HDAC Inhibitors as Epigenetic Regulators

Various clinical studies showed the association between hand BMD loss measured by DXR and RA severity, including disease activity, functional impairment and joint destruction [6,13-22]. total joint damage after 4 years with an OR (95% CI) of 3.1 (1.3-7.6). Multivariate Brefeldin A analysis showed that only progressive joint damage in the first year and anti-citrullinated protein antibody positivity were independent predictors of long-term progressive joint damage. Conclusions In the first year of RA, accelerated hand BMD loss is associated with progressive joint damage in both hands and feet. Hand BMD loss in the first year of recent-onset Brefeldin A RA predicts subsequent progressive total joint damage, however not independent of progressive joint damage in the first year. Introduction Bone damage in rheumatoid arthritis (RA) includes joint damage and accelerated bone mineral density (BMD) loss [1]. Joint damage is provoked by an increased osteoclast and decreased osteoblast activation, leading to erosive damage, and by proteolytic pathways, leading to cartilage degradation. This is all mostly regulated by TNF-, IL-1, IL-6, IL-17 and receptor activator of nuclear factor kappa B ligand (RANKL) [2-4]. It is believed that BMD loss, both localized and generalized, is also primarily the effect of increased osteoclast activity in RA [5]. In particular, bones in the proximity of inflamed joints are susceptible to BMD loss due to inflammation [6]. Furthermore, localized hand BMD loss occurs in an early phase of RA [7] and even in pre-RA undifferentiated arthritis [8], and might precede erosive damage on X-ray [9,10]. Dual energy X-ray absorptiometry (DEXA) is the gold standard for measuring BMD. Digital X-ray radiogrammetry (DXR) was developed as a method of radiogrammetry to estimate BMD in the metacarpals using standard hand radiographs [11]. BMD measured by DXR is highly correlated with Rabbit Polyclonal to Smad1 (phospho-Ser465) DEXA measurements and DXR has a high precision for detecting changes in BMD [11,12]. Various clinical studies showed the association between hand BMD loss measured by DXR and RA severity, including disease activity, functional impairment and joint destruction [6,13-22]. Two clinical studies, one of them a pilot study, showed the potential value of BMD loss in hands measured by DXR to predict radiographic joint damage in hands [23,24]. However, to date, no data are available on the Brefeldin A association between hand BMD loss and progressive joint damage in hands and feet and on the value of hand BMD loss as predictor of joint destruction in recent-onset RA patients who are treated intensively with disease modifying anti-rheumatic drugs (DMARDs) and TNF- inhibitors in a tight control setting. We examined the association between accelerated hand BMD loss and progressive joint damage in hands and feet during the first year of recent-onset active RA to see whether both types of bone damage have common pathways in their pathogenesis, and we investigated whether accelerated hand BMD loss in the first year of RA was an independent predictor of subsequent progressive joint damage after four years in patients who are treated in a tight control setting. Materials and methods Patients All measures were performed in the setting of the Behandel Strategie?n (BeSt) study [25]. Patients aged 18 years and older, who met the definition of RA as defined by the American College of Rheumatology (ACR) 1987 revised criteria, with symptom duration of less than two years and active disease with 6 or more of 66 swollen joints and 6 or more of 68 tender joints and either an erythrocyte sedimentation rate (ESR) of 28 mm/hour or more or a visual analogue scale (VAS) global health of 20 mm or more, and who were DMARD na?ve, were included in the trial from April 2000 to August 2002. Exclusion criteria have been reported previously [25]. Of the 508 patients, 236 were excluded from this study predominantly due to switch from analogue to digital radiographs. The other 272 patients had analogue radiographs at both baseline and after one year and were eligible for this study. The baseline and/or one year follow-up analogue radiographs of 16 patients could not be analysed by DXR due to underexposed images (13 patients) or improper positioning of the hands (3 patients). Hence, 256 patients were Brefeldin A included in the current study. Study design The BeSt study was conducted by rheumatologists participating in the Foundation for Applied Rheumatology Research, in 18 peripheral and 2 university.