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Quasi-brittle fracture mechanics is used to evaluate fracture of human cortical bone in aging. The approach is demonstrated using cortical bone bars extracted from one 92-year-old human male cadaver. In-situ fracture mechanics experiments in a 3D X-ray microscope are conducted. The evolution of the fracture process zone is documented. Fully developed fracture process zone lengths at peak load are found to span about three osteon diameters. Crack deflection and arrest at cement lines is a key process to build extrinsic toughness. Strength and toughness are found as size-dependent, not only for laboratory-scale experimental specimens but also for the whole femur. A scaling law for the length fracture process zone is used. Then, size-independent, tissue fracture properties are calculated. Linear elastic fracture mechanics applied to laboratory beam specimens underestimates the tissue toughness by 60%. Tissue fracture properties are used to predict the load capacity of the femur in bending within the range of documented data. The quasi-brittle fracture mechanics approach allows for the assessment of the combined effect of bone quantity and bone quality on fracture risk. However, further work is needed considering a larger range of subjects and in the model validation at the organ length scale., Competing Interests: Declaration of competing interest We declare no conflict of interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Today, continuous glucose monitoring (CGM) is a standard diagnostic option for patients with diabetes, at least for those with type 1 diabetes and those with type 2 diabetes on insulin therapy, according to international guidelines. The switch from spot capillary blood glucose measurement to CGM was driven by the extensive and immediate support and facilitation of diabetes management CGM offers. In patients not using insulin, the benefits of CGM are not so well studied/obvious. In such patients, factors like well-being and biofeedback are driving CGM uptake and outcome. Apps can combine CGM data with data about physical activity and meal consumption for therapy adjustments. Personalized data management and coaching is also more feasible with CGM data. The same holds true for digitalization and telemedicine intervention ("virtual diabetes clinic"). Combining CGM data with Smart Pens ("patient decision support") helps to avoid missing insulin boluses or insulin miscalculation. Continuous glucose monitoring is a major pillar of all automated insulin delivery systems, which helps substantially to avoid acute complications and achieve more time in the glycemic target range. These options were discussed by a group of German experts to identify concrete gaps in the care structure, with a view to the necessary structural adjustments of the health care system., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: ATh is an independent consultant and expert in CGM systems and diabetes technology; he receives gratuities and lecture fees from EvivaMed, Dexcom, IfDT Ulm, Berlin-Chemie, Novo-Nordisk, and Sanofi. TH receives fees for lectures and consultancy from Lilly, Novo-Nordisk, Sanofi, Abbott, Dexcom, MSD, Boehringer Ingelheim, and Ascensia. ATo makes presentations and takes part in the advisory boards of Astra, Bayer, Dexcom, and Lilly. BK receives fees for participation in the advisory boards of Berlin-Chemie, embecta, Insulet, Bayer, Sanofi, and Dexcom and lecture fees from Berlin-Chemie, Insulet, Dexcom, Novo-Nordisk, Sanofi, Roche Diabetes, and Hello Better. OK receives lecture/consultancy fees from Amgen, Daiichi Sankyo, Dexcom, Diamyd Medical, and Sanofi and is a stakeholder in DreaMed Inc. DE receives fees from Berlin-Chemie and Dexcom. He took part in the advisory boards of Dexcom, Roche Diabetes Care, and mySugr. JK receives fees for participation in the advisory boards of Novo-Nordisk, Lilly, BD, Abbott, Astra Zeneca, MSD, and Dexcom and lecture fees from Novo-Nordisk, Sanofi, Lilly, Berlin-Chemie, Bayer, Glaxo, MSD, Astra Zeneca, Boehringer-Ingelheim, Roche Diabetes, Abbott, Dexcom, Medtronic, and VitalAire. OS-O receives fees for lectures or participation in consultation committees of Abbott Diabetes Care, Roche Diabetes, Ypsomed, Dexcom, VitalAire, Ascensia, Medtronic, Eli Lilly, Boehringer Ingelheim, Novo-Nordisk, Berlin Chemie, Sanofi, MSD, AstraZeneca, and Chiesi. RK receives consulting fees from Dexcom and Medtronic, lecture fees, and consultation fees from Abbott. TS states having received lecture fees and participation in the advisory boards of Abbott, Dexcom, Medtronic, Roche, Ascensia, Berlin Chemie, Lilly, Novo-Nordisk, and Sanofi. NH received speaker fees from Novo-Nordisk, Ascensia, Sanofi, Roche, Lilly, Dexcom, and Abbott and participated in the advisory boards of the companies Abbott and BD. LH is a consultant for Abbott, embecta, Lifecare (also member of the Board of Directors), Medtronic EU Advisory Board, Dexcom Germany, Roche Diagnostics Diabetes Care Germany, Unomedical, Spiden, and Perfood. He is part owner of the Profil Institut für Stoffwechselforschung in Neuss, Germany, Science Consulting in Diabetes GmbH, Düsseldorf, Germany, and diateam GmbH, Bad Mergentheim, Germany.

A 2D plane strain extended finite element method (XFEM) model was developed to simulate three-point bending fracture toughness tests for human bone conducted in hydrated and dehydrated conditions. Bone microstructures and crack paths observed by micro-CT imaging were simulated using an XFEM damage model. Critical damage strains for the osteons, matrix, and cement lines were deduced for both hydrated and dehydrated conditions and it was found that dehydration decreases the critical damage strains by about 50%. Subsequent parametric studies using the various microstructural models were performed to understand the impact of individual critical damage strain variations on the fracture behavior. The study revealed the significant impact of the cement line critical damage strains on the crack paths and fracture toughness during the early stages of crack growth. Furthermore, a significant sensitivity of crack growth resistance and crack paths on critical strain values of the cement lines was found to exist for the hydrated environments where a small change in critical strain values of the cement lines can alter the crack path to give a significant reduction in fracture resistance. In contrast, in the dehydrated state where toughness is low, the sensitivity to changes in critical strain values of the cement lines is low. Overall, our XFEM model was able to provide new insights into how dehydration affects the micromechanisms of fracture in bone and this approach could be further extended to study the effects of aging, disease, and medical therapies on bone fracture., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Conventional bone imaging methods primarily use X-ray techniques to assess bone mineral density (BMD), focusing exclusively on the mineral phase. This approach lacks information about the organic phase and bone water content, resulting in an incomplete evaluation of bone health. Recent research highlights the potential of ultrashort echo time magnetic resonance imaging (UTE MRI) to measure cortical porosity and estimate BMD based on signal intensity. UTE MRI also provides insights into bone water distribution and matrix organization, enabling a comprehensive bone assessment with a single imaging technique. Our study aimed to establish quantifiable UTE MRI-based biomarkers at clinical field strength to estimate BMD and microarchitecture while quantifying bound water content and matrix organization., Methods: Femoral bones from 11 cadaveric specimens (n = 4 males 67-92 yrs of age, n = 7 females 70-95 yrs of age) underwent dual-echo UTE MRI (3.0 T, 0.45 mm resolution) with different echo times and high resolution peripheral quantitative computed tomography (HR-pQCT) imaging (60.7 μm voxel size). Following registration, a 4.5 mm HR-pQCT region of interest was divided into four quadrants and used across the multi-modal images. Statistical analysis involved Pearson correlation between UTE MRI porosity index and a signal-intensity technique used to estimate BMD with corresponding HR-pQCT measures. UTE MRI was used to calculate T 1 relaxation time and a novel bound water index (BWI), compared across subregions using repeated measures ANOVA., Results: The UTE MRI-derived porosity index and signal-intensity-based estimated BMD correlated with the HR-pQCT variables (porosity: r = 0.73, p = 0.006; BMD: r = 0.79, p = 0.002). However, these correlations varied in strength when we examined each of the four quadrants (subregions, r = 0.11-0.71). T 1 relaxometry and the BWI exhibited variations across the four subregions, though these differences were not statistically significant. Notably, we observed a strong negative correlation between T 1 relaxation time and the BWI (r = -0.87, p = 0.0006)., Conclusion: UTE MRI shows promise for being an innocuous method for estimating cortical porosity and BMD parameters while also giving insight into bone hydration and matrix organization. This method offers the potential to equip clinicians with a more comprehensive array of imaging biomarkers to assess bone health without the need for invasive or ionizing procedures., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)