Abstract
Inflammation perturbs normal bone homeostasis and is known to induce bone loss, as it promotes both local cartilage degradation and local and systemic bone destruction by osteoclasts, as well as inhibits bone formation by osteoblasts. Thus, not surprisingly, inflammatory autoimmune diseases often lead to local and/or general bone loss. However, the mechanisms that target the bone in autoimmune disease are complex and diverse, as they range from a direct attack on the bone and cartilage by the immune cells to indirect consequences of disturbances of the systemic control of bone remodeling. This Review discusses current understanding of the mechanisms of autoimmune-mediated bone loss in view of new insight from two new fields of research: osteoimmunology, which analyzes the direct effect of immune cells on bone, and the integrative metabolism approach, which established the existence of neuroendocrine loops that regulate bone remodeling.
Key Points
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Maintenance of bone homeostasis depends on the coupling between the activity of osteoblasts and osteoclasts that is locally regulated by B cells and T cells
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Bone remodeling is also dependent on regulation by the hypothalamic–pituitary–thyroid axis and a systemic regulatory system that connects bone, the β cells of the pancreas and adipose tissue
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In inflammatory arthritis—typically rheumatoid arthritis and psoriatic arthritis—bone-localized inflammation directly triggers bone loss
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In type 1 diabetes mellitus, destruction of β cells disrupts the neuroendocrine regulation between adipose tissue and bone regulation and abolishes the local positive effect of insulin signaling on bone formation
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In autoimmune thyroid diseases, while hypothyroidism in Hashimoto thyroiditis leads to decreased bone formation, hyperthyroidism in Graves disease stimulates bone destruction; bone mass decreases in both cases
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In systemic lupus erythematosus, bone loss may be the consequence of the combined effect of systemic inflammation and pro-osteopenic therapeutic adverse effects
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Schett, G., David, JP. The multiple faces of autoimmune-mediated bone loss. Nat Rev Endocrinol 6, 698–706 (2010). https://doi.org/10.1038/nrendo.2010.190
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DOI: https://doi.org/10.1038/nrendo.2010.190
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