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.

Ursula Heilmeier,Courtney Pasco,Galateia J Kazakia,Thomas M Link,Karin Darakananda,Soheyla Torabi,Julio Carballido-Gamio,Andrew J Burghardt,Jiwon Youm,Nhan Dinh,Gabby B Joseph

doi:10.3389/fendo.2021.599316

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.

Highlights

Diabetic 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
The temporal evolution of cortical porosity, bone microarchitecture, and micro-scale bone biomechanics in individuals with type 2 diabetic (T2D) are still unknown [46]. We designed this longitudinal study in order to investigate the temporal evolution of cortical porosity and of associated pore parameters via high resolution peripheral quantitative computed tomography (HR-pQCT) and to study the longitudinal alterations of bone microarchitecture and of bone strength during the course of T2D bone disease
Another potential explanation for the comparable rate of cortical porosity increase despite divergent baseline porosity may be that cortical porosity development in T2D diabetic bone disease may not necessarily follow a linear pattern, and that periods of escalated pore growth may be followed by times of slower pore growth, a phase which we might have randomly hit in the time window that we imaged in this longitudinal study

Summary

Introduction

Diabetic 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. The temporal evolution of bone microarchitecture, strength, and of cortical porosity in diabetic bone disease is still unknown. Epidemiological studies have found that patients with T2D have an increased risk for fragility fractures despite normal or even elevated bone mineral density (BMD) [4, 5, 7]. These findings suggest that diabetic bone exhibits abnormalities in bone material properties and/or microarchitecture that are independent of BMD [6]. Studies have started to investigate the factors contributing to the increased bone fragility [8,9,10,11], the mechanisms causing bone fragility in T2D remain to a large extent unclear [12,13,14]

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