Abstract
IntroductionThe aim of this study was to determine the factors, including markers of bone resorption and bone formation, which determine catabolic and anabolic periarticular bone changes in patients with rheumatoid arthritis (RA).MethodsForty RA patients received high-resolution peripheral quantitative computed tomography (HR-pQCT) analysis of the metacarpophalangeal joints II and III of the dominantly affected hand at two sequential time points (baseline, one year follow-up). Erosion counts and scores as well as osteophyte counts and scores were recorded. Simultaneously, serum markers of bone resorption (C-terminal telopeptide of type I collagen (CTX I), tartrate-resistant acid phosphatase 5b (TRAP5b)), bone formation (bone alkaline phosphatase (BAP), osteocalcin (OC)) and calcium homeostasis (parathyroid hormone (PTH), 25-hydroxyvitamin D3 (Vit D)) were assessed. Bone biomarkers were correlated to imaging data by partial correlation adjusting for various demographic and disease-specific parameters. Additionally, imaging data were analyzed by mixed linear model regression.ResultsPartial correlation analysis showed that TRAP5b levels correlate significantly with bone erosions, whereas BAP levels correlate with osteophytes at both time points. In the mixed linear model with erosions as the dependent variable, disease duration (P <0.001) was the key determinant for these catabolic bone changes. In contrast, BAP (P = 0.001) as well as age (P = 0.018), but not disease duration (P = 0.762), were the main determinants for the anabolic changes (osteophytes) of the periarticular bone in patients with RA.ConclusionsThis study shows that structural bone changes assessed with HR-pQCT are accompanied by alterations in systemic markers of bone resorption and bone formation. Besides, it can be shown that bone erosions in RA patients depend on disease duration, whereas osteophytes are associated with age as well as serum level of BAP. Therefore, these data not only suggest that different variables are involved in formation of bone erosions and osteophytes in RA patients, but also that periarticular bone changes correlate with alterations in systemic markers of bone metabolism, pointing out BAP as an important parameter.
Highlights
The aim of this study was to determine the factors, including markers of bone resorption and bone formation, which determine catabolic and anabolic periarticular bone changes in patients with rheumatoid arthritis (RA)
A total of 87.5% of the patients received disease-modifying antirheumatic drugs (DMARDs) at baseline (mostly methotrexate (MTX); mean ± SD dose: 15.15 ± 4.42 mg/week), 42.5% were treated with glucocorticoids and 55% with biologics (TNF blockers: N = 18; tocilizumab N = 4, rituximab N = 2)
Data correlating bone markers to the results from radiographs only addressed catabolic bone changes and did not account for anabolic bone changes. In this proof-of-concept investigation, we addressed the relation between catabolic and anabolic bone changes in the HRpQCT and markers of bone metabolism in arthritis patients on a cross-sectional and longitudinal basis
Summary
The aim of this study was to determine the factors, including markers of bone resorption and bone formation, which determine catabolic and anabolic periarticular bone changes in patients with rheumatoid arthritis (RA). Rheumatoid arthritis (RA) is a chronic inflammatory disease causing bone damage This process is based on imbalance between bone-resorbing osteoclasts and boneforming osteoblasts. The assessment of dynamic changes of erosions is feasible by radiography and represents the basis for demonstrating structure-sparing effects of antirheumatic drugs It takes, several months, until radiographs reveal treatment responses in RA. Several markers of bone resorption and formation have been assessed in patients with RA, linking them to radiographic data or other outcome variables [3,4,5,6,7,8,9,10,11,12] These data suggested that bone markers might be useful in reflecting bone damage in RA and potentially in serving as predictors for structural outcome. It is surprising that no study has so far linked bone markers to advanced bone imaging
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