Fracture status was documented differentiating high-impact (sport injuries and accidents) from low-impact fractures (spontaneous or fall from walking or standing position). parameters of bone were recorded. Correlations and multivariate models were used to determine the role of demographic, disease-specific and structural data of bone strength as well as its TW-37 relation to prevalent fractures. Results 276 individuals were analysed. Failure load and stiffness (both P 0.001) of bone were decreased in RA+, but not RA?, compared with HC. Lower bone strength affected both female and male patients with RA+, was related to longer disease duration and significantly (stiffness P=0.020; failure load P=0.012) associated with the occurrence of osteoporotic fractures. Impaired bone strength was correlated with altered bone density and microstructural parameters, which were all decreased in RA+. Multivariate models showed that ACPA status (P=0.007) and sex (P 0.001) were independently associated with reduced biomechanical properties of bone in RA. Conclusion In summary, FEA showed that bone strength is significantly decreased in RA+ and associated with fractures. strong class=”kwd-title” Keywords: rheumatoid arthritis, bone strength, fracture, micro-finite element analysis Introduction Rheumatoid arthritis (RA) is an inflammatory joint disease associated with bone destruction and increased fracture risk.1 2 While traditionally most attention in RA-related bone disease is drawn to periarticular bone erosions forming, the development of generalised bone loss in RA is of no less importance as it precipitates the increased fracture risk immanent to patients with RA.3 4 Accumulating evidence suggests that bone loss in RA is driven to a large extent by the presence of anti-citrullinated protein antibodies (ACPA), which enhance osteoclastogenesis and thereby accelerate skeletal disease.5C11 In support of this concept, there is good clinical evidence that local bone disease is more pronounced in patients with RA with ACPA9 11 and also some evidence for more severe systemic bone loss.10 Although several studies have documented the loss of bone mass in patients with RA and some studies provided evidence for both cortical and trabecular bone loss in RA,11 the functional impact of these structural changes for the stability of bone in RA are yet unknown. Hence, while we perceive that fracture risk is increased in TW-37 RA, we do not really Timp3 know whether the morphological changes of bone recorded in radiographic studies are indeed impacting the stability of TW-37 bone. Micro-finite element analysis (FEA) is a novel technique, which is increasingly used to characterise the biomechanical properties of bone and relate them to its microstructure.12C14 This technique has been developed based on the availability of high-quality bone structure analyses in humans in vivo using high-resolution peripheral quantitative CT (HR-pQCT) scanners.15C18 FEA uses these data and mathematically models stiffness and failure load of the radius during a fall on the outstretched hand. Studies performed in healthy individuals have shown that FEA accurately predicts bone strength and?also allows better identification of individuals with fragility fractures than it can be achieved by the measurement of bone density.14 Hence, FEA constitutes an attractive technology to better characterise the impact of bone changes in patients with systemic inflammatory diseases. ACPA-positive RA represents a paradigm disease to study FEA as it is associated by changes in the bone microstructure and complicated by increased fracture risk. To characterise the mechanical properties of bone in RA, we applied FEA in a cohort of patients with ACPA-positive RA (RA+) and ACPA-negative?RA (RA?) and compared bone strength and stiffness of the distal radius of patients with RA+?and?RA? with healthy controls. Furthermore, we aimed to define the demographic, disease-related and bone structural factors that are associated with bone strength in ACPA-positive RA. Finally, FEA results were also related to fragility fractures in patients with ACPA-positive RA. Methods Patients with RA and controls Healthy controls (HC) and patients with RA were part of the Erlangen Imaging Cohort (ERIC), which prospectively assesses bone.