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Researchers testing Tamoxifen for Scoliosis

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  • #16
    Originally posted by concerned dad View Post
    thats where I was going with my chicken or the egg thing. you stated it much better.
    Yes I knew where you were going with it and was trying to support the idea. The fact that post-surgical braced patients have different [calmodulin] trajectories from those of post-surgical non-braced patients is very important in this regard. There is no reason the concentration trajectories should differ if not due to real-time physical movement of the spine it seems.
    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."

    Comment


    • #17
      And we are talking TINY TINY movement, perhaps limited to above and below the fusion, since the modern instrumentation is so good at immobilizing the spine that 95% of kids don't have to have any physical restrictions whatsoever.

      Also, so few kids wear a brace after surgery that I'm wondering if the sample size was so small as to be completely meaningless. The group that does wear a brace post-op is by definition not representative of the vast majority of fused kids.
      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."

      Comment


      • #18
        Okay I changed my mind and will comment on this one part of your post...

        Originally posted by Dingo View Post
        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.
        These comments presume that:

        1. even if a tight connection can be established between [calmodulin] trajectories and curve progression, that IN NO WAY implies that any brace we currently have is going to stop any progression.

        2. There is no evidence either way whether night bracing is not as effective as 23/7 bracing or whether either is superior to observation.

        3. I see no way to connect the decision to brace or not to this research, irrespective of which way it goes. That is, even if you can show a tight connection between [calmodulin] concentration or trajectory and progression, that says NOTHING about the ability of any brace to stop that progression.

        4. Your suggestion to define "good" braces as those that lower [calmodulin] and "bad" braces as those that fail to do this can't relate to the final outcome of bracing because there is no evidence that I can see from the research blurb that manually manipulating the [calmodulin] with a brace is going to affect curve progression. The brace comments in the blurb strongly suggest [calmodulin] is tracking after (tiny?) the fact intra-spine movement.
        Last edited by Pooka1; 03-28-2009, 12:12 PM.
        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."

        Comment


        • #19
          Upon re-reading, it seems like points # 1 and #3 are the same. Apparently I felt strongly enough about it to note it twice.

          If bracing manually affects [calmodulin] in a good way then why isn't there any good data that any braces work?

          Isn't that consistent with the thought that [calmodulin] or trajectory isn't going to be helpful? That is, because some braced patients still go on to need fusion, and if it is only a predictor of progression, then that still leaves us with the question of whether any brace can work better than observation, yes?

          Maybe I'm missing something here.
          Last edited by Pooka1; 03-28-2009, 01:02 PM.
          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."

          Comment


          • #20
            Originally posted by Dingo View Post
            [...] I assume that Calmodulin is a marker for inflammation. If you have knowledge of how this molecule works please post.
            The blurb you posted says what calmodulin is...

            "Calmodulin is a calcium binding receptor protein which mediates muscle contractility (actin and myosin) in the platelet."
            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."

            Comment


            • #21
              Originally posted by Pooka1 View Post

              3. I see no way to connect the decision to brace or not to this research, irrespective of which way it goes. That is, even if you can show a tight connection between [calmodulin] concentration or trajectory and progression, that says NOTHING about the ability of any brace to stop that progression.

              .
              Yes, but it sure would be nice to know when you should try or not.

              I think the point they made in the Spine paper was that perhaps, with further research, they could determine if a curve was prone to progress. So, perhaps one day they will be able to say,
              "take this blood test, if your level is low, yeah, you have scoliosis but dont bother bracing because it doesnt look likely to progress" and
              "if it is high you may want to give bracing a try"
              That may reduce the number of kids needlessly braced.

              of course, for all this to work, the data has to actually be valid/meaningful.

              There is a correlation between fox deaths and divorce in Finland. Not likely they have anything to do with each other.

              Comment


              • #22
                Originally posted by concerned dad View Post
                Yes, but it sure would be nice to know when you should try or not.

                I think the point they made in the Spine paper was that perhaps, with further research, they could determine if a curve was prone to progress. So, perhaps one day they will be able to say,
                "take this blood test, if your level is low, yeah, you have scoliosis but dont bother bracing because it doesnt look likely to progress" and
                "if it is high you may want to give bracing a try"
                That may reduce the number of kids needlessly braced.
                Yes I see that point but about a quarter of the kids who didn't (hadn't yet?) progressed more than 10* had increasing [calmodulin], the same situation as all the kids who progressed. The test would suggest those kids would progress but they didn't. SO if this goes down this way, at least a quarter of the kids who might not progress will think they will and might be needlessly braced.

                of course, for all this to work, the data has to actually be valid/meaningful.

                There is a correlation between fox deaths and divorce in Finland. Not likely they have anything to do with each other.
                Good points.
                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."

                Comment


                • #23
                  I have only one second so....

                  I will respond to the rest of this thread tonight.

                  Concerned Dad

                  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.

                  Scientists know that by reducing Calmodulin levels they can reduce or perhaps eliminate curve progression.

                  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."

                  ---

                  Half of the scoliosis blood test due out in 2009/2010 is based on that discovery. It's actually 2 tests. The first measures cAMP levels to determine if a child has "Scoliosis" or just a physical abnormality. The second half of the test measures what I am 99.9% sure is Calmodulin. This test is given a few times per year to predict curve progression. When a spine is "out of whack" Calmodulin levels rise. Calmodulin is closely related to inflammation. That's why this test can be used to see if a brace is working for a particular child.

                  If you read Dr. Moreau's comments in this article from 2007 they make a considerable amount of sense now that his blood test is imminent.
                  Last edited by Dingo; 03-28-2009, 04:27 PM.

                  Comment


                  • #24
                    hmmmmm,

                    Dr. Moreau: By observing plasma levels of molecular and biochemical markers, clinicians will be better able to monitor bracing efficacy as well as improve bracing systems. This will help us to identify the best brace for a specific child.

                    Based on these changes, orthopaedic surgeons will be able to alter treatment options. Instead of putting a child in the same brace for 2 to 3 years to determine its effectiveness, physicians may be able to determine whether this is the most appropriate brace for the patient within a month, based on specific markers.


                    Interesting, so THIS is where you get this "crap".
                    Looks interesting.
                    He's from St Justine's though

                    Comment


                    • #25
                      I cannot reconcile in my mind why ANYONE would recommend an estrogen receptor blocker for adolescents.

                      Comment


                      • #26
                        Originally posted by PNUTTRO View Post
                        I cannot reconcile in my mind why ANYONE would recommend an estrogen receptor blocker for adolescents.
                        I dont think they are recommending it for humans.
                        They are recommending it for chickens.
                        Maybe because it is a convienent calmodulin antagonist.

                        If it works, maybe they will look for a more appropriate drug for use in children that also blocks calmodulin.

                        I'll let Dingo speak for him/her self but perhaps a more appropriate title for the thread would have been
                        Researchers testing Tamoxifen for Scoliosis in chickens
                        or
                        Researchers testing calmodulin antagonist for scoliosis

                        I too cant imagine anyone giving a kid tamoxifen.
                        But you never know what will come out of the chicken research,
                        Why, thats as crazy sounding as injecting botulism toxin for cosmetic reasons........ wait a minute

                        Comment


                        • #27
                          Tamoxifen for Scoliosis

                          Concerned Dad might be correct. They are using Tamoxifen for testing purposes but plan to make a different drug for children.

                          However it's important to keep in mind that although altering Estrogen levels in a growing child sounds bad there is a good chance that Estrogen levels are messed up to begin with.

                          November 2008 - Estrogen cross-talk with the melatonin signaling pathway in human osteoblasts derived from adolescent idiopathic scoliosis patients.

                          Tamoxifen is both an estrogen agonist and antagonist. It may get estrogen levels closer to normal than they would otherwise be. I don't know if that's true but it might be why scientists are testing this particular drug.
                          Last edited by Dingo; 03-28-2009, 11:09 PM.

                          Comment


                          • #28
                            Calmodulin and bracing

                            Pooka1

                            1. even if a tight connection can be established between [calmodulin] trajectories and curve progression, that IN NO WAY implies that any brace we currently have is going to stop any progression.

                            2. There is no evidence either way whether night bracing is not as effective as 23/7 bracing or whether either is superior to observation.


                            The blood test will tell your doctor if a bracing strategy is working or not. If Calmodulin levels don't drop after bracing it's probably a waste of time. If they drop like a rock you'll know that the brace is doing it's job. Right now there is no rapid way to find out if a brace is helping or even hurting. Calmodulin is closely related to inflammation. I'm not sure if that's why the feedback is so helpful but I suspect so. For obvious reasons a curved spine probably produces more inflammation than a straight spine. Calmodulin is probably a useful marker in that process.

                            I'm hoping that a microbiologist or someone who understands this molecule will explain how it functions. I can't find much helpful information on the specifics of Calmodulin.
                            Last edited by Dingo; 03-28-2009, 11:33 PM.

                            Comment


                            • #29
                              Science links

                              Pam

                              Whenever I post something I've already done my best to understand it. I certainly don't understand everything. I'm simply doing my best to sift through the latest research. I always post links so that others can make up their own minds. Better yet you may see something that I missed and help me.

                              Comment


                              • #30
                                Dingo, The thing you have to remember is that some folks here have seen a lifetimes worth of treatments and theories that have gone no where.
                                For example, electrical stimulation was once thought to be promissing.
                                I bet they could come up with other examples.

                                My point is, a new person coming here touting chemo for scoliosis is not going to get the warmest reception (even though I think it is worthwhile to at least discuss).

                                Comment

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