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Thread: Researchers testing Tamoxifen for Scoliosis

  1. #1
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    Researchers testing Tamoxifen for Scoliosis

    Scientists are testing Tamoxifen, a breast cancer drug with a variety of other uses for Scoliosis. This drug was FDA approved in 1977.

    Here are links to two very recent studies

    February 26, 2009 - The effect of calmodulin antagonists on scoliosis: bipedal C57BL/6 mice model

    "This study has demonstrated that TMX is effective in changing the natural history of scoliotic deformities in C57BL6 mice model favorably."

    March 15, 2009 - The Effect of Calmodulin Antagonists on Experimental Scoliosis: A Pinealectomized Chicken Model

    "Conclusion. The incidence and magnitude of scoliosis in pinealectomized chicken may be decreased by the administration of TMX, presumably because of this drugs' calmodulin antagonism. Further studies on higher animals and dosage and timing are required."

    Tamoxifen blocks Calmodulin which is why scientists believe it reduces curve progression. The following paper explains how Calmodulin relates to curve progression.

    Platelet Calmodulin Levels in Adolescent Idiopathic Scoliosis (AIS): A Predictor of Curve Progression and Severity?

    "Conclusions: It appears that increasing platelet calmodulin levels correlate closely with curve progression and severity and that both treatment (brace or surgery) and skeletal maturity correlate with decreasing calmodulin levels."

    I assume that Calmodulin is a marker for inflammation. If you have knowledge of how this molecule works please post. Evidently the larger the curve the more Calmodulin the body produces. The more Calmodulin the body produces the faster the curve progresses. It's a dangerous feedback loop.

    I believe that the Scoliosis blood test that is due out in 2009/2010 is designed to measure circulating levels of Calmodulin. The test also measures cAMP levels to determine which of the 3 types of Scoliosis a child has. The blood test is based on this 2004 study. Scroll to page 5 to see the chart that visually explains the 3 types of Scoliosis. cAMP levels in Osteoblasts (cells that make bone) are supposed to decline as Melatonin levels increase. All children with AIS in this study had a dysfunction in that system.

    Group 1: (17% of sample) cAMP levels increase as Melatonin concentrations increase
    Group 2: (49% of sample) cAMP levels do not decline as Melatonin concentration increases
    Group 3: (34% of sample) cAMP levels slightly decline as Melatonin concentrations increase
    Group 4: (3 subjects) In the healthy control group cAMP levels decline rapidly as Melatonin increases

    Note: -9 is the level of Melatonin a healthy body produces. -7 and -5 levels of Melatonin are achieved with drugs.
    Last edited by Dingo; 03-25-2009 at 10:37 PM.

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    Related Tamoxifen information

    Dec 13, 2005 - Tamoxifen May Boost Short Boys' Height

    Tamoxifen is thought to lengthen the total growth cycle for children, this increases their final, adult height.

    Nov 30, 1999 - Tamoxifen may lower osteoporotic fracture risk

    Tamoxifen increases bone mineral density and reduces the risk of osteoporotic bone fractures.

    Bodybuilders' 'breast drug abuse'

    Bodybuilders who abuse steroids can develop "manboobs." They use Tamoxifen to counteract this effect.

  3. #3
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    March 15, 2009 paper concludes:

    "Conclusion. The incidence and magnitude of scoliosis in pinealectomized chicken may be decreased by the administration of TMX, presumably because of this drugs' calmodulin antagonism. Further studies on higher animals and dosage and timing are required."

    Uh, yeah ... I can see them lining up for chemo now ...

    Quote Originally Posted by Dingo
    I assume that Calmodulin is a marker for inflammation. If you have knowledge of how this molecule works please post. Evidently the larger the curve the more Calmodulin the body produces. The more Calmodulin the body produces the faster the curve progresses. It's a dangerous feedback loop.
    Wow. Dude, you're really reaching over your head here, playing lay geneticist, and assuming/interpreting a LOT of crap based on a molecule you admit you don't even understand. Furthermore, I'll believe the existence/efficacy of the cAMP test when I see it. It was (according to your 2006 article) due out last year. The only test currently used (and even on the horizon) to *remotely* predict progression is the Axial Biotest/Scolioscore, and it's only applicable to a *small* subset of female patients. It's basically useless to most in its current form.

    If they've attempted to gather test subjects for cAMP, wonder why they haven't tapped this community, or anyone known to this community? (unless someone is just staying extremely close-mouthed about this revolutionary discovery). Hmmm.

    Run a search on melatonin here, and see what you find. Same ol' bunch of nothing.

    Pam
    Last edited by txmarinemom; 03-26-2009 at 05:54 AM.
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    Okay I have had only one biochem course (albeit a 500 level one) and I can't wrap my mind around why in the world anyone would think cAMP would be specific for one medical condition as opposed to a million other things. That just sounds wacky but what do I know?

    I'll look at the paper and may comment further.
    Sharon, mother of identical twin girls with scoliosis

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    cAMP and Scoliosis

    Pooka1

    In Dr. Moreau's sample all children with Scoliosis had a dysfunction in the Melatonin signaling process. This is believed to be true for the general population. Put simply Melatonin's job is to clear out cAMP molecules from Osteoblasts. For children with Scoliosis this system doesn't work properly or in some cases at all. Recent studies have strongly indicated that this has something to do with Estrogen.

    The Scoliosis blood test will be out in 2009/2010. All children with Scoliosis will get this test. The first test measures cAMP levels to determine if a child has "Scoliosis" or just a physical abnormality. The second test measures blood levels of Calmodulin (99.9% sure). This second test is given 3 times several months apart to establish a baseline for Calmodulin levels. Children with Scoliosis will continue to get blood tests every 3 to 6 months. If these levels rise doctors will know that a child is entering the danger zone for curve progression.

    This gives doctors an important diagnostic tool. Should a child be in a brace 23/7? Is night bracing good enough or are levels so low that a child doesn't need a brace at all? In addition doctors will be able to measure Calmodulin levels when a child gets a new brace. A good brace will lower Calmodulin levels, a bad brace won't.
    Last edited by Dingo; 03-26-2009 at 09:54 AM.

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    There is too much to comment on in this last post. I will demur.
    Sharon, mother of identical twin girls with scoliosis

    No island of sanity.

    Question: What do you call alternative medicine that works?
    Answer: Medicine


    "We are all African."

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    Quote Originally Posted by Pooka1 View Post
    There is too much to comment on in this last post. I will demur.
    You ain't kiddin', sister! I do, however, have to comment on:

    Quote Originally Posted by Dingo
    A good brace will lower Calmodulin levels, a bad brace won't.
    ... but only to say ~*HUH???*~!

    Where in the world are you finding this crap?

    Pam
    Fusion is NOT the end of the world.
    AIDS Walk Houston 2008 5K @ 33 days post op!


    41, dx'd JIS & Boston braced @ 10
    Pre-op 53, Post-op < 20
    Fused 2/5/08, T4-L1 ... Darrell S. Hanson, Houston


    VIEW MY X-RAYS
    EMAIL ME

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    Pam, I think you are being a bit harsh.
    Dingo posted the links of where he was getting this stuff from.

    This is, after all, the "research" forum and lets not forget the "idiopathic" qualifier on the condition.

    But the conclusion of the paper authored by no less than 7 folks with MD
    after their name says

    It appears that increasing platelet calmodulin levels correlate closely with curve progression and severity and that both treatment (brace or surgery) and skeletal maturity correlate with decreasing calmodulin levels. Further investigation is necessary to determine whether in conjunction with standard radiographs, calmodulin may serve as a biochemical marker to assist in following patients with potential curve progression and to identify curves which have stabilized.

    I have to admit the "good" brace "bad" brace thing is a leap. But I would like to hear the viewpoint defended/elaborated on.

    I have to question the chicken or the egg aspect of the statement in the conclusion where they say treatment correlates with decreased calmodulin levels.

  9. #9
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    Quote Originally Posted by txmarinemom View Post

    Originally Posted by Dingo:
    A good brace will lower Calmodulin levels, a bad brace won't.
    ... but only to say ~*HUH???*~!

    Where in the world are you finding this crap
    Dingo's statement should be nominated for "something" of the month but I'll demur on what.
    Sharon, mother of identical twin girls with scoliosis

    No island of sanity.

    Question: What do you call alternative medicine that works?
    Answer: Medicine


    "We are all African."

  10. #10
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    CD ... I'll cut you slack ... you're also new - and wanting an answer.

    Dingo ... what's your slant?
    Fusion is NOT the end of the world.
    AIDS Walk Houston 2008 5K @ 33 days post op!


    41, dx'd JIS & Boston braced @ 10
    Pre-op 53, Post-op < 20
    Fused 2/5/08, T4-L1 ... Darrell S. Hanson, Houston


    VIEW MY X-RAYS
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  11. #11
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    Quote Originally Posted by concerned dad View Post
    Pam, I think you are being a bit harsh.
    Been said before. Several times over a few years.

    Quote Originally Posted by concerned dad View Post
    This is, after all, the "research" forum and lets not forget the "idiopathic" qualifier on the condition.

    But the conclusion of the paper authored by no less than 7 folks with MD
    after their name says

    It appears that increasing platelet calmodulin levels correlate closely with curve progression and severity and that both treatment (brace or surgery) and skeletal maturity correlate with decreasing calmodulin levels. Further investigation is necessary to determine whether in conjunction with standard radiographs, calmodulin may serve as a biochemical marker to assist in following patients with potential curve progression and to identify curves which have stabilized.
    A dermalogist (M.D. following name) could have penned this. I know you're not that niave.

    Quote Originally Posted by concerned dad View Post
    I have to admit the "good" brace "bad" brace thing is a leap. But I would like to hear the viewpoint defended/elaborated on.
    Please. That was HIS leap.

    Quote Originally Posted by concerned dad View Post
    I have to question the chicken or the egg aspect of the statement in the conclusion where they say treatment correlates with decreased calmodulin levels.
    So ... give proof y'all have solved the things neither of your docs (the scoli specialists/researchers) say (we'll exclude Rivard/Colliard as IF they were) and MAYBE I'll listen. You two are intent on dx why the rest of us progressed and instrumented, and frankly, it irritates me everytime I see either of you pen you know more than MY *scoli MD's*.

    Neither of you are qualified. PERIOD.

    Pam
    Fusion is NOT the end of the world.
    AIDS Walk Houston 2008 5K @ 33 days post op!


    41, dx'd JIS & Boston braced @ 10
    Pre-op 53, Post-op < 20
    Fused 2/5/08, T4-L1 ... Darrell S. Hanson, Houston


    VIEW MY X-RAYS
    EMAIL ME

  12. #12
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    Quote Originally Posted by txmarinemom View Post

    So ... give proof y'all have solved the things neither of your docs (the scoli specialists/researchers) say (we'll exclude Rivard/Colliard as IF they were) and MAYBE I'll listen. You two are intent on dx why the rest of us progressed and instrumented, and frankly, it irritates me everytime I see either of you pen you know more than MY *scoli MD's*.

    Neither of you are qualified. PERIOD.

    Pam
    Wow, I wasnt expecting THAT. What, one minute you'll 'cut me some slack" because I'm new here and 10 minutes later I'm irritating?

    Maybe I'm missreading this. But my take on the "you two" and "everytime either of you pen" seems to be directed at me as Dingo looks like he only has 7 posts.

    Look, I never claimed any more qualifications than a concerned dad. But I never said or implied that I "know more than your Scoli MDs". Did I miss your post where you shared the opinions of your scoli MD's on the topic Dingo brough up here? I didnt question your Dr's opinion of the topic, perhaps I questioned YOUR opinion.

    And the truth be told, I read your post asking where Dingo "got this crap" and I wanted to know the same thing. I was simply pointing out that he posted his source, and the the fact that 7 of the study authors we MD's. Dont you think it is good form to post a link to a source. I wish I had been able to do it on another thread where we were discussing something w/PNUTRO and I didnt post the paper. I wasnt defending or attacking the merit of the calmodulin link to scoliosis. Seems like a valid thing to discuss in a scoliosis research thread. And I dont think "where did you get this crap" really adds to the discussion. Perhaps asing him to elaborate on the leap he seemingly made coorelating calmodulin with good or bad braces would be interesting. Yeah, it seems really strange, but lets ask him to back it up.

    Regarding me being
    intent on dx why the rest of us progressed,
    well, I suppose I am although I dont know if I would put it exactly that way. It is very important to me to try to understand this stuff. I dont think I ever attempted to diagnose (DX) why anyone progressed but yeah, I have expressed an interest in understanding predictors of curve progression (Like age, curve type, Risser, menarch status....) but that is because these are the exact issues relevant to my daughter. Yes, I have very selfish reasons for participating on this forum. Just ignore me if I irritate you.

    But please, elaborate on this statement.
    So ... give proof y'all have solved the things neither of your docs (the scoli specialists/researchers) say (we'll exclude Rivard/Colliard as IF they were) and MAYBE I'll listen.
    That leaves me scratching my head.
    Last edited by concerned dad; 03-28-2009 at 01:57 AM.

  13. #13
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    Quote Originally Posted by txmarinemom View Post


    A dermalogist (M.D. following name) could have penned this. I know you're not that niave.

    Yes, it could have been a dermatologist, but I just found another paper from the same authors presenting the same data in the Journal Spine.

    They concluded by saying
    AcknowledgmentsThe authors thank the Scoliosis Research Society for their generous support of this project.

    I hope the SRS isnt funding dermatologists

    I read the whole paper. It didnt say anything about calmodulin coorelating with a brace being good or bad.
    But there was a heck of a coorelation with calmodulin levels and progressing (10 degrees or more) curves.

    Platelet Calmodulin Levels in Adolescent Idiopathic Scoliosis
    Do the Levels Correlate With Curve Progression and Severity?


    in Spine Volume 27 Number 7 2002

    time for bed

  14. #14
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    Calmodulin

    From the link Dingo posted, all the kids who progressed more than 10* had increasing calmodulin levels whereas a fourth of the kids who progressed less than 10* had increasing calmodulin levels.

    They later say that wearing a brace after surgery has an effect on the calmodulin levels. This suggests that levels are at least in part controlled by the curvature or stability of the spine and do not predict the future but rather reflect the present. They would have an interesting case if the 26% of kids who presently haven't progressed more than 10* but have increasing calmodulin levels go on to increase more than 10*. That would be tight if I'm understanding this correctly. In other words, it might be a more precise, earlier indicator of real-time progression than radiographs.
    Last edited by Pooka1; 03-28-2009 at 09:14 AM.
    Sharon, mother of identical twin girls with scoliosis

    No island of sanity.

    Question: What do you call alternative medicine that works?
    Answer: Medicine


    "We are all African."

  15. #15
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    and do not predict the future but rather reflect the present.
    thats where I was going with my chicken or the egg thing. you stated it much better.

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