Table 3

Key findings, biomarker characterisation and functional outcome scores of included studies

Author (year)Key findingsBiomarker characterisationFunctional outcome scores
Abrams et al
(2014)16
FAC higher in non-OA group compared with those with OA (P<0.001).
In non-OA group, FAC higher in those undergoing microfracture versus those with lesser chondral pathology (P<0.05).
Age was not a predictor of FAC concentration (P>0.05) and accounted for <1% of the variance in FAC values.
FAC concentration of 2.18 µg/mL was 75% sensitive and 84% specific in predicting microfracture in non-OA group (area under ROC curve=0.87).
Mean FAC OA: 0.08 µg/mL±0.4
Mean FAC non-OA: 1.15 µg/mL±0.35
Mean FAC non-OA microfracture: 2.40 µg/mL±0.8
Mean FAC non-OA non-microfracture: 0.77 µg/mL±0.3
No significant correlation between biomarkers and preoperative functional assessment scores (mHHS, WOMAC, iHOT-33).
Bedi et al
(2013)10
24% higher serum COMP (P=0.04) in FAI group.
276% higher serum CRP (P<0.001) in FAI group.
Mean COMP FAI: 238 µg/L
Mean COMP non-FAI: 192 µg/L
Mean CRP FAI: 3.15 mg/L
Mean CRP non-FAI: 0.83 mg/L
SF-12 PCS:
22% reduction in FAI group (P<0.001).
SF-12 MCS:
No difference between FAI and non-FAI group (P=0.11).
HOOS:
21% reduction (P<0.001) in pain subscale score in FAI group
30% reduction (P<0.001) in symptoms score in FAI group.
17% decrease (P<0.001) in activities of daily living scores in FAI group.
39% decrease (P<0.001) in sport and recreation scores in FAI group.
40% reduction (P<0.001) in hip-related quality of life scores in FAI group.
Chinzei et al
(2016)11
Labrum: mRNA expression of inflammatory cytokines (IL-1β and IL-8), catabolic genes (MMP-3) and anabolic genes (COL1A1) higher in OA hips compared with FAI hips (P<0.05).
Synovium: mRNA expression of inflammatory cytokines (IL-1β and IL-8) and catabolic genes (MMP-3) higher in OA hips compared with FAI hips (P<0.05).
Cartilage: mRNA expression of inflammatory cytokines (IL-1β and IL-8) and catabolic genes (ADAMTS-4 and MMP-13) higher in FAI hips compared with OA hips (P<0.01). mRNA expression of anabolic genes (COL2A1 and ACAN) higher in OA hips compared with FAI hips (P<0.01).
FAI analysis: mRNA expression of inflammatory cytokines (IL-1β and IL-8) highest in cartilage compared with synovium and labrum (P<0.01).
OA analysis:
No significant differences in mRNA expression of cytokines among the OA tissue samples.
FAI and age: mRNA expression of inflammatory cytokines (IL-8) higher in patients >30 years old compared with patients <29 years old.
FAI and alpha angle: mRNA expression of anabolic genes (COL1A1) higher in labrum of patients with alpha angles <59° (P<0.05).
mRNA expression of anabolic genes (ACAN) and catabolic genes (ADAMTS-4) higher in cartilage of patients with alpha angles >60° (P<0.01).
NRNR
Elias-Jones et al
(2015)18
Histology:
Fewer features of degenerative changes (including thickening and mucoid changes) in FAI specimens compared with OA specimens.
More well-defined areas of hypercellular fibroblasts in FAI specimens compared with OA specimens.
Inflammation:
Greater macrophage and mast cell expression in FAI samples compared with OA samples.
Macrophages of M2 phenotype present in FAI samples – involved in regenerative process as opposed to degenerative process.
Higher levels of IL-13 in FAI samples compared with OA samples, supporting shift toward a proresolving type 2 macrophage environment.
Neovascularisation:
Greater CD34− and VEGF positive vessels in FAI samples compared with OA samples.
Correlation between mast cells and CD34 expression (r=0.4, P<0.01) in FAI samples.
NRNR
Fukushima
(2017)19
Existence of labral instability was not statistically correlated with any cytokine level.
In patients with chondral injury classified as Outerbridge grade 4, the levels of TNFα were significantly increased.
In patients with grade 3 cases of synovitis, the levels of TNFα, IL-1β, IL-6 and MMP-1 were significantly increased compared with those in cases of grade 2 synovitis (P<0.05).
NRVAS score during rest showed significant positive correlation with IL-6 (r=0.453, P=0.0071), while VAS score on walking showed a significant positive correlation with TNFα (r=0.465, P=0.0056) and ADAMTS-4 (r=0.508, P=0.0022).
mHHS pain score showed a significant negative correlation with TNFα (r=−0.472, P=0.0049), IL-6 (r=−0.455, P=0.0068) and ADAMTS-4 (r=−0.349, P=0.043).
Hashimoto et al
(2013)12
mRNA expression of IL-8, CXCL3, CXCL6, CCL3L1, ADAMTS-4, COL2A1 and ACAN greater in FAI samples compared with control samples (P<0.05).
mRNA expression of IL-8, CCL3L1, ADAMTS-4, and ACAN higher in cartilage from FAI samples compared with OA samples (P<0.05). mRNA expression of ACAN higher in OA samples than control samples (P<0.05).
mRNA expression of chemokines (IL-8, CXCL2, CXCL3 and CCL3L1) and extracellular matrix (ACAN) higher in FAI samples in the cleavage/thinning stage of articular cartilage damage as per the Beck criteria (P<0.05).
NRNR
Shapiro et al
(2016)17
No significant correlation between cytokine values versus preoperative and 2-year postoperative outcome scores (mHHS, WOMAC and iHOT-33).Biomarker=mean (SEM)
FAC (OD)=1.052 (0.361)
IFN-γ (ρg/mL)=29.047 (14.155)
IL-6=37.853 (20.534)
IL-1RA=879.174 (512.799)
IL-1β=1.273 (0.661)
MCP-1=28.110 (9.854)
Eotaxin=7.915 (4.661)
MIP-1β=5.001 (0.828)
IP-10=171.073 (43.704)
PDGF-BB=262.348 (159.806)
RANTES=318.478 (90.539)
TNFα=62.043 (34.918)
VEGF=140.264 (40.863)
Preoperative to postoperative: mHHS: 61.9–82.5 (P<0.0001)
WOMAC: 42.7–16.4 (P<0.0001)
iHOT-33: 44.6–83.4 (P<0.0001)
  • NR, not reported; ACAN, aggrecan; ADAMTS-4, a disintegrin and metalloproteinase with thrombospondin motifs-4; CCL3, chemokine (C-C) motif ligand 3;CCL3L1, chemokine (C-C) motif ligand 3-like 1; cDNA, complementary DNA; COL1A1, collagen type I alpha 1; COL2A1, collagen type II alpha 1; COMP, cartilage oligomeric matrix protein; CRP, C reactive protein; Ct, threshold cycle; CXCL1, chemokine (C-X-C) motif ligand 1; CXCL2, chemokine (C-X-C) motif ligand 2; CXCL3, chemokine (C-X-C) motif ligand 3; CXCL6, chemokine (C-X-C) motif ligand 6; FAC, fibronectin–aggrecan complex; GAPDH; glyceraldehyde-3-phosphate dehydrogenase; IFN, interferon; iHOT-33, International Hip Outcomes Tool; IL-1β, interleukin-1 beta; IL-8, interleukin-8; IP-10, interferon-inducible protein 10; MCP, monocyte chemoattractant protein; mHHS, modified Harris Hip Score; MIP, macrophage inflammatory protein; MMP-3, matrix metalloproteinase-3; MMP-13, matrix metalloproteinase-13; OD, optical density; PDGF-BB, platelet-derived growth factor-BB; qPCR, quantitative PCR; RANTES, regulated on activation normal T cell expressed and presumably secreted; TNF, tumour necrosis factor; VEGF, vascular endothelial growth factor; WOMAC, Western Ontario and McMaster Universities Arthritis Index.