Raynauld Jean-Pierre, Pelletier Jean-Pierre, Delorme Philippe, Dodin Pierre, Abram François, Martel-Pelletier Johanne
Osteoarthritis Research Unit, University of Montreal Hospital Research Centre.
Medical Imaging Research & Development, ArthroLab Inc., Montreal, Quebec, Canada.
Rheumatology (Oxford). 2017 Jun 1;56(6):989-998. doi: 10.1093/rheumatology/kew504.
Knee bone curvature assessed by MRI was associated with OA cartilage loss. A recent knee OA trial demonstrated the superiority of chondroitin sulfate over celecoxib (comparator) at reducing cartilage volume loss (CVL) in the medial compartment (condyle). The main objectives were to identify which baseline bone curvature regions of interest (BCROI) best associated with CVL and investigate whether baseline BCROI and 2-year change are correlated with the protective effect of chondroitin sulphate on CVL.
This post hoc analysis of a clinical trial used the according-to-protocol population (chondroitin sulphate, n = 57; celecoxib, n = 63) baseline and 2-year MRI to assess bone curvature and CVL. Global optimum search identified the BCROI in the medial condyle using celecoxib as reference. Statistical analyses were performed with Pearson's correlation, Mann-Whitney U -test, Student's t -test and analysis of covariance.
The BCROI including the medial posterior condyle and lateral central condyle was found to correlate best with medial condyle CVL at 2 years ( r = 0.33, P = 0.008). In patients with a baseline BCROI value less than the median (more flattened bone), chondroitin sulphate demonstrated a protective effect on CVL compared with celecoxib in the medial compartment (P = 0.037). In patients with 2-year BCROI changes greater than the median (greater severity of bone flattening), chondroitin sulphate protected against CVL in the medial compartment, condyle and central plateau (P ⩽ 0.030).
This study is the first to demonstrate the feasibility and usefulness of bone curvature measurements to predict effectiveness of OA treatment on CVL. The results identify bone curvature as a potential novel biomarker for knee OA clinical trials.
通过MRI评估的膝关节骨曲率与骨关节炎(OA)软骨损伤有关。最近一项膝关节OA试验表明,硫酸软骨素在减少内侧间室(髁)软骨体积损失(CVL)方面优于塞来昔布(对照药物)。主要目的是确定哪些基线骨曲率感兴趣区域(BCROI)与CVL相关性最佳,并研究基线BCROI和2年变化是否与硫酸软骨素对CVL的保护作用相关。
这项对一项临床试验的事后分析使用了符合方案人群(硫酸软骨素组,n = 57;塞来昔布组,n = 63)的基线和2年MRI来评估骨曲率和CVL。全局最优搜索以塞来昔布为参照确定了内侧髁的BCROI。采用Pearson相关性分析、Mann-Whitney U检验、Student's t检验和协方差分析进行统计分析。
发现包括内侧后髁和外侧中央髁的BCROI与2年内侧髁CVL相关性最佳(r = 0.33,P = 0.008)。在基线BCROI值低于中位数(骨更扁平)的患者中,与塞来昔布相比,硫酸软骨素在内侧间室对CVL具有保护作用(P = 0.037)。在2年BCROI变化大于中位数(骨扁平严重程度更高)的患者中,硫酸软骨素在内侧间室、髁和中央平台预防了CVL(P≤0.030)。
本研究首次证明了骨曲率测量用于预测OA治疗对CVL有效性的可行性和实用性。结果确定骨曲率为膝关节OA临床试验的一种潜在新型生物标志物。