patients, called as S and L, were diagnosed with active AS based on BASDAI (Bath AS disease activity index) and BASFI (Bath ankylosing spondylitis functional index) assessments, radiographic data and other clinical indices. They took methazolamide tablets at a dose of 25 mg twice every day. The patients had experienced previous unsatisfactory therapy with NSAIDs and DMARDs, the traditional treatments for AS. The previous therapy had been discontinued at least three months before the fi rst use of methazolamide. Results Obvious improvements in fatigue, morning stiffness and total back pain were observed in the two patients after 3 months' treatment. Patient S's BASDAI score fell from 5.4 to 4.4, while patient L's BASDAI fell from 2.4 to 2. Patient L's BASFI score fell from 1.2 to 0.2. The ESR values of patient S were considerably reduced, while the ESR value of patient L remained unchanged and in the normal range. The IgM level of patient S declined signifi cantly from 2.32g/L to 1.86g/L. The decline was especially signifi cant at the fi rst month following the treatment. The levels of IgM of patient L did not change signifi cantly and remained in the normal range after the treatment. The IgG levels and the IgA levels were increased for the two patients, although IgG level and the IgA level was considerably declined at the f irst month