Abstract
Objectives: Osteoporosis and bone erosions are hallmarks of rheumatoid arthritis (RA) since disease onset is underpinned by the inflammatory burden. In this observational study, we aimed to dissect the putative RA-related parameters and bone-derived biomarkers associated with systemic and focal bone loss at disease onset and with their progression.Methods: One-hundred twenty-eight patients with early rheumatoid arthritis (ERA) were recruited at disease onset. At study entry, demographic, clinical, and immunological parameters were recorded. Each ERA patient underwent plain X-rays of the hands and feet at study entry and after 12 months to assess the presence of erosions. After enrollment, each patient was treated according to the recommendations for RA management and followed up based on a treat-to-target (T2T) strategy. At baseline, blood samples for soluble biomarkers were collected from each patient, and plasma levels of osteoprotegerin (OPG), receptor activator of nuclear factor κB ligand (RANKL), Dickkopf-1 (DKK1), and interleukin 6 (IL-6) were assessed by enzyme-linked immunosorbent assay (ELISA). Seventy-one ERA patients underwent bone mineral density (BMD) measurement at the left femoral neck and second to fourth lumbar spine vertebrae (L2–L4) by dual-energy X-ray absorptiometry (DXA).Results: Among the whole cohort, 34 (26.6%) ERA patients with bone erosions at study entry had a higher disease activity (p = 0.02) and IL-6 plasma levels (p = 0.03) than non-erosive ones. Moreover, at DXA, 33 (46.5%) ERA patients had osteopenia, and 16 (22.5%) had osteoporosis; patients with baseline bone erosions were more likely osteopenic/osteoporotic than non-erosive ones (p = 0.03), regardless of OPG, RANKL, and DKK1 plasma levels. Obese ERA patients were less likely osteopenic/osteoporotic than normal weight ones (p = 0.002), whereas anti-citrullinated protein antibodies (ACPA) positive ERA patients were more likely osteopenic/osteoporotic than ACPA negative ones (p = 0.034). At logistic regression analysis, baseline Disease Activity Score measured on 44 joints (DAS44) [OR: 2.46 (1.11–5.44)] and osteopenic/osteoporosis status [OR: 7.13 (1.27–39.94)] arose as independent factors of erosiveness. Baseline osteopenic/osteoporotic status and ACPA positivity were associated with bone damage progression during the follow-up.Conclusions: Bone erosions presence is associated with systemic bone loss since the earliest phases of RA, suggesting that the inflammatory burden and autoimmune biology, underpinning RA, represent crucial enhancers of bone remodeling either locally as at systemic level.
Highlights
Patients with rheumatoid arthritis (RA) present more bone loss than age- and sex-matched healthy controls (HC), regardless of treatment regimens [1]
Each RA patient was treated according to the current recommendations for RA management [20], and at each study visit, the ACR/EULAR core data set [erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), swollen joint count (SJC), tender joint count (TJC), physician and patient global assessment, pain, and Health Assessment Questionnaire (HAQ)] was recorded
Each enrolled RA patient was followed up based on a treat-to-target (T2T) strategy, with clinical assessment every 3 months recording the clinical improvement and remission based on the Disease Activity Score measured on 44 joints (DAS44) values [21, 22] and ACR/EULAR criteria, respectively [23]
Summary
Patients with rheumatoid arthritis (RA) present more bone loss than age- and sex-matched healthy controls (HC), regardless of treatment regimens [1]. Bone loss may manifest in RA as juxta-articular loss and systemic bone loss [3], the most important feature is the focal bone loss as periarticular erosions, which are characterized by distinct differences in the pathogenesis. Given that in RA, a tight link exists between the inflammatory milieu and the bone remodeling process, a higher rate of bone loss should result as directly related to disease duration and disease activity. In early RA, where disease duration is limited, studying bone loss and bone erosions should give insights into the different mechanisms leading to the bone damage. While bone surface erosions are due to the aberrant action of activated osteoclasts at sites of synovitis [4], the mechanisms guiding the juxta-articular and systemic bone loss and the decreases in bone mineral density (BMD) are less intuitive
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