Biphasic bone loss in experimental autoimmune encephalomyelitis.

Abstract

Multiple sclerosis (MS) is a chronic autoimmune disorder of the central nervous system (CNS) and a common cause for 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.