<b>Bone Marrow Fat and Bone Mineral Density on Proton MR Spectroscopy and Dual-Energy X-Ray Absorptiometry:</b>Their Ratio as a New Indicator of Bone Weakening

Schellinger, Dieter; Lin, Chin-Shoou; Lim, Jong Youb; Hatipoğlu, Hatice Gül; Pezzullo, J C; Singer, Andrea

doi:10.2214/ajr.183.6.01831761

Cited by 125 publications

(86 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…A closer examination of these sections reveals a near absence of fat accumulation in the bone marrow of WT mice (insets on the left side of each panel) but an age-related increase in bone marrow fat content in KO mice (3 months, 8.8 Ϯ 2.4; 1 year, 17.5 Ϯ 2.6; and 2 years, 31.8 Ϯ 2.6 adipocytes/0.50 mm 2 , 3 months versus 1 year, P Ͻ 0.05; 1 year versus 2 years, P Ͻ 0.01; 3 months versus 2 years, P Ͻ 0.001). In general, there is an inverse relationship between BMD and bone marrow fat, 29 and we observe an age-related decrease in the BMD of KO mice. These findings raise the possibility that osteoblasts are being replaced with adipocytes in the bone marrow of iPLA 2 ␤-null mice.…”

Section: Fat Accumulates In Bone Marrow Of Ko Mice With Agementioning

confidence: 53%

Age-Related Changes in Bone Morphology Are Accelerated in Group VIA Phospholipase A2 (iPLA2β)-Null Mice

Ramanadham

Yarasheski

Silva

et al. 2008

The American Journal of Pathology

View full text Add to dashboard Cite

Phospholipases A 2 (PLA 2 ) hydrolyze the sn؊2 fatty acid substituent, such as arachidonic acid, from phospholipids, and arachidonate metabolites are recognized mediators of bone modeling. We have previously generated knockout (KO) mice lacking the group VIA PLA 2 (iPLA 2 ␤), which participates in a variety of signaling events; iPLA 2 ␤ mRNA is expressed in bones of wild-type (WT) but not KO mice. Cortical bone size, trabecular bone volume, bone mineralizing surfaces, and bone strength are similar in WT and KO mice at 3 months and decline with age in both groups, but the decreases are more pronounced in KO mice. The lower bone mass phenotype observed in KO mice is not associated with an increase in osteoclast abundance/activity or a decrease in osteoblast density, but is accompanied by an increase in bone marrow fat. Relative to WT mice, undifferentiated bone marrow stromal cells (BMSCs) from KO mice express higher levels of PPAR-␥ and lower levels of Runx2 mRNA, and this correlates with increased adipogenesis and decreased osteogenesis in BMSCs from these mice. In summary, our studies indicate that age-related losses in bone mass and strength are accelerated in iPLA 2 ␤-null mice. Because adipocytes and osteoblasts share a common mesenchymal stem cell origin, our findings suggest that absence of iPLA 2 Bioactive arachidonic acid (AA) metabolites (eicosanoids) generated by the actions of various oxygenases, such as the 5-lipoxygenase (5-LO) and cyclooxygenase (COX) isozymes, are important mediators of bone remodeling. The 5-LO products leukotrienes and 5-HETE (hydroxyeicosatetraenoic acid) function as negative modulators of bone formation by inhibiting osteoblast differentiation and bone formation.1 In contrast, prostaglandins (PGs), eg, PGE 2 , derived from COX metabolism of AA enhance bone formation and mass by increasing osteoblast replication and differentiation and/or by inhibiting osteoclastic resorption, [2][3][4][5]

show abstract

Section: Fat Accumulates In Bone Marrow Of Ko Mice With Agementioning

confidence: 53%

Age-Related Changes in Bone Morphology Are Accelerated in Group VIA Phospholipase A2 (iPLA2β)-Null Mice

Ramanadham

Yarasheski

Silva

et al. 2008

The American Journal of Pathology

View full text Add to dashboard Cite

show abstract

“…We suggest the following explanation. In addition to the normal agerelated increase in lipid of 7% per decade (9), the reference vertebrae themselves may become significantly changed as a result of different conditions, such as bone weakness and osteoporosis (10). This results in an additional lipid increase.…”

Section: Discussionmentioning

confidence: 99%

Vertebrae adjacent to spinal bone lesion are inconsistent reference markers: A magnetic resonance spectroscopic viewpoint

Rumpel

Chan

et al. 2006

Magnetic Resonance Imaging

View full text Add to dashboard Cite

Purpose:To ascertain the suitability of vertebrae adjacent to spinal bone lesions as a signal intensity reference on MRI, and compare the MR spectroscopic appearance of vertebral body compression fractures due to malignant tumor infiltration, bone weakening (e.g., osteoporosis), and/or minor trauma. Materials and Methods:Twenty-five patients with spinal compression fractures underwent routine spinal MRI with an additional 1 H MRS study protocol to assess the percent fat fraction of the compressed vertebrae as well as the adjacent bony environment. Peak areas for water and total lipid were calculated from short-TE single-voxel 1 H MR spectra using the LCModel analyzing tool.Results: There were consistent water-only patterns in the fractured vertebra suggesting either near complete marrow replacement by malignant tissue or local edematous fluid/ hemorrhage within the marrow spaces. However, the adjacent vertebrae showed a wide range of patterns from a dominant lipid signal to the inverse of a pronounced water level. These results far exceed the normal variation expected based on age and sex. Conclusion:The results suggest that the adjacent vertebrae may not be an accurate reference, especially in diffusion-weighted imaging (DWI), because of the large difference between the two compartments. Furthermore, in the case of gradient-echo measurements, the in-phase vs. opposed-phase effects are significant. MR IMAGES OF SPINAL VERTEBRAE reflect signals from red marrow and yellow marrow (i.e., water and lipid protons, respectively) (1). Although they are separable in MR spectroscopic techniques, in MRI the two signals become mixed within pixels. Nevertheless, the relative water/lipid composition at a location in an image can be unraveled by the use of a number of contrast-weighted techniques (1). Interpreting MR images involves making decisions as to whether regions of interest (ROIs) are hypo-, iso-, or hyperintense, which requires the use of a reference region in the same image for distinction. One can usually make an unambiguous distinction if the reference is consistent. In the case of vertebral MRI, however, it is difficult to separate lesions based on relative signal intensities (or contrast) because the reference is a priori unknown (i.e., the relative water and lipid content of the "reference" bone marrow (adjacent vertebra) is variable). This is especially true for diffusion-weighted imaging (DWI) because an unknown lipid content will affect the image intensity, which serves as the reference. The discrepancy between DWI (which depends on a reference signal) vs. the apparent diffusion coefficient (ADC) (which focuses on the lesion only) has been highlighted in a few reports (2-4). Zhou et al (2) showed that although DWI alone did not allow discrimination between benign osteoporotic fractures and pathologic malignant vertebral fractures, an ADC analysis of these lesions resulted in an improved distinction between the two pathologies. In response to Ref. 2, Mulkern and Schwartz (5) emphasized the dependency of the A...

show abstract

“…Bone marrow fat negatively affects the biomechanical strength of bone as fatty marrow is a weaker biomechanical support medium than hematopoietic marrow. Higher vertebral marrow fat content has been found in subjects with morphologic evidence of bone weakness, such as endplate depression, or compression fractures, and age-related bone loss is associated with progressive infiltration of bone marrow by fat [2,3].…”

mentioning

confidence: 99%

“…1H-MRS allows true quantification of bone marrow fat of the entire skeleton by calculating the lipid-towater ratio of spectra. Studies have shown that bone marrow fat content measured by 1H-MRS in combination with BMD is of significance in evaluating skeletal integrity, more valuable than either parameter alone [3,13]. Therefore, 1H-MRS could potentially be used as a powerful extension of diagnostic MRI.…”

mentioning

confidence: 99%

Perspective: the bone-fat connection

Bredella

2010

Skeletal Radiol

View full text Add to dashboard Cite

Bone Marrow Fat and Bone Mineral Density on Proton MR Spectroscopy and Dual-Energy X-Ray Absorptiometry:Their Ratio as a New Indicator of Bone Weakening

Abstract: An inverse relationship between bone marrow fat and BMD could not be confirmed. Bone marrow fat can be used to diagnose reduced bone strength nearly as well as BMD. The bone marrow fat/BMD ratio is a significant diagnostic indicator of bone weakening.

Cited by 125 publications

References 28 publications

Age-Related Changes in Bone Morphology Are Accelerated in Group VIA Phospholipase A2 (iPLA2β)-Null Mice

Age-Related Changes in Bone Morphology Are Accelerated in Group VIA Phospholipase A2 (iPLA2β)-Null Mice

Vertebrae adjacent to spinal bone lesion are inconsistent reference markers: A magnetic resonance spectroscopic viewpoint

Perspective: the bone-fat connection

Contact Info

Product

Resources

About