title: Anti-citrullinated protein antibodies are associated with decreased bone mineral density: baseline data from a register of early arthritis patients.
abstract: Since the previous studies showed that anti-citrullinated protein antibodies (ACPA) can induce osteoclasts differentiation and activation, even before arthritis onset, the aim of our study was to determine whether ACPA-positivity is associated with lower bone mineral density (BMD) at baseline visit of a register of early arthritis (EA) patients. The study population comprised 578 patients (80% females) from our EA clinic with a median disease duration, 5.1 months (p25-p75: 6-8); median age, 53.6 years (41.9-66.1), 38% ACPA-positive, and 55% fulfilling 2010 criteria for rheumatoid arthritis. BMD was measured using dual X-ray absorptiometry at lumbar spine, hip, and metacarpophalangeal (MCP) joints of the non-dominant hand to evaluate both systemic and juxta-articular bone mass. ACPA titers were determined through enzyme immunoassay. The effect of ACPA on BMD was analyzed using multivariable analysis based on generalized linear models adjusted for various confounders. ACPA-positive patients showed lower bone mass at lumbar spine and hip, but no differences were observed at MCP joints compared to ACPA-negative patients. However, ACPA-positive patients displayed higher disease activity and disability than ACPA-negative patients. After adjustment for gender, age, body mass index, and other bone-related variables, the presence of ACPA remained significantly associated with lower BMD at the lumbar spine, femoral neck, and hip but not at MCP joints. Disease activity was not associated with baseline bone mass. Our data reinforce the previous preclinical findings suggesting that the systemic bone loss detected at the initial phases of early ACPA-positive arthritis is independent of inflammatory status and, therefore, could be mediated by ACPA.
authors.affiliation: Rheumatology Department, Hospital Universitario de La Princesa, IIS-Princesa, C/ Diego de León 62, 28006, Madrid, Spain.
authors.forename: Irene
authors.initials: I
authors.lastname: Llorente
authors.affiliation: Rheumatology Department, Hospital Universitario de La Princesa, IIS-Princesa, C/ Diego de León 62, 28006, Madrid, Spain.|Rheumatology Department, Hospital San Pedro, Logroño, Spain.
authors.forename: Leticia
authors.initials: L
authors.lastname: Merino
authors.affiliation: Rheumatology Department, Hospital Universitario de La Princesa, IIS-Princesa, C/ Diego de León 62, 28006, Madrid, Spain.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Ortiz
authors.affiliation: Radiology Department, Hospital Universitario de La Princesa, IIS-Princesa, Madrid, Spain.
authors.forename: Eugenio
authors.initials: E
authors.lastname: Escolano
authors.affiliation: Radiology Department, Hospital Universitario de La Princesa, IIS-Princesa, Madrid, Spain.
authors.forename: Saturnino
authors.initials: S
authors.lastname: González-Ortega
authors.affiliation: Rheumatology Department, Hospital Universitario de La Princesa, IIS-Princesa, C/ Diego de León 62, 28006, Madrid, Spain.
authors.forename: Rosario
authors.initials: R
authors.lastname: García-Vicuña
authors.affiliation: Rheumatology Department, Hospital Universitario de La Princesa, IIS-Princesa, C/ Diego de León 62, 28006, Madrid, Spain.
authors.forename: Jesús A
authors.initials: JA
authors.lastname: García-Vadillo
authors.affiliation: Rheumatology Department, Hospital Universitario de La Princesa, IIS-Princesa, C/ Diego de León 62, 28006, Madrid, Spain. scastas@gmail.com.
authors.forename: Santos
authors.initials: S
authors.lastname: Castañeda
authors.affiliation: Rheumatology Department, Hospital Universitario de La Princesa, IIS-Princesa, C/ Diego de León 62, 28006, Madrid, Spain. isidoro.ga@ser.es.
authors.forename: Isidoro
authors.initials: I
authors.lastname: González-Álvaro
mesh_terms: D015502:Absorptiometry, Photon; D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D015519:Bone Density / Q000502:physiology*; D006621:Hip Joint / Q000000981:diagnostic imaging*; D006801:Humans; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging*; D008662:Metacarpophalangeal Joint / Q000000981:diagnostic imaging*; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology*; D012042:Registries
chemical_list: D001323:Autoantibodies; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide
keywords: Autoantibodies; Autoimmunity; Bone mineral density; Rheumatoid arthritis