Osteomyelitis and the microbiome

A reader asked me to research and give speculation on Chronic recurrent multifocal osteomyelitis (CRMO). The reader has been seeing an increasing number of patients referred to her with this diagnosis. ( “a prevalence of around one in a million patients” [2018]) There are some 450+ studies on PubMed.

The relationship of inflammatory bowel disease (IBD) and chronic recurrent multifocal osteomyelitis (CRMO) is understood as extraintestinal rheumatic manifestations. CRMO is a chronic, relapsing, inflammatory, noninfectious disorder of the skeletal system of unknown origin. The disease course is not always recurrent. The association of CRMO and ulcerative colitis (UC) is very rarely reported. [2019]

“Chronic non-bacterial osteomyelitis (CNO) or chronic recurrent multifocal osteomyelitis (CRMO) is an autoinflammatory disorder characterized by sterile bone osteolytic lesions…  More frequent manifestations not directly related to bone involvement were myalgia (12%), …and gastrointestinal symptoms (8%). ” [2018]

  • “that predominantly affects children… Laboratory studies can be normal,” [2018]
  • “, the potential for direct infectious causation or indirect causation by infectious stimulation of immunity cannot be entirely excluded.” [2011]
  • “Other disease associations with chronic multifocal osteomyelitis….. Inflammatory bowel disease, especially Crohn’s” [2011]

My initial probe was pub med where I found just over 400 studies of CRMO. What I noticed reviewing these was a number of studies citing “Chronic nonbacterial osteomyelitis”. This caused me to ask the question, is CRMO actually osteomyelitis with multiple bacteria involved (my “bacteria consortium” model) — and no single known bacteria cause identified?

Bacteria Associated?

Osteomyelitis has been reported to be associated with the following:

  • Mycobacterium fortuitum [2012]
  • Coxiella burnetti — Q Fever [2011] [1998]
  • Staphylococcus aureus, Staphylococcus epidermidis [2008]
  • Corynebacterium [2016]
  • “The total positive rate of culture for bacterial OM was 81.82%, with Staphylococcus aureus being the most frequently detected pathogen (44.70%). ” [2019]

A Single Strong Candidate Gut Bacteria

“A recent paper in the journal Nature discusses experiments that provide a link between a certain gut bacteria, diet, and osteomyeltis (an autoinflammatory bone disease).  Osteomyelitis occurs when there is a bacterial infection of the bone marrow.  It is often treated with antibiotics but sometimes surgery and amputation are necessary.

The discovery that diet could alter the progression of the disease led the researchers to investigate the microbiome of these mice.  The mice with low fat diets had higher amounts of Prevotella and lower amounts of Lactobacillus when compared to normal mice.  The reverse was true for the high fat diet mice, they had much less Prevotella and much more Lactobacillus in their guts, which better represents the composition in normal mice.

To further investigate if Prevotella may be causing the disease, the researchers gave antibiotics to the low fat diet mice, which destroyed the Prevotella population, and decreased the symptoms of the disease.

Finally, the researchers performed microbiome transplants into germ-free mice that were susceptible for osteomyeltis.  Any germ-free mouse that received a transplant high in Prevotella and then was fed a low fat diet developed the disease.  However, any mouse that received a transplant that was low in Prevotella, even if that mouse was on a low fat diet, did not develop the disease. ” [2014]

This appears to have additional evidence:

Bottom Line

There is an absence of microbiome studies for CRMO. I have added this official diagnosis to the symptoms list in the hope that we may as citizen scientists may slowly build up data on this.

If we run with the Prevotella hypothesis — then looking at our database for Prevotella (which is seen in only 54% of the samples) we have:

With the following to be avoided: