Prevalence of pulmonary hypertension in an unselected, mixed connective tissue disease cohort: results of a nationwide, Norwegian cross-sectional multicentre study and review of current literature.

OBJECTIVES: The aim of this study was to assess the overall prevalence of pulmonary hypertension (PH) in an unselected MCTD cohort and review the current knowledge with a systematic database search. METHODS: A nationwide multicentre cohort of 147 adult MCTD patients were initially screened for PH by echocardiography, high-resolution computed tomography (HRCT), pulmonary function tests and N-terminal pro-brain natriuretic peptide (NT-proBNP) and then followed up for a mean of 5.6 years. Right-sided heart catheterization was performed when estimated pulmonary artery systolic pressure was >40 mmHg on echocardiography. PH was diagnosed according to the 2009 European Society of Cardiology and European Respiratory Society guidelines. RESULTS: At inclusion, 2.0% (3/147) had established PH. Two additional PH patients were identified during follow-up, giving a total PH frequency in the cohort of 3.4% (5/147). All five had elevated serum NT-proBNP. Two had isolated pulmonary arterial hypertension (PAH) and three PH associated with interstitial lung disease (PH-ILD). Three PH patients died during follow-up. Nine other patients in the cohort also died, but none of them had echocardiographic signs of PH prior to death. CONCLUSION: The data from the current unselected MCTD cohort suggest that the prevalence of PH is much lower than expected from previous studies but confirm the seriousness of the disease complication.

Prevalence and severity of interstitial lung disease in mixed connective tissue disease: a nationwide, cross-sectional study.

BACKGROUND: Mixed connective tissue disease (MCTD) is an immune-mediated, systemic disorder of unknown cause. OBJECTIVE: To assess the prevalence, pattern and severity of interstitial lung disease (ILD) in a cross-sectional study of the nationwide, Norwegian MCTD cohort. METHODS: 126 patients with MCTD were systematically examined for ILD by high-resolution CT (HRCT), pulmonary function tests (PFT), 6 min walk test (6MWT) and by the New York Heart Association (NYHA) functional classification of dyspnoea. The extent and type of HRCT lung abnormalities were scored according to the CT criteria of ILD recommended by the Fleischner Society. RESULTS: All 126 patients were Caucasian, 75% women. At the time of the cross-sectional ILD study, the patients had a mean disease duration of 9.0 years. 52% of the patients had abnormal HRCT findings, most commonly reticular patterns consistent with lung fibrosis (35%). Lung fibrosis was quantified as minor in 7%, moderate in 9% and severe in 19% of the patients. Fibrosis was uniformly concentrated in the lower parts of the lungs and was not associated with smoking. Patients with severe lung fibrosis had lower PFT values, shorter 6MWT and a higher mean NYHA functional class. After a mean 4.2 years' follow-up, overall mortality was 7.9%. Mortality in patients with normal HRCT was 3.3%, as compared with 20.8% in patients with severe lung fibrosis (p<0.01). CONCLUSIONS: Severe lung fibrosis is common in MCTD, has an impact on pulmonary function and overall physical capacity and is associated with increased mortality.

Long-term in-vitro precision of direct digital X-ray radiogrammetry.

OBJECTIVE: Digital X-ray radiogrammetry (DXR) calculates peripheral bone mineral density (BMD) from hand radiographs. The short-term precision for direct DXR has been reported to be highly satisfactory. However, long-term precision for this method has not been examined. Thus, the aim of this study was to examine the long-term in-vitro precision for the new direct digital version of DXR. MATERIALS AND METHODS: The in-vitro precision for direct DXR was tested with cadaver phantoms on four different X-ray systems at baseline, 3 months, 6 months, and in one machine also at 12 months. At each time point, 31 measurements were performed. RESULTS: The in-vitro longitudinal precision for the four radiographic systems ranged from 0.22 to 0.43% expressed as coefficient of variation (CV%). The smallest detectable difference (SDD) ranged from 0.0034 to 0.0054 g/cm(2). CONCLUSIONS: The in vitro long-term precision for direct DXR was comparable to the previous reported short-term in-vitro precision for all tested X-ray systems. These data show that DXR is a stable method for detecting small changes in bone density during 6-12 months of follow-up.

Safety and efficacy of faecal microbiota transplantation by Anaerobic Cultivated Human Intestinal Microbiome (ACHIM) in patients with systemic sclerosis: study protocol for the randomised controlled phase II ReSScue trial.

INTRODUCTION: In the multisystem inflammatory disorder systemic sclerosis (SSc), gastrointestinal tract (GIT) affliction is highly prevalent. There are no known disease modifying therapies and the negative impact is substantial. Aiming for a new therapeutic principle, and inspired by recent work showing associations between gut microbiota changes and GIT symptoms in SSc, we performed a pilot study on faecal microbiota transplantation (FMT) with the single-donor bacterial culture 'Anaerobic Cultivated Human Intestinal Microbiome (ACHIM)'. Motivated by positive pilot study signals, we designed the ReSScue trial as a phase II multicentre, placebo-controlled, randomised 20-week trial to evaluate safety and efficacy on lower GIT symptoms of FMT by ACHIM in SSc. METHODS AND ANALYSES: We aim to include 70 SSc participants with moderate to severe lower GIT symptoms, defined by the validated patient-reported University of California Los Angeles Scleroderma Clinical Trial Consortium GIT 2.0 2.0 questionnaire. The trial includes three parts. In part A1 (induction phase) lasting from week 0 to week 12, participants will be randomised 1:1 to repeat infusions of 30 mL ACHIM or placebo at week 0 and 2 by gastroduodenoscopy. In part A2, which is an 8-week subsequent maintenance phase, all study participants will receive 30 mL ACHIM at week 12 and followed until week 20 on continued blind. In part B, which will last until the last participant completes part A2, the participants will be followed through a maximum 16-week extended monitoring period, for longer-term data on safety and intervention effects. Primary endpoint is change from baseline to week 12 in UCLA GIT subscale scores of diarrhoea or bloating, depending on the worst symptom at baseline evaluated separately for each patient. Secondary endpoints are safety measures and changes in UCLA GIT scores (total, diarrhoea and bloating). ETHICS AND DISSEMINATION: This protocol was approved by the Northern Norwegian Committee for Medical Ethics. Study findings will be published. TRIAL REGISTRATION NUMBER: NCT04300426; Pre-results. PROTOCOL VERSION: V.3.1.

The ability of hand digital X-ray radiogrammetry to identify middle-aged and elderly women with reduced bone density, as assessed by femoral neck dual-energy X-ray absorptiometry.

In this study, we evaluate the ability of digitized digital X-ray radiogrammetry (DXR) bone mineral density (BMD) to identify women with reduced BMD at femoral neck, assessed by dual-energy X-ray absorptiometry (DXA). The study population contained women with recent low-energy distal radius fracture and women recruited from the general population, all aged 50 yr or older. The correlation between hand BMD and femoral neck BMD was r=0.65 (p<0.001). We used a triage approach where 2 cutoffs for DXR T-score were defined at which patients with 90% sensitivity and 90% specificity could be identified to have or not have reduced BMD at femoral neck, defined as T-score ≤-2.5 standard deviation (SD). The upper and lower DXR T-score cutoffs were -1.2 and -2.7, respectively. Applying the triage approach in the whole cohort, 32% would require a central DXA assessment to determine the presence or absence of femoral neck T-score ≤-2.5 SD. Our data suggest that DXR can be used to reduce the numbers of patients in need of DXA femoral neck and may, thus, be of clinical value where access to DXA is limited.

Short-time in vitro and in vivo precision of direct digital X-ray radiogrammetry.

Digital X-ray radiogrammetry (DXR) calculates peripheral bone mineral density (BMD) from hand radiographs. The aim of this study was to examine in vitro and in vivo precision for the new direct digital version of DXR, a development of the conventional DXR. The in vitro precision for direct DXR was tested on 4 different X-ray equipment, based on 31 radiographs of the same phantom. The in vivo precision was based on duplicate hand radiographs from both hands in 39 individuals. For the 4 X-ray equipment, in vitro precision ranged from 0.14% to 0.30%, expressed as coefficient of variations (CV%) and from 0.0012 to 0.0028 g/cm2, expressed as smallest detectable difference (SDD). The precision was correlated to the resolution of the radiographic equipment (r=0.95, p=0.05). The corresponding values for the in vivo precision for mean values of both hands were: CV%=0.46%; SDD=0.0046 g/cm2, and least significant change (LSC%)=1.28%. The DXR-BMD for 1 of the X-ray equipment differed 1.1% from the overall mean. The precision for direct DXR was highly satisfactory both in vitro and in vivo. DXR-BMD values may differ between the radiographic equipment, and follow-up measurements should be performed with the same X-ray equipment.

Bone mineral density in patients with psoriatic arthritis: data from the Nord-Trøndelag Health Study 3.

BACKGROUND: The risk of osteoporosis in patients with psoriatic arthritis (PsA) remains unclear. The aim of this study was to compare bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA) in patients with PsA and controls. PATIENTS AND METHODS: Patients with PsA and controls were recruited from the Nord-Trøndelag Health Study (HUNT) 3. RESULTS: Patients with PsA (n=69) and controls (n=11 703) were comparable in terms of age (56.8 vs 55.3 years, p=0.32), gender distribution (females 65.2% vs 64.3%, p=0.87) and postmenopausal status (75.6% vs 62.8%, p=0.08). Body mass index (BMI) was higher in patients with PsA compared with controls (28.5 vs 27.2 kg/m2, p=0.01). After adjusting for potential confounding factors (including BMI), BMD was higher in patients with PsA compared with controls at lumbar spine 1-4 (1.213 vs 1.147 g/cm2, p=0.003) and femoral neck (0.960 vs 0.926 g/cm2, p=0.02), but not at total hip (1.013 vs 0.982 g/cm2, p=0.11). Controls had significantly higher odds of having osteopenia or osteoporosis based on measurements of BMD in both the femoral neck (p=0.001), total hip (p=0.033) and lumbar spine (p=0.033). CONCLUSION: Our population-based data showed comparable BMD in patients with PsA and controls. This supports that the PsA population is not at increased risk of osteoporosis.

Technologies for assessment of bone reflecting bone strength and bone mineral density in elderly women: an update.

Reduced bone mineral density is a strong risk factor for fracture. The WHO's definition of osteoporosis is based on bone mineral density measurements assessed by dual x-ray absorptiometry. Several on other techniques than dual x-ray absorptiometry have been developed for quantitative assessment of bone, for example, quantitative ultrasound and digital x-ray radiogrammetry. Some of these techniques may also capture other bone properties than bone mass that contribute to bone strength, for example, bone porosity and microarchitecture. In this article we give an update on technologies which are available for evaluation primarily of bone mass and bone density, but also describe methods which currently are validated or are under development for quantitative assessment of other bone properties.

Exploring the relationship between bone density and severity of distal radius fragility fracture in women.

BACKGROUND: Bone mineral density (BMD) has been shown to be a consistent and independent risk factor for distal radius fracture. Inconsistent data have been reported on the association between BMD and severity of distal radius fracture. Our primary aim was to explore if there is an association between cortical BMD at the hand and the severity of fragility distal radius fracture. METHODS: Consecutively recruited females aged ≥ 50 years with fragility fracture at the distal radius (n = 110) from a county hospital were included. Cortical hand BMD was assessed by the digital X-ray radiogrammetry (DXR) method. X-rays of the fracture were scored by experienced orthopedic surgeons for fracture severity according to the Müller AO classification of long bones and radiographic parameters such as ulnar variance and dorsal angle. RESULTS: A weak association between lower DXR BMD and increased ulnar variance and dorsal angle was found but not with the AO scoring system for fracture type. A history of glucocorticoid (GC) use but not DXR-BMD was found to be significantly associated with the presence of having an intra- or extra-articular fracture. CONCLUSION: Our data indicate that bone material properties which are impaired by GC use are more important for fracture severity than BMD.

Cortical hand bone porosity and its association with distal radius fracture in middle aged and elderly women.

OBJECTIVE: Reduced bone mineral density (BMD), assessed by Dual Energy X-ray absorptiometry (DXA), is a well-known risk factor for fragility fracture. A large proportion of patients with fracture have only slightly reduced BMD. Assessment of other bone structure features than BMD may improve identification of individuals at increased fracture risk. Digital X-ray radiogrammetry (DXR), which is a feasible tool for measurement of metacarpal cortical bone density, also gives an estimate of cortical bone porosity. Our primary aim was to explore the association between cortical porosity in the hand assessed by DXR and distal radius fracture. METHODS: This case-control study included 123 women >50 years with distal radius fracture, and 170 controls. DXR was used to measure metacarpal BMD (DXR-BMD), cortical porosity (DXR-porosity), thickness (DXR-CT) and bone width (DXR-W) of the hand. Femoral neck BMD was measured by DXA. RESULTS: The fracture group had a statistically significant lower DXR-BMD (0.492 vs. 0.524 g/cm(2) p<0.001), higher cortical DXR-porosity (0.01256 vs. 0.01093, p<0.001), less DXR-CT (0.148 vs. 0.161 cm, p<0.001) and lower femoral neck DXA-BMD (0.789 vs. 0.844 g/cm(2), p = 0.001) than the controls. In logistic regression analysis adjusted for age, a significant association with distal radius fracture (OR, 95% CI) was found for body mass index (0.930, 0.880-0.983), DXA-BMD (0.996, 0.995-0.999), DXR-BMD (0.990, 0.985-0.998), DXR-porosity (1.468, 1.278-1.687) and DXR-CT (0.997, 0.996-0.999). In an adjusted model, DXR-porosity remained the only variable associated with distal radius fracture (1.415, 1.194-1.677). CONCLUSION: DXR derived porosity is associated with fracture at distal radius and might be a sensitive marker for skeletal fragility.

Phalangeal densitometry compared with dual energy X-ray absorptiometry for assessment of bone mineral density in elderly women.

BACKGROUND: Reduced bone mineral density (BMD) is identified as a major risk factor for fracture. The World Health Organization criterion for diagnosis of osteoporosis (T-score ≤-2.5 SD) is based on dual energy X-ray absorptiometry (DXA) measurements. However DXA availability may be limited in some regions. In this study the ability of the phalangeal radiographic absorptiometry (RA) device, MetriScan, to identify women with reduced BMD at the femoral neck assessed by DXA was evaluated. METHODS: The study population contained women with recent low-energy distal radius fracture and women recruited from the general population, all aged ≥50 years. A triage approach was applied in which two cut-offs for RA T-score were defined at which individuals with 90% sensitivity and 90% specificity could be identified to have or not have reduced BMD at the femoral neck defined as T-score ≤-2.5 SD. RESULTS: The correlation between phalangeal RA BMD and femoral neck DXA BMD was r=0.65 (p<0.001). The upper and lower RA T-score cut-off was -1.5 SD and -2.9 SD. With the triage approach being used for the whole cohort, 34% would require a central DXA assessment to determine if the femoral neck T-score is below or above -2.5 SD. CONCLUSION: The application of the RA MetriScan device can reduce the number of DXA assessments needed to detect reduced BMD. The device may thus be of clinical value if access to DXA is limited, as well as for screening purposes.