Department of Kinesiology and Health Sciences, University of Waterloo, Room 1036 Burt Matthews Hall, 200 University Avenue, Waterloo, ON, N2L 3G1, Canada.
Department of Radiology, Stanford University, Stanford, USA.
Clin Rheumatol. 2024 Jul;43(7):2317-2327. doi: 10.1007/s10067-024-07014-2. Epub 2024 May 24.
The purpose was to investigate relationships of cumulative load and cartilage turnover biomarkers with 2-year changes in cartilage in knee osteoarthritis. From participants with Kellgren-Lawrence (KL) grades of 1 to 3, cartilage thickness and transverse relaxation time (T2) were computed from 24-month (baseline) and 48-month magnetic resonance images. Cumulative load was the interaction term of the Physical Activity Scale for the Elderly (PASE) and body mass index (BMI). Serum cartilage oligomeric matrix protein (COMP) and the nitrated form of type II collagen (Coll2-1 NO2) were collected at baseline. Multiple regressions (adjusted for baseline age, KL grade, cartilage measures, pain, comorbidity) evaluated the relationships of cumulative load and biomarkers with 2-year changes. In 406 participants (63.7 (8.7) years), interactions of biomarkers with cumulative load weakly predicted 2-year cartilage changes: (i) COMP × cumulative load explained medial tibia thickness change (R increased 0.062 to 0.087, p < 0.001); (ii) Coll2-1 NO2 × cumulative load explained central medial femoral T2 change (R increased 0.177 to 0.210, p < 0.001); and (iii) Coll2-1 NO2 × cumulative load explained lateral tibia T2 change (R increased 0.166 to 0.188, p < 0.001). Moderate COMP or Coll2-1 NO2 at baseline appeared protective. High COMP or Coll2-1 NO2, particularly with high BMI and low PASE, associated with worsening cartilage. Moderate serum concentrations of cartilage turnover biomarkers, at high and low physical activity, associated with maintained cartilage outcomes over 2 years. In conclusion, high concentrations of cartilage turnover biomarkers, particularly with high BMI and low physical activity, associated with knee cartilage thinning and increasing T2 over 2 years. Key Points • Higher quality cartilage may be better able to tolerate a larger cumulative load than poor quality cartilage. • Among participants enrolled in the Osteoarthritis Initiative Biomarkers Consortium Project, a representation of cumulative load exposure and its interaction with cartilage turnover biomarkers were weakly related with 2-year change in knee cartilage. • These findings suggest that cartilage turnover is a factor that modifies the relationship between loading exposure and cartilage loss in knee OA.
目的是研究累积负荷和软骨代谢生物标志物与膝关节骨关节炎软骨 2 年变化的关系。从 KL 分级为 1 至 3 的参与者中，根据 24 个月（基线）和 48 个月的磁共振图像计算出软骨厚度和横向弛豫时间（T2）。累积负荷是体力活动量表（PASE）和体重指数（BMI）的交互项。基线时收集血清软骨寡聚基质蛋白（COMP）和 II 型胶原的硝化形式（Coll2-1NO2）。多变量回归（调整基线年龄、KL 分级、软骨测量、疼痛、合并症）评估了累积负荷和生物标志物与 2 年变化的关系。在 406 名参与者（63.7（8.7）岁）中，生物标志物与累积负荷的相互作用微弱预测了 2 年的软骨变化：（i）COMP×累积负荷解释了内侧胫骨厚度的变化（R 值从 0.062 增加到 0.087，p<0.001）；（ii）Coll2-1NO2×累积负荷解释了中央内侧股骨 T2 的变化（R 值从 0.177 增加到 0.210，p<0.001）；（iii）Coll2-1NO2×累积负荷解释了外侧胫骨 T2 的变化（R 值从 0.166 增加到 0.188，p<0.001）。基线时中等 COMP 或 Coll2-1NO2 水平似乎具有保护作用。高 COMP 或 Coll2-1NO2，特别是与高 BMI 和低 PASE 相关，与软骨恶化相关。在高和低体力活动下，中等浓度的软骨代谢生物标志物与 2 年内软骨结局的维持相关。总之，高浓度的软骨代谢生物标志物，特别是与高 BMI 和低体力活动相关，与 2 年内膝关节软骨变薄和 T2 增加有关。关键点：• 较高质量的软骨可能比较差质量的软骨更能耐受较大的累积负荷。• 在参与骨关节炎倡议生物标志物联盟项目的参与者中，累积负荷暴露及其与软骨代谢生物标志物的相互作用与膝关节软骨 2 年变化呈弱相关。• 这些发现表明，软骨代谢是改变膝关节骨关节炎中负荷暴露与软骨丢失关系的一个因素。
