Strange Relation Between War Wounds and a Genetic Disease

[Broomstick]

There is a genetic disease called Fibrodysplasia ossificans progressiva or FOP for short. It's pretty weird. The muscles of the body gradually turn to bone. The only thing weird about the bone is the fact of it formerly being muscle and its location. Any attempt to remove the bone results in additional bone formation. Minor trauma - bruising, a vaccination - can trigger the transformation.

The most famous sufferer is Harry Eastlack, who donated his over-abundant skeleton to science:



Normally, when a skeleton is defleshed for display purposes you wind up with a couple hundred pieces that must be strung together. Not Harry - his skeleton was fused into virtually one piece.

Suffers tend to die in their 30s, typically either of starvation when their jaw locks or suffocation when their chest wall muscles turn to bone.

Unfortunately, I don't have internet links to the next item, which is heterogeneous ossification. I read an interesting article in National Geographic about treatment of war injuries in Iraq - and I really wish I could link to the x-ray in question. It seems that when traumatic injury occurs - when tissue is "shredded" I believe the article said - sometimes the body converts damaged msucle into bone. It's not the same as FOP, in that the entire muscle does not convert and this new bone can eventually be removed. But isn't it interesting that this muscle-into-bone conversion occurs in healthy, genetically normal people in some circumstances?

The gene for FOP has been discovered. And, not surprisingly, that has allowed identification of the corresponding normal gene. It has not resulted in a treatment for either of these muscle-into-bone disorders, although it HAS assisted in developing treatments to create bone, which has been invaluable in rebuilding jaws, legs, arms, etc.

Work for either a cure for FOP or at least an effective treatment to delay the progression continues.

It's a very interesting example of how the study of an obscure genetic disorder can have multiple repercussions.

[Tasoth]

That is kinda neat. Calcium is an important ion for muscle flexion, but complete ossification of muscle into a bone is just bizarre. For the ossification of wounded muscle tissue, I have no clue as to the vehicle for that, aside from an error in the mending of the torn tissue since muscle doesn't replicate like epithelial tissue.

[Admiral Valdemar]

Plus, when you damage muscle it tends to leak a lot of nasty compounds such as high potassium and myoglobin which can likely cause an immune reaction or affect biochemical relays. The genetics of it are probably quite atrociously complex when you look at how that gene interacts with the cells and their necessary metabolic pathways. In other words, it's never as cut-and-dry as "this gene causes this, simply because". Besides, removing a gene can cause more harm than good if it has several other uses given how interconnecting genetic material can be.

I have heard of this condition before, but not this extraordinary man's skeleton; the Merrick of bone disorders it would seem. Thanks for the insight, Broomstick.

[Exonerate]

Are there any theories on why this happens? Is it just some bizarre side-effect, or might there be some advantage/benefit from this?

[Admiral Valdemar]

If you can point out the advantages to becoming a living (soon to be dead) statue, I'm game. Otherwise, it's just another flaw in our genetic make-up.

[Tsyroc]

From the FAQ on the website it looks like they've been unable to determine what specifically triggers the new bone formation. The things that Broomstick mentions can trigger the bone formation but don't always do so.

I also wonder if mobility excerises can have any benefit in slowing down some of the fusing. It must not be able to stop it because the rib cage is one of the main locations for the extra bone growth, but then maybe it doesn't move enough through regular breathing.

[Broomstick]

It's clearly bad mutation - there is no benefit to having this defect which is one reason it's so rare. I don't think any FOP sufferer has managed to reproduce.

The latest hypothesis I've heard - and it's very much an early-in-the-process thing, there is much work required to make it a true theory - is that in FOP immune system activity after a muscle injury results in bone growth factors being transported to the site of the injury, in particular bone morphogenic protein (BMP). The body normally only produces BMP during the fetal period and perhaps into very early childhood. This might also explain why the ossification in FOP follows the ossification of a fetus, from the head down. The upper body is affected first and worst. If this is true, then it's not really a lack of gene, but rather a failure of the gene to shut down apporpriately. I believe there is some research into either shutting the gene down, or blocking the BMP it creates to halt the disorder. This would probably result in the need for life-long medication/treatment, but might considerably improve the lot of those who have the disorder. I doubt the muscle-into-bone conversion could be reversed, but if the conversion could be halted then at least FOP patients could undergo surgery to release frozen joints. If enough working muscle remains then motion could be restored. If not, then at least it would be much easier to get them into/out of wheelchairs, vehicles, allow more positions to avoid pressure sores, and so on.

BMP is now manufactured and used in orthopedic surgery, particularly in restoration and trauma surgery. Normally, it's also very behaved.

The heterogenous ossification can and does occur without the input of BMP. There are probably a number of chemical signals used to generate bone, with the usual suite of variations. Severe trauma could release more of these than usual, or perhaps the breakdown products of destroyed tissue might mimmic some of them. This could account for why some people get HO and some don't. It could also account for why FOP affects some sufferers more quickly and thoroughly than others.

[Broomstick]

I also wonder if mobility excerises can have any benefit in slowing down some of the fusing.

Great idea, but no go. In fact, since heavy exercise can cause muscle damage that might be a problem. In normal people that muscle damage can heal. In FOP, it might trigger the transformation.

In fact, with FOP people have been known to go to bed being able to move, say, a wrist and waking up with it locked and frozen into position.

The only thing that can slow this down is scrupulous avoidance of injury. Even that is no guarantee - the conversion can occur without any injury, as a spontanteous thing.

It really is an awful disorder.

[Tsyroc]

It really is an awful disorder.

Definately.


I guess I was thinking too much in terms of how they often have people with arthritis keep moving joints so they can maintain their overall mobility. I forgot that this is completely different.

[Oni Koneko Damien]

If you can point out the advantages to becoming a living (soon to be dead) statue, I'm game. Otherwise, it's just another flaw in our genetic make-up.

I'd assume that it could theoretically be used in the treatment of degenerative bone diseases, osteoperosis, etc.

[Sephirius]

so... shred the flesh on top of my ribcage and I'll be a space marine?

[wolveraptor]

If you can point out the advantages to becoming a living (soon to be dead) statue, I'm game. Otherwise, it's just another flaw in our genetic make-up.

What about the ossification of muscle that seems to have occurred in Iraq veterans? It doesn't seem to have the persistence of full-blown FOP, and I toyed with the idea that it was advantageous, simply because it might temporarily protect the damaged area. I have absolutely no expertise on the subject though.

[darthbob88]

so... shred the flesh on top of my ribcage and I'll be a space marine?

Ah, if only. From what I've read, you'd also need a second heart, a third lung, natural night-sight, acid venom, and a neuro-mechanical interface. Besides which, if your ribs can't flex, you can't breathe, making you a very weak Space Marine. Damn shame.

[Broomstick]

If you can point out the advantages to becoming a living (soon to be dead) statue, I'm game. Otherwise, it's just another flaw in our genetic make-up.

What about the ossification of muscle that seems to have occurred in Iraq veterans? It doesn't seem to have the persistence of full-blown FOP, and I toyed with the idea that it was advantageous, simply because it might temporarily protect the damaged area. I have absolutely no expertise on the subject though.

No, it's not as persistent and it doesn't reach beyond the area of injuries. It doesn't seem advantageous, though, in that the new bone growth has been known to choke off blood vessels and require removal or it would result in limb death and amputation. The National Geographic example involved a below-knee amputee whose femoral artery was entrapped and being crushed by the new bone. Required very finicky surgery to remove without damaging that major blood vessel.

The similarity is that the new bone growth is in the area of damaged muscle tissue. This new bone, however, is disorganized - not all the smooth shapes you see in FOP. They aren't the same thing, but there does seem to be some relationship there. It could be coincidence, different mechanisms producing bone growht, or there could be a link. Mostly, it was an intriguing line of thought.

[Broomstick]

If you can point out the advantages to becoming a living (soon to be dead) statue, I'm game. Otherwise, it's just another flaw in our genetic make-up.

I'd assume that it could theoretically be used in the treatment of degenerative bone diseases, osteoperosis, etc.

It's a possibility. I believe BMP is used in treating some forms of bone necrosis and as I mentioned, in reconstructive surgery. Osteoporosis is problematic, in that it is so widespread. BMP is not something you'd want to dump willy-nilly into the body.

[Tolya]

This is one of the creepiest things I have ever seen/heard of. Gradually becoming unable to move your chest, open your jaws...it is one of the most horrid ways of dying that I can imagine. I feel truly sorry for anyone who suffers/suffered from this.

I mean, damn...

[FSTargetDrone]

Unfortunately, I don't have internet links to the next item, which is heterogeneous ossification. I read an interesting article in National Geographic about treatment of war injuries in Iraq - and I really wish I could link to the x-ray in question. It seems that when traumatic injury occurs - when tissue is "shredded" I believe the article said - sometimes the body converts damaged msucle into bone. It's not the same as FOP, in that the entire muscle does not convert and this new bone can eventually be removed. But isn't it interesting that this muscle-into-bone conversion occurs in healthy, genetically normal people in some circumstances?

I saw the same article. Quite sobering. I recommend it to everyone.

[Broomstick]

I've been digging around some and found this article which gives some technical detail without being too dense. Interesting that brain injury increases the likelihood of HO. It also seems to occur in a significant percentage of long-bone breaks and joint breaks, but since it doesn't always progress to restricting range of motion - that is, it can be asymptomatic - most of us are unaware of it.

It's also an illustration of finding out more information by searching on variations of words or similar words, in this case heterotopic in place of heterogenous.

Also found a fairly clear image of this condition, compare to the FOP skeleton show above: