In Vivo Assessment of Bone Quality in Postmenopausal Women With Type 2 Diabetes

Abstract

While 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 non-diabetic 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 yrs) including 30 patients diagnosed with T2D for >10 yrs and 30 age-matched, non-diabetic controls. Regional BMD was measured by DXA; cortical and trabecular bone microarchitecture was assessed from 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 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 yrs was negatively correlated with BMS (r = −0.41; p=0.026). In conclusion, these findings represent the first demonstration of compromised bone material strength 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.

Women with type 2 diabetes mellitus have lower cortical porosity of the proximal femoral shaft using low-resolution CT than nondiabetic women, and increasing glucose is associated with reduced cortical porosity

“…Increased cortical porosity of distal radius or distal tibia has been invoked as one possible factor [11][12][13]. However, it is hard to explain how individuals with T2DM can exhibit high porosity [14][15][16][17], since increased cortical porosity reflects increased bone turnover from intracortical surfaces lining the Haversian canals and the endocortical surfaces adjacent to the marrow cavity [18,19]. As T2DM is a condition with low bone turnover [20,21], patients with T2DM would rather be expected to exhibit reduced cortical porosity.…”

Novel skeletal effects of glucagon-like peptide-1 (GLP-1) receptor agonists

“…However, such biopsies are not available and microarchitecture and material properties have been investigated in humans by high-resolution peripheral quantitative computed tomography (HR-pQCT) and bone microindentation. In terms of bone microarchitecture, most studies tend to indicate a preserved trabecular bone microarchitecture but an increase in cortical bone porosity in diabetic individuals with or without fracture (Burghardt et al 2010, Patsch et al 2013, Farr et al 2014. A limitation of HR-pQCT is that it can only be performed at peripheral skeletal sites and may not reflect the full bone phenotype.…”

“…A limitation of HR-pQCT is that it can only be performed at peripheral skeletal sites and may not reflect the full bone phenotype. In terms of bone material properties, the use of the OsteoProbe bone microindentation device showed that postmenopausal women with T2DM had significantly lower bone material strength index (BMSi) as compared to age-and sex-matched postmenopausal women without diabetes, suggesting altered bone material properties (Farr et al 2014).…”

Energy Excess, Glucose Utilization, and Skeletal Remodeling: New Insights

“…These include greater cortical porosity, smaller cortical area, decreased bone material strength measured by microindentation, and high bone marrow adiposity. (17)(18)(19) In addition, the composition of the skeletal matrix may be significantly altered by higher concentrations of advanced glycation end products (AGEs). (20) All may contribute to the higher frequency of fractures documented in epidemiologic studies.…”