Gender- and Age-Associated Differences in Bone Marrow Adipose Tissue and Bone Marrow Fat Unsaturation Throughout the Skeleton, Quantified Using Chemical Shift Encoding-Based Water–Fat MRI

Abstract

Bone marrow adipose tissue (BMAT) is a dynamic tissue which is associated with osteoporosis, bone metastasis, and primary bone tumors. The aim of this study is to determine region-specific variations and age- and gender-specific differences in BMAT and BMAT composition in healthy subjects. In this cross-sectional study, we included 40 healthy subjects (26 male: mean age 49 years, range 22–75 years; 14 female: mean age 50 years, range 29–71) and determined the bone marrow signal fat fraction and bone marrow unsaturation in the spine (C3-L5), pelvis, femora, and tibiae using chemical shift encoding-based water–fat imaging (WFI) with multiple gradient echoes (mGRE). Regions of interest covered the individual vertebral bodies, pelvis and proximal epimetaphysis, diaphysis, and distal epimetaphysis of the femur and tibia. The spinal fat fraction increased from cervical to lumbar vertebral bodies (mean fat fraction ( ± SD or (IQR): cervical spine 0.37 ± 0.1; thoracic spine 0.41 ± 0.08. lumbar spine 0.46 ± 0.01; p < 0.001). The femoral fat fraction increased from proximal to distal (proximal 0.78 ± 0.09; diaphysis 0.86 (0.15); distal 0.93 ± 0.02; p < 0.001), while within the tibia the fat fraction decreased from proximal to distal (proximal 0.92 ± 0.01; diaphysis 0.91 (0.02); distal 0.90 ± 0.01; p < 0.001). In female subjects, age was associated with fat fraction in the spine, pelvis, and proximal femur (ρ = 0.88 p < 0.001; ρ = 0.87 p < 0.001; ρ = 0.63 p = 0.02; ρ = 0.74 p = 0.002, respectively), while in male subjects age was only associated with spinal fat fraction (ρ = 0.40 p = 0.04). Fat fraction and unsaturation were negatively associated within the spine (r = -0.40 p = 0.01), while in the extremities fat fraction and unsaturation were positively associated (distal femur: r = 0.42 p = 0.01; proximal tibia: r = 0.47, p = 0.002; distal tibia: r = 0.35 p = 0.03), both independent of age and gender. In conclusion, we confirm the distinct, age- and gender-dependent, distribution of BMAT throughout the human skeleton and we show that, contradicting previous animal studies, bone marrow unsaturation in human subjects is highest within the axial skeleton compared to the appendicular skeleton. Furthermore, we show that BMAT unsaturation was negatively correlated with BMAT within the spine, while in the appendicular skeleton, BMAT and BMAT unsaturation were positively associated.

Raman microspectroscopy reveals unsaturation heterogeneity at the lipid droplet level and validates anin vitromodel of bone marrow adipocyte subtypes

“…The largest difference between FA species in the regulated versus constitutive marrow sites was seen in the 18:1 to 18:0 unsaturation ratio (4.40 versus 7.91, p=0.007), and the 16:1 versus 16:0 unsaturation ratio (0.11 versus 0.19, p=0.031) (Figure 7B-C). We thus conclude that human BM samples from a rBMAd-rich site in the context of BM remodeling driven by hematopoietic demand present a lower unsaturation ratio, as measured by 16:1/16:0 -and 18:1/18:0-FA content, than samples obtained from a cBMAd-rich site, which complements previously reported results for rabbit and rats marrow at steady-state (1,33–35) as summarized in Table 1.…”

“…In recent years, primary rat cBMAds from tail vertebrae and distal tibia were likewise shown to contain a higher proportion of unsaturated fatty acids in caudal vertebrae or distal tibia as compared to rat rBMAds isolated from either lumbar vertebrae or femur plus proximal tibia combined (1). Congruently MRI, 1 H-MRS, and gas chromatographic data from human subjects consistently showed that BM adipose tissue (BMAT) from sites of red marrow contained highly saturated lipids, compared to the mostly unsaturated lipids detected at yellow marrow sites (1, 33–35). From murine samples, it is considerably more challenging to obtain sufficient BMAT for analysis due to the size of the animal as well as the amount of BMAT present in the bones (32).…”

“…Additional measurements in human BM have been made by MRI spectroscopy but cannot be compiled with these data due to the different methodology(35,64). c: constitutive, r: regulated.…”

Association between osteoporosis and bone metastasis of lung cancer based on opportunistic screening by low-dose computer tomography: a retrospective cohort study

“…Beekman et al (27) studied the sex differences in bone marrow fat and found that age was significantly associated with spinal bone marrow fat only in men. Bone marrow adipocytes are a tissue associated with a variety of skeletal diseases, such as osteoporosis and bone metastases.…”

The Sexual Dimorphism of Human Adipose Depots

“…With age, in both men and women, the ratio of VAT over SAT increases with the accumulation of VAT [ 21 ]. Aging is also associated with an accumulation of bone marrow AT [ 22 ] with a reversion of sex differences and discrete age- and gender-specificity according to bone location [ 23 ].…”