Garnero P, Aronstein W S, Cohen S B, Conaghan P G, Cline G A, Christiansen C, Beary J F, Meyer J M, Bingham C O
INSERM Research Unit 664, Lyon, France.
Osteoarthritis Cartilage. 2008 Jun;16(6):660-6. doi: 10.1016/j.joca.2007.10.002. Epub 2007 Nov 13.
To investigate whether early changes in biochemical markers of bone (NTX-I) and cartilage (CTX-II [C-terminal crosslinking telopeptide of type II collagen]) degradation are associated with radiological progression in patients with knee osteoarthritis (OA) receiving risedronate.
Two thousand four hundred and eighty three patients with medial compartment knee OA were randomized in two 24-month studies in North America (NA) and European Union (EU). Studies evaluated risedronate 5 mg/day, 35 mg/week (EU), 50 mg/week (NA), and 15 mg/day (NA and EU), compared to placebo in reducing signs and symptoms and in slowing radiographic progression. One thousand eight hundred and eighty five patients from the pooled EU and NA studies with available NTX-I/CTX-II at both baseline and 6 months and radiographs at baseline and at 24 months were analyzed.
Risedronate produced a dose-dependent reduction of NTX-I and CTX-II observed at 6 months which continued up to 24 months. Patients who had CTX-II levels returned to low levels (<150 ng/mmol creatinine) at 6 months had a lower risk of radiographic progression at 24 months than patients whose CTX-II levels were increased both at baseline and 6 months [odds-ratio (95% confidence interval): 0.57 (0.39-0.85) after adjustment for demographics and joint space width]. The lowest risk of progression was observed in patients who had low CTX-II levels both at baseline and at 6 months [odds-ratio 0.36 (0.21-0.63)]. No significant association between NTX-I levels and radiological progression was observed.
CTX-II decreased with risedronate in patients with knee OA and levels reached after 6 months were associated with radiological progression at 24 months. Monitoring a marker of cartilage degradation 6 months after initiating treatment may be instructive in identifying patients with low progression.
探讨接受利塞膦酸盐治疗的膝关节骨关节炎（OA）患者骨（NTX-I）和软骨（CTX-II [II型胶原C末端交联端肽]）降解的生化标志物早期变化是否与放射学进展相关。
2483例内侧间室膝关节OA患者在北美（NA）和欧盟（EU）进行的两项为期24个月的研究中被随机分组。研究评估了利塞膦酸盐5毫克/天、35毫克/周（欧盟）、50毫克/周（北美）和15毫克/天（北美和欧盟）与安慰剂相比在减轻体征和症状以及减缓放射学进展方面的效果。对来自欧盟和北美汇总研究的1885例患者进行了分析，这些患者在基线和6个月时均有可用的NTX-I/CTX-II数据，且在基线和24个月时有X光片。
利塞膦酸盐在6个月时使NTX-I和CTX-II呈剂量依赖性降低，这种降低持续至24个月。在6个月时CTX-II水平恢复至低水平（<150纳克/毫摩尔肌酐）的患者，与在基线和6个月时CTX-II水平均升高的患者相比，在24个月时放射学进展的风险更低[调整人口统计学和关节间隙宽度后的优势比（95%置信区间）：0.57（0.39 - 0.85）]。在基线和6个月时CTX-II水平均低的患者中观察到的进展风险最低[优势比0.36（0.21 - 0.63）]。未观察到NTX-I水平与放射学进展之间存在显著关联。
膝关节OA患者使用利塞膦酸盐后CTX-II降低，6个月时达到的水平与24个月时的放射学进展相关。在开始治疗6个月后监测软骨降解标志物可能有助于识别进展缓慢的患者。
