Bone Tissue Composition in Postmenopausal Women Varies With Glycemic Control From Normal Glucose Tolerance to Type 2 Diabetes Mellitus

Hunt, Heather B.; Miller, Nicholas; Hemmerling, Kimberly J; Koga, Maho; A., None Lopez, Kelsie; Taylor, Erik A.; Sellmeyer, Deborah E.; Moseley, Kendall F.; Donnelly, Eve

doi:10.1002/jbmr.4186

Cited by 27 publications

(22 citation statements)

References 74 publications

(99 reference statements)

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“…In fact, this mineral deposit was abnormal mineralization, possibly resulting in reduced bone absorption and bone strength. Hunt et al reported that mineral crystallinity was observed in patients with diabetes by FTIR (Hunt et al, 2021). This mineral crystallinity may be related to the mineral deposit found in this study.…”

Section: Discussionsupporting

confidence: 70%

“…The few studies on histological assessments of bone in DM have only included human samples obtained by biopsy or through autopsy. Recently, Hunt et al reported that worsening glycemic control was associated with greater mineral content and narrower distributions of acid phosphate using Fourier-transform infrared (FTIR) for the samples obtained by biopsy (Hunt et al, 2021). However, the actual histological mechanism of bone quality deterioration in DM is largely unknown (Jiang and Xia, 2018).…”

Section: Introductionmentioning

confidence: 99%

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Histological Assessment of Cortical Bone Changes in Diabetic Rats

Minami

Ikoma

Onishi

et al. 2022

Preprint

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Background: Diabetes mellitus weakens bone strength due to the deterioration of bone quality; however, the histological mechanisms are still unknown. We hypothesized that histological assessment of cortical bone would enable us to determine the cause of the bone strength reduction associated with diabetes mellitus. Our aim was to evaluate the histomorphometric changes of cortical bone associated with deterioration of intrinsic bone properties and of bone quality in diabetes mellitus. Methods: We compared the outcomes of mechanical tests, bone mineral density measured using micro computed tomography, and histological assessments by applying Villanueva’s bone stain to the tibial bones of 40-week-old diabetic and control male rats. Results: With respect to mechanical testing, the maximum load and energy absorption were significantly lower in the diabetic group than in the control group, although fracture displacement and stiffness were not significantly different between the groups. Bone mineral density was significantly higher in the diabetic group than in the control group. Bone histomorphometry revealed that the diabetic rats had fewer osteocytes, greater cortical porosity, and increased mineralization in cortical bone compared with the control group. Conclusions: Increased mineralization of the cortical bone with greater cortical porosity leads to a weakening of bone strength in diabetes mellitus.

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Section: Discussionsupporting

confidence: 70%

Section: Introductionmentioning

confidence: 99%

Histological Assessment of Cortical Bone Changes in Diabetic Rats

Minami

Ikoma

Onishi

et al. 2022

Preprint

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“…Third, long-term hyperglycemia leads to the accumulation of advanced glycation end products (AGEs). Besides inhibiting the proliferation and differentiation of osteoblasts, AGEs accumulated in the body can not only promote oxidative stress and produce nonenzymatic crosslinking with type I collagen (the two best-characterized AGEs related to collagen are pentosidine and N-carboxymethyllysine) but also damage bone matrix and increase bone stiffness, increasing the chances of fractures (102,103). Although some studies indicated that serum or urinary levels of pentosidine correlated with the risk of vertebral fracture in T2DM (104, 105), the feasibility of predicting fracture risk needs to be further confirmed.…”

Section: Discussionmentioning

confidence: 99%

Fracture risk assessment in diabetes mellitus

et al. 2022

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Growing evidence suggests that diabetes mellitus is associated with an increased risk of fracture. Bone intrinsic factors (such as accumulation of glycation end products, low bone turnover, and bone microstructural changes) and extrinsic factors (such as hypoglycemia caused by treatment, diabetes peripheral neuropathy, muscle weakness, visual impairment, and some hypoglycemic agents affecting bone metabolism) probably contribute to damage of bone strength and the increased risk of fragility fracture. Traditionally, bone mineral density (BMD) measured by dual x-ray absorptiometry (DXA) is considered to be the gold standard for assessing osteoporosis. However, it cannot fully capture the changes in bone strength and often underestimates the risk of fracture in diabetes. The fracture risk assessment tool is easy to operate, giving it a certain edge in assessing fracture risk in diabetes. However, some parameters need to be regulated or replaced to improve the sensitivity of the tool. Trabecular bone score, a noninvasive tool, indirectly evaluates bone microstructure by analyzing the texture sparsity of trabecular bone, which is based on the pixel gray level of DXA. Trabecular bone score combined with BMD can effectively improve the prediction ability of fracture risk. Quantitative computed tomography is another noninvasive examination of bone microstructure. High-resolution peripheral quantitative computed tomography can measure volume bone mineral density. Quantitative computed tomography combined with microstructure finite element analysis can evaluate the mechanical properties of bones. Considering the invasive nature, the use of microindentation and histomorphometry is limited in clinical settings. Some studies found that the changes in bone turnover markers in diabetes might be associated with fracture risk, but further studies are needed to confirm this. This review focused on summarizing the current development of these assessment tools in diabetes so as to provide references for clinical practice. Moreover, these tools can reduce the occurrence of fragility fractures in diabetes through early detection and intervention.

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“…Some scholars have studied the effects of elevated blood glucose in T2DM on advanced glycation end products (AGEs), mineral content and collagen. Elevated blood glucose in T2DM increases AGEs and mineral content [ 8 – 10 ]; hyperglycemia in T2DM leads to increased bone mineral content and average maturity of collagen [ 8 ]. Changes in bone microstructure and material properties (such as bone mineral and collagen) in patients with T2DM can lead to the decrease of bone quality and strength [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Effect of verapamil on bone mass, microstructure and mechanical properties in type 2 diabetes mellitus rats

Gong

et al. 2022

BMC Musculoskelet Disord

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Background Verapamil was mainly used to treat hypertension, cardiovascular disease, inflammation and improve blood glucose in patients with diabetes, but its effects on bone mass, microstructure and mechanical properties were unclear. This study described the effects of verapamil on bone mass, microstructure, macro and nano mechanical properties in type 2 diabetic rats. Methods Rat models of type 2 diabetes were treated with verapamil at doses of 4, 12, 24 and 48 mg/kg/day by gavage respectively, twice a day. After 12 weeks, all rats were sacrificed under general anesthesia. Blood glucose, blood lipid, renal function and biochemical markers of bone metabolism were obtained by serum analysis, Micro-CT scanning was used to assess the microstructure parameters of cancellous bone of femoral head, three-point bending test was used to measure maximum load and elastic modulus of femoral shaft, and nano-indentation tests were used to measure indentation moduli and hardnesses of longitudinal cortical bone in femoral shaft, longitudinal and transverse cancellous bones in femoral head. Results Compared with T2DM group, transverse indentation moduli of cancellous bones in VER 24 group, longitudinal and transverse indentation moduli and hardnesses of cancellous bones in VER 48 group were significantly increased (p < 0.05). Furthermore, the effects of verapamil on blood glucoses, microstructures and mechanical properties in type 2 diabetic rats were dependent on drug dose. Starting from verapamil dose of 12 mg/kg/day, with dose increasing, the concentrations of P1NP, BMD, BV/TV, Tb. Th, Tb. N, maximum loads, elastic moduli, indentation moduli and hardnesses of femurs in rats in treatment group increased gradually, the concentrations of CTX-1 decreased gradually, but these parameters did not return to the level of the corresponding parameters of normal rats. Verapamil (48 mg/kg/day) had the best therapeutic effect. Conclusion Verapamil treatment (24, 48 mg/kg/day) significantly affected nano mechanical properties of the femurs, and tended to improve bone microstructures and macro mechanical properties of the femurs, which provided guidance for the selection of verapamil dose in the treatment of type 2 diabetic patients.

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Bone Tissue Composition in Postmenopausal Women Varies With Glycemic Control From Normal Glucose Tolerance to Type 2 Diabetes Mellitus

Cited by 27 publications

References 74 publications

Histological Assessment of Cortical Bone Changes in Diabetic Rats

Histological Assessment of Cortical Bone Changes in Diabetic Rats

Fracture risk assessment in diabetes mellitus

Effect of verapamil on bone mass, microstructure and mechanical properties in type 2 diabetes mellitus rats

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