Accelerated hand bone mineral density loss is associated with progressive joint damage in hands and feet in recent-onset rheumatoid arthritis

Introduction: To investigate whether accelerated hand bone mineral density (BMD) loss is associated with progressive joint damage in hands and feet in the first year of rheumatoid arthritis (RA) and whether it is an independent predictor of subsequent progressive total joint damage after 4 years. Methods: In 256 recent-onset RA patients, baseline and 1-year hand BMD was measured in metacarpals 2-4 by digital X-ray radiogrammetry. Joint damage in hands and feet were scored in random order according to the Sharp-van der Heijde method at baseline and yearly up to 4 years. Results: 68% of the patients had accelerated hand BMD loss (>-0.003 g/cm(2)) in the first year of RA. Hand BMD loss was associated with progressive joint damage after 1 year both in hands and feet with odds ratios (OR) (95% confidence intervals [CI]) of 5.3 (1.3-20.9) and 3.1 (1.0-9.7). In univariate analysis, hand BMD loss in the first year was a predictor of subsequent progressive total joint damage after 4 years with an OR (95% CI) of 3.1 (1.3-7.6). Multivariate 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 RA predicts subsequent progressive total joint damage, however not independent of progressive joint damage in the first year.Pathophysiology and treatment of rheumatic disease

Establishment of age- and sex-adjusted reference data for hand bone mass and investigation of hand bone loss in patients with rheumatoid arthritis treated in clinical practice:an observational study from the DANBIO registry and the Copenhagen Osteoarthritis Study

BACKGROUND: Rheumatoid arthritis is characterised by progressive joint destruction and loss of periarticular bone mass. Hand bone loss (HBL) has therefore been proposed as an outcome measure for treatment efficacy. A definition of increased HBL adjusted for age- and sex-related bone loss is lacking. In this study, we aimed to: 1) establish reference values for normal hand bone mass (bone mineral density measured by digital x-ray radiogrammetry (DXR-BMD)); and 2) examine whether HBL is normalised in rheumatoid arthritis patients during treatment with tumour necrosis factor alpha inhibitors (TNFI). METHODS: DXR-BMD was measured from hand x-rays in a reference cohort (1485 men/2541 women) without arthritis randomly selected from an urban Danish population. Sex- and age-related HBL/year was estimated. DXR-BMD was measured in rheumatoid arthritis patients (n = 350: at start of TNFI, and ~2 years after TNFI start), of which 135 patients had three x-rays (~2 years prior to TNFI, at start of TNFI, and ~2 years after TNFI start). Individual HBL/year prior to and during TNFI was calculated and compared to reference values. RESULTS: Estimated HBL/year varied strongly with age and sex. Compared to the reference values, 75 % of 135 patients had increased HBL prior to TNFI treatment and 59 % had increased HBL during TNFI treatment (p = 0.17, Chi-squared). In 38 % (38/101) of patients with increased HBL, HBL was normalised during TNFI treatment, whereas 47 % (16/34) of patients with normal HBL prior to TNFI had increased HBL during TNFI treatment. In the 350 patients, increased HBL during TNFI was associated with time-averaged 28-joint disease activity score (odds ratio 1.69 (95 % Confidence Interval 1.34-2.15)/unit increase, p < 0.001), and patients in time-averaged remission had lower HBL than patients without remission (0.0032 vs. 0.0058 g/cm(2)/year; p < 0.001, Mann-Whitney). CONCLUSIONS: We established age- and sex-specific reference values for DXR-BMD in a large cohort without arthritis. HBL was increased in the majority of rheumatoid arthritis patients initiating TNFI in clinical practice, and only normalised in a minority during TNFI. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13075-016-0952-y) contains supplementary material, which is available to authorized users

Reduced trabecular bone mineral density and cortical thickness accompanied by increased outer bone circumference in metacarpal bone of rheumatoid arthritis patients: a cross-sectional study

Introduction The objective of this study was to assess three-dimensional bone geometry and density at the epiphysis and shaft of the third meta-carpal bone of rheumatoid arthritis (RA) patients in comparison to healthy controls with the novel method of peripheral quantitative computed tomography (pQCT). Methods PQCT scans were performed in 50 female RA patients and 100 healthy female controls at the distal epiphyses and shafts of the third metacarpal bone, the radius and the tibia. Reproducibility was determined by coefficient of varia-tion. Bone densitometric and geometric parameters were compared between the two groups and correlated to disease characteristics. Results Reproducibility of different pQCT parameters was between 0.7% and 2.5%. RA patients had 12% to 19% lower trabecular bone mineral density (BMD) (P ≤ 0.001) at the distal epiphyses of radius, tibia and metacarpal bone. At the shafts of these bones RA patients had 7% to 16% thinner cortices (P ≤ 0.03). Total cross-sectional area (CSA) at the metacarpal bone shaft of pa-tients was larger (between 5% and 7%, P < 0.02), and relative cortical area was reduced by 13%. Erosiveness by Ratingen score correlated negatively with tra-becular and total BMD at the epiphyses and shaft cortical thickness of all measured bones (P < 0.04). Conclusions Reduced trabecular BMD and thinner cortices at peripheral bones, and a greater bone shaft diameter at the metacarpal bone suggest RA spe-cific bone alterations. The proposed pQCT protocol is reliable and allows measuring juxta-articular trabecular BMD and shaft geometry at the metacarpal bone

Evaluierung von Normwerten zur Etablierung der Digitalen Radiogrammetrie in der klinischen Anwendung

Purpose: the study presents German reference data for Digital X-ray Radiogrammetry (DXR) differentiated by male as well as female, and quantifies gender-specific and agerelated differences for all DXR-parameters. The study also documents the effects of different X-ray settings (e.g. radiographs of the wrist or the hand) on DXR-measurements. Patients and Methods: 2085 patients were prospectively enrolled (954 female / 1131 male) from data pool of 11915 patients with radiographs of the non-dominant hand or wrist. All patients underwent measurements of bone mineral density (BMD), cortical thickness (CT), bone width (W) and Metacarpal Index (MCI) using DXR-technology. Results: These data show a continuous age-related increase of the DXR-parameters to the point of peak bone mass, then a continuous decline beyond the peak bone mass with accentuated age-related cortical bone loss in women. Peak bone mass is reached at about 30-35 years for woman and 45-50 for men. Additionally males show a significantly higher DXR-BMD (mean: +12,8%) compared to the female cohort for all age groups. Rgarding the impact of various X-ray settings (X-ray wrist versus X-ray hand) no significant difference was observed between both groups in men as well as women. Conclusion: in conclusion the development of digital imaging technology has enabled more precise measurement of several radiogeometric features. The present study has estimated normative reference values for Digital X-ray Radiogrammetry in German Caucasian woman and men. Based on this reference data a valid and reliable quantification of disease-related demineralisation based on measurements of DXR-BMD and MCI is now available for the Caucasian ethnic group

Ultrasound and fluorescence optical imaging biomarkers for early diagnosis and prediction of rheumatoid arthritis

Prevention of rheumatoid arthritis (RA) is most desirable together with curative treatment which is, however, not yet available. Today, the correct timely diagnosis and early treatment interventions to prevent disease progression remain the best options for our patients. In this thesis, I explore the diagnostic and predictive value of musculoskeletal ultrasound (MSUS) and fluorescence optical imaging (FOI) in identifying biological features on images indicative of existing or emerging joint inflammation (synovitis). In study 1, we tested and compared the diagnostic utility of FOI with clinical examination and musculoskeletal ultrasound (MSUS) to detect active synovitis in 872 joints of 26 patients with different rheumatic diseases (46% early RA). Fluorescence optical imaging proved to be 80% sensitive and 96% specific, having a 77% positive predictive value (PPV) and 97% negative predictive value (NPV) for detecting silent synovitis. In study 2 we showed FOI’s ability to quantify digital disease activity (DACT) scores of 1326 joints in 39 early RA patients to be 81% sensitive and 90% specific, with 96% PPV and 61% NPV. These results justify FOI use in clinical practice, to assist the rheumatologist to make an earlier diagnosis with greater confidence. Unsupervised cluster differences emerged for seropositive and seronegative RA patients showing FOI’s ability to objectively quantify hand joint inflammation using novel DACT scoring methods. In study 3 we report good association among the two ultrasound semi-quantitative scoring (SQS) methods to that of a novel quantitative scoring (QS) measure of color Doppler pixel counts in 37 established RA patients. Although SQS well correlated with QS to assess active synovitis, the SQS methods lacked visual perceptions of raters to distinguish between grade cut-offs which may help to further revise the criteria used to objectively quantify disease activity. In study 4, we show the value of ultrasound and immune-inflammatory biomarkers in predicting arthritis onset in individuals positive for Anti-CCP with musculoskeletal complaints at risk of RA development. We propose the recognition of a high-risk RA phase characterized by presence of certain ACPA reactivities, IL15-Rα, IL6; and ultrasound detected tenosynovitis, and possibilities to identify (low and high) risk groups for arthritis progression. Overall, our findings on imaging contribute towards a) silent synovitis detection despite negative clinical investigation, b) objective quantitative measures to monitor the effects of RA therapy and c) early identification of certain predictive imaging and biological features/biomarkers that precede arthritis development (tenosynovitis and/or bursitis) in individuals at risk for developing RA, enabling closer monitoring and early diagnosis

The role of X-ray imaging and musculoskeletal ultrasound in the diagnosis and management of rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease characterized by symmetric joint inflammation that often involves the small joints of the hands and feet, with progressive destruction, deformity, and disability of the joints. Small joints of the hands and feet are frequently the first to be involved in RA, which is why methods for assessment of these joints are of particular importance at the onset of RA and early stage of the disease. The results of this thesis have highlighted the role of conventional radiography, Digital X-ray radiogrammetry (DXR) and musculoskeletal ultrasound (MSUS) in the diagnosis and management of RA. Paper I is based on the study about clinical and radiographic outcomes in patients with early RA who responded well to initial Methotrexate (MTX) monotherapy. Most early RA patients who achieved low disease activity after 3 – 4 months of MTX monotherapy continued to have low disease activity during 2 years follow-up. However, marked radiographic progression occurred in a proportion of patients, even despite sustained DAS28 remission. Paper II aimed to evaluate whether a significant decrease of cortical bone mineral density (BMD) measured by DXR during the first year of RA correlated with radiographic progression after 2 years. The results indicated that patients with significant decrease of DXR-BMD had significantly greater risk for radiographicprogression, compared with patients without. Evaluation of RA patients with significant decrease in DXR-BMD during the first year of the disease helps to identify patients with higher risk for radiographic progression later in the disease course. However, future studies should investigate whether decrease in DXR-BMD during the first 3 or 6 months of the disease could indicate the same results. Paper III is based on a study about clinical predictors at the time of RA diagnosis for rapid radiographic progression (increase>5 units according to the Sharp score modified by van der Heijde after one year). The results from paper III indicated that baseline erosions, level of acute phase reactant and current smoking status were independent predictors for radiographic progression after 1 year. These results remained after further adjustment for treatment strategy. Three dimensional risk matrix including current smoking status, erosions and C-reactive protein showed a 12–63% risk gradient from patients carrying none compared with all predictors. Paper IV aimed to assess the utility of MSUS in patients with suspected inflammatory arthritis, using a probabilistic approach. In this study, the proportion of patients with maximal diagnostic certainty for inflammatory arthritis was increased significantly after performing MSUS. The similar significant increase was also observed for diagnostic certainty of RA. The findings from MSUS agreed with the final diagnosis in more than 95% of patients