Nordic Bioscience Clinical Development, Herlev Hovedgade 82, DK2730, Herlev, Denmark.
Nordic Bioscience Biomarkers and Research, Herlev Hovedgade 207, DK2730, Herlev, Denmark.
Arthritis Res Ther. 2019 Sep 3;21(1):203. doi: 10.1186/s13075-019-1987-7.
Excessive cartilage degradation is a known characteristic of osteoarthritis (OA). Biochemical markers, such as uCTX-II, have been shown to be associated with disease severity, yet the tissue origin of CTX-II has been disputed. This analysis investigates the association between OA knee joints at different radiographic stages and pain categories with levels of uCTX-II and biomarkers of bone resorption and formation.
Baseline data of two randomised clinical trials (NCT00486434 and NCT00704847) in patients with radiographic OA and presence of pain were analysed post hoc. A subgroup with available urine samples and evaluable radiographs for both knees (N = 1241) was analysed. Urine CTX-I, urine CTX-II and serum osteocalcin were analysed for associations with combined Kellgren-Lawrence (KL) scores, gender and pain for both knees to assess the contribution of joints at different stages.
Pain, BMI, age, gender and KL grade were all significantly associated with uCTX-II. The association between pain and CTX-II appeared to be driven by weight-bearing pain. The level of uCTX-II incrementally increased with higher radiographic severity of each knee. Levels of bone markers CTX-I and osteocalcin were both significantly associated with BMI and gender, but neither were associated with radiographic severity. Biomarker levels between male or female groups of identical KL scores were found to be higher in females compared to males in some but not all KL score groups.
These results indicate that levels of uCTX-II are independently associated with radiographic severity of OA and pain intensity. CTX-II was associated with weight-bearing pain, but not non-weight-bearing pain, independent of co-variates. Bilateral OA knee joints appear to contribute to uCTX-II levels in an incremental manner according to radiographic severity of single joints. The data suggest that biomarker differences between genders should be taken into account when evaluating these markers in the context of structural features of OA.
骨关节炎（OA）的一个已知特征是软骨过度降解。生物化学标志物，如 uCTX-II，已被证明与疾病严重程度相关，但 CTX-II 的组织来源存在争议。本分析研究了不同放射学阶段和疼痛类别的 OA 膝关节与 uCTX-II 水平以及骨吸收和形成的生物标志物之间的关系。
对两项随机临床试验（NCT00486434 和 NCT00704847）的基线数据进行了事后分析，这些试验纳入了存在放射学 OA 和疼痛的患者。对有可用尿液样本且双侧膝关节均可评估放射学表现的亚组（n=1241）进行了分析。分析了尿液 CTX-I、尿液 CTX-II 和血清骨钙素与双侧膝关节的联合 Kellgren-Lawrence（KL）评分、性别和疼痛之间的关系，以评估不同阶段关节的贡献。
疼痛、BMI、年龄、性别和 KL 分级均与 uCTX-II 显著相关。疼痛与 CTX-II 之间的关系似乎是由承重疼痛驱动的。uCTX-II 水平随着每侧膝关节放射学严重程度的增加而逐渐升高。骨标志物 CTX-I 和骨钙素的水平均与 BMI 和性别显著相关，但与放射学严重程度无关。在某些但不是所有 KL 评分组中，发现相同 KL 评分的男性或女性组之间的生物标志物水平在女性中高于男性。
这些结果表明，uCTX-II 水平与 OA 的放射学严重程度和疼痛强度独立相关。CTX-II 与承重疼痛相关，与非承重疼痛无关，与协变量无关。双侧 OA 膝关节似乎根据单关节的放射学严重程度以递增方式对 uCTX-II 水平产生影响。数据表明，在评估这些标志物与 OA 结构特征相关时，应考虑性别之间的生物标志物差异。
