title: The Lyme Disease Pathogen Borrelia burgdorferi Infects Murine Bone and Induces Trabecular Bone Loss.
abstract: Lyme disease is caused by members of the Borrelia burgdorferi sensu lato species complex. Arthritis is a well-known late-stage pathology of Lyme disease, but the effects of B. burgdorferi infection on bone at sites other than articular surfaces are largely unknown. In this study, we investigated whether B. burgdorferi infection affects bone health in mice. In mice inoculated with B. burgdorferi or vehicle (mock infection), we measured the presence of B. burgdorferi DNA in bones, bone mineral density (BMD), bone formation rates, biomechanical properties, cellular composition, and two- and three-dimensional features of bone microarchitecture. B. burgdorferi DNA was detected in bone. In the long bones, increasing B. burgdorferi DNA copy number correlated with reductions in areal and trabecular volumetric BMDs. Trabecular regions of femora exhibited significant, copy number-correlated microarchitectural disruption, but BMD, microarchitectural, and biomechanical properties of cortical bone were not affected. Bone loss in tibiae was not due to increased osteoclast numbers or bone-resorbing surface area, but it was associated with reduced osteoblast numbers, implying that bone loss in long bones was due to impaired bone building. Osteoid-producing and mineralization activities of existing osteoblasts were unaffected by infection. Therefore, deterioration of trabecular bone was not dependent on inhibition of osteoblast function but was more likely caused by blockade of osteoblastogenesis, reduced osteoblast survival, and/or induction of osteoblast death. Together, these data represent the first evidence that B. burgdorferi infection induces bone loss in mice and suggest that this phenotype results from inhibition of bone building rather than increased bone resorption.
authors.affiliation: Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Toronto, ON, Canada.
authors.forename: Tian Tian
authors.initials: TT
authors.lastname: Tang
authors.affiliation: Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada.|Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, ON, Canada.
authors.forename: Lucia
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Toronto, ON, Canada.
authors.forename: Anil
authors.initials: A
authors.lastname: Bansal
authors.affiliation: Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, ON, Canada.|Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
authors.forename: Marc
authors.initials: M
authors.lastname: Grynpas
authors.affiliation: Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Toronto, ON, Canada tara.moriarty@utoronto.ca.|Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
authors.forename: Tara J
authors.identifier: http://orcid.org/0000-0002-1751-5145
authors.initials: TJ
authors.lastname: Moriarty
mesh_terms: D000469:Alkaline Phosphatase / Q000097:blood / Q000378:metabolism; D000818:Animals; D015415:Biomarkers; D001847:Bone Diseases / Q000000981:diagnostic imaging / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology*; D001851:Bone Diseases, Metabolic; D025065:Borrelia burgdorferi / Q000502:physiology*; D004269:DNA, Bacterial / Q000235:genetics; D004195:Disease Models, Animal; D008193:Lyme Disease / Q000378:metabolism / Q000382:microbiology*; D008297:Male; D051379:Mice; D010006:Osteoblasts / Q000378:metabolism; D010010:Osteoclasts / Q000378:metabolism; D010012:Osteogenesis; D010014:Osteolysis / Q000000981:diagnostic imaging / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology*; D055114:X-Ray Microtomography
chemical_list: D015415:Biomarkers; D004269:DNA, Bacterial; D000469:Alkaline Phosphatase
keywords: Borrelia burgdorferi; Lyme disease; bone; bone mineral density; histomorphometry; host-pathogen interactions; infectious disease; microcomputed tomography; mouse model; osteopenia