Association of calcium phosphate crystals with pain and inflammation among individuals with advanced knee osteoarthritis: A cross-sectional study.

Background

Basic calcium phosphate (BCP) and calcium pyrophosphate crystals (CPP) are suspected to be part of osteoarthritis (OA) pathogenesis through chondrocyte-, fibroblast-, and leukocyte-mediated inflammation and cartilage destruction. We aimed to determine whether the presence of CPP and BCP in synovial fluid (SF) was associated with pain and inflammation in patients with knee OA.

Methods

SF was sampled during the baseline visit of the Intensive Diet vs. Knee Arthroplasty (INKA) trial. BCP and CPP were detected by Raman Spectroscopy (RS). Participants were classified as Calcium crystal positive (CaC+) or negative (CaC-). Pain was evaluated using the KOOS Pain subscale. Ultrasound (US) was performed to evaluate medial and lateral synovial hypertrophy/effusion. Continuous and categorical outcomes were analysed using ANCOVA and logistic regression, respectively.

Results

Fifty-one participants from the INKA trial met the inclusion criteria; 49 samples were analysed using RS. All participants (n = 49) were calcite positive. 29 participants were calcium phosphate positive with BCP (n = 18), CPP (n = 3), or both (n = 8). Estimated between-group difference for KOOS Pain was 8.7 points (95% CI: 0.2 to 17.5; P = 00.054) with the CaC + group indicating higher KOOS Pain scores (42.32 vs 33.64), i.e. less symptoms. Prevalence of US-detected inflammation was 97% (n = 28) in the CaC + group and 95% (n = 19) in the CaC- group. Estimated odds ratio was 0.85 (95% CI, 0.04 to 20.41; P = 00.92).

Conclusion

BCP and CPP positivity in SF was neither associated with knee OA patients' symptoms nor US-detected inflammation.

Keywords

Basic calcium phosphate, Calcium pyrophosphate, Inflammation, Osteoarthritis, Raman spectroscopy, Ultrasound

Conflict of interest statement

ASP, CTN, HG, GF, TP, KE, TH, SMA reports no COIs. HB reports receiving travel and congress support from Contura A/S. KB reports receiving travel and congress support from Zimmer Biomet and Clockwork Medical. AD is president of the Danish Association of Junior Rheumatologists, has received personal speaker fees from Otsuka, Vifor and the Danish Rheumatism Organization, and has received support from the Danish Rheumatism Organization. MH is associate editor of Osteoarthritis and Cartilage. RC reports personal consulting fees from ZPD A/S (ScanDroitin™), Roche Pharmaceuticals A/S, Elos Medtech, Image Analysis Ltd (Image Analysis Group, UK), Compass Communications Ltd, and Ascendis Pharma A/S, for advice related to biostatistics, trial design, statistical inference, evidence synthesis, or clinical epidemiology. He also receives personal remuneration for editorial roles as Statistical Editor for Osteoarthritis and Cartilage and Acta Orthopaedica. In addition, he serves in unpaid scientific and methodological roles within the OMERACT Technical Advisory Group and Strategic Advisory Group, the GRADE Working Group Working Group, Cochrane, and on editorial or advisory boards of several journals, including Journal of Clinical Epidemiology, BMJ Open, Arthritis Care & Research, and Arthritis Research & Therapy. No other relationships or activities that could appear to have influenced the submitted work were disclosed.