Sclerostin Regulation, Microarchitecture, and Advanced Glycation End-Products in the Bone of Elderly Women With Type 2 Diabetes.

Increased circulating sclerostin and accumulation of advanced glycation end-products (AGEs) are two potential mechanisms underlying low bone turnover and increased fracture risk in type 2 diabetes (T2D). Whether the expression of the sclerostin-encoding SOST gene is altered in T2D, and whether it is associated with AGEs accumulation or regulation of other bone formation-related genes is unknown. We hypothesized that AGEs accumulate and SOST gene expression is upregulated in bones from subjects with T2D, leading to downregulation of bone forming genes (RUNX2 and osteocalcin) and impaired bone microarchitecture and strength. We obtained bone tissue from femoral heads of 19 T2D postmenopausal women (mean glycated hemoglobin [HbA1c] 6.5%) and 73 age- and BMI-comparable nondiabetic women undergoing hip replacement surgery. Despite similar bone mineral density (BMD) and biomechanical properties, we found a significantly higher SOST (p = .006) and a parallel lower RUNX2 (p = .025) expression in T2D compared with non-diabetic subjects. Osteocalcin gene expression did not differ between T2D and non-diabetic subjects, as well as circulating osteocalcin and sclerostin levels. We found a 1.5-fold increase in total bone AGEs content in T2D compared with non-diabetic women (364.8 ± 78.2 versus 209.9 ± 34.4 µg quinine/g collagen, respectively; p < .001). AGEs bone content correlated with worse bone microarchitecture, including lower volumetric BMD (r = -0.633; p = .02), BV/TV (r = -0.59; p = .033) and increased trabecular separation/spacing (r = 0.624; p = .023). In conclusion, our data show that even in patients with good glycemic control, T2D affects the expression of genes controlling bone formation (SOST and RUNX2). We also found that accumulation of AGEs is associated with impaired bone microarchitecture. We provide novel insights that may help understand the mechanisms underlying bone fragility in T2D. © 2020 American Society for Bone and Mineral Research (ASBMR).

Reducing Hospitalizations and Emergency Department Visits in Patients With Venous Thromboembolism Using a Multicomponent Care Transition Intervention.

Preventing utilization of hospital and emergency department after diagnosis of venous thromboembolism is a complex problem. The objective of this study is to assess the impact of a care transition intervention on hospitalizations and emergency department visits after venous thromboembolism. We randomized adults diagnosed with a new episode of venous thromboembolism to usual care or a multicomponent intervention that included a home pharmacist visit in the week after randomization (typically occurring at time of discharge), illustrated medication instructions distributed during home visit, and a follow-up phone call with an anticoagulation expert scheduled for 8 to 30 days from time of randomization. Through physician chart review of the 90 days following randomization, we measured the incidence rate of hospital and emergency department visits for each group and their ratio. We also determined which visits were related to recurrent venous thromboembolism, bleeding, or anticoagulation and which where preventable. We enrolled 77 intervention and 85 control patients. The incidence rate was 4.50 versus 6.01 visits per 1000 patient days in the intervention versus control group (incidence rate ratio = 0.71; 95% confidence interval = 0.40-1.27). Most visits in the control group were not related to venous thromboembolism or bleeding (21%) and of those that were, most were not preventable (25%). The adjusted incidence rate ratio for the intervention was 1.05 (95% confidence interval = 0.57-1.91). Our patients had a significant number of hospital and emergency department visits after diagnosis. Most visits were not related to recurrent venous thromboembolism or bleeding and of those that were, most were not preventable. Our multicomponent intervention did not decrease hospitalizations and emergency department visits.

A volumetric method for quantifying atherosclerosis in mice by using microCT: comparison to en face.

Precise quantification of atherosclerotic plaque in preclinical models of atherosclerosis requires the volumetric assessment of the lesion(s) while maintaining in situ architecture. Here we use micro-computed tomography (microCT) to detect ex vivo aortic plaque established in three dyslipidemic mouse models of atherosclerosis. All three models lack the low-density lipoprotein receptor (Ldlr(-/-)), each differing in plaque severity, allowing the evaluation of different plaque volumes using microCT technology. From clearly identified lesions in the thoracic aorta from each model, we were able to determine plaque volume (0.04-3.1 mm(3)), intimal surface area (0.5-30 mm(2)), and maximum plaque (intimal-medial) thickness (0.1-0.7 mm). Further, quantification of aortic volume allowed calculation of vessel occlusion by the plaque. To validate microCT for future preclinical studies, we compared microCT data to intimal surface area (by using en face methodology). Both plaque surface area and plaque volume were in excellent correlation between microCT assessment and en face surface area (r(2) = 0.99, p<0.0001 and r(2) = 0.95, p<0.0001, respectively). MicroCT also identified internal characteristics of the lipid core and fibrous cap, which were confirmed pathologically as Stary type III-V lesions. These data validate the use of microCT technology to provide a more exact empirical measure of ex vivo plaque volume throughout the entire intact aorta in situ for the quantification of atherosclerosis in preclinical models.