Altered Tissue Composition, Microarchitecture, and Mechanical Performance in Cancellous Bone From Men With Type 2 Diabetes Mellitus

Abstract

People with type 2 diabetes mellitus (T2DM) have normal‐to‐high BMDs, but, counterintuitively, have greater fracture risks than people without T2DM, even after accounting for potential confounders like BMI and falls. Therefore, T2DM may alter aspects of bone quality, including material properties or microarchitecture, that increase fragility independently of bone mass. Our objective was to elucidate the factors that influence fragility in T2DM by comparing the material properties, microarchitecture, and mechanical performance of cancellous bone in a clinical population of men with and without T2DM. Cancellous specimens from the femoral neck were collected during total hip arthroplasty (T2DM: n = 31, age = 65 ± 8 years, HbA1c = 7.1 ± 0.9%; non‐DM: n = 34, age = 62 ± 9 years, HbA1c = 5.5 ± 0.4%). The T2DM specimens had greater concentrations of the advanced glycation endproduct pentosidine (+ 36%, P < 0.05) and sugars bound to the collagen matrix (+ 42%, P < 0.05) than the non‐DM specimens. The T2DM specimens trended toward a greater bone volume fraction (BV/TV) (+ 24%, NS, P = 0.13) and had greater mineral content (+ 7%, P < 0.05) than the non‐DM specimens. Regression modeling of the mechanical outcomes revealed competing effects of T2DM on bone mechanical behavior. The trend of higher BV/TV values and the greater mineral content observed in the T2DM specimens increased strength, whereas the greater values of pentosidine in the T2DM group decreased postyield strain and toughness. The long‐term medical management and presence of osteoarthritis in these patients may influence these outcomes. Nevertheless, our data indicate a beneficial effect of T2DM on cancellous microarchitecture, but a deleterious effect of T2DM on the collagen matrix. These data suggest that high concentrations of advanced glycation endproducts can increase fragility by reducing the ability of bone to absorb energy before failure, especially for the subset of T2DM patients with low BV/TV. © 2019 American Society for Bone and Mineral Research.

Bone Mineral Is More Heterogeneously Distributed in the Femoral Heads of Osteoporotic and Diabetic Patients: A Pilot Study

“…Nonetheless, it is interesting that the mineral distribution is becoming more heterogeneous within this localized region; further studies are required to delineate whether changes also arise in the peripheral regions. Second, by our methods we did not observe altered mechanical properties at the tissue level despite previous observations of increased fracture risk in DB patients at the population level, which is in keeping with the findings of a study that compared the mechanical properties (compression and Reference Point Indentation) of DB femoral cancellous bone to non‐DB OA patients, although another study reported that DB bone had increased stiffness, yield, and ultimate strength . These studies highlight the challenge of delineating the underlying mechanisms for increased fracture risk in DB patients, which might be associated with properties not distinguishable through our approach, in particular, fracture toughness.…”

“…These studies highlight the challenge of delineating the underlying mechanisms for increased fracture risk in DB patients, which might be associated with properties not distinguishable through our approach, in particular, fracture toughness. Moreover, similar to other studies, we used OA bone as a surrogate control as no healthy human bone was available and, although we could distinguish between the two groups in terms of mineralization, this might explain the lack of difference in mechanical properties. Nano‐indentation and fracture toughness testing is thus required to further investigate whether the increased mineral heterogeneity plays a role in the propensity for DB human bone to fracture.…”

“…In fact, studies have reported that patients with T2DM have normal to high BMD by DEXA . Recent studies have found that the trabecular microarchitecture and mechanical properties of cancellous bone of T2DM (measured by cyclic reference point indentation and unconfined compression) are indistinguishable from osteoarthritic (OA) controls, whereas the apparent stiffness and yield strength were increased in cancellous cores from the femoral neck of patients with T2DM (and osteoarthritis) compared with OA controls . Impaired mechanical properties (decreased strength, stiffness, and toughness) have been reported for hyperglycemic mouse femurs tested in bending .…”

“…(29,30) Recent studies have found that the trabecular microarchitecture and mechanical properties of cancellous bone of T2DM (measured by cyclic reference point indentation and unconfined compression) are indistinguishable from osteoarthritic (OA) controls, (31) whereas the apparent stiffness and yield strength were increased in cancellous cores from the femoral neck of patients with T2DM (and osteoarthritis) compared with OA controls. (32) Impaired mechanical properties (decreased strength, stiffness, and toughness) have been reported for hyperglycemic mouse femurs tested in bending. (33) Although fracture risk might be attributed to an increased risk of falls caused by other complications associated with T2DM (eg, obesity, poor balance, reduced muscle quality, slight problems brought on by hyperglycemia), important cellular and compositional changes also occur.…”

Bone Quality Sleuths: Uncovering Tissue-Level Mechanisms of Bone Fragility in Human Type 2 Diabetes

“…In summary, the study by Hunt and colleagues bridges the gap between epidemiologic and experimental analyses of bone fragility in T2DM. With a careful experimental and theoretical analysis of human T2DM bone quality, the investigators elucidate crucial relationships between bone matrix material properties and bone fragility in this clinically relevant human patient population.…”