Osteoporosis in rheumatoid arthritis

The literature is replete with reports of osteoporosis in rheumatoid arthritis, but the mechanism of bone loss remains obscure. This is probably due to the overlap with bone loss of aging and the menopause, whose exact mechanisms are also poorly understood. Against this background, a study was designed to evaluate generalised bone loss in young, premenopausal (if female), patients with rheumatoid arthritis. The protocol was designed to record demographic data, as well as information pertaining to the disease. Cortical bone mass was measured at the metacarpals and left femur, using an automated, computer-controlled technique. Trabecular bone was evaluated at the left femur (Singh index) as well as at the 3rd lumbar vertebra (Saville index). Bone kinetics were studied by the measurement of urinary excretion of calcium, phosphate and hydroxy-praline (resorption) and serum alkaline phosphatase (formation). Disease activity was measured clinically and with laboratory indices. Physical activity was indirectly measured by quantitating the disability, using the Keitel function test as well as a modified health assessment questionnaire (HAQ). The radiograph of the right wrist was scored by the Larsen index. The carpometacarpal ratio was also calculated from the radiograph. Numerous statistical techniques were applied in the analysis of the data. Healthy volunteers were used as controls. Patients with SLE were also studied, in order to compare the 2 inflammatory diseases. Patients with RA had generalised cortical bone loss (metacarpal and femur) (p < 0.001). Trabecular bone measurements were not significantly different from normals, using the crude radiographic techniques. Duration of disease was the most important clinical determinant of this bone loss. The relative contributions of disease activity and lack of physical activity to the loss of bone could not be adequately separated using conventional statistical techniques. Corticosteroid therapy did not promote metacarpal bone loss in these subjects, but may have contributed to thinning of the femoral cortex. Nonsteroidal anti-inflammatory drugs and disease modifying agents did not seem to influence the extent of the bone loss. Nutritional status and skinfold thickness did not correlate with bone mass. Dietary factors played no role in the genesis of bone loss, but may have had some effect on disease activity. Metacarpal measurements showed a sensitivity of 80% and specificity of 85% in discriminating between osteopaenic and normopaenic groups with RA. Osteopaenia could not be adequately predicted in the absence of metacarpal measurements. Metacarpal bone loss in RA was due to endosteal resorption, while in SLE it was due to periosteal resorption. The semi-automatic technique for measurement of metacarpal bone mass showed good reproducibility among 5 observers and at 2 different centres. The pathogenesis of bone loss in RA was multifactorial, the largest contribution probably coming from a humoral factor in the circulation, closely related to disease activity. Ionised calcium was elevated in 55% of RA patients, but only 5% of SLE patients. Serum PTH levels were normal in 99% of the RA subjects. Elevations in alkaline phosphatase. (25%) probably reflected disease activity rather than increased bone formation. Factor analysis of 27 variables showed that disease activity was central to the development of OP in RA. CS therapy tended to be used in the presence of active disease. Disability was not an important determinant of bone loss in RA, but may be a useful measure of activity of the disease. This study did not evaluate the relationships with sex hormonal status or vitamin D metabolism. Future research should aim at cohort analysis at 2 different periods, in order to improve our understanding of the pathogenesis of bone loss in RA

Quantitative imaging techniques for the assessment of osteoporosis and sarcopenia

Bone and muscle are two deeply interconnected organs and a strong relationship between them exists in their development and maintenance. The peak of both bone and muscle mass is achieved in early adulthood, followed by a progressive decline after the age of 40. The increase in life expectancy in developed countries resulted in an increase of degenerative diseases affecting the musculoskeletal system. Osteoporosis and sarcopenia represent a major cause of morbidity and mortality in the elderly population and are associated with a significant increase in healthcare costs. Several imaging techniques are currently available for the non-invasive investigation of bone and muscle mass and quality. Conventional radiology, dual energy X-ray absorptiometry (DXA), computed tomography (CT), magnetic resonance imaging (MRI) and ultrasound often play a complementary role in the study of osteoporosis and sarcopenia, depicting different aspects of the same pathology. This paper presents the different imaging modalities currently used for the investigation of bone and muscle mass and quality in osteoporosis and sarcopenia with special emphasis on the clinical applications and limitations of each technique and with the intent to provide interesting insights into recent advances in the field of conventional imaging, novel high-resolution techniques and fracture risk

Metacarpal radiographic indices in the assessment of bone strength and fracture risk.

Osteoporotic fractures are associated with morbidity and increased mortality, and treating fractures is an increasing expenditure for national health systems. Targeting fracture preventative measures appropriately starts with finding those at risk of fracture, services for which can be expensive and poorly available. Metacarpal morphometry can potentially be an inexpensive and widely available method of skeletal strength assessment. In this study a semi-automated metacarpal morphometry (SMCM) technique and a fully automated digital x-ray radiogrammetry (OXR) technique were studied for fracture prediction ability. 9 OXR was studied in a nested case-control setting with hip fracture patients and controls (Hip fracture Prevention Study, HIPS), and OXR bone mineral density (BMO) and OXR metacarpal index (MCI) were found to predict hip fracture risk (odds ratio, OR 1.79 and 1.72 respectively for 1 standard deviation (SO) decrease in measurement). OXR was also studied in a prospective setting for vertebral fracture prediction (Vertebral Osteoporosis Trial), and OXR-BMO and OXR-MCI were found to predict vertebral fracture risk (OR 1.56 and 1.81 respectively). SMCM was studied in a prospective setting (HIPS), and average MCI of 6 metacarpals (AMCI) was found to predict all fracture risk and hip fracture risk (OR 1.30 and 1.42 respectively), but not clinical vertebral fracture risk. In all these settings however, hip, spinal and forearm OXA measures had similar or higher point estimates for the respective fracture risk predictions. There was a trend for disproportionately greater bone loss with age at the metacarpals by MCM measures, compared to hip or forearm OXA measures, especially when associated with other medical conditions such as rheumatoid arthritis. Although MCM measures were not superior to OXA measures in fracture risk prediction, there may be a useful role for them in epidemiological studies or providing a clinical service where access to OXA is limited

Osteoimmunology and osteoporosis

The concept of osteoimmunology is based on growing insight into the links between the immune system and bone at the anatomical, vascular, cellular, and molecular levels. In both rheumatoid arthritis (RA) and ankylosing spondylitis (AS), bone is a target of inflammation. Activated immune cells at sites of inflammation produce a wide spectrum of cytokines in favor of increased bone resorption in RA and AS, resulting in bone erosions, osteitis, and peri-inflammatory and systemic bone loss. Peri-inflammatory bone formation is impaired in RA, resulting in non-healing of erosions, and this allows a local vicious circle of inflammation between synovitis, osteitis, and local bone loss. In contrast, peri-inflammatory bone formation is increased in AS, resulting in healing of erosions, ossifying enthesitis, and potential ankylosis of sacroiliac joints and intervertebral connections, and this changes the biomechanical competence of the spine. These changes in bone remodeling and structure contribute to the increased risk of vertebral fractures (in RA and AS) and non-vertebral fractures (in RA), and this risk is related to severity of disease and is independent of and superimposed on background fracture risk. Identifying patients who have RA and AS and are at high fracture risk and considering fracture prevention are, therefore, advocated in guidelines. Local peri-inflammatory bone loss and osteitis occur early and precede and predict erosive bone destruction in RA and AS and syndesmophytes in AS, which can occur despite clinically detectable inflammation (the so-called 'disconnection'). With the availability of new techniques to evaluate peri-inflammatory bone loss, osteitis, and erosions, peri-inflammatory bone changes are an exciting field for further research in the context of osteoimmunology

Inflammatory localized and generalized bone loss in recent-onset rheumatoid arthritis

Lems, W.F. [Promotor]Huizinga, T.W.J. [Promotor]Dijkmans, B.A.C. [Promotor]Allaart, C.F. [Copromotor

Evaluación de la medición de la masa ósea de metacarpianos con densitometría dual de rayos X como predictor de mal curso evolutivo en pacientes con artritis de reciente comienzo

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Medicina. Fecha de lectura: 19-01-202

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

Hand X-ray absorptiometry for measurement of bone mineral density on a slot-scanning X-ray imaging system

Includes bibliographical references.Bone mineral density (BMD) is an indicator of bone strength. While femoral and spinal BMDs are traditionally used in the management of osteoporosis, BMD at peripheral sites such as the hand has been shown to be useful in evaluating fracture risk for axial sites. These peripheral locations have been suggested as alternatives to the traditional sites for BMD measurement. Dual-energy X-ray absorptiometry (DXA) is the gold standard for measuring BMD due to low radiation dose, high accuracy and proven ability to evaluate fracture risk. Computed digital absorptiometry (CDA) has also been shown to be very effective at measuring the bone mass in hand bones using an aluminium step wedge as a calibration reference. In this project, the aim was to develop algorithm s for accurate measurement of BMD in hand bones on a slot - scanning digital radiography system. The project assess e d the feasibility of measuring bone mineral mass in hand bones using CDA on the current system. Images for CDA - based measurement were acquired using the default settings on the system for a medium sized patient. A method for automatic processing of the hand images to detect the aluminium step wedge, included in the scan for calibration, was developed and the calibration accuracy of the step wedge was evaluated. The CDA method was used for computation of bone mass with units of equivalent aluminium thickness (mmA1). The precision of the method was determined by taking three measurements in each of 1 6 volunteering subjects and computing the root - mean - square coefficient of variation (CV) of the measurements. The utility of the method was assessed by taking measurements of excised bones and assessing the correlation between the measured bone mass and ash weight obtained by incinerating the bones. The project also assessed the feasibility of implementing a DXA technique using two detectors in a slot-scanning digital radiography system to acquire dual-energy X-ray images for measuring areal and volumetric BMD of the middle phalanx of the middle finger. The dual-energy images were captured in two consecutive scans. The first scan captured the low- energy image using the detector in its normal set-up. The second scan captured the high- energy image with the detector modified to include an additional scintillator to simulate the presence of a second detector that would capture the low-energy image in a two-detector system. Scan parameters for acquisition of the dual-energy images were chosen to optimise spectral separation, entrance dose and image quality. Simulations were carried out to evaluate the spectral separation of the low- and high-energy spectra

Improving disease outcomes in early phases of rheumatoid arthritis

First year results of a randomized clinical trial in patients with early rheumatoid or undifferentiated arthritis, treated according to a remission steered treatmetn strategyReumafonds, Abbvie, Roche, Pfizer, UCB PharmaUBL - phd migration 201

Analyzing fibrous tissue pattern in fibrous dysplasia bone images using deep R-CNN networks for segmentation

Predictive health monitoring systems help to detect human health threats in the early stage. Evolving deep learning techniques in medical image analysis results in efficient feedback in quick time. Fibrous dysplasia (FD) is a genetic disorder, triggered by the mutation in Guanine Nucleotide binding protein with alpha stimulatory activities in the human bone genesis. It slowly occupies the bone marrow and converts the bone cell into fibrous tissues. It weakens the bone structure and leads to permanent disability. This paper proposes the study of FD bone image analyzing techniques with deep networks. Also, the linear regression model is annotated for predicting the bone abnormality levels with observed coefficients. Modern image processing begins with various image filters. It describes the edges, shades, texture values of the receptive field. Different types of segmentation and edge detection mechanisms are applied to locate the tumor, lesion, and fibrous tissues in the bone image. Extract the fibrous region in the bone image using the region-based convolutional neural network algorithm. The segmented results are compared with their accuracy metrics. The segmentation loss is reduced by each iteration. The overall loss is 0.24% and the accuracy is 99%, segmenting the masked region produces 98% of accuracy, and building the bounding boxes is 99% of accuracy