Research ArticleINFECTIOUS DISEASE

Plasmodium products persist in the bone marrow and promote chronic bone loss

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Science Immunology  02 Jun 2017:
Vol. 2, Issue 12, eaam8093
DOI: 10.1126/sciimmunol.aam8093

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Plasmodium leftovers cause bone loss

Individuals who recover from malarial infection may develop long-term consequences, such as bone loss and growth retardation. Lee et al. now report that Plasmodium by-products retained in the bone marrow lead directly to bone loss. Infection with a mutant Plasmodium that lacked the by-product hemozoin did not induce bone loss. Mechanistically, these products induced MyD88-dependent inflammatory responses in osteoclast and osteoblast precursors, resulting in bone resorption. Treating infected animals with alfacalcidol, a vitamin D3 analog, could prevent this bone loss, suggesting that combining bone therapies with antimalarial drugs may prevent bone loss in infected individuals.

Abstract

Although malaria is a life-threatening disease with severe complications, most people develop partial immunity and suffer from mild symptoms. However, incomplete recovery from infection causes chronic illness, and little is known of the potential outcomes of this chronicity. We found that malaria causes bone loss and growth retardation as a result of chronic bone inflammation induced by Plasmodium products. Acute malaria infection severely suppresses bone homeostasis, but sustained accumulation of Plasmodium products in the bone marrow niche induces MyD88-dependent inflammatory responses in osteoclast and osteoblast precursors, leading to increased RANKL expression and overstimulation of osteoclastogenesis, favoring bone resorption. Infection with a mutant parasite with impaired hemoglobin digestion that produces little hemozoin, a major Plasmodium by-product, did not cause bone loss. Supplementation of alfacalcidol, a vitamin D3 analog, could prevent the bone loss. These results highlight the risk of bone loss in malaria-infected patients and the potential benefits of coupling bone therapy with antimalarial treatment.

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