Abstract

Background:Obesity is highly overrepresented in psoriatic arthritis (PsA) and associated with increased disease activity. We have previously shown in 41 patients with PsA (Caspar criteria) and obesity (here body mass index BMI ≥33 kg/m2) that weight loss treatment including Very Low Energy Liquid Diet (VLED) resulted in a median weight loss of 18.6% and concomitantly a significant improvement in CRP and disease activity in joints, entheses and skin at six months (M6) follow up.Objectives:To analyze serum biomarkers associated with inflammation, cartilage and bone metabolism before and after weight loss treatment in PsA patients compared with controls, without PsA or psoriasis, matched for age, sex and weight.Methods:The weight loss treatment included VLED (640 kcal/day) during 12 or 16 weeks (depending on baseline (BL) BMI <40 or ≥40 kg/m2), followed by a structured reintroduction of an energy restricted diet. cs/bDMARDs were held unchanged from 3 months before BL until M6. The patients were assessed with 66/68 joints counts.Serum levels of vascular endothelial growth factor (VEGF), S100A8, S100A9, matrix metalloproteinases (MMP-3, 8 and 13), hepatocyte growth factor (HGF), B-cell activating factor (BAFF), Dickkopf (DKK)-1, sclerostin (SOST), soluble receptor activator of nuclear factor-kB ligand (RANKL), osteprotegerin (OPG) and aggrecan were measured at BL and M6 in PsA patients and controls with Magnetic Luminex Assays (R&D-systems) following the manufacturer’s instructions using a Bio-Plex 200 system (BioRad). Serum cartilage oligomeric matrix protein (COMP) (R&D-systems), carboxyterminal telopeptide of type-1 collagen (CTX-1) (Immunodiagnostics systems: IDS) and osteocalcin (IDS) were measured with enzyme-linked immunosorbent assay (ELISA).Results:Totally 41 PsA patients [age median 54 (IQR 48-62) yrs; 63 % women] and 39 controls [age 55 (46-60) yrs, 72 % women] were included. At M6 the weight-loss since BL was 18.7 (14.6-26.5) kg in the PsA patients and 22.6 (14.7-28.4) kg in the controls (p=0.546). Significant reductions in DAS28CRP [2.9 (2.1–3.7) vs. 2.4 (1.7–3.0)] and DAPSA [15.3(6.6-29.1) vs. 11.0 (2.8–17.6)] (p<0.001) were seen in the PsA patients.At BL serum levels of the biomarkers were not significantly different in patients vs. controls.After weight-loss significant reductions were seen in serum VEGF, S100A8, MMP-8, HGF, BAFF, COMP and DKK-1, whereas serum SOST and CTX-1 were significantly increased in both patients and controls (Table 1). The other biomarkers were not significantly changed.Conclusion:Weight loss in patients with PsA and controls was associated with lowered serum levels of several biomarkers related to inflammation and cartilage degradation, along with increased levels of biomarkers for bone turnover.Table 1.PsA (N=41)BL median (IQR)PsA (N=41)M6 median (IQR)PsAp-valueCtrl (N=39)BL median (IQR)Ctrl (N=39)M6 median (IQR)Ctrlp-valueBMI (kg/m2)35.2 (34.1-38.1)29.8 (26.6-31.5)<0.00137.7 (36.7–41.5)30.4 (27.9–33.2)<0.001CRP (mg/L)4 (2–8.5)2 (1–6.5)0.0414 (2–6)2 (1–4)<0.001VEGF (pg/mL)79.6 (55.9–113.5)69.6 (53.1–105.3)0.01082.3 (48.0–125.9)65.0 (42.2-85.5)<0.001S100A8 (pg/mL)75.5 (48.0–99.5)63.3 (42.8–93.6)0.02171.8 (40.5–101.0)63.3 (40.3-85.7)0.006MMP-8 (pg/mL)9975.4(6811.8–14154.8)9202.6(5767.1–12049.6)0.0177494.7(4805.2-12616.9)7218.3(3466.0-9785.3)0.112HGF (pg/mL)327.9 (250.3–413.6)271.3 (206.9–331.0)<0.001307.9 (239.1–348.3)239.8 (200.3-276.0)<0.001BAFF (pg/mL)794.4 (716.4–868.2)674.6 (613.2–790.5)<0.001760.8 (664.1–827.3)678.1 (603.7–719.8)<0.001COMP (pg/mL)266.1 (209.8–366.0)217.0 (156.0–272.0)0.008293.6 (185.2–340.5)221.6 (163.5-300.0)0.018Dkk-1 (pg/mL)3608.4(3055.0–4401.3)3382.6(2802.5–4218.2)0.0023635.8(3212.8-4380.6)3480.4(2948.9–4087.3)0.007SOST (pg/mL)52.9 (32.5–65.4)60.3 (37.2–85.6)0.01450.0 (30.8–79.3)61.3(35.7–81.4)0.019CTX-1 (ng/mL)0.27 (0.20–0.39)0.51 (0.35–0.64)<0.0010.23 (0.16–0.34)0.50(0.30–0.61)<0.001Disclosure of Interests:None declared.

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