Cotofana S, Benichou O, Hitzl W, Wirth W, Eckstein F
Institute of Anatomy, Paracelsus Medical University, Salzburg, Austria; Chondrometrics GmbH, Ainring, Germany.
Eli Lilly & Co, Indianapolis, IN, USA.
Osteoarthritis Cartilage. 2014 Dec;22(12):2059-66. doi: 10.1016/j.joca.2014.09.020. Epub 2014 Sep 26.
Anti-catabolic disease modifying drugs (DMOADs) aim to reduce cartilage loss in knee osteoarthritis (KOA). Testing such drugs in clinical trials requires sufficient rates of loss in the study participants to occur, preferably at a mild disease stage where cartilage can be preserved. Here we analyze a "progression" model in mild radiographic KOA (RKOA), based on contra-lateral radiographic status.
We studied 837 participants (62.4 ± 9 yrs; 30 ± 4.9 kg/m²; 61.8% women) from the Osteoarthritis Initiative (OAI) with mild to moderate RKOA (Kellgren Lawrence grade [KLG] 2-3) and with/without Osteoarthritis Research Society International (OARSI) atlas radiographic joint space narrowing (JSN). These had quantitative measurements of subregional femorotibial cartilage thickness from magnetic resonance imaging (MRI) at baseline and 1-year follow-up. They were stratified by contra-lateral knee status: no (KLG 0/1), definite (KLG2) and moderate RKOA (KLG 3/4).
KLG2 knees with JSN and moderate contra-lateral RKOA had (P = 0.008) greater maximum subregional cartilage loss -220 μm [95% confidence interval (CI) -255, -184 μm] than those without contra-lateral RKOA -164 μm [-187, -140 μm]. Their rate of subregional cartilage loss was similar and not significantly different (P = 0.61) to that in KLG 3 knees without contra-lateral RKOA (-232 μm; [-266; -198 μm]). The effect of contra-lateral RKOA status was less in KLG2 knees without JSN, and in KLG3 knees.
KLG2 knees with JSN and moderate contra-lateral RKOA, display relatively high rates of subregional femorotibial cartilage loss, despite being at a relatively mild stage of RKOA. They may therefore provide a unique opportunity for recruitment in clinical trials that explore the efficacy of anti-catabolic DMOADs on structural progression.
抗分解代谢疾病修饰药物(DMOADs)旨在减少膝关节骨关节炎(KOA)中的软骨损失。在临床试验中测试此类药物需要研究参与者有足够的软骨损失率,最好是在软骨可保留的轻度疾病阶段。在此,我们基于对侧放射学状态分析轻度放射学KOA(RKOA)中的“进展”模型。
我们研究了骨关节炎倡议(OAI)中的837名参与者(62.4±9岁;30±4.9kg/m²;61.8%为女性),他们患有轻度至中度RKOA(凯尔格伦·劳伦斯分级[KLG]2 - 3级),且有/无国际骨关节炎研究学会(OARSI)图谱放射学关节间隙变窄(JSN)。这些参与者在基线和1年随访时通过磁共振成像(MRI)对股胫关节亚区域软骨厚度进行了定量测量。他们根据对侧膝关节状态进行分层:无(KLG 0/1)、明确(KLG2)和中度RKOA(KLG 3/4)。
伴有JSN且对侧为中度RKOA的KLG2膝关节,其最大亚区域软骨损失为-220μm[95%置信区间(CI)-255,-184μm],比无对侧RKOA的膝关节(-164μm[-187,-140μm])更大(P = 0.008)。它们的亚区域软骨损失率与无对侧RKOA的KLG 3级膝关节(-232μm;[-266;-198μm])相似,且无显著差异(P = 0.61)。对侧RKOA状态的影响在无JSN的KLG2膝关节和KLG3膝关节中较小。
伴有JSN且对侧为中度RKOA的KLG2膝关节,尽管处于RKOA相对较轻的阶段,但显示出相对较高的股胫关节亚区域软骨损失率。因此,它们可能为探索抗分解代谢DMOADs对结构进展疗效的临床试验提供独特的招募机会。