POS0345 ASSESSMENT OF THE EFFECT OF TOFACITINIB ON BONE MARROW ADIPOCYTES AND BONE-FORMING OSTEOBLASTS UNDER NON-INFLAMMATORY AND INFLAMMATORY CONDITIONS

Background Systemic inflammation is the main factor underlying secondary osteoporosis in patients with rheumatoid arthritis (RA). The JAK inhibitors, such as Tofacitinib (Tofa), can control systemic and have beneficial effects on bone various models. This might be due to direct microenvironment not exclusively based their anti-inflammatory function. Bone marrow adipocytes (BMAds) are abundant microenvironment. effect of inhibitors BMAds unknown, but evidence suggests that there competition between human marrow-derived stromal cell (hBMSCs) differentiation routes toward osteoblasts (Ob) osteoporosis. Objectives To determine models whether Tofa influences directly committment adipogenesis osteoblastogenesis. Then, a prospective pilot study, investigate potential adiposity RA. Methods study cellular commitment, hBMSCs were cultured for 3 days appropriate Ob- BMAd- media (Ob-3d BMAd-3d), together at 200, 400 (equivalent therapeutic dose 5 mg twice day RA patients) or 800 nM. mimic inflammatory conditions, TNFα was added 1 ng/ml. also conducted mature similar treatment applied 6 14 (BMAd-20d). impact determined by gene expression profile analysis, western-blot analysis density monitoring. In parallel, 9 treated (TOFAT study: NCT04175886 ), proton fat fraction (PDFF) measured MRI (Dixon technique) lumbar spine start months. Results non-inflammatory Runx2 decreased Ob-3d nM(p<0.05). Conversely, BMAd-3d (at nM) exhibited substantial increase PPARγ2, C/EBPα Perilipin (a marker associated lipid droplet formation) compared controls (p<0.05). confirmed protein level. markers considerably (PPARy2 RUNX2, respectively, p<0.05), addition did change profiles controls. On contrary, PPARy2 showed limited negative BMAd positive adipocyte (BMAd-20d) under conditions supported an differentiated (p<0.001). These findings consolidated PDFF months (+6.9%, p<0.01). Conclusion Overall, vitro clinical results suggest stimulatory commitment differentiation, which does support Disclosure Interests Jean-Guillaume Letarouilly Consultant of: Sêmeia, Grant/research from: Pfizer, Julien Paccou: None declared, Sammy Badr: René-Marc Flipo member advisory board Christophe Chauveau: Bernard Cortet: Odile Broux: Aline Clabaut: declared