The Effect of Inflammation on Bone

Abstract

Bone remodeling is the continual process to renew the adult skeleton through the sequential action of osteoblasts and osteoclasts. Nuclear factor RANK, an osteoclast receptor, and its ligand RANKL, expressed on the surface of osteoblasts, result in coordinated control of bone remodeling. Inflammation, a feature of illness and injury, plays a distinct role in skewing this process toward resorption. It does so via the interaction of inflammatory mediators and their related peptides with osteoblasts and osteoclasts, as well as other immune cells, to alter the expression of RANK and RANKL. Such chemical mediators include TNFα, glucocorticoids, histamine, bradykinin, PGE2, systemic RANKL from immune cells, and interleukins 1 and 6. Conditions, such as periodontal disease and alveolar bone erosion, aseptic prosthetic loosening, rheumatoid arthritis, and some sports related injuries are characterized by the result of this process. A thorough understanding of bone response to injury and disease, and ability to detect such biomarkers, as well as imaging to identify early structural and mechanical property changes in bone architecture, is important in improving management and outcomes of bone related pathology. While gut health and vitamin and mineral availability appear vitally important, nutraceuticals also have an impact on bone health. To date most pharmaceutical intervention targets inflammatory cytokines, although strategies to favorably alter inflammation induced bone pathology are currently limited. Further research is required in this field to advance early detection and treatments.

Endogenous Glucocorticoid Metabolism in Bone: Friend or Foe

“…Given the potent suppression of bone formation by therapeutic GCs, and the efficacy of transgenic deletion of 11b-HSD1 in preventing this, it could be predicted that inhibition of 11b-HSD1 in patients with chronic inflammation and receiving therapeutic GCs might have a similar protection from their anti-anabolic actions in osteoblasts and osteocytes (99). However, considering the exacerbation of inflammation in response to 11b-HSD1 deletion it may be that the inflammatory suppression of bone formation is increased and coupled with a shift towards increased pro-inflammatory factors by osteoblasts, such as RANKL, TNFa and IL-6 by osteoblasts that would favour osteoclast mediated bone resorption and bone loss (9,26,104,105). Further considerations should include the lesser role of dysregulated bone formation in acute inflammatory bone loss where osteoclast mediated bone resorption has been shown to play a greater role (106)(107)(108).…”

“…targeted deletion of 11b-HSD1, revealing a critical role for local GC activation by this enzyme in suppressing osteoclast numbers and activity in chronic inflammation. Whether these effects reflect a direct autocrine effect of GC activation by 11b-HSD1 within the osteoclast, or instead reflect wider changes in proinflammatory factors such as RANKL, TNFa and IL-6 that drive osteoclast driven bone resorption has yet to be determined (26,104,105). 11b-HSD1 has been shown to influence the RANKL/ OPG ratio in murine models of inflammation and this could play a role in regulating inflammatory bone resorption (81).…”

Lupin-Derived Bioactive Peptides: Intestinal Transport, Bioavailability and Health Benefits

“…As an inducer of inflammation, LPS also increases the gene expression of nuclear factor kappa B (NF-ĸB) which promotes the gene expression and production of inflammatory cytokines (TNF-α, IL-1β, and IL-6), leading to monocyte activation and the consequent induction of osteoclastogenesis (OG-differentiation of osteoclasts), a condition that increases bone resorption, osteoporosis, and other bone diseases [ 102 , 103 ]. This occurs through elevated expression of cytokines such as receptor activator for nuclear factor-κB (RANK) ligand (RANKL) and macrophage colony-stimulating factor (M-CSF)-induced downregulation of expression of osteoprotegerin, a protein known to protect the bones by suppresses the RANKL’s ability to induce OG and survival of bone-resorbing osteoclasts [ 104 , 105 ].…”

New Insights to the Crosstalk between Vascular and Bone Tissue in Chronic Kidney Disease–Mineral and Bone Disorder

“…Historically, the bone disease in CKD has been attributed to the disturbances in PTH and 1,25 vitamin D activity. However, research is identifying more and more bone-derived or systemic factors affecting bone metabolism in CKD [90,[128][129][130].…”