Pos0040 the Decrease in Bone Mineral Density Depends on the Concentrations of Angiopoietin-Like Protein Type 4 in Patients With Rheumatoid Arthritis

Abstract

Background:New serological markers that can serve as objective indicators of osteoporotic changes in patients with rheumatoid arthritis (RA) are being currently searched [1, 2, 3, 4, 5].Objectives:To reveal the connection between the concentrations of serum angiopoietin-like protein type 4 (ANGPTL4) and the decrease in bone mineral density (BMD) in patients with RA.Methods:114 patients with reliable RA (90.4% of women, 9.6% of men) aged 21 to 80 years (mean age 55.4 ± 11.2 years old, disease duration - 11.18 ± 9.03 years, positive for rheumatoid factor (RF-IgM) - 63.2%, positive for anti-citrullinated protein antibody (ACPA) - 59.7%) were examined using a bone X-ray densitometer LUNAR DPX (GE, USA). Patients with an advanced clinical stage - 49%, moderate activity according to DAS28 - 58.8%, II-III radiological stage - 85.1% and functional class II - 64.9% prevailed. ANGPTL4 measurement in blood serum was carried out by enzyme immunoassay using a commercial test system “RayBio Human ANGPTL4 ELISA Kit” (RayBiotech, USA). ESR, RF, as well as C-reactive protein (CRP), ACPA, and antibodies to modified vimentin (anti-MCV) in an ELISA test were determined in all RA patients.Results:ANGPTL4 indices in RA patients correlated with the CRP level (r = 0.34, p = 0.001) and the DAS-28 (r = 0.29, p = 0.002). There was no correlation between the level of ANGPTL4 and the intake of glucocorticoids, both at the time of the study (p = 0.678) and with their long-term (more than 3 months) use (p = 0.097). There was a negative correlation of weak strength between ANGPTL4 and the dose of non-steroidal anti-inflammatory drugs (r = -0.21, p = 0.035). There was no correlation between ACPA, anti-MCV, and ANGPTL4 levels (p> 0.1 and p = 0.084). A direct correlation was found between the level of ANGPTL4 and the presence of osteopenia in RA patients (r = 0.43, p = 0.036), as well as a negative correlation between ANGPTL4 and bone mineral density in the spine (BMD L1-4, r = -0.631, p <0.001), but not in the femur (p> 0.05). Densitometry data also allowed to establish a negative correlation between low values of the T-criterion and increased titers of anti-MCV (r = -0.51, p = 0.029), but not ACPA (p = 0.276). It has previously been noted that anti-MCV are able to activate osteoclasts with a consequent decrease in periarticular BMD.Conclusion:The absence of a relationship between anti-MCV and the level of ANGPTL4 may indicate different mechanisms of osteoporosis development and localization of osteoporotic changes in groups of anti-MCV or ANGPTL4 positive patients with RA.References:[1]Ramli FF, Chin KY. A Review of the Potential Application of Osteocyte-Related Biomarkers, Fibroblast Growth Factor-23, Sclerostin, and Dickkopf-1 in Predicting Osteoporosis and Fractures. Diagnostics (Basel). 2020;10(3):145. doi: 10.3390/diagnostics10030145[2]Aleksandrov V., Aleksandrov A. Angiopoetin-like protein type 3 as an indicator of rheumatoid inflammation and resorption of bone tissue in rheumatoid arthritis. Ann Rheum Dis. 2020;79(s1):1340. doi: 10.1136/annrheumdis-2020-eular.2174[3]Nagy EE, Nagy-Finna C, Popoviciu H, Kovács B. Soluble Biomarkers of Osteoporosis and Osteoarthritis, from Pathway Mapping to Clinical Trials: An Update. Clin Interv Aging. 2020;15:501-518. doi: 10.2147/CIA.S242288[4]Aleksandrov A.V., Alekhina I.Y., Aleksandrova N.V., Shilova L.N., Aleksandrov V.A. High antibody titers to cyclic citrullinated vimentin promote the development of periarticular osteoporosis in patients with rheumatoid arthritis. Osteoporosis International. 2019; 30(s2):680.[5]Donati S, Ciuffi S, Palmini G, Brandi ML. Circulating miRNAs: A New Opportunity in Bone Fragility. Biomolecules. 2020;10(6):927. doi: 10.3390/biom10060927Disclosure of Interests:None declared.

Antibodies to cyclic citrullinated peptide and angiopoietin-like protein type 4 as markers of immune inflammation and osteoporotic processes in rheumatoid arthritis patients

“…Increased ANGPTL4 expression in bone tissue (in both osteoclasts and osteoblasts) has been noted in inflammatory arthritis, especially in hypoxia [10]. Our earlier preliminary study of the role of ANGPTL4 in increasing bone resorption and the development of osteopenia in patients with RA showed a negative correlation between ANGPTL4 and bone mineral density in the spine [3].…”