Inflammatory chemokine RANTES elevated in jawbone & serum of ME/CFS patients (link to jawbone cavitation infections)

[Hip]

Jawbone cavitations are hollow pockets in the jawbone containing dead or dying bone marrow (osteonecrosis). These jawbone cavitations may also be infected (osteomyelitis).

The osteonecrosis in jawbone cavitations have been shown to induce the inflammatory chemokine RANTES, as well as FGF-2. Both RANTES and FGF-2 have been preliminarily implicated as possible hidden causal factors in systemic diseases such as rheumatoid arthritis, multiple sclerosis and chronic fatigue syndrome, as well as in breast cancer. Refs: 1 2

RANTES (which is also known as CCL5) may drive systemic disease by its ability to modulate the immune system: RANTES sends T-cells, dendritic cells, eosinophils, natural killer cells, mast cells and basophils to the sites of inflammation and infection in the body.

RANTES also targets the central nervous system and promotes MS and Parkinson’s disease. When targeting mast cells, RANTES is involved in allergies, alopecia, and thyroid disorders. Ref: 1



A 2017 study found that both RANTES and FGF-2 were elevated in the jawbone samples and in the serum of ME/CFS patients:

Impact of Rantes from jawbone on Chronic Fatigue Syndrome

A full text version of this study is found here and here.

This study looked at jawbone samples taken from 21 ME/CFS patients who had dental surgery in the wisdom tooth area. All these jawbone samples showed clinical fatty degenerative osteonecrosis.

In the 13 ME/CFS patients they took blood samples from, the average serum RANTES level was 42.6 ng/ml, whereas the normal range for RANTES is < 29 ng/ml. Furthermore, the study found a correlation between each patient's RANTES level in their jawbone samples and the RANTES level in their blood serum, indicating that the elevated serum RANTES likely derived from the jawbone cavitations.



There are a couple of accounts on this forum of ME/CFS patients making rapid and major improvements after dental surgery removal of the necrotic tissue in a jawbone cavitation. See these threads:

My recovery story
Cavitations and root canals

Note that jawbone cavitations are also called fatty degenerative osteonecrosis of jawbone (FDOJ), and when these cavitations cause facial pain, they may be referred to as neuralgia-inducing cavitational osteonecrosis (NICO).



The main cause of jawbone cavitations is an improperly performed tooth extraction (such as a Wisdom tooth extraction), where the periodontal ligament was not fully removed from the extraction site, which means the jawbone may not properly heal and close up the extraction hole. The theory is that "the continued presence of any portion of the ligament gives the biological message to the surrounding jawbone that all is well and no new bone growth is needed". Ref: 1

Periodontal Ligament of Tooth (Shown in Purple)

Jawbone cavitations may also arise from osteonecrosis (the death of bone tissue) due to poor blood flow to the bone.

Osteonecrosis due to poor blood supply can occur in any bone, not just the jawbone. Such osteonecrosis most commonly occurs in the ends of the femur bone; other sites of osteonecrosis include: the upper arm bone, knees, shoulders, and ankles. The early stages of osteonecrosis may be locally asymptotic, but as the condition progresses, there may be pain, especially when putting weight on the affected joint. Ref: 1

However, I am not sure if these body-wide sites of osteonecrosis can also induce RANTES and FGF-2 like jawbone osteonecrosis has been shown to do.

But with up to 30,000 patients diagnosed with osteonecrosis each year in the US (ref: 1), it does make you wonder whether osteonecrosis in the body might also be releasing RANTES and FGF-2, and thereby driving systemic diseases.



Jaw bone cavitations can be hard to detect, as they often cause only very minimal local symptoms. Sometimes a jaw bone cavitation may cause chronic facial pain, but such facial pain is not always present. A simple test for a jaw bone cavitation is applying pressure with a finger on the gums to the jaw bone beneath; if any area feels painful, this indicates a possible bone cavitation. Jaw bone cavitations may cause a sour, bitter taste in the mouth causing bad breath or even gagging.

Panoramic dental X-rays can detect jaw bone cavitations, but are not very reliable, and they also require skilled interpretation by dentists experienced with detecting cavitations (very few dentists have this experience). Ordinary MRI scans or CT scans are not good at detecting jaw bone cavitations, but the MRI STIR scan is accurate and effective in detection. A handheld ultrasound device called the Cavitat scanner is the best and most effective way to detect jaw bone cavitations.

More info on the diagnosis and treatment of jaw bone cavitations given here:

Symptoms and Location of Cavitations
The Appearance of NICO Lesions
Diagnosis and Treatment of Cavitational Lesions
Cavitations of the Jawbone

 

[Manganus]

I wondered how established this fatty necrotic osteolytic jawbone cavities may be.

Googling didn't give much.
But an article from 1992 seems to be confirmed now, 2017, with technology that we didn't dream of in 1992.

 

[jump44]

This seems like an expensive road to go down, but would be so worth it if it ended up being an actual underlying cause.. I have pretty much every symptom of this lol, but then again I have had symptoms of a million things..but Ive never had my wisdom teeth extracted. I did suffer a head injury though, actually a facial/head injury-symptoms started 6 months after the incident. I have constant facial pressure/jaw pain/pressure now-which extends up into my temples- top left side of my head.. jaw twitching that gets worse when I am in a worse state. But..these only appeared in the last few years, and Ive been sick longer than that..Very confusing.

 

[Hip]

I wondered how established this fatty necrotic osteolytic jawbone cavities may be.

Yes, that's a good question: how common are jawbone cavitations?

Removal of teeth and wisdom teeth is common, and I understand that most dentists are unaware of the theory that not fully removing the periodontal ligament during tooth extraction may later lead to jawbone cavitations. So there is the potential for a subset of the population to have jawbone cavitations, which may be pumping out the inflammatory chemokine RANTES.

This article says that in one study, jawbone cavitations were found in around 75% of all tooth extraction sites. So that suggests that jawbone cavitations are pretty common in the general population.



If you look at figure 2B of this study, you see that RANTES serum concentrations are raised in patients with moderate ME/CFS. Healthy controls had an average of 30 ng/ml of RANTES, whereas the moderate ME/CFS patients had around 37 ng/ml (though for some reason, severe ME/CFS patients had lower levels, around 28 ng/ml).

Thought I am not sure if we can interpret this study as indicating that moderate ME/CFS patients have jawbone cavitations, because the paper points out that RANTES is produced spontaneously by NK cells, so the higher levels of RANTES in these moderate ME/CFS patients might come from sources other than jawbone cavitations. But it certainly suggests that more research needs to be done on the role of jawbone cavitations in ME/CFS.

 

[Hip]

I did suffer a head injury though, actually a facial/head injury-symptoms started 6 months after the incident.

This dental website states that a physical blow to the jaw, or falling on your chin, are one of the factors that can lead to jawbone cavitations.

It's interesting that ME/CFS and fibromyalgia can appear after a physical trauma like a car accident; perhaps the creation of bone or jawbone cavitations might explain this.


In terms of the various different initiating factors that can lead to jawbone cavitations, in this article by Prof Mauro Marincola, he states that:

Initiating factors

Probably the major initiating factors are of dental origin in terms of physical, bacterial and toxic traumas.

– Physical trauma: tooth extractions, dental injections, periodontal surgery, root canal procedures, grinding and clenching, electrical trauma from dissimilar metal restorations, incomplete removal of periodontal ligament after tooth extraction, overheat from high-speed drilling.

– Bacterial trauma: periodontal disease, cysts, abscesses, root canal bacteria from non-vital teeth, infected wisdom teeth.

–Toxic trauma: dental materials, root canal toxins, anaesthetics with vasoconstrictors, chemical toxins.

Just how much evidence there is for these initiators to precipitate jawbone cavitations, I am not sure.


You might want to read the "Physical trauma" section of the roadmap of chronic fatigue syndrome testing and treatment , for other ways in which physical traumas (like car accidents) can lead to ME/CFS, or conditions like hypopituitarism with similar symptoms to ME/CFS (and which can be mistaken for ME/CFS).

 

[Hip]

I just noticed something very interesting in that article by Prof Mauro Marincola:

The results of recent research by Dr Boyd Haley, former Chairman of the Department of Chemistry at the University of Kentucky, show that the cavitation tissue samples he tested contained toxins that significantly inhibit one or more of the five basic body enzyme systems necessary for the production of energy.2 These toxins, which are most likely metabolic waste products of anaerobic bacteria, may produce significant systemic effects, as well as play an important role in localised disease processes that negatively affect the blood supply in the jawbone.

So independently of the effects of RANTES, Dr Haley says that bacterial toxins from jawbone cavitations can inhibit cellular energy production, and if true, this could be another way that jawbone cavitations might cause or worsen ME/CFS.

 

[jump44]

Have to say the thought of having a chronic infection in the jaw just leaking toxins and god knows what else into the bloodstream/ brain is making my skin crawl.

 

[CaptainA]

I've had multiple head injuries including breaking my jaw twice along with some botched dental work. My jaw is always sore, I have bad breath and have done everything I could to find out why, my teeth hurt when eating even though I've been to the dentist multiple times to find out why and they can't tell me, and my ME/CFS started the day after head trauma so.....I would say that if this theory is true you could use me as a prime example. This is really interesting. I think I may need to find someone that can do the tests.

 

[Hip]

Perhaps of related interest: how chronic inflammation in the nasopharynx area of the throat (nasopharyngitis) may be linked to autoimmune diseases — see this post.

 

[RogerBlack]

Or, perhaps there is a confounder.
Do ME/CFS patients avoid the dentist, either due to distrust in the medical system, poor health coverage (if appropriate), or simply being unable to properly take care of 'minor' issues, leading to more severe ME/CFS correlating with worse jaw issues, though the arrow of causation is backwards.

 

[Hip]

Do ME/CFS patients avoid the dentist, either due to distrust in the medical system, poor health coverage (if appropriate), or simply being unable to properly take care of 'minor' issues, leading to more severe ME/CFS correlating with worse jaw issues, though the arrow of causation is backwards.

We can rule out that possibly quite easily: jawbone cavitations are not on the radar of regular dentists. If you had a jawbone cavitation, your dentist would not be aware of it, as they do not have the equipment nor expertise to detect it. It is just a very tiny group of dentists that are aware of the jawbone cavitation link to systemic disease. Indeed, it is very hard to find a dentist who can diagnose and treat jawbone cavitations.

Furthermore, jawbone cavitations are not directly caused by neglect of dental health or hygiene or lack of visits to the dentist. They most commonly arise from tooth extractions; I suppose if you were very neglectful of dental health, that might in some cases result in a tooth extraction.

It says here that 85% of adults have had their wisdom teeth removed: so most people (even with excellent dental health) will have had some tooth extractions, which can lead to jawbone cavitations. And I mentioned above a statistic that jawbone cavitations were found in around 75% of all tooth extraction sites.

 

[Wonko]

Or, perhaps there is a confounder.
Do ME/CFS patients avoid the dentist, either due to distrust in the medical system, poor health coverage (if appropriate), or simply being unable to properly take care of 'minor' issues, leading to more severe ME/CFS correlating with worse jaw issues, though the arrow of causation is backwards.

I certainly avoid dentists, for several reasons, the 2 main ones being I mainly can't afford the downtime afterwards (my baseline is normally low enough so that I simply can't deal with anything that's liable to disrupt things for a week or more unless it's urgent) and I also have aspergers, I really hate/detest the social and physical contact etc., for the same reason I cut my own hair, even when my ME was mild moderate I didn't go to restaurants, coffee shops etc. (anywhere with unscripted contact.)

And a 3rd reason, if one was needed, that might be more understandable to some, is I've been to soem real butchers in the past, and the common dental anesthetic has little to no effect on me, it's no longer a dislike/fear of the pain (the TN took care of that - dental work is negligible in comparison), it's more an ingrained dislike of dentistry.

Which given I have 1 hole on the gum line and a tooth a filling fell out of a year or so ago eroding nicely, and I have very twisted roots so self dentistry isn't really an option....may not be good thing - but who has the time/resources - it's only pain..

 

[Manganus]

I agree, Hip, with all of what you write below.

But I would like to raise the old wellknown issue of causation.
I can't see any convincing arguments for either ME causing these cavitations, nor for the opposite.
I think we ought to consider both possibilities.

We can rule out that possibly quite easily: jawbone cavitations are not on the radar of regular dentists. If you had a jawbone cavitation, your dentist would not be aware of it, as they do not have the equipment nor expertise to detect it. It is just a very tiny group of dentists that are aware of the jawbone cavitation link to systemic disease. Indeed, it is very hard to find a dentist who can diagnose and treat jawbone cavitations.

Furthermore, jawbone cavitations are not directly caused by neglect of dental health or hygiene or lack of visits to the dentist. They most commonly arise from tooth extractions; I suppose if you were very neglectful of dental health, that might in some cases result in a tooth extraction.

It says here that 85% of adults have had their wisdom teeth removed: so most people (even with excellent dental health) will have had some tooth extractions, which can lead to jawbone cavitations.

 

[snowathlete]

I looked into this a few years ago because I had some dental problems and needed a tooth out. But in the end I decided the likelihood of this being a problem for lots of people wasn't large enough and the costs were expensive. I had my tooth out locally and talked to the dentist about the periodontal ligament and needing to remove it but his opinion, which I decided was sound, was that it was unnecessary and would actually increase the chance of problems. He left the ligament and took out the offending tooth. It healed over very well and hasn't caused me any problems. If you had solid evidence of cavitation though then I'd certainly try and get that sorted.

I do think that dental bacteria may be a cause of ME and I am frustrated that no one seems to have looked very much at this. Dental spirochetes are quite common but little is really known about them, but they're related to other disease causing pathogens including Borelia (Lyme disease). There have been some studies showing that these dental spirochetes end up in heart tissue and stuff like that, so it does seem they leave the dental area and may cause broader disease. When I had a blood test for Lyme I was negative but did test positive for band 41 (I think it was) which is a non-specific marker for spirochete flagella. So I have spirochetes in my blood. Seems lots of people do. I also bought a uBiome test and tested my tonsils, and that came back with various dental spirochetes (I figure this is probably the source of the ones in my blood). I think this is very interesting and I wish researchers would look into it.

 

[Hip]

I can't see any convincing arguments for either ME causing these cavitations, nor for the opposite.
I think we ought to consider both possibilities.

The anecdotal evidence we have to hand for jawbone cavitations causing or worsening ME/CFS comes from a couple of cases on this forum (linked to in my first post) of ME/CFS patients who very quickly got much better after their jawbone cavitations were surgically cleaned out of the tissue necrosis and infections within them.

But I guess it would take a proper study to identify jawbone cavitations in ME/CFS patients, and then observe if their symptoms improve after cleaning out these cavitations.

 

[CaptainA]

@Hip I found a video of the Author of the main study. You can use google auto translate but its pretty bad. There are two patients giving testimonials and both of them complained of ME/CFS like symptoms. They do mention metal fillings a lot in the case of the woman. There is a second part to this video as well: Part 1

Part 2:

There are also some cases stated during this presentation (Its in English):

 

[Hip]

Here is another video (in English) in which Dr Johann Lechner talks about the connection of RANTES to breast cancer metastasis.

 

[Pauline91]

I've had multiple head injuries including breaking my jaw twice along with some botched dental work. My jaw is always sore, I have bad breath and have done everything I could to find out why, my teeth hurt when eating even though I've been to the dentist multiple times to find out why and they can't tell me, and my ME/CFS started the day after head trauma so...

Hi CaptainA, did you get your mouth checked for hidden infections? Did you get surgery ? How are you doing now?

 

[CaptainA]

Hi CaptainA, did you get your mouth checked for hidden infections? Did you get surgery ? How are you doing now?

I did see a dentist that specializes in this. Well, he threw some crystals on my chest and pulled out a molar he said was infected and injected ozone in it. I'm still interested in the idea since I've had issues with bacteria here.

 

[Pauline91]

I did see a dentist that specializes in this. Well, he threw some crystals on my chest and pulled out a molar he said was infected and injected ozone in it. I'm still interested in the idea since I've had issues with bacteria here.

Did you get a Cone Beam CT? It's commonly used by bio dentists to diagnose infections, and quite accurate.
Did he use a piezzo tool? And put a PRF membrane to ensure proper bone healing?
Have you ever had a tooth removed ? I have 4 cavitations where my wisdom teeth used to be.