Catabolic and anabolic periarticular bone changes in patients with rheumatoid arthritis: a computed tomography study on the role of age, disease duration and bone markers

Arthritis research & therapy (Impact Factor: 4.12). 05/2013; 15(3):R62. DOI: 10.1186/ar4235
Source: PubMed

ABSTRACT INTRODUCTION: 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). METHODS: Forty 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 collagen type I: CTX I, tartrate resistant acid phosphatase 5b: TRAP5b), bone formation (bone alkaline phosphatase: BAP, osteocalcin: OC) and calcium homeostasis (parathyroid hormone: PTH, 25-hydroxy-vitamin 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. RESULTS: Partial 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. CONCLUSIONS: This 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, also periarticular bone changes correlate with alterations in systemic markers of bone metabolism, pointing out BAP as an important parameter.

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    ABSTRACT: Recently, the traditional Chinese medicine Tripterygium wilfordii Hook f (TwHF) of the Celastraceae family has attracted increasing attention for its potential therapeutic application in patients with rheumatoid arthritis (RA). It is well accepted that TwHF exerts the antirheumatic activity and mainly depends on its potent anti-inflammatory property. To further explore the therapeutic potential of the well-defined TwHF-derived single compound — celastrol in RA, we study the therapeutic efficacy of celastrol on bone erosion in collagen-induced arthritis (CIA) mice and delineate its effects on osteoclast differentiation and functions in RANKL-induced osteoclast precursors RAW264.7 cell line. In CIA mice, daily injection of celastrol (beginning on day 28 after arthritis induction) markedly suppressed arthritis, and reduced bone damage in the joints as demonstrated by histology and bone micro-computed tomography (CT). The effects were accompanied by reductions of osteoclast cells in joints, serum tartrate-resistant acid phosphatase (TRAP) 5b, and expression of osteoclastic genes (Trap, Ctsk, Ctr, Mmp-9) and transcriptional factors (c-Fos, c-Jun and NFATc1). When RAW264.7 cells were treated with RANKL, celastrol inhibited the formation of TRAP + multinucleated cells and the bone-resorbing activity in dose-dependent manners. Furthermore, celastrol reduced the RANKL-induced expression of osteoclastic genes and transcriptional factors, as well as phosphorylation of NF-kB and mitogen-activated protein kinases (MAPK). These findings show that celastrol could directly inhibit osteoclast formation and function, suggesting a novel therapeutic strategy of celastrol for managing RA, especially in preventing bone destruction.
    International Immunopharmacology 12/2014; 24(2). DOI:10.1016/j.intimp.2014.12.012 · 2.71 Impact Factor
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    ABSTRACT: High resolution peripheral quantitative computed tomography (HR‐pQCT) is a new technology commercially available for less than 10 years that allows performing in vivo assessment of bone parameters. HR‐pQCT assesses the trabecular thickness, trabecular spacing, trabecular number and connectivity density and, in addition, cortical bone density and thickness and total bone volume and density in high‐definition mode, which additionally allows obtaining digital constructs of bone microarchitecture. The application of mathematics to captured data, a method called finite element analysis (FEA), allows the estimation of the physical properties of the tissue, simulating supported loads in a non‐invasive way. Thus, HR‐pQCT simultaneously acquires data previously provided separately by dual energy x‐ray absorptiometry (DXA), magnetic resonance imaging and histomorphometry, aggregating biomechanical estimates previously only possible in extracted tissues. This method has a satisfactory reproducibility, with coefficients of variation rarely exceeding 3%. Regarding accuracy, the method shows a fair to good agreement (r2 = 0.37‐0.97).The main clinical application of this method is in the quantification and monitoring of metabolic bone disorders, more fully evaluating bone strength and fracture risk. In rheumatoid arthritis patients, this allows gauging the number and size of erosions and cysts, in addition to joint space. In osteoarthritis, it is possible to characterize the bone marrow edema‐like areas that show a correlation with cartilage breakdown.Given its high cost, HR‐pQCT is still a research tool, but the high resolution and efficiency of this method reveal advantages over the methods currently used for bone assessment, with a potential to become an important tool in clinical practice.
    Revista Brasileira de Reumatologia 11/2014; DOI:10.1016/j.rbr.2014.07.010 · 0.99 Impact Factor
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    ABSTRACT: Objective. The aim of this review is to clarify the usefulness of bone, cartilage, and synovial biomarker in the management of rheumatoid arthritis (RA) therapy in remission. Synovial Biomarkers. High MMP-3 levels are associated with joint progression in RA patients, but there is no data about their utility in clinical remission. IIINys and Glc-Gal-PYD seem to be more specific to synovium, but more studies are required. Cartilage Biomarkers. Unbalance between cartilage break-down biomarkers (urinary CTX II and COMP) and cartilage formation biomarker (PIIANP) was described. This unbalance is also associated with joint destruction and prognosis of destruction. No data are available on patients in remission. Bone Biomarkers. RA activity is correlated with an increase of bone resorption markers such as CTX I, PYD, and TRACP 5b and a decrease of bone formation markers such as OC and BALP. RA therapies seem to improve bone turnover in limiting bone resorption. There is no study about bone marker utility in remission. Conclusion. Biomarkers seem to correlate with RA activity and progression. They also could be used to manage RA therapies, but we need more data on RA remission to predict relapse.
    Mediators of Inflammation 03/2014; 2014:537324. DOI:10.1155/2014/537324 · 2.42 Impact Factor

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Stephanie Finzel