Associations of incidental vertebral fractures and longitudinal changes of MR-based proton density fat fraction and T2* measurements of vertebral bone marrow.

Background: Quantitative magnetic resonance imaging (MRI) techniques such as chemical shift encoding-based water-fat separation techniques (CSE-MRI) are increasingly applied as noninvasive biomarkers to assess the biochemical composition of vertebrae. This study aims to investigate the longitudinal change of proton density fat fraction (PDFF) and T2* derived from CSE-MRI of the thoracolumbar vertebral bone marrow in patients that develop incidental vertebral compression fractures (VCFs), and whether PDFF and T2* enable the prediction of an incidental VCF.

Methods: In this study we included 48 patients with CT-derived bone mineral density (BMD) measurements at baseline. Patients that presented an incidental VCF at follow up (=12, mean age 70.5 ± 7.4 years, 5 female) were compared to controls without incidental VCF at follow up (=36, mean age 71.1 ± 8.6 years, 15 females). All patients underwent 3T MRI, containing a significant part of the thoracolumbar spine (Th11-L4), at baseline, 6-month and 12 month follow up, including a gradient echo sequence for chemical shift encoding-based water-fat separation, from which PDFF and T2* maps were obtained. Associations between changes in PDFF, T2* and BMD measurements over 12 months and the group (incidental VCF vs. no VCF) were assessed using multivariable regression models. Mixed-effect regression models were used to test if there is a difference in the rate of change in PDFF, T2* and BMD between patients with and without incidental VCF.

Results: Prior to the occurrence of an incidental VCF, PDFF in vertebrae increased in the VCF group (Δ=6.3 ± 3.1%) and was significantly higher than the change of PDFF in the group without VCF (Δ=2.1 ± 2.5%, =0.03). There was no significant change in T2* (Δ=1.7 ± 1.1ms vs. Δ=1.1 ± 1.3ms, =0.31) and BMD (Δ=-1.2 ± 11.3mg/cm vs. Δ=-11.4 ± 24.1mg/cm, = 0.37) between the two groups over 12 months. At baseline, no significant differences were detected in the average PDFF, T2* and BMD of all measured vertebrae (Th11-L4) between the VCF group and the group without VCF (=0.66, P=0.35 and = 0.21, respectively). When assessing the differences in rates of change, there was a significant change in slope for PDFF (2.32 per 6 months, 95% confidence interval (CI) 0.31-4.32; P=0.03) but not for T2* (0.02 per 6 months, CI -0.98-0.95; P=0.90) or BMD (-4.84 per 6 months, CI -23.4-13.7; P=0.60).

Conclusions: In our study population, the average change of PDFF over 12 months is significantly higher in patients that develop incidental fractures at 12-month follow up compared to patients without incidental VCF, while T2* and BMD show no significant changes prior to the occurrence of the incidental vertebral fractures. Therefore, a longitudinal increase in bone marrow PDFF may be predictive for vertebral compression fractures.