Microvascular disease not type 2 diabetes is associated with increased cortical porosity: A study of cortical bone microstructure and intracortical vessel characteristics

Abstract

Introduction: Fracture risk is elevated in type 2 diabetes (T2D) despite normal or even high bone mineral density (BMD). Microvascular disease (MVD) is a diabetic complication, but also associated with other diseases, for example chronic kidney disease. We hypothesize that increased fracture risk in T2D could be due to increased cortical porosity (Ct.Po) driven by expansion of the vascular network in MVD. The purpose of this study was to investigate associations of T2D and MVD with cortical microstructure and intracortical vessel parameters.

Methods: The study group consisted of 75 participants (38 with T2D and 37 without T2D). High-resolution peripheral quantitative CT (HR-pQCT) and dynamic contrast-enhanced MRI (DCE-MRI) of the ultra-distal tibia were performed to assess cortical bone and intracortical vessels (outcomes). MVD was defined as ≥1 manifestation including neuropathy, nephropathy, or retinopathy based on clinical exams in all participants. Adjusted means of outcomes were compared between groups with/without T2D or between participants with/without MVD in both groups using linear regression models adjusting for age, sex, BMI, and T2D as applicable.

Results: MVD was found in 21 (55 %) participants with T2D and in 9 (24 %) participants without T2D. In T2D, cortical pore diameter (Ct.Po.Dm) and diameter distribution (Ct.Po.Dm.SD) were significantly higher by 14.6 μm (3.6 %, 95 % confidence interval [CI]: 2.70, 26.5 μm, p = 0.017) and by 8.73 μm (4.8 %, CI: 0.79, 16.7 μm, p = 0.032), respectively. In MVD, but not in T2D, cortical porosity was significantly higher by 2.25 % (relative increase = 12.9 %, CI: 0.53, 3.97 %, p = 0.011) and cortical BMD (Ct.BMD) was significantly lower by -43.6 mg/cm³ (2.6 %, CI: -77.4, -9.81 mg/cm³, p = 0.012). In T2D, vessel volume and vessel diameter were significantly higher by 0.02 mm³ (13.3 %, CI: 0.004, 0.04 mm³, p = 0.017) and 15.4 μm (2.9 %, CI: 0.42, 30.4 μm, p = 0.044), respectively. In MVD, vessel density was significantly higher by 0.11 mm^-3 (17.8 %, CI: 0.01, 0.21 mm^-3, p = 0.033) and vessel volume and diameter were significantly lower by -0.02 mm³ (13.7 %, CI: -0.04, -0.004 mm³, p = 0.015) and - 14.6 μm (2.8 %, CI: -29.1, -0.11 μm, p = 0.048), respectively.

Conclusions: The presence of MVD, rather than T2D, was associated with increased cortical porosity. Increased porosity in MVD was coupled with a larger number of smaller vessels, which could indicate upregulation of neovascularization triggered by ischemia. It is unclear why higher variability and average diameters of pores in T2D were accompanied by larger vessels.

Keywords: Cortical bone; Dynamic contrast-enhanced MRI; HR-pQCT; Microvascular disease; Porosity; Type 2 diabetes.

Fig. 1

Dot plots with means and standard deviations (dot and line) of HR-pQCT parameters stratified by T2D status (A-F) or presence of MVD (G-L). P-values are from linear regression models adjusting for age, sex, and BMI in models comparing participants with/without T2D and, additionally, adjusting for T2D status in models comparing participants with/without MVD.

Fig. 2

Dot plots with means and standard deviations (dot and line) of intracortical vessel metrics assessed by DCE-MRI and stratified by T2D status (A-D) or presence of MVD (E-F). P-values are from linear regression models adjusting for age, sex, and BMI in models comparing participants with/without T2D and, additionally, adjusting for T2D status in models comparing participants with/without MVD.

Fig. 3

DCE-MRI of ultra-distal tibia of a 70-year-old man without diabetes (A and A') and of a 56-year-old man with T2D (B and B′). Neither participant showed any clinical signs of MVD. Red voxels in axial views (A and B) represent detected intracortical vessels. Radial maximum intensity projections (MIPs, A' and B′) show metaphyseal vessels in column-like arrangement. Purple lines in axial views represent circumference origins of MIPs. Resolution is limited to larger diameter (>230 μm) vessels. The participant with T2D had fewer and on average larger intracortical vessels compared to the participant without diabetes.

Fig. 4

DCE-MRI of ultra-distal tibia of a 59-year-old female T2D participant with neuropathy and proliferative diabetic retinopathy. Red voxels in axial view (A) and radial MIP (A') represent detected intracortical vessels. This T2D participant with MVD had relatively more and smaller intracortical vessels compared to a healthy control (Fig. 3). See legend of Fig. 3 for more details on image creation.