Longitudinal Evolution of Bone Microarchitecture and Bone Strength in Type 2 Diabetic Postmenopausal Women With and Without History of Fragility Fractures—A 5-Year Follow-Up Study Using High Resolution Peripheral Quantitative Computed Tomography

Abstract

IntroductionDiabetic bone disease is characterized by an increased fracture risk which may be partly attributed to deficits in cortical bone quality such as higher cortical porosity. However, the temporal evolution of bone microarchitecture, strength, and particularly of cortical porosity in diabetic bone disease is still unknown. Here, we aimed to prospectively characterize the 5-year changes in bone microarchitecture, strength, and cortical porosity in type 2 diabetic (T2D) postmenopausal women with (DMFx) and without history of fragility fractures (DM) and to compare those to nondiabetic fracture free controls (Co) using high resolution peripheral quantitative computed tomography (HR-pQCT).MethodsThirty-two women underwent baseline HR-pQCT scanning of the ultradistal tibia and radius and a FU-scan 5 years later. Bone microarchitectural parameters, including cortical porosity, and bone strength estimates via µFEA were calculated for each timepoint and annualized. Linear regression models (adjusted for race and change in BMI) were used to compare the annualized percent changes in microarchitectural parameters between groups.ResultsAt baseline at the tibia, DMFx subjects exhibited the highest porosity of the three groups (66.3% greater Ct.Po, 71.9% higher Ct.Po.Volume than DM subjects, p < 0.022). Longitudinally, porosity increased significantly over time in all three groups and at similar annual rates, while DMFx exhibited the greatest annual decreases in bone strength indices (compared to DM 4.7× and 6.7× greater decreases in failure load [F] and stiffness [K], p < 0.025; compared to Co 14.1× and 22.2× greater decreases in F and K, p < 0.020).ConclusionOur data suggest that despite different baseline levels in cortical porosity, T2D women with and without fractures experienced long-term porosity increases at a rate similar to non-diabetics. However, the annual loss in bone strength was greatest in T2D women with a history of a fragility fractures. This suggests a potentially non-linear course of cortical porosity development in T2D bone disease: major porosity may develop early in the course of disease, followed by a smaller steady annual increase in porosity which in turn can still have a detrimental effect on bone strength—depending on the amount of early cortical pre-damage.

Meta-analysis of Diabetes Mellitus-Associated Differences in Bone Structure Assessed by High-Resolution Peripheral Quantitative Computed Tomography

“…This may explain the large degree of variation we found between studies and suggests that cortical porosity may reflect presence of multiple diabetes-related complications, although heterogeneity may also reflect variable endosteal contour placement among study centres [ 49 ] that may cause misinterpretation of trabeculae in the endosteal transition zone as porous cortical bone [ 17 ]. Our findings are consistent with a recent longitudinal first-generation HR-pQCT investigation indicating that fracture patients with T2DM had favourable trabecular microarchitecture accompanied by a non-linear rise in cortical porosity [ 50 •]. Enhanced trabecular features possibly reflect a natural compensatory response to T2DM-associated cortical weakness.…”

The role of advanced glycation end products in fracture risk assessment in postmenopausal type 2 diabetic patients

“…The optimal AGEs cut-off value leading to a high fracture risk was 4.156mmol/L, which suggests postmenopausal T2D patients have an increased fracture risk when the AGEs level is higher than 4.156mmol/L. Previous studies indicated that the impaired bone microarchitecture has a considerable influence on bone strength and is essential in fracture initiation and propagation (50,51). A meta-analysis reported the increase of cortical porosity is relevant to bone quality decline and increased fracture risk.…”

Insulin resistance and skeletal health

“…The HR-pQCT is often referred to as an 'in-vivo bone biopsy' due to its high-resolution capabilities. Most studies involving metabolic health and HR-pQCT-derived bone outcomes focus specifically on diabetes, rather than insulin resistance per se [69][70][71][72]. Nonetheless, these studies provide a potential explanation for the higher fracture risk experienced by individuals with T2D despite greater BMD outcomes as measured via DXA.…”