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Old 14-06-2010, 08:56 AM
Dingo Dingo is offline
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[SIZE="4"]Part 4[/SIZE]

Question 14) When mice donít produce Osteopontin Scoliosis doesnít occur. The following quote is from your patent, ďOPN-knockout mice do not develop a scoliosis (NS) even if they are in the same genomic background (C57BI6/J)Ē. What does this tell us about OPN and Scoliosis?

Dr. Moreau) This experiment indicates that OPN is required to trigger scoliosis onset. It is worth mentioning that bipedal surgeries (amputation of forelimbs) performed on C57Bl6 mice, which are naturally deficient in melatonin synthesis, induce scoliosis through an acute condition (the surgery) resulting in an elevation of OPN levels (since wound healing is a naturally inflammatory process), which cannot be decreased in absence of melatonin because melatonin is a powerful OPN inhibitor. The same phenomenon occurs after a pinealectomy (removal of the pineal gland, which is the main source of melatonin) in chickens. The fact that treatments of pinelactomized animals with pharmacological doses of melatonin prevent scoliosis has nothing to do with a lack of melatonin but is rather associated with the property of melatonin to repress the production of OPN. Having said that, I do not recommend the use of melatonin because (1) melatonin may trigger many side effects including the promotion of dormant tumours and (2) genetic predisposition toward scoliosis may affect how the cells respond to melatonin and so far the results published by my colleague Dr. Machida are not at all convincing about the usefulness of melatonin.

Question 15) Can Osteopontin stay elevated even after skeletal maturity?

Dr. Moreau) Osteopontin levels decline in healthy females at around 15 years of age and typically remain low during adulthood. Interestingly, in most of IS patients, OPN levels decline during puberty, which may explain why spinal deformities progressing toward surgery occur only in less than 1% of IS patients. It is also worth mentioning that elevation of OPN has been detected in adult pathologies like cancers (mesothelioma, bone metastases associated with breast or prostate cancers), cardiac conditions, Parkinsonís diseases, etc but the presence of other factors like sCD44 protect these patients against the development of scoliosis.

Question 16) High levels of Osteopontin are associated with a variety of autoimmune diseases and cancers (source). Does this suggest that children or adults with Scoliosis may have an increased susceptibility to other disease processes?

Dr. Moreau) It may be premature to make such a claim. However the opposite may be true since scoliosis is a clinical feature (phenotype) often associated with many syndromes and pathological conditions.

Question 17) Most adolescents with Scoliosis have small curves that donít progress significantly. Osteopontin is known to increase in the presence of bacterial infections (source). Could some of these small curves be the artifacts of childhood disease?

Dr. Moreau) As mentioned previously, many factors can stimulate the production of OPN, including some bacterial infections, especially those with mycobacteria. For most healthy individuals exhibiting no genetic predisposition for scoliosis, OPN is a protective cytokine that helps fight, among others, mycobacterial infections. It that case, elevation of OPN wonít trigger scoliosis because other factors like sCD44 are there to counteract the negative effect of OPN on scoliosis. In children having a genetic predisposition for scoliosis, exposure to mycobacteria and other environmental factors could induce scoliosis onset. Having said that, I want to clarify to parents and patients that scoliosis is not an infectious disease!

Question 18) In 2003 Dr. Vert Mooney, a spine surgeon from California released a study that found that Torso Rotation Strength training was beneficial for children with Scoliosis (source). Since that time two small studies produced similar results (source) (source). Here is a short news video of a young girl doing TRS (news video). Does your research shed any light on why this kind of strength training might be helpful?

Dr. Moreau) I cannot comment about the validity of these studies because it is difficult to actually demonstrate the degree of effectiveness of any method or device to prevent scoliosis or spinal deformity progression, because the natural history of most IS patients indicates that they are non-progressors. In other words, this method like any other should be challenged by performing clinical trials only with individuals presenting a high risk of progression. Such a selection will be possible using our scoliosis blood tests.
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