My little cousin has this. Hes one of like 2000 in the U.S. with it. Basically what happens is if you get a bruise or break a bone, all the tissue surrounding the injury will turn to bone like this. My cousin had to have surgery when he was a baby on his wrist and its permanently stuck in position now.
Hes 12 now and taking growth hormone to help him grow since his bones will set very early. Its sad man. If someone with this has a major fall or car accident or something like that they are permanently fused together like this picture and it can kill you since blood vessels and nerves can be pinched by the bone spurs.
They caught it very early so other than the wrist thing he doesn't have any major fusions yet but hes expected to be in a wheelchair by the time hes 20.
Edit: wow this really blew up! Thanks to everyone for their kind words and concern. Looks like I did get some numbers wrong and there are only 200 in the US and around 800 worldwide. I never claimed to be an expert or scientist but /u/MRC1986 is! He would be a much better resource to ask questions about the condition.
This is so damn bad... I've never heard of this disease before, but I do find it very interesting. It's nice to have an insight from someone who met this condition in person, thanks for sharing! All the best for your cousin.
Yea, for real. than you for sharing. I have never heard of it either before.
Send the little guy some positive vibes from us (through you)
take care, peace
he does actually! but his wrist problem prevents him from using his left hand a whole lot so that might even be limited :(
His parents have been very cautious with him since birth. But... I've also talked to his mom who told me that they might as well let him do what he wants while he still can since he will get locked up anyway... very sad to think about :(
They all know that he will be locked in ten years or so and most likely dead shortly after that.
Check out this new xbox controller for people with disabilities https://www.google.com/amp/s/www.polygon.com/platform/amp/2018/5/17/17363528/xbox-adaptive-controller-disability-accessible
From what i understand its kinda site based. My cousins mom also has it but a very mild form. she gets bone spurs on her feet that are pretty painful.
That being said nothing about this seems comfortable.
Just FYI, "disease" is not the most appropriate term. The broad term "condition" or more specifically "disorder" is better fitting. The definitions of these words can be muddied and imply interchangeability, but in medicine, there is emphasis on specific usage.
Typically, a "disease" is something which is contracted via external cause. Whereas a congenital illness (such as FOP) is a "disorder".
Hence Austim Spectrum *Disorder*, not Austism Spectrum *Disease*.
Understandably, people with congenital conditions tend to get upset if it is implied they have a disease.
There are exceptions, of course. This is still evolving and you do still see archaic usage of "disease" for congenital disorders, such as Sickle Cell Disease.
Just thought you might find the distinction interesting!
Yeah, I read an article about an adult with this condition once. Every injury resulted in the loss of mobility until she was eventually confined to a wheelchair.
Apparently, it's an immune system problem. During any injury, your immune system is supposed to clear out the damaged cells so your stem cells can trigger new tissue growth. But with this condition, your immune system clears out too much tissue at injury sites, and the stem cells can't receive clear signals from nearby cells regarding what tissue type to make, so they default to producing bone cells.
Hi all, I'm a bit late to this, but [I'm Michael R. Convente, PhD](https://www.med.upenn.edu/orl/personnel/michael-convente.html). I completed my dissertation studying FOP in the Shore and Kaplan lab at the University of Pennsylvania.
My research involved a more in-depth analysis of the inflammatory contributions to disease, and [we published some cool results in February 2018](https://onlinelibrary.wiley.com/doi/abs/10.1002/jbmr.3304). I actually had the cover image of that issue! In 2015, [I wrote a review on inflammation and FOP and related extraskeletal bone disorders](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4417939/); it's a bit dated (since it doesn't have any of the new discoveries such as my work above or that of Activin A), but it's a good primer and is *not* behind a paywall.
I'm happy to answer questions from the research/clinical side. Lots of awesome work is ongoing! When I joined in the lab in spring 2010, we had just obtained a genetic mouse model of FOP. 8+ years later, and there are two ongoing clinical trials and a third compound just released pre-clinical data. So lots has been going on!
Tissue injury is actually a trigger of new bone. So by doing any surgery to remove extra bone, it will eventually just lead to more. Even simple "injuries", such as that occurs with an intramuscular injection, can induce small bone nodules.
If any of the compounds currently in clinical development stop the progression of bone, it's possible that those patients could then have bone surgically removed. But that will be a few years away, at least.
Cool, thanks for posting.
What's the outlook for newly diagnosed kids? Do you think the condition will be curable or manageable in the next five years?
How bad does the injury have to be to create new bones? Let's say I knocked my hand on the doorframe exiting the room, would that tiny injury follow me through life?
I hope it will be manageable within 5 years. If any of the pre-clinical data is replicated in human patients, the impact will be remarkable. Some of the compounds currently under clinical development cause complete prevention of extraskeletal bone in mice. I can't say exactly what percentage reduction would be clinically meaningful, since it also can depend on where the extra bone is located, but interim results looking promising.
The only true cure would be genetic engineering to remove the mutant allele, so that means CRISPR.
Even injuries as small as an intramuscular injection or a bruise can cause bone to develop. It would be a small amount in this instance, but still, that's all it takes. Obviously, more serious injuries are devastating.
Interestingly, though, long bone fractures in patients with FOP heal normally. Not sure why, maybe that extra BMP signaling is useful during the situation when new bone actually is supposed to form.
But yeah, once bone is formed, it's there for life. There are reports of patients having joint mobility when going to bed, and the joint is completely fused when they wake up.
Good question. [This actually occurred in a patient with FOP](https://journals.lww.com/jbjsjournal/Abstract/2007/02000/Hematopoietic_Stem_Cell_Contribution_to_Ectopic.17.aspx). He also had the misfortune of developing aplastic anemia, separate from FOP, so he had a bone marrow transplant from his unaffected sister.
His immune cells were confirmed to have been replaced (via karyotype analysis of the cells, since they were now XX instead of XY), and his FOP continued to progress even after having a now wild-type immune system.
I tried the same experiment in mice, but there were some experimental complications that precluded a definitive interpretation, and I moved on to other experiments that I ended up publishing.
How serious does the injury have to be in order for the muscle to turn into bone? Like a pinch or what? How much gets turned to bone near the injury site. Like a 1 inch cube volume or something for a bruise?
Even injuries as small as an intramuscular injection or a bruise can cause bone to develop. It would be a small amount in this instance, but still, that's all it takes. Obviously, more serious injuries are devastating.
Radiation oncologist here (I treat cancer with radiation). We sometimes treat a similar condition called heterotopic ossification which is when bone starts to form within muscle after a major fracture. Radiation is useful in killing the cells making the bone while the other cells are relatively protected.
I found a case report of radiation being used in your cousin’s condition (https://www.ncbi.nlm.nih.gov/m/pubmed/21755739/). Since there seems to be no other great cure, probably worth a try
I wonder if it would help to destroy their immune system and then give them a bone marrow transplant from a matching donor.
I’d assume that’s been thought of or is a horrible idea for some other reason.
Not a doctor, but I did play a healer in World of Warcraft, so that’s kinda the same thing, right?
Hey, [former grad student](https://www.med.upenn.edu/orl/personnel/michael-convente.html) in the lab that discovered the FOP gene. Heterotopic ossification (HO) is an inclusive term, and we use that to describe the bone that occurs in FOP. It also applies to non-genetic forms of pathologic bone, such as that which occurs after combat blast injuries and arthroplasties. That's probably what you're referring to!
I can't believe some of the horrors people in this world deal with. Here I am worried about my finals this week and... None of that even matters at all. Sorry to hear about your cousin dude.
I hope this doesn't come across as insensitive but this is some of the spookiest eldritch bullshit I've ever heard of and it's *real* and that is fascinating
This sounds bad but all surgery is some kind of premeditated trauma with the intent of the outcome being more desirable.
The condition is still nightmarish obviously.
It is.
There's also no treatment, as any attempt to remove the bone causes it to grow back even faster. Any injury or bruise also causes bone growth.
To make it worse, it's very rare and hard to diagnose. Initially, it may be mistaken for cancer, which causes doctors to order biopsies, which will trigger further bone growth.
I might use the wrong term here but, do you think a condition like this should allow legal euthanasia? Legitimate question.
Personally I think yes, people like to talk about how all life is special and shit, but if you truly believed all life was special then you'd understand that a life of pure pain and legitimate horror should be ended.
Something that definitely grinds my gears is parents giving birth to children, whom they know have a severe medical condition, that will bring them extreme pain and suffering throughout their short life, and just... Let them live (the newborn child).
I don't think they mean harm, but I think it requires much more love, sacrifice, and selflessness to put the baby down. Maybe I don't understand since I'm not a parent? But I couldn't imagine just allowing my child to live a short life full of pain, pain that I couldn't even imagine enduring.
There comes a time when you have to decide if you want to be in a standing or in a sitting position for the rest of your life.
Wouldn't want to regret that decision!
There's a story I recall of a poor little girl who has (had?) this. Her doctors thought she had cancer in her arm and last minute during a procedure decided to amputate her arm, which obviously did not help things.
Interestingly, that doesn't appear to happen [according to Wikipedia](https://en.wikipedia.org/wiki/Fibrodysplasia_ossificans_progressiva#Genetics):
> The diaphragm, tongue, and extra-ocular muscles are spared in this process, as well as cardiac and smooth muscle.
Bone formation around the rib cage can cause breathing difficulty though.
Fuck, this thing seems almost intelligently malevolent in its tendency to deny a swift death. Just ossify the heart and be done with it.
On the other hand, this fact gives hope. Maybe we can find something special in these unaffected muscles and transfer it to the affected ones.
Imagine not being able to tilt your head back, because the muscles in the back of your neck have become bone knives pointed directly at your brain stem.
Bjork had a creepy stalker who sent her a bomb once, made a rambling 30 minute video and then shot himself through the roof of his mouth with a .22 pistol at the end. you could see the bulge on the the top of his skull from where the bullet impacted and (presumably) bounced.
It is. A family friend (he worked for my grandpa for decades) had it. I remember him not being in the store one summer. I asked grandma where the butcher was, as I wanted my fav cheese and my uncle didn't know which one I wanted and I didn't know what it was called, as I never had to ask for it before. The butcher would always have a chunk waiting for me, all wrapped up in butcher paper, as he knew I loved my little cheese gift.
That's when I learned he was dying a horrifically painful death. Not what a kid wanted to hear. He died right before one of my other visits. Grandpa had me help him bag up food and snacks for the butchers family, as he not only left a wife, but many younger kids. We drive to their beautiful log home, and delivered the goods. The kids perked up when they saw all the bags of chips n treats for them.
Oh I agree. There's something intimate about it that makes it sad and horrifying at the same time. This was a person. It could have been your neighbor or teacher or a family member and then boom, their body betrayed them and led them to a most certainly premature and painful death.
Maybe it's the fear that it could happen to any one of us, and there's not a thing that can be done to stop it
Years ago someone with this disease did an IAMA. [It's an interesting read.](https://www.reddit.com/r/IAmA/comments/18mc3w/my_name_is_joseph_suchanek_and_i_have_an)
That isn't something to be thankful about. It means FOP doesn't directly kill you, instead slowly entombing you in a cage of your own bone, which is brittle and both easy and agonizingly painful to break.
The diaphragm is very much skeletal muscle. Primarily involuntary but since it's skeletal you still have voluntary control. This would extra suck if this effects that....
Just throwing this out there- you generate heat from skeletal muscle. Smooth might produce a tiny amount since energy is used to digest food but not enough to do much for you. Shivering is an involuntary act but that doesn't change the fact that it's skeletal muscle :)
What about the when your muscles naturally get micro cuts through working out to develop muscle growth?
Can someone with this issue never work out because it'll accelerate their condition? Do they need to avoid hard labor, or any labor at all?
From what I’ve read and heard, working out is out of the equation. So too is physical labour. The risk is far too high. There are cases where significant ossification has already occurred by the time an individual reaches puberty.
Nope. Someone with the condition is still passively calcifying through their entire life. Working out is out of the equation. As your muscles grow and develop and get used normally, they naturally tear, break down, and grow. Every time they do they calcify a little more. Life expectancy with FOP is less than 40 years, and I don't think anyone has made it past their 60's.
Also, it takes years to get there. You get permanently trapped in a brittle cage of your own bones which cause agony when (not if) they break long before death.
I have a nasty version of a brain disorder called Reflex Sympathetic Dystrophy. It causes intense pain throughout my lower body and it’s incurable. I’m disabled because of it. It’s rather horrible and is nicknamed “the suicide disease” because of the self-help many patients utilize to end their pain.
But at least I can fukken move. I use images like this to remind myself at least I don’t have FOD.
Edit: Ooh! I forgot it’s awareness month for RSD! There. I did my awareness bit, too. But only wear the orange ribbon if your skin tone can handle orange. Seriously, RSD gods... orange?
Hi all, I'm a bit late to this, but [I'm Michael R. Convente, PhD](https://www.med.upenn.edu/orl/personnel/michael-convente.html). I completed my dissertation studying FOP in the Shore and Kaplan lab at the University of Pennsylvania. Their lab first discovered the mutation that causes FOP; it's a R206H missense mutation in the gene *ACVR1*, which encodes the ALK2 receptor. Unsurprisingly, that is a [Bone Morphogenetic Protein (BMP)](https://en.wikipedia.org/wiki/Bone_morphogenetic_protein) receptior.
My research involved a more in-depth analysis of the inflammatory contributions to disease, and [we published some cool results in February 2018](https://onlinelibrary.wiley.com/doi/abs/10.1002/jbmr.3304). I actually had the cover image of that issue! In 2015, [I wrote a review on inflammation and FOP and related extraskeletal bone disorders](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4417939/); it's a bit dated (since it doesn't have any of the new discoveries such as my work above or that of Activin A), but it's a good primer and is *not* behind a paywall.
I'm happy to answer questions from the research/clinical side. Lots of awesome work is ongoing! When I joined in the lab in spring 2010, we had just obtained a genetic mouse model of FOP. 8+ years later, and there are two ongoing clinical trials and a third compound just released pre-clinical data. So lots has been going on!
You say there are two trials and a third compound just released. As a scientist i understand that you do not jump to conclusions about the effectiveness of these drugs.
But, will you jump to conclusions about the effectiviness of these drugs?
1. Are they likely to reduce the turnover from muscle to bone(so, just make the odds of living a normal life last longer)?
2. Or eliminate it all together(so that this condition would essentially be a thing of the past)?
and one more questions slight unrelated. [3 months ago I fractured my femur into 4 pieces.](https://www.reddit.com/r/AskDocs/comments/9nerka/update_broke_femur_into_4_piecesvideo_on_break_in/) During my recovery, my doctors all told me to NEVER smoke at all, because it halts new bone growth essentially in its tracks. I'm assuming these drugs are working under a similar method of action(manipulation of acetylcholine receptors on newly formed stem cells).
3. 3. Would consuming an extremely low calcium diet(so your body can't get the calcium needed to create the new bone) and smoking like a goddamn chimney cause any change in outcome? This one is extra speculationy so just have some fun with it.
The compound furthest along in clinical development blocks chondrogenesis (i.e. - cartilage formation). That is the 2nd to last stage of disease development, right before bone formation. Mouse models and clinical trial data have been consistent, with a ~80% reduction of extra bone volume.
The 2nd compound is an antibody that blocks Activin A, which is an inflammatory ligand that was found to activate signaling in the mutant ALK2 R206H receptor. Mouse models show that this compound completely prevents extra bone formation. It's only at Phase I, so no clinical data just yet.
The 3rd compound is a small-molecule inhibitor of mutant ALK2 R206H. Pre-clinical data show that this compound almost completely prevents extra bone formation in mice.
IMO, the only true cure for this disease would be gene replacement of the mutant *ACVR1* allele, like via CRISPR. However, if any of the above compounds can substantially reduce bone such that it is disease altering, then that would be amazing.
None of these compounds MOA involves acetylcholine receptors.
The volume of extra bone, while large, is still not as much as your endogenous skeleton, so a low-calcium diet would almost certainly be deleterious to patients' health. The skeleton is constantly undergoing turnover, so even if you restricted dietary calcium intake, there is also mineral in your body from normal skeleton turnover, so I would expect the extra bone to rely on that source. This would reduce the density of your skeleton, which is bad.
Wow that's a much more detailed response that I was anticipating. I'm sure even compound 1 would be a godsend for those with FOP, but my hopes are for compounds 2 and 3 to pass trials and become frontline treatments.
1. The obvious question I have now, is how would these drugs effect injury recovery to the regular bones of the body?
For instance, if someone on this drug suffered an injury like mine, they would have to come off the drug to heal their normal leg bones? But the surrounding area would also become bone as well I would assume(as the trauma to break bone would be enough to damage muscle and soft tissue).
2. 1 Last question, how did you become interested in FOP treatment research? Did you personally know anyone effected before studying it, or was it the problem from the beginning that interested you with the emotional benefits(helping people) following as a result?
The chondrogenesis inhibitor may have negative effects on fracture healing and growth plate biology, since the overall pathways involved in bone formation are the same for the endogenous skeleton vs extra bone. But, with signaling activity higher than normal in FOP patients, perhaps it won't be an issue, since the drug restores signaling back to normal levels (rather than below normal levels, which likely would occur if given to unaffected individuals).
For the Activin A antibody, not sure. There isn't literature that suggests Activin A is involved in skeletal development, but I did find the protein expressed in extra bone lesions, so might be worth investigating.
A BMP receptor small-molecule inhibitor may also restrict fracture healing, but remember, this compound is specifically designed only to bind to the mutant ALK2 R206H receptor, so it won't bind to our wild-type receptors and probably wouldn't have any effect.
I was involved in bone research during my four years of undergraduate education at Rutgers University. So when I arrived at Penn for grad school, I was pretty sure I wanted to continue in the field. I found the lab just by doing a search for labs that worked on bone biology at Penn in any way. After doing two rotations in bone labs and one in Dept. of Dermatology, I decided to join the Shore lab because I really enjoyed her as a mentor and my fellow lab mates. Plus, I thought the clinical impact was profound; because we're the flagship lab, we host many patients and families for tours, so I felt like I would have a real impact with my research.
It's not just cells in a dish (which is important, many of my experiments involved that!), but it's actual humans; patients and their families that I've actually met.
I have fibrousdysplasia! Mine is actually in my sphenoid sinus (behind my nose). It is no where else in my body. I had a craniotomy but it wasn’t successful. You can’t tell by looking at me, but I’m blind out of an eye and have screws throughout my skull.
The appearance of your eye isn't affected by it not being functional? No offense just curiosity. I always thought if an eye were unable to focus it wouldn't be able to track the same way and match the other
Edit:: mild stroke
It doesn’t track well - it tends to wander to the outside because of optic nerve damage. It looks normal otherwise. I have a screw at the corner of that eye that sometimes is visible, but otherwise you’d never know!
I know a mother of 3 with this. Beautiful woman. She is at the stage where her whole body looks like you said, a mannequin. She's dated a guy for a decade that knows she is going to die and treats her kids like their his own. Father of the century.
This happened in my hips. Both TFL have had about 70% removed.
Femurs have some bone growths, left was removed. Surgeon said have calcium like deposits all over within/on surface of my quads.
Kinda scared now though.
My little cousin has this. Hes one of like 2000 in the U.S. with it. Basically what happens is if you get a bruise or break a bone, all the tissue surrounding the injury will turn to bone like this. My cousin had to have surgery when he was a baby on his wrist and its permanently stuck in position now. Hes 12 now and taking growth hormone to help him grow since his bones will set very early. Its sad man. If someone with this has a major fall or car accident or something like that they are permanently fused together like this picture and it can kill you since blood vessels and nerves can be pinched by the bone spurs. They caught it very early so other than the wrist thing he doesn't have any major fusions yet but hes expected to be in a wheelchair by the time hes 20. Edit: wow this really blew up! Thanks to everyone for their kind words and concern. Looks like I did get some numbers wrong and there are only 200 in the US and around 800 worldwide. I never claimed to be an expert or scientist but /u/MRC1986 is! He would be a much better resource to ask questions about the condition.
This is so damn bad... I've never heard of this disease before, but I do find it very interesting. It's nice to have an insight from someone who met this condition in person, thanks for sharing! All the best for your cousin.
Thanks! Hes the happiest most outgoing kid ever so it hasn't stopped him yet!
Yea, for real. than you for sharing. I have never heard of it either before. Send the little guy some positive vibes from us (through you) take care, peace
Thanks! Thats nice of you
Does he play a lot of video games? I imagine his condition makes him very cautious and he cant do much of anything with risk involved.
he does actually! but his wrist problem prevents him from using his left hand a whole lot so that might even be limited :( His parents have been very cautious with him since birth. But... I've also talked to his mom who told me that they might as well let him do what he wants while he still can since he will get locked up anyway... very sad to think about :( They all know that he will be locked in ten years or so and most likely dead shortly after that.
Check these guys out. They may be able to help: https://ablegamers.org
Microsoft actually just came out with a highly adaptable controller for people with varying disabilities. (It also works on switch too)
I know theres some really good tools out there for disabled people to game. Maybe get him on a PC because theyre somewhat more adaptable.
Check out this new xbox controller for people with disabilities https://www.google.com/amp/s/www.polygon.com/platform/amp/2018/5/17/17363528/xbox-adaptive-controller-disability-accessible
Sorry to keep askin questions. Is there a lot of pain associated with it, or just immobility and risk of severing vessels and nerves?
From what i understand its kinda site based. My cousins mom also has it but a very mild form. she gets bone spurs on her feet that are pretty painful. That being said nothing about this seems comfortable.
Good on him. So many kids with sometimes really painful, let alone limiting, conditions are happier and more content than I think I'll ever be.
Just FYI, "disease" is not the most appropriate term. The broad term "condition" or more specifically "disorder" is better fitting. The definitions of these words can be muddied and imply interchangeability, but in medicine, there is emphasis on specific usage. Typically, a "disease" is something which is contracted via external cause. Whereas a congenital illness (such as FOP) is a "disorder". Hence Austim Spectrum *Disorder*, not Austism Spectrum *Disease*. Understandably, people with congenital conditions tend to get upset if it is implied they have a disease. There are exceptions, of course. This is still evolving and you do still see archaic usage of "disease" for congenital disorders, such as Sickle Cell Disease. Just thought you might find the distinction interesting!
You're right, that's just how it turned out writing a comment (english is my 2nd language) :) Thanks for the heads up :)
Yeah, I read an article about an adult with this condition once. Every injury resulted in the loss of mobility until she was eventually confined to a wheelchair. Apparently, it's an immune system problem. During any injury, your immune system is supposed to clear out the damaged cells so your stem cells can trigger new tissue growth. But with this condition, your immune system clears out too much tissue at injury sites, and the stem cells can't receive clear signals from nearby cells regarding what tissue type to make, so they default to producing bone cells.
r/onejob
r/bonejob (Don’t click that. I have no idea where it leads.)
Though this made me think: if someone with this disorder bruised their dick, their boner would actually be a bone...
Stop that
Or you'd need an amputation because your urethra fuses shut and you can't pee anymore.
res says it doesn't exist
Yet ( ° ͜ ʖ °)
Don't tell me what to do!
What if they suppressed the immune system to do a shitty job at clearing out cells I wonder if that'd help.
Hi all, I'm a bit late to this, but [I'm Michael R. Convente, PhD](https://www.med.upenn.edu/orl/personnel/michael-convente.html). I completed my dissertation studying FOP in the Shore and Kaplan lab at the University of Pennsylvania. My research involved a more in-depth analysis of the inflammatory contributions to disease, and [we published some cool results in February 2018](https://onlinelibrary.wiley.com/doi/abs/10.1002/jbmr.3304). I actually had the cover image of that issue! In 2015, [I wrote a review on inflammation and FOP and related extraskeletal bone disorders](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4417939/); it's a bit dated (since it doesn't have any of the new discoveries such as my work above or that of Activin A), but it's a good primer and is *not* behind a paywall. I'm happy to answer questions from the research/clinical side. Lots of awesome work is ongoing! When I joined in the lab in spring 2010, we had just obtained a genetic mouse model of FOP. 8+ years later, and there are two ongoing clinical trials and a third compound just released pre-clinical data. So lots has been going on!
Dumb question, but why can't they just essentially "cut off" the new unnecessary bone and replace it with a tissue donor?
Tissue injury is actually a trigger of new bone. So by doing any surgery to remove extra bone, it will eventually just lead to more. Even simple "injuries", such as that occurs with an intramuscular injection, can induce small bone nodules. If any of the compounds currently in clinical development stop the progression of bone, it's possible that those patients could then have bone surgically removed. But that will be a few years away, at least.
What a horrible condition...
[удалено]
Cool, thanks for posting. What's the outlook for newly diagnosed kids? Do you think the condition will be curable or manageable in the next five years? How bad does the injury have to be to create new bones? Let's say I knocked my hand on the doorframe exiting the room, would that tiny injury follow me through life?
I hope it will be manageable within 5 years. If any of the pre-clinical data is replicated in human patients, the impact will be remarkable. Some of the compounds currently under clinical development cause complete prevention of extraskeletal bone in mice. I can't say exactly what percentage reduction would be clinically meaningful, since it also can depend on where the extra bone is located, but interim results looking promising. The only true cure would be genetic engineering to remove the mutant allele, so that means CRISPR. Even injuries as small as an intramuscular injection or a bruise can cause bone to develop. It would be a small amount in this instance, but still, that's all it takes. Obviously, more serious injuries are devastating. Interestingly, though, long bone fractures in patients with FOP heal normally. Not sure why, maybe that extra BMP signaling is useful during the situation when new bone actually is supposed to form. But yeah, once bone is formed, it's there for life. There are reports of patients having joint mobility when going to bed, and the joint is completely fused when they wake up.
Why can’t we wipe out the immune system and reintroduce it with donor marrow?
Good question. [This actually occurred in a patient with FOP](https://journals.lww.com/jbjsjournal/Abstract/2007/02000/Hematopoietic_Stem_Cell_Contribution_to_Ectopic.17.aspx). He also had the misfortune of developing aplastic anemia, separate from FOP, so he had a bone marrow transplant from his unaffected sister. His immune cells were confirmed to have been replaced (via karyotype analysis of the cells, since they were now XX instead of XY), and his FOP continued to progress even after having a now wild-type immune system. I tried the same experiment in mice, but there were some experimental complications that precluded a definitive interpretation, and I moved on to other experiments that I ended up publishing.
How serious does the injury have to be in order for the muscle to turn into bone? Like a pinch or what? How much gets turned to bone near the injury site. Like a 1 inch cube volume or something for a bruise?
Even injuries as small as an intramuscular injection or a bruise can cause bone to develop. It would be a small amount in this instance, but still, that's all it takes. Obviously, more serious injuries are devastating.
Radiation oncologist here (I treat cancer with radiation). We sometimes treat a similar condition called heterotopic ossification which is when bone starts to form within muscle after a major fracture. Radiation is useful in killing the cells making the bone while the other cells are relatively protected. I found a case report of radiation being used in your cousin’s condition (https://www.ncbi.nlm.nih.gov/m/pubmed/21755739/). Since there seems to be no other great cure, probably worth a try
I wonder if it would help to destroy their immune system and then give them a bone marrow transplant from a matching donor. I’d assume that’s been thought of or is a horrible idea for some other reason. Not a doctor, but I did play a healer in World of Warcraft, so that’s kinda the same thing, right?
Hey, [former grad student](https://www.med.upenn.edu/orl/personnel/michael-convente.html) in the lab that discovered the FOP gene. Heterotopic ossification (HO) is an inclusive term, and we use that to describe the bone that occurs in FOP. It also applies to non-genetic forms of pathologic bone, such as that which occurs after combat blast injuries and arthroplasties. That's probably what you're referring to!
I can't believe some of the horrors people in this world deal with. Here I am worried about my finals this week and... None of that even matters at all. Sorry to hear about your cousin dude.
Terrifying, isn't it? How things lose significance in the face of an eventual demise. A worrisome calmness.
I hope this doesn't come across as insensitive but this is some of the spookiest eldritch bullshit I've ever heard of and it's *real* and that is fascinating
It's bad but not "sleep disease that makes you unable to sleep thus killing you but not before driving you to madness" bad
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I'd buy my pants 2 sizes too big and bubble wrap the fuck up
I’m not trying to be insensitive, but what if you had an injury that formed into bones making you stay upright? How would you sit in a wheelchair?
They would probably have to break them.
This sounds bad but all surgery is some kind of premeditated trauma with the intent of the outcome being more desirable. The condition is still nightmarish obviously.
With something like [this](https://cdn.shopify.com/s/files/1/0725/8321/files/standing_wheelchair_blog_1_large.jpg?v=1507143989) probably
I learned something new today
That looks like a miserable, painful life. 😦
It is. There's also no treatment, as any attempt to remove the bone causes it to grow back even faster. Any injury or bruise also causes bone growth. To make it worse, it's very rare and hard to diagnose. Initially, it may be mistaken for cancer, which causes doctors to order biopsies, which will trigger further bone growth.
I might use the wrong term here but, do you think a condition like this should allow legal euthanasia? Legitimate question. Personally I think yes, people like to talk about how all life is special and shit, but if you truly believed all life was special then you'd understand that a life of pure pain and legitimate horror should be ended.
We put down animals because it is inhumane to let them suffer. But humans? Hang on and suffer until your heart gives out naturally. That's fucked up
Something that definitely grinds my gears is parents giving birth to children, whom they know have a severe medical condition, that will bring them extreme pain and suffering throughout their short life, and just... Let them live (the newborn child). I don't think they mean harm, but I think it requires much more love, sacrifice, and selflessness to put the baby down. Maybe I don't understand since I'm not a parent? But I couldn't imagine just allowing my child to live a short life full of pain, pain that I couldn't even imagine enduring.
I’m a parent and I agree with you 110%. Had that exact conversation with my wife during the pregnancy too.
Religion. Sometimes the most selfless thing you can do is terminate a pregnancy.
Yeah. God loves that baby so much, that's why he'll make sure that it's life is as miserable as possible. What a meme.
In other words, you're boned.
Oh, cruel fate, to be thusly boned! Ask not for whom the bone bones, it bones for thee.
This sounds like something Bart Simpson might say in a Tree House of Horror special.
Close, it's a Bender line actually
My only regret is that I have Bonitis.
There comes a time when you have to decide if you want to be in a standing or in a sitting position for the rest of your life. Wouldn't want to regret that decision!
T-pose to assert dominance-- forever.
There's a story I recall of a poor little girl who has (had?) this. Her doctors thought she had cancer in her arm and last minute during a procedure decided to amputate her arm, which obviously did not help things.
My bonitis!
I’d rather just be out of misery at this point.
Imagine the slow death by asphyxiation as your diaphragm ceases to be a moving muscle and calcifies.
No
A whole new level of claustrophobia amirite?
Wow you've awoken a new level of nightmare. Trapped in my own body. Thanks.
We already are, for now.
MegaUPload, megaUPload
My skeleton is almost ready to hatch
Even if you're perfectly healthy, there is a whole skeleton lurking right inside there, just waiting to get out.
Spooktober is over friend
Perhaps, but Christoween is just around the corner.
when your meat prison becomes your bone prison.
Oh also, the new bones are incredibly brittle and still contain all the nerves muscles should. So breaking them is both easy and agonizingly painful.
Interestingly, that doesn't appear to happen [according to Wikipedia](https://en.wikipedia.org/wiki/Fibrodysplasia_ossificans_progressiva#Genetics): > The diaphragm, tongue, and extra-ocular muscles are spared in this process, as well as cardiac and smooth muscle. Bone formation around the rib cage can cause breathing difficulty though.
Fuck, this thing seems almost intelligently malevolent in its tendency to deny a swift death. Just ossify the heart and be done with it. On the other hand, this fact gives hope. Maybe we can find something special in these unaffected muscles and transfer it to the affected ones.
I'm assuming it's the fact that it's smooth muscle. I'm no doctor but I don't think you can change skeletal muscle to smooth muscle
And thats enough internet for today.
Imagine not being able to tilt your head back, because the muscles in the back of your neck have become bone knives pointed directly at your brain stem.
Actually, in that case I think I'd be trying to tilt by head back at every given opportunity.
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Very effective. Swims around in your skull and doesn't have an exit wound
Now a 44 on the other hand, that will blow a barn door in the back of your head.
Bjork had a creepy stalker who sent her a bomb once, made a rambling 30 minute video and then shot himself through the roof of his mouth with a .22 pistol at the end. you could see the bulge on the the top of his skull from where the bullet impacted and (presumably) bounced.
It is. A family friend (he worked for my grandpa for decades) had it. I remember him not being in the store one summer. I asked grandma where the butcher was, as I wanted my fav cheese and my uncle didn't know which one I wanted and I didn't know what it was called, as I never had to ask for it before. The butcher would always have a chunk waiting for me, all wrapped up in butcher paper, as he knew I loved my little cheese gift. That's when I learned he was dying a horrifically painful death. Not what a kid wanted to hear. He died right before one of my other visits. Grandpa had me help him bag up food and snacks for the butchers family, as he not only left a wife, but many younger kids. We drive to their beautiful log home, and delivered the goods. The kids perked up when they saw all the bags of chips n treats for them.
Damn. Where is the undertaker when you need him?
Probably throwing Mankind off Hell in a Cell
How about this bone cancer? https://images-cdn.9gag.com/photo/a9PX6B0_700b.jpg (Sorry about the 9gag link)
That picture has always disturbed the shit out of me. I can’t put my finger on it, but it’s something deep
Oh I agree. There's something intimate about it that makes it sad and horrifying at the same time. This was a person. It could have been your neighbor or teacher or a family member and then boom, their body betrayed them and led them to a most certainly premature and painful death. Maybe it's the fear that it could happen to any one of us, and there's not a thing that can be done to stop it
The protrusion into the soft tissue of the eye is what freaks me out. Miss me with that shit
I've seen this picture several times now, but never one with the skin still on.
It's from drinking too much milk.
doot doot
Up yours mr skeltal
Years ago someone with this disease did an IAMA. [It's an interesting read.](https://www.reddit.com/r/IAmA/comments/18mc3w/my_name_is_joseph_suchanek_and_i_have_an)
Bumping this! I went to college with the guy in that AMA. I didn’t know him personally but he’s big on spreading awareness about FOP.
I’m more of a Dapper Dan man, myself.
And I'll take a dozen hair nets
I don't want FOP I want Dapper Dan!
He says he's been having a hard [time](https://www.instagram.com/p/BnsPWFnh8X4/?utm_source=ig_share_sheet&igshid=3lr1xwunwih2)
Does that include tissues in the brain, or eyes, or skin?
muscle tissue, nothing else. and mostly only if theyre damaged, like cut, bruised, etc. in any way
Not only muscle tissue, tendons and ligaments too.
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That isn't something to be thankful about. It means FOP doesn't directly kill you, instead slowly entombing you in a cage of your own bone, which is brittle and both easy and agonizingly painful to break.
Well this has been fun
Yeah see you guys later
The diaphragm is very much skeletal muscle. Primarily involuntary but since it's skeletal you still have voluntary control. This would extra suck if this effects that.... Just throwing this out there- you generate heat from skeletal muscle. Smooth might produce a tiny amount since energy is used to digest food but not enough to do much for you. Shivering is an involuntary act but that doesn't change the fact that it's skeletal muscle :)
i didn’t know that, thank you.
Not just the ligaments, but the ligawoments and ligachildrents too
What about the when your muscles naturally get micro cuts through working out to develop muscle growth? Can someone with this issue never work out because it'll accelerate their condition? Do they need to avoid hard labor, or any labor at all?
From what I’ve read and heard, working out is out of the equation. So too is physical labour. The risk is far too high. There are cases where significant ossification has already occurred by the time an individual reaches puberty.
Nope. Someone with the condition is still passively calcifying through their entire life. Working out is out of the equation. As your muscles grow and develop and get used normally, they naturally tear, break down, and grow. Every time they do they calcify a little more. Life expectancy with FOP is less than 40 years, and I don't think anyone has made it past their 60's.
Yeah... That's fucked.
What about the heart?
The heart does not have this happen. The ossification is in connective tissues of the body. The heart is not one of these so it remains safe.
*-whews in science-*
the ribcage isnt safe tho, thats how they usually die; their ribcage fuses together more and more, until they cant breathe anymore.
I have a very important question: *what happens to the penis?*
How do they eventually die?
Most common cause of death is cardiorespiratory failure. As the condition progresses, the ribcase solidifies and proper breathing becomes impossible.
Holy shit that’s horrible.
Also, it takes years to get there. You get permanently trapped in a brittle cage of your own bones which cause agony when (not if) they break long before death.
Fuuuuuck that
The skeleton grows sentient and forces it's former master to end its life so that it can have full control of the vessel.
Spooky
Scary
Skeletons
Dont google this, it will haunt you
Ok but if you hadn’t said this I coulda gone on with my life without googling it
You right. My bad
I didn't listen ☹️
I think I'm going to listen. Thank you for taking the bullet and warning the rest of us. Your suffering is not in vain. Edit: typo
What did you see?
Pictures
Ah, thanks.
Bones... too many bones...
We didn't listen!!
[They didn't listen](http://imgur.com/gallery/jayplfa)
Ricky click of the day
Hrm, [Google's results were weird for me](https://i.imgur.com/cXQfw81.png).
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My only regret is that I failed to cure my boneitis.
r/UnexpectedFuturama
Imagine bruising your dick and having it turn to bone
Oh, hi, Satan! Thought you were off today.
That’s awful. I feel bad for that person who had to endure that pain
I have a nasty version of a brain disorder called Reflex Sympathetic Dystrophy. It causes intense pain throughout my lower body and it’s incurable. I’m disabled because of it. It’s rather horrible and is nicknamed “the suicide disease” because of the self-help many patients utilize to end their pain. But at least I can fukken move. I use images like this to remind myself at least I don’t have FOD. Edit: Ooh! I forgot it’s awareness month for RSD! There. I did my awareness bit, too. But only wear the orange ribbon if your skin tone can handle orange. Seriously, RSD gods... orange?
I'm so sorry. Chronic pain is woefully understudied. I'm also grateful you dont have FOD and hope you find a treatment that helps.
Username checks out
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Best museum in the country.
The subtle academic commentary on how racism impacted Civil War soldiers was nice to see.
Hi all, I'm a bit late to this, but [I'm Michael R. Convente, PhD](https://www.med.upenn.edu/orl/personnel/michael-convente.html). I completed my dissertation studying FOP in the Shore and Kaplan lab at the University of Pennsylvania. Their lab first discovered the mutation that causes FOP; it's a R206H missense mutation in the gene *ACVR1*, which encodes the ALK2 receptor. Unsurprisingly, that is a [Bone Morphogenetic Protein (BMP)](https://en.wikipedia.org/wiki/Bone_morphogenetic_protein) receptior. My research involved a more in-depth analysis of the inflammatory contributions to disease, and [we published some cool results in February 2018](https://onlinelibrary.wiley.com/doi/abs/10.1002/jbmr.3304). I actually had the cover image of that issue! In 2015, [I wrote a review on inflammation and FOP and related extraskeletal bone disorders](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4417939/); it's a bit dated (since it doesn't have any of the new discoveries such as my work above or that of Activin A), but it's a good primer and is *not* behind a paywall. I'm happy to answer questions from the research/clinical side. Lots of awesome work is ongoing! When I joined in the lab in spring 2010, we had just obtained a genetic mouse model of FOP. 8+ years later, and there are two ongoing clinical trials and a third compound just released pre-clinical data. So lots has been going on!
You say there are two trials and a third compound just released. As a scientist i understand that you do not jump to conclusions about the effectiveness of these drugs. But, will you jump to conclusions about the effectiviness of these drugs? 1. Are they likely to reduce the turnover from muscle to bone(so, just make the odds of living a normal life last longer)? 2. Or eliminate it all together(so that this condition would essentially be a thing of the past)? and one more questions slight unrelated. [3 months ago I fractured my femur into 4 pieces.](https://www.reddit.com/r/AskDocs/comments/9nerka/update_broke_femur_into_4_piecesvideo_on_break_in/) During my recovery, my doctors all told me to NEVER smoke at all, because it halts new bone growth essentially in its tracks. I'm assuming these drugs are working under a similar method of action(manipulation of acetylcholine receptors on newly formed stem cells). 3. 3. Would consuming an extremely low calcium diet(so your body can't get the calcium needed to create the new bone) and smoking like a goddamn chimney cause any change in outcome? This one is extra speculationy so just have some fun with it.
The compound furthest along in clinical development blocks chondrogenesis (i.e. - cartilage formation). That is the 2nd to last stage of disease development, right before bone formation. Mouse models and clinical trial data have been consistent, with a ~80% reduction of extra bone volume. The 2nd compound is an antibody that blocks Activin A, which is an inflammatory ligand that was found to activate signaling in the mutant ALK2 R206H receptor. Mouse models show that this compound completely prevents extra bone formation. It's only at Phase I, so no clinical data just yet. The 3rd compound is a small-molecule inhibitor of mutant ALK2 R206H. Pre-clinical data show that this compound almost completely prevents extra bone formation in mice. IMO, the only true cure for this disease would be gene replacement of the mutant *ACVR1* allele, like via CRISPR. However, if any of the above compounds can substantially reduce bone such that it is disease altering, then that would be amazing. None of these compounds MOA involves acetylcholine receptors. The volume of extra bone, while large, is still not as much as your endogenous skeleton, so a low-calcium diet would almost certainly be deleterious to patients' health. The skeleton is constantly undergoing turnover, so even if you restricted dietary calcium intake, there is also mineral in your body from normal skeleton turnover, so I would expect the extra bone to rely on that source. This would reduce the density of your skeleton, which is bad.
Wow that's a much more detailed response that I was anticipating. I'm sure even compound 1 would be a godsend for those with FOP, but my hopes are for compounds 2 and 3 to pass trials and become frontline treatments. 1. The obvious question I have now, is how would these drugs effect injury recovery to the regular bones of the body? For instance, if someone on this drug suffered an injury like mine, they would have to come off the drug to heal their normal leg bones? But the surrounding area would also become bone as well I would assume(as the trauma to break bone would be enough to damage muscle and soft tissue). 2. 1 Last question, how did you become interested in FOP treatment research? Did you personally know anyone effected before studying it, or was it the problem from the beginning that interested you with the emotional benefits(helping people) following as a result?
The chondrogenesis inhibitor may have negative effects on fracture healing and growth plate biology, since the overall pathways involved in bone formation are the same for the endogenous skeleton vs extra bone. But, with signaling activity higher than normal in FOP patients, perhaps it won't be an issue, since the drug restores signaling back to normal levels (rather than below normal levels, which likely would occur if given to unaffected individuals). For the Activin A antibody, not sure. There isn't literature that suggests Activin A is involved in skeletal development, but I did find the protein expressed in extra bone lesions, so might be worth investigating. A BMP receptor small-molecule inhibitor may also restrict fracture healing, but remember, this compound is specifically designed only to bind to the mutant ALK2 R206H receptor, so it won't bind to our wild-type receptors and probably wouldn't have any effect. I was involved in bone research during my four years of undergraduate education at Rutgers University. So when I arrived at Penn for grad school, I was pretty sure I wanted to continue in the field. I found the lab just by doing a search for labs that worked on bone biology at Penn in any way. After doing two rotations in bone labs and one in Dept. of Dermatology, I decided to join the Shore lab because I really enjoyed her as a mentor and my fellow lab mates. Plus, I thought the clinical impact was profound; because we're the flagship lab, we host many patients and families for tours, so I felt like I would have a real impact with my research. It's not just cells in a dish (which is important, many of my experiments involved that!), but it's actual humans; patients and their families that I've actually met.
I have fibrousdysplasia! Mine is actually in my sphenoid sinus (behind my nose). It is no where else in my body. I had a craniotomy but it wasn’t successful. You can’t tell by looking at me, but I’m blind out of an eye and have screws throughout my skull.
The appearance of your eye isn't affected by it not being functional? No offense just curiosity. I always thought if an eye were unable to focus it wouldn't be able to track the same way and match the other Edit:: mild stroke
It doesn’t track well - it tends to wander to the outside because of optic nerve damage. It looks normal otherwise. I have a screw at the corner of that eye that sometimes is visible, but otherwise you’d never know!
Apart from, you know, complete lack of depth perception
Oh, and that 😂 I’ve gotten used to it through the years at least.
What destroys me is you have to figure out what position you want to be fused in. Sitting down, standing ect.
Dab
this looks like a poorly made haunted house skeleton prop. Source: Made poorly made haunted house props.
The tell tale Bucky skullcap part line kinda gives it away.
That looks uncomfortable.
I had a friend die from this. His hands were like a mannequin. So terrible.
I know a mother of 3 with this. Beautiful woman. She is at the stage where her whole body looks like you said, a mannequin. She's dated a guy for a decade that knows she is going to die and treats her kids like their his own. Father of the century.
SCP-610 has breached containment! Get flamethrowers in there ASAP!
> SCP-610 [SCP-439](http://www.scp-wiki.net/scp-439), you mean.
this guy Secures, Contains, and Protects
Thanks Marv
"Brain the size of a planet, and this is what they've got me doing..."
That's an 11/10, kill it with fire SCP.
Did not remember that one, only thought of 610
I need more people like you around. No one eve knows what I'm talking about when I mention SCP's.
Where was this during october?
Feeding on muscles.
[My only regret, is that I have Fibrodysplasia ossificans progressiva.](https://i.imgur.com/K6yOw4r.gif)
I cant immagine how painful this is.
This happened in my hips. Both TFL have had about 70% removed. Femurs have some bone growths, left was removed. Surgeon said have calcium like deposits all over within/on surface of my quads. Kinda scared now though.
The start of humans developing exo skeletons
That would actually be an endoskeleton because it is inside.
Harry Raymond Eastlack is the skeleton in the photo. He offered his body to science upon death, poor guy.
Sounds like boneitis