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Determinants of bone strength and quality in diabetes mellitus in humans.

ABSTRACT: There is growing evidence that the higher fracture rate observed in patients with type 2 diabetes mellitus (T2DM) is associated with normal, or even increased, areal bone mineral density (aBMD) by DXA. This has led to the hypothesis that patients with T2DM may have abnormalities in bone microarchitecture and/or material composition - i.e., key determinants of bone "quality." Consistent with this hypothesis, several studies using high-resolution peripheral quantitative computed tomography (HRpQCT) have demonstrated preserved indices of trabecular microarchitecture but increased cortical porosity in T2DM patients. In addition, a recent study using a novel in vivo microindentation device found an impairment in a measure of bone material properties (bone material strength index, BMSi) in postmenopausal women with longstanding T2DM; notably, the reduction in BMSi was associated with chronic glycemic control, suggesting that the skeleton should be included as another target organ subject to diabetic complications. The underlying pathogenesis of skeletal fragility in T2DM remains to be defined, although high levels of advanced glycation endproducts (AGEs) may play a role. In addition, T2DM is associated with reduced bone turnover, perhaps with an imbalance between bone resorption and bone formation. Although several studies have found increased serum sclerostin levels in patients with T2DM, the role of these increased levels in mediating the observed increases in cortical porosity or reduction in BMSi remains to be defined. Thus, although bone quality appears to be impaired in T2DM, the pathogenesis of these abnormalities and their relationship to the increased fracture risk observed in these patients needs further study.

SUBMITTER: Farr JN

PROVIDER: S-EPMC4679576 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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Determinants of bone strength and quality in diabetes mellitus in humans.

Farr Joshua N JN Khosla Sundeep S

Bone 20150726

There is growing evidence that the higher fracture rate observed in patients with type 2 diabetes mellitus (T2DM) is associated with normal, or even increased, areal bone mineral density (aBMD) by DXA. This has led to the hypothesis that patients with T2DM may have abnormalities in bone microarchitecture and/or material composition - i.e., key determinants of bone "quality." Consistent with this hypothesis, several studies using high-resolution peripheral quantitative computed tomography (HRpQCT ...[more]

PMID: 26211989

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Project description:BackgroundThe purpose of this study was to develop an optimal diabetes-osteoarthritis (DM-OA) mouse model to validate that diabetes aggravates osteoarthritis (OA) and to evaluate the microarchitecture, chemical composition, and biomechanical properties of subchondral bone (SB) as a consequence of the DM-OA-induced damage induced.MethodsMice were randomly divided into three groups: DM-OA group, OA group, and sham group. Blood glucose levels, body weight, and food intake of all animals were recorded. Serum calcium (Ca) and osteocalcin (OCN) levels were compared in the three groups. The messenger ribonucleic acid (mRNA) and protein expression of key regulators for bone metabolism were detected. A semi-quantitative grading system [Osteoarthritis Research Society International (OARSI)] was used to evaluate cartilage and SB degeneration. Microspectroscopy, microindentations, micro-computed tomography (CT) imaging, and fracture load of compression testing were also used to evaluate trabecular SB properties.ResultsGlycemic monitoring and pancreas pathological results indicated stable high blood glucose and massive destruction of pancreas and islet cells in the DM-OA group. Serum levels of bone speciﬁc alkaline phosphatase (ALP-B) and tartrate-resistant acid phosphatase 5b (TRACP-5b) in the DM-group were higher than those of the other two groups while levels of serum Ca and OCN were lower. Meanwhile, the protein and mRNA expression of osteoblast-specific biomarkers [osteoprotegerin/receptor activator of nuclear factor kappa-B ligand (OPG/RANKL) ratio, collagen type I (COL-I), Runt-related transcription factor 2 (RUNX-2), OCN] were suppressed, and osteoclast-specific biomarkers [sclerostin (SOST)] was elevated in the DM-OA group. The mineral-to-collagen ratio, microindentation elastic modulus, hardness, micro-architectural parameters, bone mineral density, and fracture load of SB trabecular bone of the DM-OA group joint were lower than those of the other two groups. On the other hand, The OARSI score, trabecular spacing, and structural model index of the DM-OA group joint were higher than those of the other two groups.ConclusionsThe glycemic and pancreatic pathological results indicated that the DM-OA model was a simple and reliable model induced by streptozotocin (STZ) and surgery. The results revealed the mechanisms through which diabetes accelerates OA; that is, by damaging and deteriorating the functions of SB, including its microarchitecture, chemical composition, and biomechanical properties.

Project description:Type 1 diabetes (T1DM) is associated with an increased fracture risk, specifically at nonvertebral sites. The influence of glycemic control and microvascular disease on skeletal health in long-standing T1DM remains largely unknown. We aimed to assess areal (aBMD) and volumetric bone mineral density (vBMD), bone microarchitecture, bone turnover, and estimated bone strength in patients with long-standing T1DM, defined as disease duration ≥25 years. We recruited 59 patients with T1DM (disease duration 37.7 ± 9.0 years; age 59.9 ± 9.9 years.; body mass index [BMI] 25.5 ± 3.7 kg/m2 ; 5-year median glycated hemoglobin [HbA1c] 7.1% [IQR 6.82-7.40]) and 77 nondiabetic controls. Dual-energy X-ray absorptiometry (DXA), high-resolution peripheral quantitative computed tomography (HRpQCT) at the ultradistal radius and tibia, and biochemical markers of bone turnover were assessed. Group comparisons were performed after adjustment for age, gender, and BMI. Patients with T1DM had lower aBMD at the hip (p < 0.001), distal radius (p = 0.01), lumbar spine (p = 0.04), and femoral neck (p = 0.05) as compared to controls. Cross-linked C-telopeptide (CTX), a marker of bone resorption, was significantly lower in T1DM (p = 0.005). At the distal radius there were no significant differences in vBMD and bone microarchitecture between both groups. In contrast, patients with T1DM had lower cortical thickness (estimate [95% confidence interval]: -0.14 [-0.24, -0.05], p < 0.01) and lower cortical vBMD (-28.66 [-54.38, -2.93], p = 0.03) at the ultradistal tibia. Bone strength and bone stiffness at the tibia, determined by homogenized finite element modeling, were significantly reduced in T1DM compared to controls. Both the altered cortical microarchitecture and decreased bone strength and stiffness were dependent on the presence of diabetic peripheral neuropathy. In addition to a reduced aBMD and decreased bone resorption, long-standing, well-controlled T1DM is associated with a cortical bone deficit at the ultradistal tibia with reduced bone strength and stiffness. Diabetic neuropathy was found to be a determinant of cortical bone structure and bone strength at the tibia, potentially contributing to the increased nonvertebral fracture risk. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

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Determinants of bone strength and quality in diabetes mellitus in humans.

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Determinants of bone strength and quality in diabetes mellitus in humans.

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