https://orcid.org/0000-0002-2013-4212
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Constantin Schmidt, Marcel S Woo, Assil-Ramin Alimy, Anke Baranowsky, Susanne Krasemann, Timur A Yorgan, Frank Timo Beil, Thorsten Schinke, Johannes Keller, Manuel A Friese, Michael Amling, Tim Rolvien, Biphasic bone loss in experimental autoimmune encephalomyelitis, Journal of Bone and Mineral Research, Volume 40, Issue 4, April 2025, Pages 522–534, https://doi.org/10.1093/jbmr/zjaf027
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Abstract
Multiple sclerosis (MS) is a chronic autoimmune disorder of the central nervous system (CNS) and a common cause of neurological disabilities in young adults. Although it is known that the peripheral immune landscape is altered in people with MS (pwMS), the impact on other organ systems than the CNS is frequently overlooked. In addition to neurological deficits, pwMS suffer from impaired bone health and increased fracture risk. However, the mechanisms underlying bone loss in pwMS are poorly understood. Here, we investigated the compartment-specific bone microarchitecture as well as cellular and molecular mechanisms of altered bone remodeling in pwMS and the corresponding mouse model of experimental autoimmune encephalomyelitis (EAE). We show that pwMS and EAE mice have reduced bone mineral density characterized by a combined loss of trabecular and cortical bone. Intriguingly, bone loss in EAE followed a biphasic dynamic defined by increased osteocyte apoptosis associated with decreased bone formation in acute EAE and increased bone resorption in the chronic phase, which could be explained by increased CXCL13/CXCR5 signaling. In conclusion, the identified stage-dependent mechanism for bone loss in EAE may help to develop improved strategies for osteoporosis treatment in pwMS.
Lay Summary
Multiple sclerosis (MS) is a disease in which the immune system attacks the central nervous system, often resulting in neurological disability. People with MS also tend to have weaker bones and a higher risk of fractures, but the reasons for this are not well understood. In this study, the bone status was investigated in both people with MS and in the corresponding mouse model. The results showed that bone loss is stage-specific and that different processes occur in the acute and chronic phases. Understanding these processes could lead to better treatment of bone loss in patients with MS.
