Stiffness post-total knee replacement: A proof of principle study investigating the effect of gene expression analysis of markers of fibrosis

To establish proof of principle of a link between phenotypic expression and stiffness after TKR.

From 100 patients, genetic expression of markers of fibrosis was performed for 15 synovial samples from patients categorised as ‘best post-operative range of movement (ROM)’ and 15 samples from patients with ‘worst ROM’. These markers included Matrix Metalloproteinases (MMPs), A Disintegrin and Metalloproteinases with Thrombospondin (ADAMTS) and Tissue Inhibitors of Matrix Metalloproteinases (TIMPs). Genetic marker data were compared to Oxford Knee Scores (OKS) and Pain Catastrophizing Scores (PCS).

Quantitative markers for gene expression demonstrated more outliers in stiff compared to non-stiff knees, suggesting a greater imbalance in pro- and anti-fibrotic markers in stiff knees. Whilst there was a significant difference in the range of post-operative knee flexion (p = 0.001) and extension (p = 0.001), there was no statistically significant difference between stiff and non-stiff knees in pre-operative or post-operative OKS (p ≥ 0.06). There was no difference in the individual components of the individual PCS score items nor the PCS total scores when stiff and non-stiff knees were compared (p > 0.05).

Biological factors, namely gene expression of MMPs, TIMPs and ADAMTS, may contribute towards post-TKR stiffness. This now warrants further investigation to better understand this relationship based on larger, multi-centre, cohorts.

Level 3.