Lyme disease pathogen induces murine bone loss

Topics with information and discussion about published studies related to Lyme disease and other tick-borne diseases.
dlf
Posts: 294
Joined: Sun 7 Apr 2013 15:36

Lyme disease pathogen induces murine bone loss

Postby dlf » Mon 9 Jan 2017 2:02

IAI Accepted Manuscript Posted Online 12 December 2016
Infect. Immun. doi:10.1128/IAI.00781-16
Copyright © 2016 Tang et al.

The Lyme disease pathogen Borrelia burgdorferi infects murine bone and induces trabecular bone loss

http://iai.asm.org/content/early/2016/1 ... 81-16.long

Running Title: Lyme disease pathogen induces murine bone loss
Tian Tian Tang1, Lucia Zhang2,3, Anil Bansal1, Marc Grynpas3,4, and Tara J. Moriarty1,
Author Affiliations
1 Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Toronto, ON, Canada
2 Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada
3 Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital; Toronto, ON, Canada
4 Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON,
Canada

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 reduction in areal and trabecular volumetric BMD. Trabecular regions of femora exhibited significant, copy number-correlated microarchitectural disruption, but BMD, microarchitectural, or 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 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.


The full text is fascinating, including the supplementary materials found after the references.

There was also an article published in the University of Toronto News that explains what inspired this avenue of research:

https://www.utoronto.ca/news/u-t-resear ... -discovery

Named after the Ötzal Alps where he was discovered, Ötzi, the oldest known European mummy was just 45 when he died around 3,300 BCE.

Mitochondrial DNA analysis has shown that the bacteria responsible for Lyme disease resided deep in Ötzi’s bones. Though he didn’t die from complications of the disease, work from a team of scientists at the University of Toronto’s Faculty of Dentistry now suggests that the 5,000-year-old man might have suffered from bone loss as a result of his infection.

The ancient man’s infection was enough of a clue for a team of scientists from U of T to set out to hunt for the mysterious Borrelia burgdorferi bacteria that cause Lyme disease in modern subjects. While scientists have long established a link between advanced Lyme disease and the development of osteoarthritis, until now no one has systematically studied the effects of this disease on bones.

“Bone pain has been reported since Lyme disease has been studied, but it’s not something that has been investigated,” said Tara Moriarty, assistant professor at the Faculty of Dentistry and senior author of the study, which was published last month in the journal Infection and Immunity.

The bacteria were not only detectable in the bones of mice, they were seen to cause significant bone loss in the longer bones, mere weeks after infection.

In fact, the bone loss developed at a rapid rate, taking just four weeks to advance to osteopenia, a forerunner to the more severe form of bone loss disease, osteoporosis. The study found that the amount of bone loss directly correlated to the bacterial load found in the bones. The more bacteria present, the greater the rate of bone loss.

The findings suggest that monitoring bone loss in human Lyme disease patients may be warranted, especially because bone loss is a significant risk factor for fractures later in life. At the same time, the study raises new questions about the mysterious disease and its debilitating effects.

“One of our main focuses right now is on the mechanism that induces the bone loss,” said Tian Cornelia Tang, first author of the study who recently graduated with a master's from the Faculty of Dentistry.

Cellular studies are currently underway to determine just how the bacteria interact with the bone building cells of the body, osteoblasts, with the hope of finding new drug targets to combat not just the bacteria, but the newly discovered associated bone loss.

“We need to know how long the osteopenia lasts after bacterial infection, and whether it progresses to osteoporosis,” added Moriarty.

Although the fate of the ancient Ötzi may be fixed forever in time, his infection could soon help thousands of people infected each year avoid the devastating complications of Lyme disease.

lou
Posts: 210
Joined: Fri 2 Nov 2007 0:41

Re: Lyme disease pathogen induces murine bone loss

Postby lou » Fri 13 Jan 2017 2:15

This is not actually surprising, considering why syphilis does to bone.

NotJustInMyHead
Posts: 2
Joined: Fri 3 Feb 2017 14:16

Re: Lyme disease pathogen induces murine bone loss

Postby NotJustInMyHead » Fri 3 Feb 2017 18:40

I have not been officially diagnosed (yet) but I'm only 30 and have osteoporosis..I found out when I was 27.


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