Bone Microarchitecture and Strength in Long-Standing Type 1 Diabetes

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/m(2); 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. (c) 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).

Automated summary

Type 1 diabetes (T1DM) is associated with an increased risk of nonvertebral fractures, and the influence of glycemic control and microvascular disease on skeletal health in long-standing T1DM is not well understood. This study found that patients with long-standing T1DM had lower bone mineral density (BMD), decreased bone turnover, and weaker bones at the ultradistal tibia compared to non-diabetic controls. The presence of diabetic peripheral neuropathy was found to contribute to the altered cortical microarchitecture and reduced bone strength in T1DM patients.