Bone strength is characterised by bone mineral density (BMD) and bone quality. While cohort studies have found an increased risk of bone fractures in patients with type 2 diabetes, type 2 diabetics do not appear to have lower BMD than non-diabetics.¹ The current gold standard for measuring areal BMD is Dual-energy X-ray Absorptiometry (DXA); being a projection method, cortical and trabecular bone are not differentiated nor is bone quality assessed. Three-dimensional imaging methods are needed in order to determine whether volumetric BMD (vBMD) or bone quality may be a potential biomarker for diabetes risk. The purpose of this work is to assess the feasibility of utilising proximal femur cortical bone quality obtained from quantitative imaging as a biomarker for diabetes risk in post-menopausal Chinese-Singaporean (C-S) women.

100 post-menopausal C-S women will be recruited for this ongoing study. The non-dominant proximal femur of each subject is assessed for vBMD with quantitative CT (QCT, Siemens Biograph mCT) and T1 weighted in-phase gradient echo (T1-VIBE-DIXON) MRI sequence (Siemens Prisma, 18-channel body array coil), and cortical bone porosity with an MRI ultrashort echo-time (UTE) sequence; see Table 1 for imaging parameters.

QCT images are converted to dipotassium phosphate (K₂HPO₄) equivalent densities using a commercial calibration phantom (Mindways QCT Pro) and the region of maximum cortical thickness in the field of view, found distally from the junction of the lesser trochanter and femoral shaft, are determined from images segmented for cortical bone (threshold > 350 mg/cc). The total effective dose is kept below 2 mSv for each subject.

MRI vBMD is quantified using a T1-VIBE-DIXON MRI sequence with two external calibration references (oil; 400 mg/cc calcium hydroxyapatite (CaHA) in H₂O). CaHA equivalent BMDs are estimated from the signal relationship and known concentration of CaHA in the calibration references ², for the volume of interest (VOI) determined on QCT.

Bone water concentration (BWC, shown to be a surrogate to cortical bone porosity ¹) is quantified using a coronal UTE sequence (10,000 radial spokes) and an external reference (10% H₂O in D₂O doped with MAGNEVIST^®). The transverse relaxation time (T2*) is determined by fitting a mono-exponential curve to images with TE<1.0 ms for all voxels within the VOI determined on QCT. BWC is calculated using the method previously described ³; J-modulation is included in the fitting model ⁴.

For the eight subjects analysed to date (age range 50-67 years; mean age 58.6 years), the mean T2* of cortical bone was found to be 583 ± 22 µs and the mean BWC 16.9 ± 3.6 % at the region of greatest cortical thickness. As would be expected, a negative correlation between BWC calculated from MRI and vBMD from QCT is shown in Table 2; this correlation is not significant (p>0.1).

The absolute vBMDs for each imaging modality are not comparable as they are equivalent to materials with different inherent densities. However, a significant (p<0.01) positive correlation between vBMD derived from MRI and QCT for the region of maximum cortical thickness is shown in Table 2.

The T2* of cortical bone was consistent with that found in literature, however, the resultant BWC matched that expected for pre-menopausal women ²; the correlation with QCT vBMD was not significant (p>0.1). Radiofrequency inhomogeneity across the imaging volume and depth-dependent receive-coil sensitivity could be causing signal variations between the external reference and the deep-lying cortical bone resulting in the discrepancies seen. The use of an internal reference standard to calibrate to an external reference of known composition should be investigated.

MRI vBMD significantly positively correlates with QCT vBMD (p<0.01) in the region of maximum cortical thickness in the proximal femur. This correlation suggests that the previously reported signal model ², used for calculating MRI vBMD, is appropriate.

While initial results indicate that MRI derived cortical bone vBMD has the potential to be used in the assessment of bone quality, more extensive evaluation to determine the method’s clinical potential in the early identification of diabetes risk is needed. Other questions of particular clinical interest would be whether MRI vBMD is associated with fracture risk, whether it is sensitive to changes due to dietary or drug intervention and whether there is the potential to use this low ionising radiation method for greater population screening.