Lyme in your bones
New analysis of Lyme disease symptoms
Written by: Reed Owens-Kurtz
Edited by: Katie Kelly, Namrata Damle
Lyme disease has often been overlooked in the era of antibiotic resistance and new infectious disease like Zika, yet this less dramatic disease is no less threatening. Minnesota has some of the highest incidence of Lyme disease, caused by the bacterium Borrelia burgdorferi which is transmitted by the deer tick, genus Ixodes1. Normally just a nuisance, when the deer tick hosts Borrelia in its gut, the tick spits some of this disease-causing microbe into whatever animal it bites. The actual effects and symptoms of Borrelia once it enters the human bloodstream are poorly understood, often impairing efficient diagnosis and treatment of Lyme. Tang et al. found that Borrelia causes a loss of bone mineral density in a mouse model of the disease. Realizing the role of this pathogen in bone loss could improve treatment of Lyme symptoms.
Most Minnesotans have been warned to look for the characteristic bull’s-eye rash of Lyme disease following any trips in the woods, but not all patients manifest this symptom1. Even cases with the typical rash are not always treated immediately, leading to late-stage Lyme disease. Untreated, the disease can result in fatigue, headaches, nerve and joint pain, facial palsy, and meningitis, just to name a few of the numerous possible symptoms1. This wide array of effects is peculiar as the disease does not appear specific in its target. Most pathogens infect one cell type or system of the human body, while Borrelia hinders the nervous system, skin, heart, and recently shown by Tang et al., the skeletal system. The unusual variety of symptoms results from the unusual nature of Borrelia, which is a spirochete bacteria. These have a flexible cell wall containing an embedded flagellum rather than the typical tail-like flagellum that propels other bacteria. Instead, spirochetes undulate by twisting their entire cell when they rotate their flagellum. Once they enter a human host, Borrelia bacteria have high motility from this bizarre mechanism of propulsion, and can travel through many tissue types. The hallmark bull’s eye rash, called erythema migrans, is a signature of the bacteria’s movement as they spread in all directions from the site of origin. Borrelia do not produce any known toxin, rather the symptoms of Lyme disease originate from a person’s immune response to bacteria traveling through their tissue2. The human immune system tries to combat the strange and versatile foreigner in one’s body, inadvertently causing inflammation of one’s own tissue with the toxic chemicals immune cells secrete. Therefore, the majority of Lyme symptoms are inflammatory, including meningitis and arthritis. Arthritis in particular, the painful inflammation of joints, is the most common in late-stage Lyme, yet previous research only investigated its effects on the surfaces of bone exposed to other tissues2. Tang et al. demonstrated in their 2017 article that Borrelia infection affects the entire bone by decreasing bone formation and subsequently lowering bone density.
The scientists measured levels in mice infected with Borrelia burgdorferi of a molecule indicative of bone formation. As they had anticipated, the biomarker was reduced in infected mice, evidence that bone formation itself was reduced2. The mechanism through which Borrelia decrease bone formation was still unknown, so the researchers tested both long bones and vertebra of infected mice for bacterial DNA. Long bones, the dense bones characterized by a thin shaft and make up human arms and legs, have a very different structure from compact vertebra, so both bone types were studied. They found the same levels of Borrelia DNA in the tibia, a long bone, as previous studies have found in other body tissues like the skin2. This finding alone is startling: it suggests Borrelia infects long bones just as well as the rest of the body. The trabecular regions of long bones are the interior and contain the most bone mass. Bone mass density measurements were proven to be significantly correlated to the amount of Borrelia DNA in long bones; this means that increased Borrelia bacterial colonization of a bone was correlated with loss of bone mass.
Tang et al. had found a clear link between decline in bone density and Lyme disease, but they did not stop there. Bone mass is regulated through many mechanisms in both humans and mice, so a loss of bone can be due to numerous factors. The body is constantly breaking down old bone cells and recycling the minerals to build new bone. This means bone loss can occur from the body breaking down too much bone or from not building enough new bone. To get to the bottom of this, the team of researchers measured the number of osteoclasts, a specialized cell that breaks down bone, and of osteoblasts, which are specialized to make more bone. They found that Borrelia infected mice and uninfected mice only differed in the number of osteoblasts, with fewer osteoblasts in the long bones of Lyme-diseased mice. This suggests that the bone loss particularly in long bones may result from less bone-building by osteoblasts2. In this model, osteoclast activity would continue in infected bones, but the degraded osteoids (subunits of bone architecture) would not be replaced at the normal rate because not enough osteoblasts would be working to reform the bone.
Through their methodical research, Tang et al. identified bone density loss as an effect of Lyme disease and subsequently determined the origins of this loss to be reduced number of osteoblasts, primarily in long bones. This provides a clear path to improving Lyme disease treatment if osteoblast numbers can be increased or if other means of reforming bone can be enacted in the patient. The unusual pathogen Borrelia burgdorferi presents a challenge in the number and variety of symptoms it causes, but effects related to bone pain could be mitigated now that the cellular origins have been examined. In the meantime, check yourself for ticks after walks in the woods to keep this peculiar, spiral bacterium out of your bones.
[1] Centers for Disease Control and Prevention. Lyme Disease (2016). Web: https://www.cdc.gov/lyme/signs_symptoms/index.html
[2] Tang TT et al. http://iai.asm.org/content/85/2/e00781-16.abstract
[3] Sanchez JL. https://www.ncbi.nlm.nih.gov/pubmed/26593256
