Rheumatology, Boston University, Boston, Massachusetts, USA.
Biostatistics, School of Public Health, Boston, Massachusetts, USA.
Ann Rheum Dis. 2020 Aug;79(8):1105-1110. doi: 10.1136/annrheumdis-2020-217363. Epub 2020 May 7.
Although treatment development in osteoarthritis (OA) focuses on chondroprotection, it is unclear how much preventing cartilage loss reduces joint pain. It is also unclear how nociceptive tissues may be involved.
Using data from the Osteoarthritis Initiative, we quantified the relation between cartilage loss and worsening knee pain after adjusting for bone marrow lesions (BMLs) and synovitis, and examined how much these factors mediated this association. 600 knee MRIs were scored at baseline, 12 months and 24 months for quantitative and semiquantitative measures of OA structural features. We focused on change in medial cartilage thickness using an amount similar to that seen in recent trials. Linear models calculated mean change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score with cartilage loss, adjusted for baseline BMLs, synovitis and covariates. Mediation analysis tested whether change in synovitis or BMLs mediated the cartilage loss-pain association. We carried out a subanalysis for knees with non-zero baseline WOMAC pain scores and another for non-valgus knees.
Cartilage thickness loss was significantly associated with a small degree of worsening in pain over 24 months. For example, a loss of 0.1 mm of cartilage thickness over 2 years was associated with a 0.32 increase in WOMAC pain (scale 0-20). The association of cartilage thickness loss with pain was mediated by synovitis change but not by BML change. Subanalysis results were similar.
Cartilage thickness loss is associated with only a small amount of worsening knee pain, an association mediated in part by worsening synovitis. Demonstrating that chondroprotection reduces knee pain will be extremely challenging and is perhaps unachievable.
尽管骨关节炎(OA)的治疗重点在于软骨保护,但尚不清楚预防软骨损失能在多大程度上减轻关节疼痛。此外,疼痛感受器组织(nociceptive tissues)是否也会参与其中,目前也不清楚。
我们利用 Osteoarthritis Initiative 的数据,在调整骨髓病变(BML)和滑膜炎后,量化了软骨损失与膝关节疼痛恶化之间的关系,并研究了这些因素在多大程度上介导了这种关联。在基线、12 个月和 24 个月时,对 600 个膝关节 MRI 进行了定量和半定量的 OA 结构特征评分。我们主要关注内侧软骨厚度的变化,使用的量与近期试验中观察到的相似。线性模型计算了 Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC)疼痛评分与软骨损失的平均变化,调整了基线 BML、滑膜炎和协变量。中介分析测试了滑膜炎或 BML 的变化是否介导了软骨损失与疼痛之间的关联。我们对基线 WOMAC 疼痛评分不为零的膝关节进行了亚分析,对非内翻膝关节也进行了另一项亚分析。
软骨厚度损失与疼痛在 24 个月内的轻度恶化显著相关。例如,在 2 年内损失 0.1 毫米的软骨厚度与 WOMAC 疼痛增加 0.32 相关(范围 0-20)。软骨厚度损失与疼痛之间的关联部分通过滑膜炎变化介导,但不是通过 BML 变化介导。亚分析结果相似。
软骨厚度损失仅与膝关节疼痛的轻度恶化相关,这种关联部分是由滑膜炎的恶化介导的。证明软骨保护可以减轻膝关节疼痛将极具挑战性,或许是无法实现的。