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Aim: To study the association between femoral neck (FN) bone mineral density (BMD) T‐score and fracture risk in individuals with and without type 2 diabetes (T2D). Materials and Methods: We performed a single‐centre retrospective cohort study using the Danish National Health Service. BMD of the FN was measured by dual‐energy X‐ray absorptiometry. Cox proportional hazards regression models were used to study the association between FN BMD T‐score and fractures in individuals with and without T2D separately, adjusted for age, comorbidities and comedication. The results from this analysis were used to estimate the 10‐year absolute fracture risk. Results: In total, there were 35,129 women (2362 with T2D) and 7069 men (758 with T2D). The FN BMD T‐score was significantly associated with risk of any, hip and major osteoporotic fracture in men and women with [adjusted hazard risk ratios (aHR) women, hip: 1.57; 95% confidence interval (CI) 1.24–2.00, incidence rate (IR) 8.7; aHR men, hip: 1.55; 95% CI 1.01–2.36, IR 4.6] and without T2D (aHR women, hip: 1.75; 95% CI 1.64–1.87, IR 7.0; aHR men, hip: 1.97, 95% CI 1.73–2.25, IR 6.3), and its ability to predict fracture risk was similar. Fracture IRs were not significantly different for individuals with or without T2D, nor was the estimated cumulative 10‐year fracture risk. Conclusions: The FN BMD T‐score was significantly associated with hip, non‐spine and major osteoporotic fracture risk in men and women with and without T2D. Fracture risk for a given T‐score and age was equal in individuals with and without T2D, as was the ability of the FN BMD T‐score to predict fracture risk. [ABSTRACT FROM AUTHOR]

Aim: To determine the association of diabetes-related characteristics with fractures at different sites in individuals with type 2 diabetes (T2D)., Materials and Methods: We conducted a cohort study using the Clinical Practice Research Datalink (CPRD) GOLD. Patients aged over 30 years with T2D were identified within the CPRD. Patients were followed from the start of diabetes treatment until the end of data collection, death, or the occurrence of a fracture. Cox proportional hazards models were used to estimate the hazard ratios for the association of the individual characteristics (diabetes duration, glycated haemoglobin [HbA1c] level, and microvascular complications) with fracture risk, adjusted for demographics, comorbidities and comedication., Results: A diabetes duration of >10 years was associated with an increased risk of any fracture and major osteoporotic fractures (MOFs), while a diabetes duration of >8 years was associated with an increased hip fracture risk, compared to a duration <2 years. An HbA1c level <6% was associated with an increased fracture risk compared to HbA1c values of 6% to <7%. The presence of one or two microvascular complications was associated with an increased risk of any fracture and MOFs and the presence of two microvascular complications was associated with an increased hip fracture risk, compared to no microvascular complications., Conclusion: In conclusion, our study shows that a diabetes duration of 10 years or more, strict glycaemic control resulting in HbA1c levels below 6%, and/or the presence of at least one microvascular complication increased the risk of any fracture, hip fractures, MOFs, and humerus fractures, but not ankle, scapula or skull fractures., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Type 2 diabetes (T2D) is a prevalent disease and has been associated with an increased fracture risk despite normal or even higher areal BMD. The aim of this study was to estimate the association between glucose metabolism status (GMS) and measurements of glycemic control with HRpQCT parameters of bone microarchitecture and strength. Participants of the Maastricht study who underwent an HRpQCT scan at the distal radius and tibia were included. GMS was determined by use of an oral glucose tolerance test and grouped into a normal glucose metabolism (NGM), prediabetes, or T2D. Linear regression models were used, stratified by sex with multiple adjustments. This study incorporated cross-sectional data from 1400 (796 [56.9%] NGM, 228 [16.3%] prediabetes, and 376 [26.9%] T2D) men and 1415 (1014 [71.7%] NGM, 211 [14.9%] prediabetes, and 190 [13.4%] T2D) women. The mean age was 59.8 ± 8.6 and 57.6 ± 9.0 yr for men and women, respectively. After adjustment, T2D was associated with a higher total BMD measured by HRpQCT and cortical thickness, and a smaller total and trabecular area in men and women compared with NGM. In women, T2D was additionally associated with a higher stiffness and failure load at the radius. Results were more pronounced at the distal radius than at the distal tibia. To conclude, these findings suggest that in this cohort of Maastricht study participants, total and trabecular bone area are smaller, but bone microarchitecture, density, and bone strength assessed by HRpQCT are not impaired in individuals with T2D., Competing Interests: Peter Vestergaard is head of research in the Steno Diabetes Center North Denmark sponsored by the Novo Nordisk Foundation. Joop van den Bergh receives an unrestricted research grant and lecture fee from Amgen and UCB, and is a consultant for PoroUS. Nicklas H. Rasmussen holds shares in Novo Nordisk and has lecture fees from Boehringer Ingelheim and travel expenses from UCB. Veerle van Hulten, Cindy Sarodnik, Johanna Driessen, Piet Geusens, Coen Stehouwer, and Sandrine Bours declare that they have no conflict of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research.)

Aim: To investigate whether sodium-glucose cotransporter-2 (SGLT2) inhibitor use as compared to dipeptidyl peptidase-4 (DPP-4) inhibitor use as add-on to metformin is associated with the risk of any fracture or major osteoporotic fractures (MOFs)., Methods: A cohort study using the Clinical Practice Research Datalink (CPRD) Aurum database was conducted. All patients aged 18 years and older with a first-ever prescription for a DPP-4 inhibitor or an SGLT2 inhibitor as add-on to metformin between January 1, 2013 and June 30, 2020 were selected. Patients starting with SGLT2 inhibitors were matched (up to 1:3) on propensity scores to patients starting with DPP-4 inhibitors. Propensity scores were calculated based on sex, age, body mass index, comorbidities, comedication and lifestyle factors. Cox proportional hazard models were used to estimate the risk of fracture with SGLT2 inhibitor use as compared to DPP-4 inhibitor use., Results: A total of 13 807 SGLT2 inhibitor users (age 55.4 ± 10.6 years, 36.7% female) were included in this study, matched with 28 524 DPP-4 inhibitor users (age 55.4 ± 8.0 years, 36.4% female). The risk of any fracture with current SGLT2 inhibitor use was similar compared with current DPP-4 inhibitor use (adjusted hazard ratio [aHR] 1.09, 95% confidence interval [CI] 0.91-1.31), as was the risk of MOFs (aHR 0.89, 95% CI 0.64-1.22) and the risk of fractures at any of the individual MOF sites. Additionally, no association was found with duration of SGLT2 inhibitor use (longest duration >811 days) for any of the individual SGLT2 inhibitor agents, or after stratification by sex and age., Conclusion: Use of SGLT2 inhibitors was not associated with the risk of any fracture, MOFs or fracture at the individual MOF sites when compared to DPP-4 inhibitor use., (© 2023 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Background: Type 2 diabetes (T2D) is frequently reported to be associated with an increased fracture risk. Epidemiological data on prevalent morphometric vertebral fractures (VFs) in T2D are sparse and even less is known in the prediabetic state., Purpose: To determine the association between prevalence and severity of morphometric VFs and glucose metabolism state: normal glucose metabolism (NGM), impaired glucose metabolism (prediabetes) or T2D., Methods: This study included cross-sectional data from 3625 participants of the Maastricht Study who had a vertebral fracture assessment on lateral Dual Energy X-Ray Absorptiometry images. VFs were classified based on morphometric assessment into mild, moderate and severe VFs (respectively 20-24%, 25-39% or ≥40% reduction in expected vertebral body height). Logistic regression models were used to investigate the association between glucose metabolism status and the prevalence and severity of VFs. Analyses were adjusted for subject characteristics and life-style factors., Results: T2D individuals were older (62.8 ± 7.5 years old) and less often female (30.5%) compared to the NGM group (57.7 ± 8.5 years old, and 58.8% female, respectively). At least one mild, moderate or severe prevalent VF was found in 8.6% of the men and 2.2% of the women in the T2D group, in 9.4% and 8.4% in the prediabetes group and in 9.1% and 4.8% in the NGM group, respectively. After adjustment T2D in women was associated with a lower probability of having a prevalent VF compared to NGM [adjusted OR 0.25 (95% CI 0.09-0.65)], while this was not the case for prediabetes. Furthermore, women with T2D had a significantly lower probability of a prevalent moderate or severe VF [adjusted OR 0.32 (95% CI 0.11-0.96)]. In men there was no significant association between T2D or prediabetes and prevalent VFs., Conclusion: Women with T2D had a lower probability of prevalent VFs compared to women with a normal glucose metabolism, while this was not the case for men with T2D and participants with prediabetes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 van Hulten, Sarodnik, Driessen, Schaper, Geusens, Webers, Dinant, Ottenheijm, Rasmussen, Viggers, Stehouwer, van der Kallen, Schram, Bours, Dagnelie and van den Bergh.)

Humans living at a higher altitude are less prone to suffer from impaired glucose homeostasis and type 2 diabetes mellitus (T2DM), which might at least partly be explained by lower oxygen availability at higher altitudes. The present systematic review aimed to provide an overview of the current literature on the effects of hypoxia exposure on glucose homeostasis in metabolically compromised humans. Several databases were searched up to August 10 th , 2020. The search strategy identified 368 unique records. Following assessment for eligibility based on the selection criteria, 16 studies were included in this review. Six studies (2 controlled studies; 4 uncontrolled studies) demonstrated beneficial effects of hypoxia exposure on glucose homeostasis, while 10 studies (8 controlled studies; 2 uncontrolled studies) reported no improvement in glucose homeostasis following hypoxia exposure. Notably, passive hypoxia exposure seemed to improve glucose homeostasis, whereas hypoxic exercise training (2-8 weeks) appeared to have no additional/synergistic effects on glucose homeostasis compared to normoxia exposure. Due to the heterogeneity in study populations and intervention duration (acute studies / 2-8 wks training), it is difficult to indicate which factors may explain conflicting study outcomes. Moreover, these results should be interpreted with some caution, as several studies did not include a control group. Taken together, hypoxia exposure under resting and exercise conditions might provide a novel therapeutic strategy to improve glucose homeostasis in metabolically compromised individuals, but more randomized controlled trials are warranted before strong conclusions on the effects of hypoxia exposure on glucose homeostasis can be drawn.