Association of synovial fluid and urinary C2C-HUSA levels with surgical outcomes post-total knee arthroplasty

Amit Sandhu; Osvaldo Espin-Garcia; Jason S Rockel; Starlee Lively; Kimberly Perry; Nizar N Mohamed; Y Raja Rampersaud; Anthony V Perruccio; A Robin Poole; Rajiv Gandhi; Mohit Kapoor

doi:10.1016/j.joca.2023.09.009

Association of synovial fluid and urinary C2C-HUSA levels with surgical outcomes post-total knee arthroplasty

Osteoarthritis Cartilage. 2024 Jan;32(1):98-107. doi: 10.1016/j.joca.2023.09.009. Epub 2023 Oct 5.

Authors

Affiliations

¹ Division of Orthopaedics, Osteoarthritis Research Program, Schroeder Arthritis Institute, University Health Network, Toronto, Ontario, Canada; Krembil Research Institute, University Health Network, Toronto, Ontario, Canada.
² Division of Orthopaedics, Osteoarthritis Research Program, Schroeder Arthritis Institute, University Health Network, Toronto, Ontario, Canada; Krembil Research Institute, University Health Network, Toronto, Ontario, Canada; Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada; Dalla Lana School of Public Health and Department of Statistical Sciences, University of Toronto, Toronto, Ontario, Canada.
³ Division of Orthopaedics, Osteoarthritis Research Program, Schroeder Arthritis Institute, University Health Network, Toronto, Ontario, Canada; Krembil Research Institute, University Health Network, Toronto, Ontario, Canada; Department of Surgery and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
⁴ Division of Orthopaedics, Osteoarthritis Research Program, Schroeder Arthritis Institute, University Health Network, Toronto, Ontario, Canada; Krembil Research Institute, University Health Network, Toronto, Ontario, Canada; Department of Surgery and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada; Institute of Health Policy, Management and Evaluation, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
⁵ Department of Surgery, Faculty of Medicine and Health Sciences, McGill University, Montréal, Quebec, Canada.
⁶ Division of Orthopaedics, Osteoarthritis Research Program, Schroeder Arthritis Institute, University Health Network, Toronto, Ontario, Canada; Krembil Research Institute, University Health Network, Toronto, Ontario, Canada; Department of Surgery and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada. Electronic address: mkapoor@uhnresearch.ca.

PMID: 37805006
DOI: 10.1016/j.joca.2023.09.009

Abstract

Objectives: After total knee arthroplasty (TKA), ∼30% of knee osteoarthritis (KOA) patients show little symptomatic improvement. Earlier studies have correlated urinary (u) type 2 collagen C terminal cleavage peptide assay (C2C-HUSA), which detects a fragment of cartilage collagen breakdown, with KOA progression. This study determines whether C2C levels in urine, synovial fluid, or their ratio, are associated with post-surgical outcomes.

Methods: From a large sample of 489 subjects, diagnosed with primary KOA undergoing TKA, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and function scores were collected at baseline (time of surgery) and one-year post-TKA. Baseline urine (u) and synovial fluid (sf) were analysed using the IBEX-C2C-HUSA assay, with higher values indicating higher amounts of cartilage degradation. For urine, results were normalised to creatinine. Furthermore, subjects' changes in WOMAC scores were categorised based on percent reduction in pain or improvement in function, compared to baseline, such that >66.7%, >33.3 to ≤66.7%, and ≤33.3% denoted "strong", "moderate" and "mild/worse" responses, respectively. Associations of individual biofluid C2C-HUSA levels, or their ratio, with change in WOMAC pain and function scores up to one-year post-TKA, or category of change, were analysed by linear, logistic, or cumulative odds models.

Results: Higher baseline uC2C-HUSA levels or a lower ratio of baseline sfC2C-HUSA to uC2C-HUSA were associated with improvements in WOMAC pain by linear multivariable modelling [odds ratio -0.40 (95% confidence interval -0.76, -0.05) p = 0.03; 0.36 (0.01, 0.71), p = 0.04, respectively], while sfC2C-HUSA alone was not. However, lower ratios of sfC2C-HUSA to uC2C-HUSA were associated with improvements in WOMAC function [1.37 (0.18, 2.55), p = 0.02], while sfC2C-HUSA and uC2C-HUSA alone were not. Lower ratios of sfC2C-HUSA to uC2C-HUSA were also associated with an increased likelihood of a subject being categorised in a group where TKA was beneficial in both univariable [pain, 0.81 (0.68, 0.96), p = 0.02; function, 0.92 (0.85, 0.99), p = 0.035] and multivariable [pain, 0.81 (0.68, 0.97) p = 0.02; function, 0.92 (0.85, 1.00), p = 0.043] ordinal modelling, while sfC2C-HUSA and uC2C-HUSA alone were not.

Conclusions: Overall, ratios of baseline sfC2C-HUSA to uC2C-HUSA, and baseline uC2C-HUSA, may play an important role in studying post-TKA surgical outcomes.

Keywords: C2C-HUSA assay; Cartilage degradation; Collagen; Osteoarthritis; Total knee arthroplasty.

MeSH terms

Arthroplasty, Replacement, Knee*
Humans
Knee Joint
Osteoarthritis, Knee* / metabolism
Pain
Synovial Fluid / metabolism
Treatment Outcome