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Review
. 2023 Oct 7;13(10):1056.
doi: 10.3390/metabo13101056.

Understanding the Consequences of Fatty Bone and Fatty Muscle: How the Osteosarcopenic Adiposity Phenotype Uncovers the Deterioration of Body Composition

Kelsey Hu  1 , Elizabeth Deya Edelen  1 , Wenqing Zhuo  1 , Aliya Khan  1 , Josselyne Orbegoso  1 , Lindsey Greenfield  1 , Berna Rahi  2 , Michael Griffin  1 , Jasminka Z Ilich  3 , Owen J Kelly  1
Affiliations
Review

Understanding the Consequences of Fatty Bone and Fatty Muscle: How the Osteosarcopenic Adiposity Phenotype Uncovers the Deterioration of Body Composition

Kelsey Hu et al. Metabolites. .

Abstract

Adiposity is central to aging and several chronic diseases. Adiposity encompasses not just the excess adipose tissue but also body fat redistribution, fat infiltration, hypertrophy of adipocytes, and the shifting of mesenchymal stem cell commitment to adipogenesis. Bone marrow adipose tissue expansion, inflammatory adipokines, and adipocyte-derived extracellular vesicles are central to the development of osteopenic adiposity. Adipose tissue infiltration and local adipogenesis within the muscle are critical in developing sarcopenic adiposity and subsequent poorer functional outcomes. Ultimately, osteosarcopenic adiposity syndrome is the result of all the processes noted above: fat infiltration and adipocyte expansion and redistribution within the bone, muscle, and adipose tissues, resulting in bone loss, muscle mass/strength loss, deteriorated adipose tissue, and subsequent functional decline. Increased fat tissue, typically referred to as obesity and expressed by body mass index (the latter often used inadequately), is now occurring in younger age groups, suggesting people will live longer with the negative effects of adiposity. This review discusses the role of adiposity in the deterioration of bone and muscle, as well as adipose tissue itself. It reveals how considering and including adiposity in the definition and diagnosis of osteopenic adiposity, sarcopenic adiposity, and osteosarcopenic adiposity will help in better understanding the pathophysiology of each and accelerate possible therapies and prevention approaches for both relatively healthy individuals or those with chronic disease.

Keywords: adiposity; fat infiltration; obesity; osteopenic adiposity; osteoporosis; osteosarcopenic adiposity; osteosarcopenic obesity; sarcopenia; sarcopenic adiposity.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The transformation of adipose tissue to adipocytic adipose tissue. This figure summarizes how healthy adipose tissue develops into adipocytic adipose tissue. Abbreviations: (↓ = decreased; ↑ = increased; IL-6 = interleukin 6; IL-1 = interleukin 1; GH/IGF-1 axis = growth hormone/insulin-like growth factor-1 axis; Ebf1 = early B-cell factor 1; TNF-α = tumor necrosis factor-alpha; miRNA = micro RNA; MSC = mesenchymal stem cell. Created with BioRender.com.
Figure 2
Figure 2
Osteopenic adiposity syndrome. This figure summarizes how healthy bone develops into osteopenic adiposity syndrome. Increased BMAT and fat infiltration are represented by yellow circles within the bone. Abbreviations: (↓ = decreased; ↑ = increased; BMSC = bone marrow stem cell; GLP-1 = glucagon-like peptide-1; GH/IGF-1 axis = growth hormone/insulin-like growth factor-1 axis; Ebf1 = early B-cell factor 1; RANKL = receptor activator of NF-κB (RANK) ligand; TNF-α = tumor necrosis factor-alpha; IL-6 = interleukin 6; BMAT = bone marrow adipose tissue; miRNA = micro RNA. Created with BioRender.com.
Figure 3
Figure 3
Proposed developmental stages of sarcopenic adiposity. This figure summarizes the concept that fat infiltration into muscle, in combination with muscle mass loss, accounts for the physical and clinical outcomes observed in sarcopenic adiposity. The greater the combined increase in adiposity and decrease in muscle mass, the worse the outcomes. Created with BioRender.com.
Figure 4
Figure 4
Sarcopenic adiposity syndrome. This figure summarizes how healthy muscle develops into sarcopenic adiposity syndrome. Increased fat infiltration, reduced type 2 fibers, and less innervation of motor neurons. Abbreviations: (↓ = decreased; ↑ = increased; IL-6 = interleukin 6; IL-8 = interleukin 8; IL-10 = interleukin 10; IL-15 = interleukin 15; BDNF = brain-derived neurotrophic factor; LIF = leukemia inhibitory factor; FL-1 = follistatin-like 1; FGF-21 = fibroblast growth factor-21; IL1-RA = interleukin-1 receptor antagonist protein; TNF I = tumor necrosis factor I; TNF II = tumor necrosis factor II; Pax7 = Paired Box 7; MyoD = myoblast determination protein 1; GH/IGF-1 axis = growth hormone/insulin-like growth factor-1 axis; TNF-α = tumor necrosis factor-alpha; miRNA = micro RNA; MSC = mesenchymal stem cell.
Figure 5
Figure 5
Clinical manifestations of adiposity in bone and fat. The presence of fat in bone and muscle is a key contributor to the pathophysiology and clinical diagnoses of low bone and fat mass and excess fat mass. This new model places adiposity at the center of osteopenic adiposity, sarcopenic adiposity, and osteosarcopenic adiposity. There is the possibility that adiposity, osteoporosis, sarcopenia, and osteosarcopenia can exist independently; therefore, these are also represented. These may also develop into OA, SA, or OSA. Created with BioRender.com Abbreviations: (↓ = decreased; ↑ = increased; Ebf1 = early B-cell factor 1; BMAT = bone marrow adipose tissue. Created with BioRender.com.
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