The Association of Blood Biomarkers and Body Mass Index in Knee Osteoarthritis: A Cross-Sectional Study

Abstract

Objective Despite massive efforts, there are no diagnostic blood biomarkers for knee osteoarthritis (KOA). This study investigated several candidate diagnostic biomarkers and the metabolic phenotype in end-stage KOA in the context of obesity. Design In this cross-sectional study, adult patients undergoing knee arthroplasty were enrolled and KOA severity was assessed using the Lequesne index. Blood biomarkers with an important role in obesity, the metabolic syndrome, or KOA (oxidized form of low-density lipoprotein [oxLDL], advanced glycation end product [AGE], soluble AGE receptor [sRAGE], fatty acid binding protein 4 [FABP4], phospholipase A2 group IIA [PLA2G2A], fibroblast growth factor 23 [FGF-23], ghrelin, leptin, and resistin) were measured using enzyme-linked immunosorbent assay (ELISA; n = 70) or Luminex technique (subgroup of n = 35). H1-NMR spectroscopy was used for the quantification of metabolite levels (subgroup of n = 31). The hip-knee-ankle angle was assessed. Multivariable and multivariate regression analysis was used to examine the relationship of biomarkers with body mass index (BMI) and KOA severity in complete case and multiple imputation analysis. Results While most of the investigated biomarkers were not associated with KOA severity, FABP4 and leptin were found to correlate with BMI and gender. Resistin was associated with Lequesne index in complete case analysis. Using a targeted metabolomics approach, BMI-dependent changes in the metabolome were hardly visible. Conclusions Our findings confirm studies on FABP4, leptin, and resistin with regard to obesity and the metabolic syndrome. There was no association of the investigated biomarkers with KOA severity, most likely due to the patient selection (end-stage KOA patients). Based on this absence of BMI-dependent changes in the metabolome, we might assume that BMI is not correlated with KOA severity in this specific patient group.

Altered co-expression patterns of synovial fluid proteins related to the immune system and extracellular matrix organization in late stage OA, compared to non-OA controls

“…Previous studies have reported that downregulation of FABP4 promotes osteoclast formation (9). However, contrary to our findings, it has been reported that FABP4 is up-regulated in SF and plasma in individuals with OA (10,11). Follistatin-like protein 3 (FSTL3) is a glycoprotein that is involved in regulating inflammation and suppresses osteoblast differentiation of bone marrow mesenchymal cells during that process (12).…”

Emerging molecular biomarkers in osteoarthritis pathology

“…32 However, targeted nuclear magnetic resonance (NMR)-spectroscopy of serum from 31 KOA patients showed no detectable differences in metabolites between underweight and obese individuals. 33 This suggests that the contribution of weight to OA is complex. Age is another likely contributor to the metabolome of OA patients, as analysis of plasma from a cohort of 346 subjects (152 KOA, 194 healthy volunteers) by targeted metabolomics found that individual levels of select lysoPC and PC analogs were associated with individuals with KOA in older populations, particularly males.…”

Biomarkers of Osteoarthritis—A Narrative Review on Causal Links with Metabolic Syndrome

“…PLA2G2A is a known cartilage degradation enzyme and in serum has been shown to positively correlate with knee OA, but not to disease severity or MetS; the authors argued that this finding may be due to the inclusion of patients with end-stage disease undergoing arthroplasty [ 59 ]. Further, PLA2G2A polymorphisms have been linked to an increased risk of developing MetS and T2DM [ 60 ]; thus, it may be prudent for further investigation to corroborate a lack of correlation between PLA2G2A and MetS-OA, especially in early disease sufferers.…”

“…Detracting somewhat from the meta-inflammation theory in OA progression, however, is that, surprisingly, no differences in resistin levels were seen between diabetic and non-diabetic counterparts, nor was there a correlation with BMI [ 65 ]. Further, a cross sectional study investigating blood biomarkers involved in obesity and MetS in patients undergoing TKR for end stage OA did show a correlation between FABP4, leptin and resistin with obese females; these findings were independent of MetS and not associated with knee OA severity [ 59 ]. A case control study has described Resistin as a potentially useful biomarker of worsening disease, as a positive correlation of serum resistin with WOMAC scores was demonstrated in knee OA [ 66 ].…”