The primary goal of this study was to assess peripheral bone microarchitecture and strength in diabetic postmenopausal women with fragility fractures (DMFx) and to compare them with diabetic women without fracture (DM). Secondary goals were to assess differences in non-diabetic women with (Fx) and without fragility fractures (Co) and in women with (DM) and without diabetes (Co). Eighty women (mean age 61.3±5.7 yrs) were recruited into these groups (n=20 per group). Participants underwent DXA and high-resolution peripheral quantitative computed tomography (HR-pQCT) of the ultradistal and distal radius and tibia. In the HR-pQCT images volumetric bone mineral density, cortical and trabecular structure measures, including cortical porosity, were calculated. Bone strength was estimated using micro-finite element analysis (μFEA). Differential strength estimates were obtained with and without open cortical pores. At the ultradistal and distal tibia, DMFx had greater intracortical pore volume (+52.6%, p=0.009; +95.4%, p=0.020), relative porosity (+58.1%; p=0.005; +87.9%, p=0.011) and endocortical bone surface (+10.9%, p=0.031; +11.5%, 0.019) than DM. At the distal radius DMFx had 4.7-fold greater relative porosity (p=0.000) than DM. At the ultradistal radius, intracortical pore volume was significantly higher in DMFx than DM (+67.8%, p=0.018). DMFx also displayed larger trabecular heterogeneity (ultradistal radius; +36.8%, p=0.035), and lower total and cortical BMD (ultradistal tibia: −12.6%, p=0.031; −6.8%, p=0.011) than DM. DMFx exhibited significantly higher pore-related deficits in stiffness, failure load and cortical load fraction at the ultradistal and distal tibia, and the distal radius than DM. Comparing non-diabetic Fx and Co, we only found a non-significant trend with increase in pore volume (+38.9%, p=0.060) at the ultradistal radius. The results of our study suggest that severe deficits in cortical bone quality are responsible for fragility fractures in postmenopausal diabetic women.

The goal of this MR-imaging study was to quantify vertebral bone marrow fat content and composition in diabetic and non-diabetic postmenopausal women with fragility fractures and to compare them with non-fracture controls with and without type-2 diabetes mellitus. Sixty-nine postmenopausal women (mean age 63±5 years) were recruited. Thirty-six patients (47.8%) had spinal and/or peripheral fragility fractures. Seventeen fracture patients were diabetic. Thirty-three women (52.2%) were non-fracture controls. Sixteen women were diabetic non-fracture controls. To quantify vertebral bone marrow fat content and composition, patients underwent MR-spectroscopy (MRS) of the lumbar spine at 3 Tesla. Bone mineral density (BMD) was determined by dual-energy X-Ray-absorptiometry (DXA) of the hip and lumbar spine (LS) and quantitative computed tomography (QCT) of the LS. To evaluate associations of vertebral marrow fat content and composition with spinal and/or peripheral fragility fractures and diabetes, we used linear regression models adjusted for age, race, and spine vBMD by QCT. At the LS, non-diabetic and diabetic fracture patients had lower vBMD than controls and diabetics without fractures (p=0.018; p=0.005). However, aBMD by DXA did not differ between fracture and non-fracture patients. After adjustment for age, race, and spinal vBMD, the prevalence of fragility fractures was associated with -1.7% lower unsaturation levels (confidence interval [CI] -2.8% to - 0.5%, p=0.005) and +2.9% higher saturation levels (CI 0.5% to 5.3%, p=0.017). Diabetes was associated with -1.3% (CI -2.3% to -0.2%, p=0.018) lower unsaturation and +3.3% (CI 1.1% to 5.4%. p=0.004) higher saturation levels. Diabetics with fractures had the lowest marrow unsaturation and highest saturation. There were no associations of marrow fat content with diabetes or fracture. Our results suggest that altered bone marrow fat composition is linked with fragility fractures and diabetes. MRS of spinal bone marrow fat may therefore serve as a novel tool for BMD-independent fracture risk assessment.

Purpose To compare vertebral bone marrow fat content quantified with proton MR spectroscopy (1H-MRS) with the volume of abdominal adipose tissue, lumbar spine volumetric bone mineral density (vBMD), and blood biomarkers in postmenopausal women with and without type 2 diabetes mellitus (T2DM). Materials and Methods Thirteen postmenopausal women with T2DM and 13 age- and BMI-matched healthy controls were included in this study. All subjects underwent 1H-MRS of L1–L3 to quantify vertebral bone marrow fat content (FC) and unsaturated lipid fraction (ULF). QCT was performed to assess vBMD of L1–L3. The volumes of abdominal subcutaneous/visceral/total adipose tissue were determined from the QCT images and adjusted for abdominal body volume (SATadj/VATadj/TATadj). Fasting blood tests included plasma glucose and HbA1c. Results Mean FC showed an inverse correlation with vBMD (r=−0.452; p<0.05) in the whole study population. While mean FC was similar in the diabetic women and healthy controls (69.3 ± 7.5% vs. 67.5 ± 6.1%; p>0.05), mean ULF was significantly lower in the diabetic group (6.7 ± 1.0% vs. 7.9 ± 1.6%; p<0.05). SATadj and TATadj correlated significantly with mean FC in the whole study population (r=0.538 and r=0.466; p<0.05). In contrast to the control group, significant correlations of mean FC with VATadj and HbA1c were observed in the diabetic group (r=0.642 and r=0.825; p<0.05). Conclusion This study demonstrated that vertebral bone marrow fat content correlates significantly with SATadj, TATadj, and lumbar spine vBMD in postmenopausal women with and without T2DM, but with VATadj and HbA1c only in women with T2DM.

Purpose To show the feasibility of assessing the spatial distribution of skeletal muscle adipose tissue using chemical shift-based water/fat separation and to characterize differences in calf intermuscular adipose tissue (IMAT) compartmentalization in patients with type 2 diabetes mellitus (T2DM) compared to healthy age-matched controls. Materials and Methods A chemical shift-based water/fat separation approach using a multi-echo 3D spoiled gradient echo sequence was applied in a study of 64 patients, including 35 healthy controls and 29 subjects with T2DM. Masks were defined based on manual segmentations to compute fat volume within different compartments, including regions of subcutaneous adipose tissue (SAT) and six muscular regions. IMAT was divided into two compartments representing fat within the muscular regions (intraMF) and fat between the muscular regions (interMF). Two sample Student’s t-tests were used to compare fat volumes between the two groups. Results The subjects with T2DM had a lower volume of SAT compared to the healthy controls (p=4×10−5). There was no statistically significant difference in the IMAT volume between the two groups. However, the intraMF volume normalized by the IMAT volume was higher in the diabetics compared to the controls (p=0.006). Conclusion Chemical shift-based water/fat separation enables the quantification of fat volume within localized muscle regions, showing that the IMAT regional distribution is significantly different in T2DM compared to normal controls.

Vertebral bone marrow fat quantification using single-voxel MRS is confounded by overlapping water-fat peaks and the difference in T2 relaxation time between water and fat components. The purposes of the present study were: (i) to determine the proton density fat fraction (PDFF) of vertebral bone marrow using single-voxel multi-TE MRS, addressing these confounding effects; and (ii) to investigate the implications of these corrections with respect to the age dependence of the PDFF. Single-voxel MRS was performed in the L5 vertebral body of 86 subjects (54 women and 32 men). To reliably extract the water peak from the overlying fat peaks, the mean bone marrow fat spectrum was characterized based on the area of measurable fat peaks and an a priori knowledge of the chemical triglyceride structure. MRS measurements were performed at multiple TEs. The T2 -weighted fat fraction was calculated at each TE. In addition, a T2 correction was performed to obtain the PDFF and the T2 value of water (T2w ) was calculated. The implications of the T2 correction were investigated by studying the age dependence of the T2 -weighted fat fractions and the PDFF. Compared with the PDFF, all T2 -weighted fat fractions significantly overestimated the fat fraction. Compared with the age dependence of the PDFF, the age dependence of the T2 -weighted fat fraction showed an increased slope and intercept as TE increased for women and a strongly increased intercept as TE increased for men. For women, a negative association between the T2 value of bone marrow water and PDFF was found. Single-voxel MRS-based vertebral bone marrow fat quantification should be based on a multi-TE MRS measurement to minimize confounding effects on PDFF determination, and also to allow the simultaneous calculation of T2w , which might be considered as an additional parameter sensitive to the composition of the water compartment.

Whole spine vertebral bone marrow fat could be reproducibly assessed by using chemical shift-encoding based water-fat MRI and showed anatomical variations.

Objective The goal of this study was to compare the semi-quantitative Goutallier classification for fat infiltration with quantitative fat-fraction derived from a magnetic resonance imaging (MRI) chemical shift-based water/fat separation technique. Methods Sixty-two women (age 61±6 years), 27 of whom had diabetes, underwent MRI of the calf using a T1-weighted fast spin-echo sequence and a six-echo spoiled gradient-echo sequence at 3 T. Water/fat images and fat fraction maps were reconstructed using the IDEAL algorithm with T2* correction and a multi-peak model for the fat spectrum. Two radiologists scored fat infiltration on the T1-weighted images using the Goutallier classification in six muscle compartments. Spearman correlations between the Goutallier grades and the fat fraction were calculated; in addition, intra-observer and inter-observer agreement were calculated. Results A significant correlation between the clinical grading and the fat fraction values was found for all muscle compartments (P<0.0001, R values ranging from 0.79 to 0.88). Goutallier grades 0–4 had a fat fraction ranging from 3.5 to 19%. Intra-observer and inter-observer agreement values of 0.83 and 0.81 were calculated for the semi-quantitative grading. Conclusion Semi-quantitative grading of intramuscular fat and quantitative fat fraction were significantly correlated and both techniques had excellent reproducibility. However, the clinical grading was found to overestimate muscle fat.

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