Bone marrow fat content in 70 adolescent girls with anorexia nervosa: Magnetic resonance imaging and magnetic resonance spectroscopy assessment

Abstract

Background: Adolescents and women with anorexia nervosa have increased bone marrow fat and decreased bone formation, at least in part due to hormonal changes leading to preferential stem cell differentiation to adipocytes over osteoblasts.

Objective: The purpose of this study was to evaluate marrow fat content and correlate with age and disease severity using knee MRI with T1 relaxometry (T1-R) and MR spectroscopy (MRS) in 70 adolescents with anorexia nervosa.

Materials and methods: We enrolled 70 girls with anorexia nervosa who underwent 3-T knee MRI with coronal T1-W images, T1-R and single-voxel proton MRS at 30 and 60 ms TE. Metaphyses were scored visually on the T1-W images for red marrow. Visual T1 score, T1 relaxometry values, MRS lipid indices and fat fractions were analyzed by regression on age, body mass index (BMI) and bone mineral density (BMD) as disease severity markers. MRS measures included unsaturated fat index, T2 water, unsaturated and saturated fat fractions.

Results: All red marrow measures declined significantly with age. T1-R values were associated negatively with BMI and BMD for girls ≤16 years (P=0.03 and P=0.002, respectively) and positively for those≥17 years (P=0.05 and P=0.003, respectively). MRS identified a strong inverse association between T2 water and saturated fat fraction from 60 ms TE data (r=-0.85, P<0.0001). There was no association between unsaturated fat index and BMI or BMD.

Conclusions: The association between T1 and BMI and BMD among older girls suggests more marrow fat in those with severe anorexia nervosa. In contrast, the physiological association between marrow fat content and age remained dominant in younger patients. The strong association between T2 water and saturated fat may relate to the restricted mobility of water with increasing marrow fat.

Keywords: Adolescents; Anorexia nervosa; Bone marrow; Fat; Magnetic resonance imaging; Magnetic resonance spectroscopy.

Conflict of interest statement

Compliance with ethical standards: Conflicts of interest: None.

Figures

Fig. 1

Qualitative bone marrow scoring system on coronal T1-weighted images. 0=homogeneous hyperintensity, no red marrow (a). 1=few hypointense striations (arrow), mild red marrow (b). 2=scattered hypointense areas, moderate red marrow (c). 3=more diffuse hypointense regions, extensive red marrow (d). Marrow patterns (c) and (d) are expected in similarly aged healthy girls, as we determined in our original study comparing girls with anorexia nervosa to those with age-matched control subjects [29]

Fig. 2

T1 map obtained from the variable repetition time spin-lattice (T1) relaxometry acquisition in a 14-year-old girl. For calculation of T1 values, 25 mm2 regions of interest were placed on the T1 maps in the medial and lateral distal femoral metaphyses

Fig. 3

MR spectroscopy in the same 14-year-old girl as in Fig. 2. Manually phased spectral fits from the medial distal femoral metaphysis at echo times 30 ms (left) and 60 ms (right). Saturated methylene represents the largest peak (lipid 2) while the unsaturated olefinic peak is the smaller, left-most peak (lipid 5). Water is to the right of and larger than the olefinic peak in this case. Inserts show coronal and axial localizer images used to position the spectroscopy voxels

Fig. 4

The relationship of marrow relaxometry T1 value to body mass index (BMI) (a) and bone mineral density (BMD) (b), analyzed by multiple linear regression with effect modification by age. Age was modeled as a continuous variable; displayed lines correspond to subjects at selected ages near the sample minimum (12 years, ⋯⋯), median (15 years, – - - -), and maximum (19 years, ───). Association of T1 with BMI and BMD was negative at the youngest ages (P=0.03 and P=0.002, respectively) and changed significantly toward positive association with increasing age (P=0.05 and P=0.003 for age interaction, respectively)

Fig. 5

The relationship of bone mineral density (BMD) to bone marrow saturated fat fraction (Rsat, in a) and unsaturated fat fraction (Runsat, in b) is analyzed by multiple linear regression with effect modification by skeletal maturity. Association of Rsat and Runsat with BMD differed among subjects with open physes (○⋯⋯), subjects with open femoral but closed tibial physes (Δ - - - - -), and subjects with both physes closed (■ ───); P=0.02 and P=0.01 for BMD × closure interaction effect on Rsat and Runsat, respectively

Fig. 6

Marrow T2 of water was inversely related to skeletal maturity as indicated by physeal closure (a) (P<0.0001 by one-way analysis of variance), as well as age (b) (−2.48 ± 0.55 ms/yr, linear regression coefficient ± standard error, P<0.0001). Box plots (a) summarize the distribution of T2 for each category of physeal closure. Cross (+) indicates the mean; center line the median; top and bottom the interquartile range (IQR). Vertical lines extend to the farthest data point within 1.5 × IQR above or below the box. Data points farther than 1.5 × IQR from the box are considered outliers (●). Fitted line (b) from simple regression analysis