Effectiveness and cost-effectiveness of dynamic bracing versus standard care alone in patients suffering from osteoporotic vertebral compression fractures: protocol for a multicentre, two-armed, parallel-group randomised controlled trial with 12 months of follow-up.

INTRODUCTION: Patients with osteoporosis may suffer from a fracture after minimal trauma. Osteoporotic vertebral compression fractures (OVCFs) are among the most common fractures, often leading to substantial pain. There is a need for evidence-based conservative treatment to aid in the management of OVCFs. The objective of this randomised controlled trial (RCT) is to evaluate the effectiveness and cost-effectiveness of dynamic bracing in addition to standard care for improving quality of life (QoL) in patients suffering from an OVCF. METHODS AND ANALYSIS: Ninety-eight postmenopausal women from two academic and four community hospitals with a recent symptomatic thoracolumbar OVCF will be randomised into either the standard care or dynamic bracing group. In the dynamic bracing group, the Spinova Osteo orthosis will be used in addition to standard care. Standard care comprises pain control with analgesics, physical therapy and osteoporosis medication. The primary outcome parameter is QoL 1 year after inclusion, as measured by the Quality of Life Questionnaire of the European Foundation for Osteoporosis (QUALEFFO-41). Secondary outcome parameters are pain, pain medication used, functional disability, sagittal spinal alignment, recurrence rate of OVCFs and physical activity in daily life. A trial-based economic evaluation consisting of both cost-effectiveness analysis and cost-utility analysis will be performed based on empirical data obtained in the RCT. A process evaluation will assess the feasibility of dynamic bracing. All outcomes will be assessed at baseline, 6 weeks, 3 months, 6 months, 9 months and 12 months. ETHICS AND DISSEMINATION: Ethical approval has been granted by the Medical Ethics Committee, University Hospital Maastricht and Maastricht University (METC azM/UM) (NL74552.068.20/METC 20-055). Patients will be included only after verification of eligibility and obtaining written informed consent. Results will be disseminated via the Dutch National Osteoporosis Patient Society and via publications and conferences. TRIAL REGISTRATION NUMBER: NL8746.

Adaptive local thresholding can enhance the accuracy of HR-pQCT-based trabecular bone morphology assessment.

High-resolution peripheral quantitative computed tomography (HR-pQCT) devices can scan extremities at bone microstructural level in vivo and are used mainly in research of bone diseases. Two HR-pQCT scanners are commercially available to date: XtremeCT (first generation) and XtremeCT-II (second generation) from Scanco Medical AG (Switzerland). Recently, we have proposed an adaptive local thresholding (AT) technique and showed that it can improve quantification accuracy of bone microstructural parameters, with visually less sharp cone-beam CT (CBCT) images providing a similar accuracy than XtremeCT. The aim of this study was to evaluate whether the AT segmentation technique could enhance the accuracy of HR-pQCT in quantifying bone microstructural images and to assess whether the agreement between XtremeCT and XtremeCT-II could be improved. Nineteen radii were scanned with three scanners from Scanco Medical AG: (1) XtremeCT at 82 µm, (2) XtremeCT-II at 60.7 µm and (3) the small animal microCT scanner VivaCT40 at 19 µm voxel size. The scans were segmented applying two different methods, once following the manufacturer standard technique (ST), and once by means of AT. Three-dimensional (3D) morphological analysis was performed on the trabecular volume of the segmented images using the manufacturer's standard software to calculate bone volume fraction (BV/TV), trabecular thickness (Tb.Th), separation (Tb.Sp) and number (Tb.N). The average accuracy of XtremeCT improved from R2 = 0.76 (ST) to 0.85 (AT) and reached the same level of accuracy as XtremeCT-II with ST (R2 = 0.86). The largest improvements were obtained for BV/TV and Tb.Th. For XtremeCT-II, mean accuracy improved slightly from R2 = 0.86 (ST) to 0.89 (AT). For both segmentations and both scanners, the standard section was quantified slightly more accurate than the subchondral section. The agreement between the scanners was enhanced from R2 = 0.89 (ST) to 0.98 (AT). In conclusion, AT can enhance the accuracy of XtremeCT to quantify distal radius bone microstructural parameters close to XtremeCT-II level and increases the agreement between the two HR-pQCT scanners. High-resolution peripheral quantitative computed tomography, segmentation, bone microstructural parameters.

Epidemiology of fractures in the United Kingdom 1988-2012: Variation with age, sex, geography, ethnicity and socioeconomic status.

UNLABELLED: Rates of fracture worldwide are changing. Using the Clinical Practice Research Datalink (CPRD), age, and gender, geographical, ethnic and socioeconomic trends in fracture rates across the United Kingdom were studied over a 24-year period 1988-2012. Previously observed patterns in fracture incidence by age and fracture site were evident. New data on the influence of geographic location, ethnic group and socioeconomic status were obtained. INTRODUCTION: With secular changes in age- and sex-specific fracture incidence observed in many populations, and global shifts towards an elderly demography, it is vital for health care planners to have an accurate understanding of fracture incidence nationally. We aimed to present up to date fracture incidence data in the UK, stratified by age, sex, geographic location, ethnicity and socioeconomic status. METHODS: The Clinical Practice Research Datalink (CPRD) contains anonymised electronic health records for approximately 6.9% of the UK population. Information comes from General Practitioners, and covers 11.3 million people from 674 practices across the UK, demonstrated to be representative of the national population. The study population consisted of all permanently registered individuals aged ≥18years. Validated data on fracture incidence were obtained from their medical records, as was information on socioeconomic deprivation, ethnicity and geographic location. Age- and sex-specific fracture incidence rates were calculated. RESULTS: Fracture incidence rates by age and sex were comparable to those documented in previous studies and demonstrated a bimodal distribution. Substantial geographic heterogeneity in age- and sex adjusted fracture incidence was observed, with rates in Scotland almost 50% greater than those in London and South East England. Lowest rates of fracture were observed in black individuals of both sexes; rates of fragility fracture in white women were 4.7 times greater than in black women. Strong associations between deprivation and fracture risk were observed in hip fracture in men, with a relative risk of 1.3 (95% CI 1.21-1.41) in Index of Multiple Deprivation category 5 (representing the most deprived) compared to category 1. CONCLUSIONS: This study presents robust estimates of fracture incidence across the UK, which will aid decisions regarding allocation of healthcare provision to populations of greatest need. It will also assist the implementation and design of strategies to reduce fracture incidence and its personal and financial impact on individuals and health services.

Increased fracture risk in patients with type 2 diabetes mellitus: an overview of the underlying mechanisms and the usefulness of imaging modalities and fracture risk assessment tools.

Type 2 diabetes mellitus has recently been linked to an increased fracture risk. Since bone mass seems to be normal to elevated in patient with type 2 diabetes, the increased fracture risk is thought to be due to both an increased falling frequency and decreased bone quality. The increased falling frequency is mainly a result of complications of the disease such as a retinopathy and polyneuropathy. Bone quality is affected through changes in bone shape, bone micro-architecture, and in material properties such as bone mineralization and the quality of collagen. Commonly used methods for predicting fracture risk such as dual energy X-ray absorptiometry and fracture risk assessment tools are helpful in patients with type 2 diabetes mellitus, but underestimate the absolute fracture risk for a given score. New imaging modalities such as high resolution peripheral quantitative computed tomography are promising for giving insight in the complex etiology underlying the fragility of the diabetic bone, as they can give more insight into the microarchitecture and geometry of the bone. We present an overview of the contributing mechanisms to the increased fracture risk and the usefulness of imaging modalities and risk assessment tools in predicting fracture risk in patients with type 2 diabetes.

Assessment of the healing process in distal radius fractures by high resolution peripheral quantitative computed tomography.

In clinical practice, fracture healing is evaluated by clinical judgment in combination with conventional radiography. Due to limited resolution, radiographs don't provide detailed information regarding the bone micro-architecture and bone strength. Recently, assessment of in vivo bone density, architectural and mechanical properties at the microscale became possible using high resolution peripheral quantitative computed tomography (HR-pQCT) in combination with micro finite element analysis (µFEA). So far, such techniques have been used mainly to study intact bone. The aim of this study was to explore whether these techniques can also be used to assess changes in bone density, micro-architecture and bone stiffness during fracture healing. Therefore, the fracture region in eighteen women, aged 50 years or older with a stable distal radius fracture, was scanned using HR-pQCT at 1-2 (baseline), 3-4, 6-8 and 12weeks post-fracture. At 1-2 and 12 weeks post-fracture the distal radius at the contra-lateral side was also scanned as control. Standard bone density, micro-architectural and geometric parameters were calculated and bone stiffness in compression, torsion and bending was assessed using µFEA. A linear mixed effect model with time post-fracture as fixed effect was used to detect significant (p-value ≤0.05) changes from baseline. Wrist pain and function were scored using the patient-rated wrist evaluation (PRWE) questionnaire. Correlations between the bone parameters and the PRWE score were calculated by Spearman's correlation coefficient. At the fracture site, total and trabecular bone density increased by 11% and 20%, respectively, at 6-8 weeks, whereas cortical density was decreased by 4%. Trabecular thickness increased by 23-31% at 6-8 and 12 weeks and the intertrabecular area became blurred, indicating intertrabecular bone formation. Compared to baseline, calculated bone stiffness in compression, torsion and bending was increased by 31% after 12 weeks. A moderate negative correlation was found between the stiffness and the PRWE score. No changes were observed at the contra-lateral side. The results demonstrate that it is feasible to assess clinically relevant and significant longitudinal changes in bone density, micro-architecture and mechanical properties at the fracture region during the healing process of stable distal radius fractures using HR-pQCT.

Assessment of individual fracture risk: FRAX and beyond.

The World Health Organization fracture risk assessment tool (FRAX) and the Garvan fracture risk calculator are both widely available tools for individualized fracture risk prediction in daily practice. The FRAX model is implemented in several guidelines and most widely used at present. However, clinicians should take into account the differences between the models, especially with regard to the effect of the number of falls, number and clustering of previous fractures, and the number of clinical risk factors on the outcome of predicted fracture risk. Further development will be needed for optimal integration of bone- and fall-related risks, clustering of fractures, and dosing of risk factors to validate the models in different populations and to validate the ability to select patients who will achieve fracture risk reduction with anti-osteoporosis therapy. FRAX may be used as the primary model, and in patients with recurrent fractures and falls the use of the Garvan model may be of additional value.