Thudium Christian S, Rasmussen Sten, Karsdal Morten A, Bay-Jensen Anne-Christine
Nordic Bioscience A/S, Herlev, Denmark.
Department of Clinical Medicine, Aalborg University, Denmark.
Osteoarthr Cartil Open. 2024 Oct 12;6(4):100527. doi: 10.1016/j.ocarto.2024.100527. eCollection 2024 Dec.
The development of disease-modifying drugs is limited by OA's heterogeneity and the challenge of defining clinical endpoints. Serological biomarkers are considered potential surrogate endpoints, but their contribution from single joints to systemic levels in OA patients is unclear. In this exploratory study we longitudinally assessed systemic biomarker levels' response to tissue damage and healing before and after surgery in patients undergoing knee or hip joint replacement revision for aseptic failure. Patients with chronic pain associated with a prior hip or knee arthroplasty, but not receiving revision surgery were included as control.
The serological biomarker of MMP mediated type III collagen degradation C3M, associated with synovial tissue degradation, was measured at baseline before revision surgery, after revision surgery and at a 6-month follow-up in 48 patients with aseptic loosening of a knee or hip prosthesis and in 18 patients with chronic pain from a hip or knee prosthesis. Longitudinal changes in biomarkers were modeled using linear mixed models.
No differences between the aseptic loosening and chronic pain groups were observed at baseline. Revision surgery in the aseptic loosening group led to a swift increase in C3M, which normalized within 2-3 months. No changes in biomarker level were observed in chronic pain patients over three months.
These findings suggest that tissue damage in a single joint significantly impacts systemic biomarker levels and underscores the relevance of systemic biomarkers in assessing local tissue remodeling.
疾病修饰药物的研发受到骨关节炎异质性以及确定临床终点的挑战的限制。血清生物标志物被认为是潜在的替代终点，但其在骨关节炎患者中从单个关节到全身水平的贡献尚不清楚。在这项探索性研究中，我们纵向评估了接受膝关节或髋关节置换翻修术以治疗无菌性失败的患者手术前后全身生物标志物水平对组织损伤和愈合的反应。将患有与先前髋关节或膝关节置换术相关的慢性疼痛但未接受翻修手术的患者作为对照。
在48例膝关节或髋关节假体无菌性松动患者和18例因髋关节或膝关节假体导致慢性疼痛的患者中，于翻修手术前基线、翻修手术后及6个月随访时测量与滑膜组织降解相关的基质金属蛋白酶介导的III型胶原降解的血清生物标志物C3M。使用线性混合模型对生物标志物的纵向变化进行建模。
在基线时，无菌性松动组和慢性疼痛组之间未观察到差异。无菌性松动组的翻修手术导致C3M迅速增加，并在2 - 3个月内恢复正常。慢性疼痛患者在三个月内生物标志物水平未发生变化。
这些发现表明单个关节的组织损伤会显著影响全身生物标志物水平，并强调了全身生物标志物在评估局部组织重塑中的相关性。
