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

Correlation between genomic index lesions and mpMRI and 68Ga-PSMA-PET/CT imaging features in primary prostate cancer

Abstract Magnetic resonance imaging (MRI) and prostate specific membrane antigen (PSMA)- positron emission tomography (PET)/computed tomography (CT)-imaging of prostate cancer (PCa) are emerging techniques to assess the presence of significant disease and tumor progression. It is not known, however, whether and to what extent lesions detected by these imaging techniques correlate with genomic features of PCa. The aim of this study was therefore to define a genomic index lesion based on chromosomal copy number alterations (CNAs) as marker for tumor aggressiveness in prostate biopsies in direct correlation to multiparametric (mp) MRI and 68Ga-PSMA-PET/CT imaging features. CNA profiles of 46 biopsies from five consecutive patients with clinically high-risk PCa were obtained from radiologically suspicious and unsuspicious areas. All patients underwent mpMRI, MRI/TRUS-fusion biopsy, 68Ga-PSMA-PET/CT and a radical prostatectomy. CNAs were directly correlated to imaging features and radiogenomic analyses were performed. Highly significant CNAs (≥10 Mbp) were found in 22 of 46 biopsies. Chromosome 8p, 13q and 5q losses were the most common findings. There was an strong correspondence between the radiologic and the genomic index lesions. The radiogenomic analyses suggest the feasibility of developing radiologic signatures that can distinguish between genomically more or less aggressive lesions. In conclusion, imaging features of mpMRI and 68Ga-PSMA-PET/CT can guide to the genomically most aggressive lesion of a PCa. Radiogenomics may help to better differentiate between indolent and aggressive PCa in the future