Abstract
The mechanism for bone fragility in type 1 diabetes (T1D) is unclear. We performed advanced analyses on HR-pQCT images from participants with T1D (n = 183, 59.5 ± 7.0 yr, 50.8% female, T1D duration 38.0 ± 4.8 yr) enrolled in the Epidemiology of Diabetes Interventions and Complications (EDIC) study and a demographically similar group of nondiabetic controls (n = 94, 60.5 ± 8.2 yr, 65.6% female). Between participants and controls, we compared trabecular morphology by individual trabecula segmentation (ITS) analysis (decomposes trabeculae into plate-like and rod-like structures), and assessed cortical topology by cortical pore skeletonization (CPS) analysis (classifies pores as slab-like or tube-like and analyzes connectivity) and by cortical laminar analysis (CLA) (quantifies distribution, number, and area of pores). By ITS, EDIC participants had worse trabecular morphology with lower plate-rod bone volume ratio (radius: 0.36 ± 0.21 vs 0.41 ± 0.25 [p = .031]; tibia: 0.75 ± 0.42 vs 0.88 ± 0.52 [p = .016]), plate tissue fraction (radius: 0.25 ± 0.10 vs 0.27 ± 0.10 [p = .020]; tibia: 0.40 ± 0.12 vs 0.43 ± 0.14 [p = .040]), and higher rod tissue fraction (radius: 0.75 ± 0.10 vs 0.73 ± 0.10 [p = .020]; tibia: 0.60 ± 0.12 vs 0.57 ± 0.14 [p = .040]) compared with controls. Epidemiology of Diabetes Interventions and Complications participants also had worse cortical pore network topology by CPS compared with controls, with increased tube-tube junctions (81.07 ± 74.84 vs 59.90 ± 45.25 [p = .017]) at the radius, and a higher ratio of slab-like to tube-like pores (0.490 ± 0.057 vs 0.472 ± 0.071 [p = .013]) at the tibia. By CLA, EDIC participants had higher pore size at midcortical (0.039 ± 0.007 vs 0.038 ± 0.007 mm(2) [p = .005]) and periosteal layers (0.037 ± 0.005 vs 0.035 ± 0.006 mm(2) [p < .001]), a biomechanically detrimental pattern. Among EDIC participants, higher HbA1c and advanced glycation end products, as well as kidney disease, retinopathy, and neuropathy, were associated with unfavorable trabecular morphology and cortical pore network connectivity. These findings reveal novel microarchitectural abnormalities previously associated with reduced mechanical properties of bone in participants with long-standing T1D, in association with modifiable diabetes risk factors. Trial registration: Clinicaltrials.gov NCT00360815 and NCT00360893.