Association of high titers of anti-carbamylated protein antibodies with decreased bone mineral density in early arthritis patients

• Published in: PloS one 2018-08, Vol.13 (8), p.e0202583-e0202583
• Main Authors: Regueiro, Cristina, Ortiz, Ana M, Boveda, Maria Dolores, Castañeda, Santos, Gonzalez-Alvaro, Isidoro, Gonzalez, Antonio
• Format: Article
• Language: English
• Subjects: Absorptiometry, Photon; Adult; Aged; Anti-Citrullinated Protein Antibodies - blood; Anti-Citrullinated Protein Antibodies - immunology; Antibodies; Antibodies, Anti-Idiotypic - blood; Antibodies, Anti-Idiotypic - immunology; Arthritis; Arthritis, Rheumatoid - complications; Arthritis, Rheumatoid - diagnostic imaging; Arthritis, Rheumatoid - physiopathology; Autoantibodies; Autoantibodies - blood; Autoantibodies - immunology; Biology and Life Sciences; Biomedical materials; Bone Density; Bone loss; Bone mineral density; Bone Resorption - blood; Bone Resorption - complications; Bone Resorption - physiopathology; Citrulline; Disease; Dual energy X-ray absorptiometry; Female; Hip; Humans; Immunoglobulins; Inflammation; Joint diseases; Laboratories; Lumbar Vertebrae - diagnostic imaging; Lumbar Vertebrae - physiopathology; Male; Medicine and Health Sciences; Metacarpophalangeal Joint - physiopathology; Middle Aged; Osteoclasts - immunology; Osteoclasts - pathology; Osteolysis - complications; Osteolysis - diagnostic imaging; Osteolysis - physiopathology; Patients; Physical Sciences; Protein Carbamylation - immunology; Proteins; Regression analysis; Research and Analysis Methods; Rheumatic diseases; Rheumatoid arthritis; Rheumatology; Spine; Spine (lumbar); Studies; Subgroups; Surgical implants
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0202583

Rheumatoid arthritis (RA) has a negative impact on bone that is partly mediated by anti-citrullinated proteins antibodies (ACPA). These antibodies are associated with erosions, and with juxta-articular and systemic bone loss. Other RA autoantibodies, the anti-carbamylated protein antibodies (anti-CarPA), are independently associated with erosions. However, we do not know if they are also associated with juxta-articular and systemic bone loss. Here, we have addressed this question with data from 548 early arthritis (EA) patients. Bone mineral density (BMD) was assessed by dual-energy x-ray absorptiometry at the lumbar spine (LS), total hip (TH) and metacarpophalangeal joints (MCP). The 25.9% anti-CarPA positive patients did not show significant differences in BMD Z-scores with the negative patients. Nevertheless, this result was due to the similarity between negative and low-positive (below the median of the positive) patients, whereas the high-positive patients showed significant decrease of BMD at LS (β = -0.39, p = 0.01) and TH (β = -0.30, p = 0.02); but not at the juxta-articular bone of MCP. Given the overlap between anti-CarPA and ACPA, we included the two autoantibodies in an analysis that showed significantly lower BMD Z-scores at LS and TH (p< 0.01) only in the ACPA positive/anti-CarPA high-positive subgroup. However, the similar coefficients of regression between the ACPA positive/anti-CarPA high-positive and the ACPA negative/anti-CarPA high-positive subgroups (β = -0.50 vs. -0.52 at LS, and β = -0.37 vs. -0.30 at TH) suggested an independent association. Overall, these results support a contribution of anti-CarPA to systemic bone loss in EA patients.