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

Abstract

Purpose of review: Diabetes mellitus is defined by elevated blood glucose levels caused by changes in glucose metabolism and, according to its pathogenesis, is classified into type 1 (T1DM) and type 2 (T2DM) diabetes mellitus. Diabetes mellitus is associated with multiple degenerative processes, including structural alterations of the bone and increased fracture risk. High-resolution peripheral computed tomography (HR-pQCT) is a clinically applicable, volumetric imaging technique that unveils bone microarchitecture in vivo. Numerous studies have used HR-pQCT to assess volumetric bone mineral density and microarchitecture in patients with diabetes, including characteristics of trabecular (e.g. number, thickness and separation) and cortical bone (e.g. thickness and porosity). However, study results are heterogeneous given different imaging regions and diverse patient cohorts.

Recent findings: This meta-analysis assessed T1DM- and T2DM-associated characteristics of bone microarchitecture measured in human populations in vivo reported in PubMed- and Embase-listed publications from inception (2005) to November 2021. The final dataset contained twelve studies with 516 participants with T2DM and 3067 controls and four studies with 227 participants with T1DM and 405 controls. While T1DM was associated with adverse trabecular characteristics, T2DM was primarily associated with adverse cortical characteristics. These adverse effects were more severe at the radius than the load-bearing tibia, indicating increased mechanical loading may compensate for deleterious bone microarchitecture changes and supporting mechanoregulation of bone fragility in diabetes mellitus. Our meta-analysis revealed distinct predilection sites of bone structure aberrations in T1DM and T2DM, which provide a foundation for the development of animal models of skeletal fragility in diabetes and may explain the uncertainty of predicting bone fragility in diabetic patients using current clinical algorithms.

Keywords: Bone microarchitecture; Diabetes mellitus; High-resolution peripheral quantitative computed tomography; Osteoporosis.

Fig. 1

PRISMA diagram of information flow through systematic review with the number of studies (N) and colourmap blue indicating included studies; orange arrows denote excluded studies. For different HR-pQCT metrics, the number of individuals included in the meta-analysis ranged from 187 to 227 T1DM subjects with 345 to 405 controls and 225 to 516 T2DM subjects with 1260 to 3067 controls. Studies predominantly investigated Caucasian populations, some mixed (Hispanic/Caucasian) and one Black population. Studies of patients with T2DM included older patients with an average age of 63 years. Studies investigating bone characteristics of patients with T1DM included two studies in children aged 6 to 18 [26, 27] and three studies in adults older than 18 with an average age of 47 years [28, 29]

Fig. 2

Type 1 and type 2 diabetes mellitus associated with distinct differences in bone microarchitecture. Mean difference and 95% confidence intervals between patients with diabetes and controls (dashed lines). Bone microarchitecture measurements include total cross-sectional area (Tt.Ar), bone mineral density (BMD), trabecular volumetric bone mineral density (Tb.BMD), cortical volumetric bone mineral density (Ct.BMD), trabecular number (Tb.N), trabecular separation (Tb.Sp), trabecular thickness (Tb.Th), inhomogeneity of trabecular network (Tb.1/N.SD), cortical thickness (Ct.Th), cortical porosity (Ct.Po) and estimated failure load (FL). Significant differences between patients with diabetes and controls are indicated (*p < 0.01)

Fig. 3

Diabetes-related variations in radial and tibial trabecular volumetric bone mineral density (Tb.BMD) forest plot. The data represent study-level percent differences between persons with and without diabetes, with a 95% confidence interval. Within each stratum, studies are classified by participant age. Red markers represent tibial measurements, black markers represent radial measurements and a dashed black line represents nondiabetic reference. Age in years, BMI in kg/m², diabetes duration in years, female subject ratio (F) in percent, glycated haemoglobin (HbA1c) in percent, number of radius scans (n_radius) and number of tibia scans (n_tibia). The numbers in parenthesis are for patients with diabetes (DM). The sizes of the markers are proportionate to the study-level weights

Fig. 4

Diabetes-related variations in radial and tibial trabecular number (Tb.N) forest plot. The data represent study-level per cent differences between persons with and without diabetes, with a 95% confidence interval. Within each stratum, studies are classified by participant age. Red markers represent tibial measurements, black markers represent radial measurements and a dashed line represents nondiabetic reference. Age in years, BMI in kg/m², diabetes duration in years, female subject ratio (F) in percent, glycated haemoglobin (HbA1c) in percent, number of radius scans (n_radius) and number of tibia scans (n_tibia). The numbers in parenthesis are for patients with diabetes (DM). The sizes of the markers are proportionate to the study-level weights

Fig. 5

Graphical summary of the meta-analysis. Computer generated illustration of distal radius and distal tibia bone microarchitecture in type 1 and type 2 diabetes mellitus compared to healthy controls. Annotations 1–3 show impaired bone microarchitecture characteristics, while annotations 4–5 show enhanced bone microarchitecture characteristics. Increased loading (6) at the weight-bearing tibia may explain differences in bone microarchitecture at the radius and tibia