Interplay of calcium pyrophosphate crystals, oxidative stress, and clinical features on knee osteoarthritis severity

Deposition of calcium pyrophosphate (CPP) crystals is observed in most joints affected by severe osteoarthritis (OA). CPP may cause local damage by inducing an inflammatory process and oxidative stress (OS).

To evaluate inflammation and OS induced by CPP deposition and their association with the degree of knee OA.

Synovial fluid (SF) from patients with OA classified as grade 3 and 4 (ACR criteria) was analyzed. Reactive oxygen species (ROS) and H₂O₂ levels were quantified, and inflammation by white blood cell (WBC) count. CPPs were detected by polarized light microscopy. Multifactorial dimensionality reduction (MDR) was used to visualize possible interactive effects between variables.

Fifty-six SF were analyzed, 22 (39.28%) were in moderate OA and 34 (60.71%) in severe OA. CPPs were identified in 17 moderate OA and 18 severe OA samples. In the moderate OA, ROS levels were significantly higher in the CPP + group (5.0% vs 2.0%, P = 0.03). Body mass index and CPP were significantly correlated (r =  - 0.439, P = 0.041). In the severe OA group, there were significant correlations of age with WBC (r =  - 0.431, P = 0.011), WBC with H₂O₂ (r = 0.454, P = 0.007), and ROS with H₂O₂ (r = 0.387, P = 0.024). MDR analysis revealed strong synergistic interactions between H₂O₂ and sex (6.68%) for moderate OA, while for severe OA, there were interactions between sex and ROS (6.99%) and between sex and inflammation (4.39%).

ROS and inflammation may be factors that potentiate damage in knee OA, and this may help in the development of antioxidant interventions for CPP-associated OA. Key Points • This study evaluated CPP crystal-induced oxidative stress and inflammation and their effect on OA severity. • In the moderate OA phenotype, CPP crystals modify ROS levels. • ROS and inflammation are factors that increase damage in knee OA, especially when CPP crystals are present.