Mechanisms Underlying Bone Loss Associated with Gut Inflammation

Abstract

Patients with gastrointestinal diseases frequently suffer from skeletal abnormality, characterized by reduced bone mineral density, increased fracture risk, and/or joint inflammation. This pathological process is characterized by altered immune cell activity and elevated inflammatory cytokines in the bone marrow microenvironment due to disrupted gut immune response. Gastrointestinal disease is recognized as an immune malfunction driven by multiple factors, including cytokines and signaling molecules. However, the mechanism by which intestinal inflammation magnified by gut-residing actors stimulates bone loss remains to be elucidated. In this article, we discuss the main risk factors potentially contributing to intestinal disease-associated bone loss, and summarize current animal models, illustrating gut-bone axis to bridge the gap between intestinal inflammation and skeletal disease.

Gut microbiome depletion and repetitive mild traumatic brain injury differentially modify bone development in male and female adolescent rats

“…Given that adolescence is a critical period in gut microbiota and skeletal bone growth, it was not surprising that microbiome depletion reduced femur growth in adolescent males that experienced either sham or RmTBIs. There are numerous mechanisms by which the microbiome has been postulated to regulate bone growth including, the SCFA regulation of Insulin Growth Factor-1 (IGF-1) ( Medina-Gomez, 2018 ), production of pro- and anti-inflammatory cytokines (IL-6, IL-1β, TNF-α) ( Hernandez et al, 2016 ) and sex hormones ( Imai et al, 2009 ), regulation of immune cells (T-cells and dendritic cells) ( Ke et al, 2019 ), and importantly nutrient absorption ( Chen et al, 2017 ). For example, gut dysbiosis is not only involved in proinflammatory cytokine production, which reduces calcium absorption ( Ding et al, 2020 ), but also the activation of CD4 + T cells, both of which stimulate of NF-kβ ligands and bone resorption, thereby altering bone growth ( Hernandez et al, 2016 ; Li et al, 2007 ; Cho et al, 2012 ).…”

Heat-Killed Lacticaseibacillus paracasei GMNL-653 Exerts Antiosteoporotic Effects by Restoring the Gut Microbiota Dysbiosis in Ovariectomized Mice

“…Gut dysbiosis is associated with many diseases, including metabolic liver diseases, cardiometabolic diseases, obesity, and type 2 diabetes (1). Moreover, studies and emerging evidence have indicated that dysregulated gut microbiota correlate with decreased bone density, and inflammatory bowel disease (IBD) (3)(4)(5). A close relationship between bone health and gut microbiota exist that may involve in calcium absorption, bone mineralization, and immune signaling (6,7).…”

Denosumab Regulates Gut Microbiota Composition and Cytokines in Dinitrobenzene Sulfonic Acid (DNBS)-Experimental Colitis

“…While RANKL has been shown to play a major role in the development of osteoporosis by promoting excessive osteoclastogenesis, its role in the development of CD is not clear. Due to the role played by the RANK/RANKL axis in the pro-inflammatory pathway of the immune system, it is expected that this pathway could also contribute to the regulation of CD ( Ke et al, 2019 ).…”