Mylène Jansen

SF biomarker changes upon KJD 331 16 Table 2 : Baseline characteristics of study participants KJD patients (n=20) Male sex, n (%) 13 (65) Age (years) 55.5 BMI (kg/m 2 ) 29.3 Kellgren and Lawrence, n (%) - Grade 2 - Grade 3 - Grade 4 2 (10) 10 (50) 8 (40) KOOS 4 (0–100) 30.11 Mean or n (%) is given. BMI: body mass index; KOOS 4 : Knee injury and osteoarthritis outcome score-4. 6/10 SF analytes showed changes between baseline and 6 weeks (IL-6: ES 56.6, p =0.0043; MCP-1: ES 155.1, p=0.0016; FGF-2: ES 164.7, p=0.0123; TGF β -1: ES 2.1, p =0.0003; LTBP2: ES 0.4, p=0.0475; activin A: ES -6.8, p=0.0002) (Figure 2A and Supplementary Table 1). Of these, IL-6, MCP-1, FGF-2 and TGF β -1 showed a predominant increase in levels, while activin A mainly decreased (to within normal range for most individuals). There was variation in response between individuals, exemplified by LTBP-2. For several analytes, change was detectable within 3 weeks of distraction (activin A, TGF β -1 and IL-6) (Supplementary Table 1). 2 further molecules, IL-8 and TIMP-1 were different at 3 weeks (ES 73.5 and 389, respectively), but not at 6 weeks (ES 10.5 and 115.2, respectively) (Figure 2B, upper panels). The remaining 2 analytes (MMP3, TSG-6) did not change over the distraction period (ES -75.3, p =0.53 and 41508, p =0.21 respectively) (Figure 2B, lower panels). Several analytes correlated with each other in their change over the 6 week distraction period (Figure 3). Associations between changes in markers could also be seen over the initial 3 weeks of knee joint distraction (Supplementary Figure 1). Higher correlations were found for TGF β -1 and FGF-2 ( R= 0.68); IL-6, TIMP-1 and either MMP3 or TSG-6; (all pairs R >0.5). LTBP2 and activin A had low correlation with other analytes over time. TGF β -1 and IL-6 were negatively correlated ( R= -0.43). The association of change in candidate molecules over the distraction period with subsequent change in KOOS 4 was examined. Change in 4 molecules was associated with change in KOOS 4 over the first 3 months: activin A, TGF β -1, FGF-2 and MCP-1 (Figure 4A). For all except activin A, an increase in the analyte was associated with greater improvement in KOOS 4 , but the effects were weak (Supplementary Table 2). The low effect sizes were primarily because the unit of change of a marker within the regression model was per 1 pg/ml, whereas often much larger changes in markers than 1 pg/ml were seen. Similar associations persisted at 6 months for all 4 molecules.