Bone microarchitecture, biomechanical properties, and advanced glycation end-products in the proximal femur of adults with type 2 diabetes.

Skeletal fragility is a major complication of type 2 diabetes mellitus (T2D), but there is a poor understanding of mechanisms underlying T2D skeletal fragility. The increased fracture risk has been suggested to result from deteriorated bone microarchitecture or poor bone quality due to accumulation of advanced glycation end-products (AGEs). We conducted a clinical study to determine whether: 1) bone microarchitecture, AGEs, and bone biomechanical properties are altered in T2D bone, 2) bone AGEs are related to bone biomechanical properties, and 3) serum AGE levels reflect those in bone. To do so, we collected serum and proximal femur specimens from T2D (n = 20) and non-diabetic (n = 33) subjects undergoing total hip replacement surgery. A section from the femoral neck was imaged by microcomputed tomography (microCT), tested by cyclic reference point indentation, and quantified for AGE content. A trabecular core taken from the femoral head was imaged by microCT and subjected to uniaxial unconfined compression tests. T2D subjects had greater HbA1c (+23%, p ≤ 0.0001), but no difference in cortical tissue mineral density, cortical porosity, or trabecular microarchitecture compared to non-diabetics. Cyclic reference point indentation revealed that creep indentation distance (+18%, p ≤ 0.05) and indentation distance increase (+20%, p ≤ 0.05) were greater in cortical bone from T2D than in non-diabetics, but no other indentation variables differed. Trabecular bone mechanical properties were similar in both groups, except for yield stress, which tended to be lower in T2D than in non-diabetics. Neither serum pentosidine nor serum total AGEs were different between groups. Cortical, but not trabecular, bone AGEs tended to be higher in T2D subjects (21%, p = 0.09). Serum AGEs and pentosidine were positively correlated with cortical and trabecular bone AGEs. Our study presents new data on biomechanical properties and AGEs in adults with T2D, which are needed to better understand mechanisms contributing to diabetic skeletal fragility.

Incorporation of CT-based measurements of trunk anatomy into subject-specific musculoskeletal models of the spine influences vertebral loading predictions.

We created subject-specific musculoskeletal models of the thoracolumbar spine by incorporating spine curvature and muscle morphology measurements from computed tomography (CT) scans to determine the degree to which vertebral compressive and shear loading estimates are sensitive to variations in trunk anatomy. We measured spine curvature and trunk muscle morphology using spine CT scans of 125 men, and then created four different thoracolumbar spine models for each person: (i) height and weight adjusted (Ht/Wt models); (ii) height, weight, and spine curvature adjusted (+C models); (iii) height, weight, and muscle morphology adjusted (+M models); and (iv) height, weight, spine curvature, and muscle morphology adjusted (+CM models). We determined vertebral compressive and shear loading at three regions of the spine (T8, T12, and L3) for four different activities. Vertebral compressive loads predicted by the subject-specific CT-based musculoskeletal models were between 54% lower to 45% higher from those estimated using musculoskeletal models adjusted only for subject height and weight. The impact of subject-specific information on vertebral loading estimates varied with the activity and spinal region. Vertebral loading estimates were more sensitive to incorporation of subject-specific spinal curvature than subject-specific muscle morphology. Our results indicate that individual variations in spine curvature and trunk muscle morphology can have a major impact on estimated vertebral compressive and shear loads, and thus should be accounted for when estimating subject-specific vertebral loading. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2164-2173, 2017.