The Axial Biotech Test is Here

[LindaRacine]

SALT LAKE CITY, Dec. 9 /PRNewswire/ -- Axial Biotech, Inc. announced today the commercial launch of a new DNA-based test that indicates the likelihood of progression to a severe curve for children diagnosed with Adolescent Idiopathic Scoliosis (AIS). This new molecular diagnostic tool marks a major advancement in which medical treatments can be personalized to patients diagnosed with this deforming disease. The test will be marketed under the name of ScoliScore(TM) AIS Prognostic Test.


Scoliosis is an abnormal curvature of the spine that affects two to three percent of the population, or an estimated 7 million people in the United States. Most often scoliosis is identified during school or sport screenings. Girls are eight times more likely than boys to have a curve progress to a point that treatment is required.


Currently, to determine whether or not a curve will progress patients are observed over a period of several years with the uncertainty of not knowing what the long-term outcome is likely to be. If the curve does continue to progress, the most widely accepted treatments are spinal bracing or ultimately spinal fusion surgery.


"For decades, spine surgeons have been looking for ways to determine which patients may progress and which may not," stated Ken Ward, M.D., Chief Scientific Officer for Axial Biotech. "Currently, most patients diagnosed with scoliosis have spinal x-rays repeated over several years because of the lack of precise clinical indicators or markers that can identify the likelihood of severe curve progression. This lack of predictive information is very inefficient and can cause adolescents to be given years of unnecessary radiation exposure."


ScoliScore(TM) was developed by utilizing a genome wide association study that identified a panel of 53 genetic markers associated with severe curve progression. This scoliosis research involved collecting DNA samples from over 9,500 patients from 85 clinical sites throughout the world. The test was then further validated in two separate clinical trials.


John Climaco, CEO and President of Axial Biotech, said that the launch of ScoliScore(TM) illustrates the company's commitment to making critical information from molecular diagnostic tests more broadly available to spinal surgeons, patients, and their family members. "Our long-term vision is to utilize the knowledge and capabilities gained from the development of this test and apply it to other spinal diseases," said Mr. Climaco.


The initial launch of the ScoliScore(TM) test will be to a small group of physicians in the U.S. The test will be processed solely at Axial's CLIA certified laboratory, which meets all applicable state and federal guidelines. It will be made commercially available to physicians nationwide in 2009. Axial Biotech has signed an agreement with DePuy Spine, Inc. to sell and market ScoliScore(TM).


For more information on the ScoliScore(TM) test, please contact Axial Biotech Customer Service at 877-AXIAL98 (877-294-2598) or visit the company's website at www.axialbiotech.com

[flowerpower]

Thanks for posting Linda, I was wondering when it would start being put to use. Our ortho dr. said he was going to start utilizing this test soon and I am eagerly anticipating this for my 10 yr. old.

Renee

[flowerpower]

Well, we saw our dr. this week for my older son's 3 yr. post op checkup and was able to ask about the ScoliScore testing for my 10 y.o. We were told that the testing should begin soon sometime after the first of the year BUT they will initially only be offering the test to girls between 9-13 y.o. with an initial scoliosis diagnosis of 16-25 deg. I'm bummed, my son falls perfectly w/in that range.

Renee

[nate03]

Yes, I just got the same type of disappointing news. My older son, just turned 14 and was diagnosed with a 22 degree curve last week, but he also is not eligible for the test. We were given the possible option of having him participate in the next trial, which we will gladly do to help others..........but it won't benefit him any personally. My daughter has been told she has mild scoli, and she is age 11, so I may try to have her tested. But, it is offered at very few hospitals right now and with it being so narrow I honestly don't know if I would find it very meaningful at this point anyhow.

At least they are getting a step closer to some answers.........but it definitely has a long way to go!

-Cara

[Rayknox]

If this test is accurate, does this mean that they will recommend spinal surgery for any child that qualifies irrespective of the degree of curvature at the time of testing.

[Pooka1]

If this test is accurate, does this mean that they will recommend spinal surgery for any child that qualifies irrespective of the degree of curvature at the time of testing.

:confused:

I think the main outcomes will be to:

1. avoid bracing kids who will not progress to surgery territory, and

2. avoid bracing kids who are going to progress to surgery territory absent some robust evidence bracing works.

[leahdragonfly]

The idea of the test also is to guide follow-up care. If a curve has a low risk for progression they would space out the doctor's visits and x-rays to reduce radiation exposure. And of course they are not going to recommend surgery for a kid based on the results irregardless of curve! Only kids with curves large enough for surgery will receive surgery recommendations. The genetic test will just be one more piece of information.

[ecnw]

It's too bad that they're only testing on girls, and at age 9. I would think most parents who would be interested in having it done would be those who have a family history, in which case it can start much younger than that.
Emily

[txmarinemom]

I've been wondering when this would become a huge revelation ... that really isn't.

Also would LOVE to hear what weight the SRS doctors place on this. Surely it will be a big topic (or ... not) in San Antonio for the 2009 conference (I am SO not missing this one! ;-).

Yes, it's a start ... but I also believe the efficacy (and applicable group of patients) is overrated. Your mileage may vary, as always ... but my JIS curve was ±35° when diagnosed at age 10. Beyond the parameters (even as a female) others have mentioned.

And, LMAO they signed with Depuy - and a "small group of physicians in the U.S." will initially be afforded the tools to launch. Makes you wonder where the organizations interests lie.

From the press release:

"ScoliScore(TM) was developed by utilizing a genome wide association study that identified a panel of 53 genetic markers associated with severe curve progression. This scoliosis research involved collecting DNA samples from over 9,500 patients from 85 clinical sites throughout the world. The test was then further validated in two separate clinical trials.

John Climaco, CEO and President of Axial Biotech, said that the launch of ScoliScore(TM) illustrates the company's commitment to making critical information from molecular diagnostic tests more broadly available to spinal surgeons, patients, and their family members. "Our long-term vision is to utilize the knowledge and capabilities gained from the development of this test and apply it to other spinal diseases," said Mr. Climaco."

9,500 patients from 85 clinical sites throughout the world isn't enough to prove it out? And what OTHER spine diseases when they can't even say it's effective for scoli prediction??

Pam

[concerned dad]

Well, it would be a great medical breakthrough if it worked.
I looked at their website to try to see some information about accuracy/ reliabality. They really dont have too much in their "publications" portion. It looks like a few poster sessions and presentations.
I would think a physician would want to see the basis of proof of just how and why this test works. Heck, a parent would want to see the same.
Of course, since the test does no harm (unless medical decisions are made based on results) I guess it doesnt hurt to try it.
The 13 year old cut off seems random. Does DNA change as you age?

I saw two things that were pretty interesting from their website (although not directly related to the DNA test discussion).

One of the presentations was given last year at the SRS meeting in Utah. I looked at the program here (http://www.srs.org/professionals/meetings/am08/Prelim.pdf) The talk was only 4 minutes long. Many of the talks were just 4 minutes. Is that usual for these medical conferences?
8:30 - 8:34 am Predicting Brace-Resistant Adolescent
Paper #6 Idiopathic Scoliosis (I dont suppose anyone here has a copy of the proceedings)
It looks like the talks were in rapid fire progression and they finished that day at noon. Perhaps physicians are used to processing information rapidly, but that seemed odd to me.

the other thing I was amused to see was from the axialbiotech website where they were talking about how great it was to do DNA work in Utah. They said:
Known Paternity: Fewer errors occur when studying extended families in Utah because the incidence of “non-paternity” (unknown or incorrectly attributed fathers) is lower. (<1% among Utah residents verses approximately 10% for the rest of the U.S. )

10%? wow.

Maybe I should get off the computer and spend more time with my dear wife.

[Pooka1]

the other thing I was amused to see was from the axialbiotech website where they were talking about how great it was to do DNA work in Utah. They said:
Known Paternity: Fewer errors occur when studying extended families in Utah because the incidence of “non-paternity” (unknown or incorrectly attributed fathers) is lower. (<1% among Utah residents verses approximately 10% for the rest of the U.S. )

10%? wow.

Maybe I should get off the computer and spend more time with my dear wife.

That could be explained easily if only about 5 guys fathered most of the kids in the state. :cool:

[LindaRacine]

One of the presentations was given last year at the SRS meeting in Utah. I looked at the program here (http://www.srs.org/professionals/meetings/am08/Prelim.pdf) The talk was only 4 minutes long. Many of the talks were just 4 minutes. Is that usual for these medical conferences?

I think it's different for every conference. SRS papers are 5 minutes long. They're pretty strict about it.

--Linda

[nate03]

Hi,
I recently came across this powerpoint presentation posted on the web regarding the genetic testing:


http://www.vinzenzgruppe.at/vinzenzgruppe/media/pdf/03Ogilivie.pdf/



I do not know much about the accuracy or validity of this presentation - the company who posted it is in Austria I think.........but I thought it might be interesting reading for those following the genetic testing progress.

[Pooka1]

Thanks for posting that, Cara!

Very interesting.

I note that their ideal future doesn't include bracing.

This is consistent with the literature on the efficacy of bracing in my opinion.

(I further note the ideal future doesn't include woo-woo "treatments" but I won't dwell on that.)

Evidence-based medicine... more than just a good idea.

sharon

[PNUTTRO]

Hi,
I recently came across this powerpoint presentation posted on the web regarding the genetic testing:


http://www.vinzenzgruppe.at/vinzenzgruppe/media/pdf/03Ogilivie.pdf/



I do not know much about the accuracy or validity of this presentation - the company who posted it is in Austria I think.........but I thought it might be interesting reading for those following the genetic testing progress.



Cara, this was authored by the same people in SLC, Utah--James Ogilvie

[PNUTTRO]

I really hate this test. 53 markers! are you out of your living mind?!

The first paper from Axial on the subject is from 2006, which ruled out a founder effect in related families. That is, there is not a single gene responsible. This isn't surprising given the variability of penetrence in families. It is neither dominant nor recessive trait.

The search for idiopathic scoliosis genes.
Ogilvie JW, Braun J, Argyle V, Nelson L, Meade M, Ward K.
Spine. 2006 Mar 15;31(6):679-81.

There are no subsequent publications of the larger study. Only the presentation at the SRS meeting. The power point presentation that Cara posted previously as well as the abstract and press release have inconsistent statements.

The power point states that all of their scoliosis patients are related. I find that quite peculiar.

The larger study that includes "1,200 unrelated Caucasian" patients. I don't see how this helps anyone of a different ethnicity.

The press release and the power point indicate 53 different markers. The abstract says 30. There is no public description of those markers because they are proprietary. But if their patent is in place, surely they could let us know some of them. Maybe they are related to previously identified genes. It would at least give Axial some validation.

Anyway. I don't know why I felt like I had to put in my two cents, but there it is. I guess I am just a pessimist about companies that will have a press release before publishing their results. Abstracts don't count--usually conference presentations are about incomplete or cutting edge data. Axial presented zero details. The abstract contains 2 figures that are proof of principle diagrams, not data.

p

[PNUTTRO]

http://www.axialbiotech.com/files/fda_approval.pdf

[concerned dad]

Above on Dec 30th I said
"They really dont have too much in their "publications" portion. It looks like a few poster sessions and presentations. "

I was suprised to see PNUTTRO discuss a paper in SPINE. I could swear that wasnt in their publications section 6 weeks ago. It certainly is there now. Maybe my mind is failing, I dont know. I went to look on the internet archive (Wayback machine) to see if their website was updated and when. They (Wayback) lags about 6 months so I'll have to wait and see if I'm loosing my mind.

[PNUTTRO]

I was suprised to see PNUTTRO discuss a paper in SPINE. I could swear that wasnt in their publications section 6 weeks ago. It certainly is there now. Maybe my mind is failing, I dont know. I went to look on the internet archive (Wayback machine) to see if their website was updated and when. They (Wayback) lags about 6 months so I'll have to wait and see if I'm loosing my mind.

I don't know about their website, but the publication in SPINE doesn't discuss data for this test anyway. It was a genetic study to see if they could ascertain a single mutation in their study population. They found none. Wishful thinking I suppose.

I wouldn't worry too much about losing your mind. You likely have a lot on your mind anyway.

p

[PNUTTRO]

Does anyone know if Axial provides genetic counseling with their DNA test, or do they give you the risk score and say see ya' later?


p

[debbei]

I asked my 9 year old's scoliosis doctor about this test a few weeks ago, and I was disappointed when he described the whole thing as a money-making venture that wasn't worth anything. :(

[concerned dad]

IMO, there is nothing wrong with a venture out to make money. In a weird way we are fortunate there are so many potential patients. An obscure illness would not necessarily draw the attention of the people with the money, skills and knowledge to investigate it.
But because of the money involved, discernment and oversight is necessary.

I wonder why your doctor thinks the test has no merit. It is my understanding that it is still in an alpha testing stage.

[LindaRacine]

http://www.orlandosentinel.com/news/local/orl-new-scoliosis-saliva-test-043009,0,6348003.story

Saliva test can predict scoliosis risk

By Robyn Shelton | Sentinel Staff Writer
April 29, 2009


Carly Bosse, 13, with her mom Maurie Bosse, holds her brace that she wears at night. She is benefiting from a new DNA test to determine the severity of scioliosis, or curvature of the spine. Carly was diagnosed with scioliosis at 11. (George Skene, Orlando Sentinel / March 18, 2009)

Doctors have learned more about the curve in Carly Bosse's spine from her genes than her X-rays.

A DNA screening that is being tested in Orlando shows the teen's scoliosis – an abnormal curving of the spine – probably will not need surgery.

The test, called ScoliScore, identifies patients at risk of severe curves, said Dr. Raymond Knapp, a pediatric orthopedic surgeon at Arnold Palmer Hospital for Children. It also indicates when youngsters are in little danger.

"We know when we have to treat someone aggressively, and when we can reassure parents that it's not going to get much worse," Knapp said. "This will basically change the way we treat scoliosis."

In Carly's case, the genetic profile puts her in an intermediate risk category, said her mother Maurie Bosse of Oviedo. That's good news because the curve is not bad enough to warrant an operation. But it's also fair warning to the 13-year-old, who wears a brace overnight.

"I know that she must keep wearing that brace every single night without fail," Bosse said. "She cannot go one night without it."

As many as three in 10 people suffer from some form of scoliosis, though many don't have noticeable problems from it. The side-to-side curve often is detected during routine exams, when a child bends at the waist with arms dangling and one shoulder appears higher than the other. Measurements and X-rays can be done to make a formal diagnosis.

Doctors typically follow patients with X-rays every six months to track the curve's progression, said Dr. Richard E. McCarthy, president-elect of the Scoliosis Research Society. Physicians will continue to watch patients closely, but the test helps them do so with more confidence.

"It's not something that replaces anything that we're currently doing, but it enhances what we're doing," said McCarthy from the University of Arkansas for Medical Sciences.

ScoliScore is based on 53 different stretches of DNA that have been linked to scoliosis. To take the test, patients spit into a cup to provide a saliva sample that contains their DNA. The sample is evaluated by ScoliScore's maker, Utah-based Axial Biotech.

The analysis is complicated, measuring genes that provide protection from scoliosis versus those that have been found to exacerbate the problem. Patients get a score from 0 to 200 – 40 and below is considered low risk; 41 to 180 is intermediate; and 181 to 200 is high.

"We're not diagnosing whether or not someone has the disease," said Eric Olson, a spokesman for Axial Biotech. "We're actually diagnosing something much more complex, which is how it will progress."

ScoliScore is being used on a limited basis for now at about 35 locations nationwide, including Arnold Palmer hospital, which has been involved in its initial testing. The screening costs nearly $3,000, but it is being given for free in the short-term, because most insurance companies do not currently pay for it. Olson expects health plans to cover the test as it becomes more widely used.

[leahdragonfly]

I asked my 9 year old's scoliosis doctor about this test a few weeks ago, and I was disappointed when he described the whole thing as a money-making venture that wasn't worth anything. :(



Hi Debbe,

I'm just wondering, did your daughter's doctor elaborate about his opinion of the ScoliScore? I know some Shriner's Hospitals are using the test, along with some other prominent scoliosis surgeons. My daughter doesn't fit the test criteria since she has JIS, but I would certainly be curious about it if she was eligible.

Take care,

[debbei]

Hi Debbe,

I'm just wondering, did your daughter's doctor elaborate about his opinion of the ScoliScore? I know some Shriner's Hospitals are using the test, along with some other prominent scoliosis surgeons. My daughter doesn't fit the test criteria since she has JIS, but I would certainly be curious about it if she was eligible.

Take care,


No he didn't. AFter I read the article last night his whole attitude just bothers me and I don't know what I want to do about it. :(

[txmarinemom]

As many as three in 10 people suffer from some form of scoliosis, though many don't have noticeable problems from it.

How did they arrive at a 30% figure, I wonder, vs. the standard 2-3% of the population?

[PNUTTRO]

http://www.orlandosentinel.com/news/local/orl-new-scoliosis-saliva-test-043009,0,6348003.story

Saliva test can predict scoliosis risk

By Robyn Shelton | Sentinel Staff Writer
April 29, 2009



"We know when we have to treat someone aggressively, and when we can reassure parents that it's not going to get much worse," Knapp said. "This will basically change the way we treat scoliosis."

In Carly's case, the genetic profile puts her in an intermediate risk category, said her mother Maurie Bosse of Oviedo. That's good news because the curve is not bad enough to warrant an operation. But it's also fair warning to the 13-year-old, who wears a brace overnight.

"I know that she must keep wearing that brace every single night without fail," Bosse said. "She cannot go one night without it."


I love this article. The kid has a genetic test done. She already wears a brace. She has to continue wearing the brace and be monitored. If she does progress anyway--this is a risk assessment, not a fact--she will have surgery.

How does this "change the way we treat scoliosis"?

[Dingo]

It's certainly possible that children with particular genes have a greater risk of curve progression. By comparison buildings constructed under different standards can be more or less earthquake resistant.

But regardless of construction methods buildings don't usually topple unless they are hit by an earthquake or some other destructive force. The Scoliometer isn't designed to tell us what that force is. The Scoliometer tells us the likelihood that a child's spine can withstand the force. Every teenage girl could take the Scoliometer and get a curve progression risk. Obviously the results which range from high risk to low risk would only be important to those few girls with the disease.

PNUTTRO said something that I think deserves a comment.

The first paper from Axial on the subject is from 2006, which ruled out a founder effect in related families. That is, there is not a single gene responsible. This isn't surprising given the variability of penetrence in families. It is neither dominant nor recessive trait.

The idea that a very common, worldwide childhood disease like Scoliosis could be due to founder effect (http://en.wikipedia.org/wiki/Founder_effect) is silly. I don't mean it's wrong because a lot of good ideas turn out to be wrong. I mean that hypothesis is silly. Did the scientists at Axial think that Scoliosis genes spread from one village in Britain to all of Britan to every nation around the globe at around a 2% or 3% frequency? Whoever came up with that hypothess probably shouldn't be working in science.

[leahdragonfly]

Dingo,

You have your terminology mixed up! The Scoliometer is also called the inclinometer and is a non-invasive measure of spinal rotation. It is used in school screening programs among other uses. You can purchase one from the NSF for about $55 I believe.

The new genetic test is called the ScoliScore, and I think that is what you are referring to.

BTW, I am personally not ready to throw out the idea of a genetic basis for scoliosis. My father has mild scoliosis, I was braced for moderate scoliosis and still have a 36 degree lumbar curve, my sister has a very mild curve, and now my young daighter has JIS. The jury is still out for my 4 y/o son, but his spine is definitely not quite straight either.

[Dingo]

Scolimeter - Scoliscore

DOH!

Thanks Leah! I have my terms mixed up. :eek:

I wouldn't absolutely discount genetics for every case of Scoliosis.

Your family might share a new, genetic mutation that causes spine disorders. Natural selection tends to be tough on these types of genes so in all likelihood it's new and very rare. These types of genetic disorders usually hit one child in thousands or even tens of thousands.

Maybe you guys share a genetic susceptability to an environmental trigger that leads to Scoliosis. This trigger could be a particular medicine, pollution or even a common virus like RSV.

Reyes syndrome (http://www.reyessyndrome.org/) works something like that. If you give the wrong kid Aspirin he is in big trouble.

Microbes tend to be far deadlier and more prolific. Flu virus appears to trigger Autism and Schizophrenia (http://www.sciencedaily.com/releases/2007/10/071016090135.htm) in kids with a particular genetic susceptability.

Endocardial Fibroelastosis (http://emedicine.medscape.com/article/896375-overview) was a fatal heart disorder that hit 1 child in about 5,000. Scientists noticed that it hit some families harder than others which suggested some kind of susceptability. They also noticed a correlation with mumps. When mumps vaccinations became widespread this heart condition completely disappeared.

My money is on something like that. Children with Scoliosis probably have a genetic susceptability to something. We just don't know what that is.

Scoliosis only has a 13% identical twin concordance rate (http://www.scoliosis.org/forum/showthread.php?t=8480). For most children environment is playing a huge part.

[txmarinemom]

Reyes syndrome (http://www.reyessyndrome.org/) works something like that. If you give the wrong kid Aspirin he is in big trouble.

Dingo, the use of aspirin - and risk of Reyes - has been well documented since the *late 70's*.

Don't tout it like it's something new.

[concerned dad]

Don't tout it like it's something new.

ummm, I missed the part where he suggested/ implied/ hinted/ alluded to (our understanding of) the relationship between Reyes and Aspirin being something new.
:confused:

[concerned dad]

I found an interesting paper this afternoon while looking for something else (I was trying to find out about the "International Scoliosis Society" as mentioned by DT in another thread – no luck)

The paper I did find was:

A History of Bracing for Idiopathic Scoliosis in North America
Reginald S. Fayssoux MD, Robert H. Cho MD, Martin J. Herman MD
Clin Orthop Relat Res
Published online May 22, 2009


(Dingo will appreciate the timeliness of the information.)

They went throught he history of bracing, starting with Hippocrates.

Their reasoning for the historical perspective is:
‘‘If you would understand anything, observe its beginning and its development.’’—Aristotle

They gave a discussion of all the braces we've talked about here from the Milwaukee to the SpineCor.

In the discussion section they talked about one of my favorite topics, assessing skeletal maturity by ways other than Risser. They then go on to discuss the genetic testing (hence, a posting in this thread);

Advances in genetic research have been the most exciting developments to date. James W. Ogilvie and colleagues have identified genetic markers, two major genetic loci and 12 minor loci, related to the development of scoliosis [41]. They found 95% of patients with idiopathic curves greater than 40* had these genetic markers. Using a simple genetic test, it may be possible to identify individuals at highest risk of developing severe scoliosis at the time of initial diagnosis. Armed with this information, followup care and treatment considerations can be individualized. Early bracing or minimally invasive surgical procedures may be recommended for those with a positive screen for severe scoliosis, whereas those at low risk based on DNA analysis may be spared unnecessary treatment.

Then they discuss internal bracing and fusionless procedures which I take to be VBS techniques.

All in all, an interesting paper.

Here is the link to the Abstract (http://www.ncbi.nlm.nih.gov/pubmed/19462214?dopt=Abstract)

[leahdragonfly]

Hi CD,

Thanks for the link to the abstract--it looks like a very interesting article, and I just e-mailed my friendly medical librarian to ask if she can get me the complete article. If I can maybe I can figure out how to place a hot link to it here (no idea how--haha).

Take care,

[Ballet Mom]

Wow, this looks like a very interesting article. Seems to touch on all the things we've been discussing on this forum. I would love to read it. If anyone does get access to it, please post if you're able. Thanks!

[leahdragonfly]

I have the entire History of Bracing article and it is very interesting. If someone can please tell me how, I will post it or a link to it--it is 11 pages long. Anyone out there who knows how to do this? I have it in PDF form.

[LindaRacine]

Hi Leah...

If you picked up the PDF on the internet, you can simply copy the link location by right clicking on the link that you used to get to the PDF. If not, I think all you have to do is attach the file to a message (see Additional Options below the Reply to Thread box).

Regards,
Linda

[leahdragonfly]

Ok Linda, I followed your instructions but the file limit for attaching PDF's is 100 kb, and the article is 364 kb. CD, are you out there? You're good at attaching files and links, any tips?

[concerned dad]

Sorry, been out of town for a couple of days.

Leah, the issue isnt so much attaching the file (we could work around that by breaking the PDF into 100K chunks and posting in pieces). The issue is copyright infringement.
Papers published in Scoliosis Journal (SOSORT) are posted online. There is no problem linking to them.
Some SpineCor papers are posted online (presumably after having received permission).
But I believe this paper is protected by copyright. I do not know the specifics of the law. I have shared, via email, certain papers with other members here and at least my conscious was fine as it was between parent and parent (our intent is to help our kids, not open a commercial enterprise).

If memory serves me correctly, it is OK to post extracts (I think the limit is 10% of the text) so long as it is attributed.

I could be wrong on this and if anyone has any details or workarounds it would be great if all of us could share the literature openly. But, until then, I think we're going to be limited to sharing relevant papers via email.

[concerned dad]

In another thread in research I mentioned this paper (http://www.sosort-lyon.net/pdf/saa1.pdf)by the Axial Biotech guys that was presented at SOSORT last week.

I was hoping it might be a topic of interest, and perhaps it is more appropriate to post it here.

They have a graph at the bottom of the Abstract comparing the calculated risk of progression for two groups of kids. One is braced and the other is not. This is a whole new way of looking at the issue of bracing and I think it is fascinating.

It took me a while to figure out just what they were plotting but I think I have it. To get a data point for the two groups at, say, Scolioscore 100, they take all the kids with that Scolioscore and present the percent of those who progressed to 50 degrees. (it looks to me like 25% of the observation group and 35% of the braced group with scolioscores of 100 progressed).

If bracing had a positive effect, we would expect to see a significant divergence of the curves. (They didnt see that, in fact, they saw the opposite which would suggest, if you had a scolioscore of 100 your risk of progression would be decreased if you did NOT wear a brace).

Now, they didnt go on to make any major conclusions about bracing efficacy. I would love to see the actual data points on their curves to see just how scattered things are but I am betting it is proprietary.

The conclusion they did make was that in designing bracing studiies, not only do researches need to consider all the usual stuff (curve type, age, maturity, etc) but they also need to consider genotype homogeneity. You can't compare bracing efficacy between, say, two 11 year old girls, Risser 0, 30 degree curves with one having a "scolioscore" of 25 and the other having a "scolioscore" of 150.

But I thought this was an interesting way to use the data they collected. I wonder if they have enough detail to break it down and analyze other differences between the kids (besides braced vs no braced, maybe by geographic latitude (to look at Dingo's Melatonin thing) or by brace type or by use of an excercise therapy.

Comments anyone?

[LindaRacine]

Ok Linda, I followed your instructions but the file limit for attaching PDF's is 100 kb, and the article is 364 kb. CD, are you out there? You're good at attaching files and links, any tips?
Leah...

Would you mind sending the PDF to me in an email? (linda@scoliosislinks.com).

--Linda

[LindaRacine]

CD...

That's pretty interesting. As always, however, we don't know how good the braces were (did they all get at least 50% in brace correction?). And, we don't really know how compliant the kids were (the study says compliant, but I'm sure that's self reported at best).

Regards,
Linda

[Ballet Mom]

Hi CD,

I guess after looking at that chart by the Axial Biotech guys, I just don't believe it. It makes me think there's something wrong with the Scolioscore, not with bracing. Or, as Linda pointed out, something wrong with the bracing used in this study. Of course, I'm sure they're a lot smarter than me and I don't have any of the info, but just on the face of it, don't you think that if bracing caused a greater risk of progression than not bracing, that all these very intelligent orthopedic surgeons would have continued to brace in the face of years of evidence? I just don't buy it. And especially with the results my daughter has had....surely she is not the only patient out there who has been successful with bracing. (Yes, yes, I know that she could continue to progress once she stops bracing, but I'm thrilled to have that roll of the dice, nothing is guaranteed for anyone in this scoliosis world I'm afraid).

Are the Scolioscore guys sure they're pinpointing the risk of scoliosis progression itself and not something else like the tendency towards double-jointedness in people, which seems to be a possible indicator for potential scoliosis? I could see genes being detected by the test that reflect double-jointedness and then there could be an additional trigger that causes the progression of scoliosis (like Dingo's hypotheses) that would not be being shown with the DNA test, which make the results not useful in my thought process.

Anyhow, for what it's worth, their study just doesn't make logical sense to me .

[concerned dad]

Hi CD,


Are the Scolioscore guys sure they're pinpointing the risk of scoliosis progression itself and not something else like the tendency towards double-jointedness in people, which seems to be a possible indicator for potential scoliosis? .

Well, whatever they are pinpointing they sure think it is related to scoliosis.

A risk of progression score was calculated using 53 genetic markers with utility for calculating the risk of AIS curve progression from <25° to >40° before skeletal maturity or >50° at maturity (1-200).

I would likke to know just strong the predictive capabality of the test is.


They calculate a "risk". Qualitatively, a higher scolioscore yields a higher risk. But, say you have a scolioscore of 100 which equates roughly to a risk of 35% that you will progress to either greater than 40* (before maturity) or greater than 50* (at maturity), it still doesnt tell you "for sure" anything. It just tells you you have a 35% chance of that happening.

The greater utility (in my mind at least) is for comparisons of groups like they did in this study. You would have expected different outcomes for the same genotype with bracing and observation, and they didnt see it (with a fairly large sample size).

It would be nice to see a full paper discussing this rather that a brief abstract. Maybe one will be out soon.

[Pooka1]

Several good points being made by folks.

First, I agree the bracing efficacy could be artificially low due to many factors:

1. non-perfect compliance
2. not weeding out connective tissue cases from AIS
3. improperly fitted braces
4. etc.

These issues and others make the bracing literature a mess which also means there could be a cohort out there who do respond to bracing and can avoid surgery in their life. We may never know because it is so hard to do a study and because the treatment is not benign.

It is interesting that this isn't the first reference we have seen to bracing being LESS effective to stop progression that observation. Maybe there is a cohort out there whose scoliosis does get worse with muscle atrophy from brace wear. (Note I don't think this applies to part-time, night-time bracing if the kid is exercising during the day.) As I have suggested, bracing and PT work in opposite fashions so they likely both can't work for keeping a person sub-surgical their entire life. But if true, that means there is something to the muscle tone theory which I trashed just yesterday. :D

In re Scoliscore, they may be pin-pointing other things like double-jointedness also but they are definitely pin-pointing the risk of progression in scoliosis also. It's the only thing they measured (or at least showed on that graph) so it has to be what they are pin-pointing. Now if they don't have enough subjects or they otherwise have holes in their method then it is still a false conclusion.

Also, I am suspicious of graphs without error bars. In this case, though, they are not trying to tease out a nuance between the two curves so it seems okay to say they are the same curve.

[PNUTTRO]

It would be nice to see a full paper discussing this rather that a brief abstract. Maybe one will be out soon.

Yeah, you'll never see that paper. This has been one of my biggest complaints about this group.

The problem with the chart is that it is a self fulfilling prophecy. They plot ScolioScore against Risk of Curve progression. Isn't that what the scolioscore is supposed to predict? If they showed actual curve progression then it would validate the scolioscore--but they don't show that. It would be nice some actual numbers. I haven't been able to find any numbers in any publication. They cover it by saying the data is proprietary.

Let us know if you can find any real data.

I checked the references in the paper that you linked to, regarding genetics data.

James W. Ogilvie and colleagues have identified genetic markers, two major genetic loci and 12 minor loci, related to the development of scoliosis [41].
The above statement is not supported by data in the paper (ref 41). They say that there is a founder effect for 2 different genetic loci, but there is no linkage data to support it and no mention of 12 other minor loci. They don't even say what those 2 major loci are. Granted, I only spent a little time on it, but I am pretty sure its not there.

p

[Pooka1]

Yeah, you'll never see that paper. This has been one of my biggest complaints about this group.

The problem with the chart is that it is a self fulfilling prophecy. They plot ScolioScore against Risk of Curve progression. Isn't that what the scolioscore is supposed to predict? If they showed actual curve progression then it would validate the scolioscore--but they don't show that. It would be nice some actual numbers. I haven't been able to find any numbers in any publication. They cover it by saying the data is proprietary.

Let us know if you can find any real data.

Wait a minute. They are calibrating the Scoliscore with the known outcomes (percentage/risk of progression seen for each patient in which a scoliscore of a given magnitude was determined).

That is a calibration curve, not a self-fulfilling prophecy as I understand what they are doing. I could be wrong. It is interesting how certain ranges of Scolisores yield the same risk.

Having so many markers reminds me of the guys who try to fit curves empirically with high order polynomials rather than work for a determinisitic solution from known physical principles. So they just keep adding terms to improve the fit but other problems ensue. I don't know the specifics.

[PNUTTRO]

Having so many markers reminds me of the guys who try to fit curves empirically with high order polynomials rather than work for a determinisitic solution from known physical principles. So they just keep adding terms to improve the fit but other problems ensue. I don't know the specifics.


I'm not sure I really understand their graph, but your right, it just seems a little too perfect.

[Pooka1]

I'm not sure I really understand their graph, but your right, it just seems a little too perfect.

I know why you are suspicious of the graph... it can easily seem "cooked" which is what I think you were picking up on.

I had to ponder it for a long time but I think both the x-axis and the y-axis are actual data.

The independent variable (x-axis) is the suite of markers that go into generating a "scoliscore." These markers were identified from a population of kids with scoliosis with known outcomes, perhaps the same set of kids that they calculated progression risk from. Now that sounds circular and "self fulfilling" but I don't think it actually matters if the same population of kids that was used to generate the marker suite is used for the dependent variable (y-axis) because they are only calibrating at the moment.

The Y-axis is generated by knowing the outcome of each patient and generating the risk of progression just from knowing the outcome. They then calibrate that with the scoliscore.

It sounds fishy because there are really three things here... scoliscore, risk of progression, and calculating scoliscore using risk of progression. It's like hindcasting I believe which is done with data in hand where you know the answer ahead of time. It's okay to calibrate only. But I think once they calibrate their scoliscore, it can then be used as advertised... to predict the risk of progression based on the suite of markers that go into the scoliscore.

That's what I think is going on and I certainly could be wrong. I wonder if they will ever get this stuff out in a peer-reviewed format. And I hope the journal gets some math guys to look it over.

[Pooka1]

Had another thought...

What bothered me at first is that they don't tell us how they calculate the scoliscore. At some point, that has to be the dependent variable, not the independent variable like the graph shows.

What I think they did was determine the marker suites of patients with known outcomes by having a graph of risk (%) on the x-axis as the independent variable versus VARIOUSLY CALCULATED scoliscores on the y-axis (i.e., opposite to the graph they show). Then they picked the one that yielded the best curve (highest slope maybe).

Then they took the optimized scoliscore and calibrated it against the risk, making the scoliscore the independent variable which is how it has to be if they want to use it the way they do.

I wish we had a math guy on the group. Maybe Ti Ed, as an engineer, could comment.

[Pooka1]

There's a problem that I just noticed here...

The text states,

"There was little statistical difference in the curves representing risk of progression versus curve severity when the two groups were compared. Graph 1"

But the graph is labeled (at least) risk of curve progression (%) versus scoiliscore.

It is impossible to know what they mean but my best guess is that is their calibration curve.

[rohrer01]

the other thing I was amused to see was from the axialbiotech website where they were talking about how great it was to do DNA work in Utah. They said:
Known Paternity: Fewer errors occur when studying extended families in Utah because the incidence of “non-paternity” (unknown or incorrectly attributed fathers) is lower. (<1% among Utah residents verses approximately 10% for the rest of the U.S. )


That is funny, considering if this is the same test that me and my family contributed our DNA to, and I'm pretty sure it is, we are not from Utah. My father is "Mormon" but I am not. Maybe they used the LDS geneological records to choose candidates. That would be the only way they could have tracked me down. Now how did they find out I had scoliosis? Hmmmmm..... It's a scary world out there! LOL :eek::DCan they do that?

[debbei]

the other thing I was amused to see was from the axialbiotech website where they were talking about how great it was to do DNA work in Utah. They said:
Known Paternity: Fewer errors occur when studying extended families in Utah because the incidence of “non-paternity” (unknown or incorrectly attributed fathers) is lower. (<1% among Utah residents verses approximately 10% for the rest of the U.S. )


That is funny, considering if this is the same test that me and my family contributed our DNA to, and I'm pretty sure it is, we are not from Utah. My father is "Mormon" but I am not. Maybe they used the LDS geneological records to choose candidates. That would be the only way they could have tracked me down. Now how did they find out I had scoliosis? Hmmmmm..... It's a scary world out there! LOL :eek::DCan they do that?

I was referred by a friend, and all 3 of my children and I participated. We are not Mormon, and I know who my kids' father is. :) Axial has sent a letter for the second time asking for more DNA from son#2.

I think I'll be getting my daughter's test results tomorrow.

[rohrer01]

They never gave us any personal results. Just updates on the progress of the study. It is very encouraging, at least maybe my grandchildren will benefit from it. After talking to more of my family members, scoliosis is way more prevalent than I knew. I never knew ANYONE in my family has it. As it turns out I have a paternal grandmother, maternal aunt, and a neice. My daughter also developed a very mild case. And of course, myself. Definitely sounds genetic to me! Axial Biotech doesn't have all that history on me because I found out AFTER me and my parents sent in our DNA. I would like to know if it recessive, dominant, or a combination type gene, or many genes contributing. I was hoping they would send me this information at least, but nothing. :(

[debbei]

They never gave us any personal results. Just updates on the progress of the study. It is very encouraging, at least maybe my grandchildren will benefit from it. After talking to more of my family members, scoliosis is way more prevalent than I knew. I never knew ANYONE in my family has it. As it turns out I have a paternal grandmother, maternal aunt, and a neice. My daughter also developed a very mild case. And of course, myself. Definitely sounds genetic to me! Axial Biotech doesn't have all that history on me because I found out AFTER me and my parents sent in our DNA. I would like to know if it recessive, dominant, or a combination type gene, or many genes contributing. I was hoping they would send me this information at least, but nothing. :(

No, we were part of the study but didn't get any personal results either. About a month ago, my daughter took the test that is now on the market which resulted from the study. That's the one we're getting results on.

[rohrer01]

No, we were part of the study but didn't get any personal results either. About a month ago, my daughter took the test that is now on the market which resulted from the study. That's the one we're getting results on.


It will be very interesting to hear the results of this test, if you are willing to share. Maybe they only needed a second sample of your son's DNA because a labby dropped it, it got contaminated, or it didn't turn out in the PCR machine, or they left the gel running too long and lost it all? Could have been many things gone wrong with his sample. I'm sure it's nothing to be too concerned about.
My daughter is too old to be in the study sample, she is 20. She won't even get another x-ray unless she has pain. She doesn't want to be exposed to the radiation, can't say that I blame her, though. There are risks with everything.
Something kind of interesting though, is my son has such a slight curvature that it's not considered "scoliosis" but he does have spina bifida occulta, which I also have. I wonder if there is a correlation there. Maybe a different study is being conducted on that. I'm not up on all the current studies, my life has been going in a completely different direction until recently.
I also wonder if there is a correlation to the gene/s connected with Marfan's syndrome, as scoliosis is very common in people with Marfan's. I have a nephew with Marfan's. My personal opinion is that it is that not one single gene is involved. And if a person gets a "good" copy of a gene and a "bad" copy of the same gene, there can still be enough bad protein (gene product) floating around that the good stuff isn't enough to completely suppress the disease. That would explain why my daughter has a very mild case.
In conclusion to this, all I can say is I need to read the reasearch that's been done. Something I have obviously neglected to do. I feel priviledged to have been part of the study and hope some good comes from it.
I look forward to hearing from you. I hope I wasn't confusing or too off topic.
:o

[debbei]

It will be very interesting to hear the results of this test, if you are willing to share. Maybe they only needed a second sample of your son's DNA because a labby dropped it, it got contaminated, or it didn't turn out in the PCR machine, or they left the gel running too long and lost it all? Could have been many things gone wrong with his sample. I'm sure it's nothing to be too concerned about.
My daughter is too old to be in the study sample, she is 20. She won't even get another x-ray unless she has pain. She doesn't want to be exposed to the radiation, can't say that I blame her, though. There are risks with everything.
Something kind of interesting though, is my son has such a slight curvature that it's not considered "scoliosis" but he does have spina bifida occulta, which I also have. I wonder if there is a correlation there. Maybe a different study is being conducted on that. I'm not up on all the current studies, my life has been going in a completely different direction until recently.
I also wonder if there is a correlation to the gene/s connected with Marfan's syndrome, as scoliosis is very common in people with Marfan's. I have a nephew with Marfan's. My personal opinion is that it is that not one single gene is involved. And if a person gets a "good" copy of a gene and a "bad" copy of the same gene, there can still be enough bad protein (gene product) floating around that the good stuff isn't enough to completely suppress the disease. That would explain why my daughter has a very mild case.
In conclusion to this, all I can say is I need to read the reasearch that's been done. Something I have obviously neglected to do. I feel priviledged to have been part of the study and hope some good comes from it.
I look forward to hearing from you. I hope I wasn't confusing or too off topic.
:o

Sure, I'll let you know when I find out. Apparently, the results are into the Dr's office, but my daughter's ortho doesn't want to 'interpret the results for us'. Instead, he wants this Axial representative who he works with to give us the info. My daughter is one of the first in his office to have the test, so I guess they're trying to work out their process.

As for my son, this is the 3rd sample he is sending in. They told us on the 2nd sample that there was someting exciting with his DNA, and they even sent him a gift card as compensation for the 2nd sample. He's sending it in for free this time. :) I don't know--it just makes me want to watch him carefully as he gets older. He turns 18 this fall, so maybe I'll bring him back to the ortho one more time for a look over.

I'll keep you posted,

[rohrer01]

Wow! I wonder what exciting thing they found? Does he have scoliosis?

[debbei]

Wow! I wonder what exciting thing they found? Does he have scoliosis?

Hi,
yes the son who they've requested extra DNA twice does have a mild case of scoliosis.