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In vivo assessment of bone quality in postmenopausal women with type 2 diabetes.

ABSTRACT: Although patients with type 2 diabetes (T2D) are at significant risk for well-recognized diabetic complications, including macrovascular disease, retinopathy, nephropathy, and neuropathy, it is also clear that T2D patients are at increased risk for fragility fractures. Furthermore, fragility fractures in patients with T2D occur at higher bone mineral density (BMD) values compared to nondiabetic controls, suggesting abnormalities in bone material strength (BMS) and/or bone microarchitecture (bone "quality"). Thus, we performed in vivo microindentation testing of the tibia to directly measure BMS in 60 postmenopausal women (age range, 50-80 years) including 30 patients diagnosed with T2D for >10 years and 30 age-matched, nondiabetic controls. Regional BMD was measured by dual-energy X-ray absorptiometry (DXA); cortical and trabecular bone microarchitecture was assessed from high-resolution peripheral quantitative computed tomography (HRpQCT) images of the distal radius and tibia. Compared to controls, T2D patients had significantly lower BMS: unadjusted (-11.7%; p<0.001); following adjustment for body mass index (BMI) (-10.5%; p<0.001); and following additional adjustment for age, hypertension, nephropathy, neuropathy, retinopathy, and vascular disease (-9.2%; p=0.022). By contrast, after adjustment for confounding by BMI, T2D patients had bone microarchitecture and BMD that were not significantly different than controls; however, radial cortical porosity tended to be higher in the T2D patients. In addition, patients with T2D had significantly reduced serum markers of bone turnover (all p<0.001) compared to controls. Of note, in patients with T2D, the average glycated hemoglobin level over the previous 10 years was negatively correlated with BMS (r=-0.41; p=0.026). In conclusion, these findings represent the first demonstration of compromised BMS in patients with T2D. Furthermore, our results confirm previous studies demonstrating low bone turnover in patients with T2D and highlight the potential detrimental effects of prolonged hyperglycemia on bone quality. Thus, the skeleton needs to be recognized as another important target tissue subject to diabetic complications. © 2014 American Society for Bone and Mineral Research.

SUBMITTER: Farr JN

PROVIDER: S-EPMC3961509 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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In vivo assessment of bone quality in postmenopausal women with type 2 diabetes.

Farr Joshua N JN Drake Matthew T MT Amin Shreyasee S Melton L Joseph LJ McCready Louise K LK Khosla Sundeep S

Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 20140401 4

Although patients with type 2 diabetes (T2D) are at significant risk for well-recognized diabetic complications, including macrovascular disease, retinopathy, nephropathy, and neuropathy, it is also clear that T2D patients are at increased risk for fragility fractures. Furthermore, fragility fractures in patients with T2D occur at higher bone mineral density (BMD) values compared to nondiabetic controls, suggesting abnormalities in bone material strength (BMS) and/or bone microarchitecture (bone ...[more]

PMID: 24123088

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Project description:BackgroundThe aim of the study were to analyze the lumbar volumetric bone mineral density (BMD), fat distribution and changes of skeletal muscle with quantitative computed tomography (QCT) in postmenopausal women with type 2 diabetes mellitus (T2DM), and to evaluate the relationship between body composition and BMD.MethodsOne hundred seventy-seven postmenopausal women with T2DM and 136 postmenopausal women without diabetes were included in the study and were divided into two groups according to age, 50-65 years age group and over 65 years of age group. The lumbar BMD (L1-L3), visceral fat mass (VFM), visceral fat area (VFA), subcutaneous fat mass (SFM), subcutaneous fat area (SFA), psoas major mass (PMM) and psoas major area (PMA) of each group were compared. Univariable and multivariable linear regression analysis were used to analyze the contribution of each variable to BMD in postmenopausal women with T2DM.ResultsIn women aged 50-65, the patients in the T2DM group had higher body mass index (BMI), VFM, VFA, and SFM (p < 0.05), compared with non-T2DM group. Over 65 years old, the BMI, BMD, VFM, VFA, and SFM was found to be much higher in participants with T2DM than in non-T2DM group (p < 0.05). Compared with women aged in 50-65 years old, those over 65 years old had higher VFA and VFM and lower BMD (p < 0.05), whether in the T2DM group or the non-T2DM group. Age, VFA and VFM were negatively correlated with BMD (r = -0.590, p ≤ 0.001; r = -0.179, p = 0.017; r = -0.155, p = 0.040, respectively). After adjusting for age, VFM and VFA were no longer correlated with BMD. No correlations between fat distribution or psoas major muscle and BMD in postmenopausal women with T2DM were observed.ConclusionsT2DM can affect abdominal fat deposition in postmenopausal women. Postmenopausal elderly women with diabetes have higher BMD than normal elderly women. There was no correlation between fat distribution or psoas major and BMD in postmenopausal women with diabetes mellitus.

Project description:Individuals with type 2 diabetes mellitus (T2DM) have a greater risk of bone fracture compared with those with normal glucose tolerance (NGT). In contrast, individuals with impaired glucose tolerance (IGT) have a lower or similar risk of fracture. Our objective was to understand how progressive glycemic derangement affects advanced glycation endproduct (AGE) content, composition, and mechanical properties of iliac bone from postmenopausal women with NGT (n = 35, age = 65 ± 7 years, HbA1c = 5.8% ± 0.3%), IGT (n = 26, age = 64 ± 5 years, HbA1c = 6.0% ± 0.4%), and T2DM on insulin (n = 25, age = 64 ± 6 years, HbA1c = 9.1% ± 2.2%). AGEs were assessed in all samples using high-performance liquid chromatography to measure pentosidine and in NGT/T2DM samples using multiphoton microscopy to spatially resolve the density of fluorescent AGEs (fAGEs). A subset of samples (n = 14 NGT, n = 14 T2DM) was analyzed with nanoindentation and Raman microscopy. Bone tissue from the T2DM group had greater concentrations of (i) pentosidine versus IGT (cortical +24%, p = 0.087; trabecular +35%, p = 0.007) and versus NGT (cortical +40%, p = 0.003; trabecular +35%, p = 0.004) and (ii) fAGE cross-link density versus NGT (cortical +71%, p < 0.001; trabecular +44%, p < 0.001). Bone pentosidine content in the IGT group was lower than in the T2DM group and did not differ from the NGT group, indicating that the greater AGE content observed in T2DM occurs with progressive diabetes. Individuals with T2DM on metformin had lower cortical bone pentosidine compared with individuals not on metformin (-35%, p = 0.017). Cortical bone from the T2DM group was stiffer (+9%, p = 0.021) and harder (+8%, p = 0.039) versus the NGT group. Bone tissue AGEs, which embrittle bone, increased with worsening glycemic control assessed by HbA1c (Pen: R2 = 0.28, p < 0.001; fAGE density: R2 = 0.30, p < 0.001). These relationships suggest a potential mechanism by which bone fragility may increase despite greater tissue stiffness and hardness in individuals with T2DM; our results suggest that it occurs in the transition from IGT to overt T2DM. © 2022 American Society for Bone and Mineral Research (ASBMR).

Dataset Information

In vivo assessment of bone quality in postmenopausal women with type 2 diabetes.

Publications

In vivo assessment of bone quality in postmenopausal women with type 2 diabetes.

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