|
Displaying items by tag: Scoliosis blood test
One of the most common questions I have parents and patients ask me in regards to idiopathic scoliosis is “is there anything we can do from nutritional stand point?” Nutrition and scoliosis is a poorly researched and understood topic to say the least and while many theories and “experts” claim to have developed a scoliosis nutritional supplement, none (to date) have had any significant impact on the natural course of the idiopathic scoliosis condition.
A rare study into the topic of nutrition and scoliosis, published in 2007 by online publisher Wiley Interscience, examined the hair samples of 59 idiopathic scoliosis patients with scoliosis spine curves ranging from mild to very severe. The researcher tested for copper, zinc, and selenium levels in each patient. The researchers discovered no statistically significant differences in the levels of copper or zinc in the scoliosis test group in comparison to a non-scoliosis spine group, but the selenium levels did differ significantly.
The selenium levels in the scoliosis spine tested group were significantly lower than the non-scoliosis spine group, however this information in and of itself is not sufficient to conclude idiopathic scoliosis is caused by selenium deficiency.
This new piece of information in regards to idiopathic scoliosis may have been lost or disregarded as trivial, but not particularly helpful, except some of the group breaking work being done in the development of the much anticipated scoliosis blood test could help researchers learn more about the effect of selenium on idiopathic scoliosis progression.
The one of the two parts of the scoliosis blood test measures the patient’s levels of a cytokine called Osteopontin (OPN), which primarily regulates bone growth. The scoliosis blood test researchers found levels of OPN levels elevated 2 to 3 times higher than normal in patients with severe scoliosis and could potentially be used to screen “at risk” patients before they even start to develop a scoliosis spine curvature.
So what’s the connection between low selenium levels and increased Osteopontin levels in patients with idiopathic scoliosis you ask? Well, it’s a little know fact that therapeutic doses of selenium (200 micrograms) can have the effect of naturally decreasing OPN levels, which, logically, means that selenium deficiency could increase the risk of allowing Osteopontin levels to risk must more rapidly and to higher amounts in the genetically pre-disposed scoliosis patient.
Idiopathic scoliosis is a complex and multi-factorial condition with many possible environmental risk factors/triggers. Selenium deficiency may play role in some case, but not in others. Further research on the relationship between selenium deficiency and OPN levels in the scoliosis needs conducted to determine if selenium supplementation can potentially be used to prevent the development of a scoliosis spine in genetically “at risk” patients.
Please click here to receive a FREE SCOLIOSIS TREATMENT INFORMATION KIT.
The first scoliosis brace attempts date back to as early as 400 A.D. and have been applied in every conceivable manner (without success) since then. The first metal scoliosis brace we constructed by Ambrose Pare in 1575 and again, didn’t work. Since then scoliosis brace makers have continued to innovate without success. Hard scoliosis brace, soft scoliosis brace, night time scoliosis brace, flexible scoliosis brace, rotational scoliosis brace, traction scoliosis brace; in the end each attempt has prove to be as feeble as the last (not due to lack of effort, application, or funding).
Please click here to receive a FREE SCOLIOSIS TREATMENT INFORMATION KIT.
The first scoliosis brace attempts date back to as early as 400 A.D. and have been applied in every conceivable manner (without success) since then. The first metal scoliosis brace we constructed by Ambrose Pare in 1575 and again, didn’t work. Since then scoliosis brace makers have continued to innovate without success. Hard scoliosis brace, soft scoliosis brace, night time scoliosis brace, flexible scoliosis brace, rotational scoliosis brace, traction scoliosis brace; in the end each attempt has prove to be as feeble as the last (not due to lack of effort, application, or funding). The main problem with scoliosis brace treatment isn’t application, but rather process. As it turns out, treating a condition that is primarily a neurological condition like it is primarily a skeletal spine problem doesn’t work too well (shocking….sarcasm). This very simple understanding of idiopathic scoliosis makes almost 3500 years of scoliosis brace treatment completely obsolete and practically worthless. In fact, Axial Bio-Tech (developers of the Scoliscore genetic test) did a comparison study of brace treated and un-treated scoliosis patients and found absolutely no difference between the two groups long-term treatment outcomes, even when compared genetically. Scoliosis brace treatment has absolutely no effect on the natural course of the idiopathic scoliosis condition. Essentially scoliosis brace treatment and doing nothing have exactly the same effect….None. So why do orthopedic doctors and some mis-guided chiropractors continue to prescribe a worthless and obsolete protocol like scoliosis brace treatment. Well the long answer is “this is the way we do things around here” syndrome and the short answer is financial gain. Thousands of academic reputations and careers are based on the faulty logic that scoliosis brace treatment works and is effective, so to do an about face and reverse one’s position on the topic (even in the face of over-whelming evidence) would be career suicide for most. The other motivation (financial gain) is a less complicated explanation, but probably more compelling. Scoliosis brace treatment generate hundreds of millions of dollars worldwide every year and you know what they stay about not finding the solution, when there is good money in prolonging the problem. So how do we break out of this never-ending cycle of scoliosis brace treatment failure? Well, the good news is that we probably don’t have to; prognostic idiopathic scoliosis technology (Scoliscore genetic testing for idiopathic scoliosis, the scoliosis blood test, ect) will probably spell the death of scoliosis brace treatment all by itself. These new technologies will provide a “heads up” to parents and patients in regards to their child’s idiopathic scoliosis condition and long before scoliosis brace treatment is indicated, so the scoliosis treatment market will naturally move towards more pro-active scoliosis treatment solutions like the Early Stage Scoliosis Intervention program we feature on this website. In fact, preliminary flowcharts and treatment models that focus on Scoliscore genetic testing for idiopathic scoliosis that completely eliminate scoliosis brace treatment and scoliosis surgery have already been developed and are being tested as you read this right now. Please click here to receive a FREE SCOLIOSIS TREATMENT INFORMATION KIT.
Scoliosis spine treatment is confusing and getting more so by the day. Scoliscore genetic testing for scoliosis, scoliosis blood test, 3-D CAT scan images, the recent boom in prognostic testing for idiopathic scoliosis has only served to further muddy the waters for parents whose experience with the condition thus far includes a 3-5 minute conversation with an orthopedic doctor who says “your child’s spine is crooked, where it should be straight”. So where does one begin? Well, at the beginning of course. Idiopathic scoliosis is multi-factorial condition in which a person’s genetic predisposition and environmental influences (trauma, nutritional, infection, daily living habits, ect) combine to create the condition. Approximately 80+% of scoliosis of spine cases occur between the ages of 9-14 and 7 times more frequently in females than males (which remains unknown, but it is believed to be due to the earlier timing of adolescent female growth spurts). Idiopathic scoliosis of spine seems to be stemming a neurological under-development in the brain stem that becomes apparent when the child’s skeletal growth out paces their ability to coordinate the pelvis, lower trunk, upper truck, and/or head position. This neurological under-development is most likely the result of a genetically inherited combination. It is important to note that these child’s brains aren’t broken, nor are they missing pieces, they are appear to simply be under-developed; which means they can be neurologically “caught up” with a specialized neuro-muscular rehabilitation program that specifically targets the involuntary postural control centers in the brain. This fundamentally and basic understanding of idiopathic scoliosis as primarily a neurological condition that has its primary effects on the scoliosis spine make the very essence of scoliosis brace treatment and scoliosis surgery obsolete. Current scoliosis treatment for scoliosis of spine mandates no scoliosis treatment of any kind (Observation only every 6 months), based on the clinical data showing “only” 20% of idiopathic scoliosis of spine case progress to a significant degree. Unfortunately, that is little comfort to those 20% whom do develop progressive curvatures and only slightly more comfort to the 80% of cases whom live in a state of fear and anxiety for the next 4-5 years hoping they aren’t part of the other 20% of idiopathic scoliosis case that are progressive. The problem in this situation has always been how can we separate out the 20% likely progressors from the 80% non-progressors? That’s where the scoliscore genetic testing for scoliosis comes in. It can very accurately predict the genetic likelihood of a scoliosis spine progressing to the scoliosis surgery threshold. The information from the scoliscore genetic test for scoliosis can be combined with the environmental influences provides the patient and parents with a comprehensive and accurate outlook on the scoliosis of spine condition. Once armed with this information, a scoliosis treatment plan can focus an appropriate amount of attention and invasiveness towards reducing and minimizing the impact of the environmental factors which combine with the genetic predisposition and cause the scoliosis of spine to begin progressing regardless of scoliosis brace treatment and possibly leading to scoliosis surgery. However, it one can successfully dis-engage enough of the environmental influences from the genetic predisposition it is conceivably possible to alter the natural course of the condition and even one day lead to a cure for idiopathic scoliosis. Please click here to receive a FREE SCOLIOSIS TREATMENT INFORMATION KIT.
Scoliosis of spine is a mulit-factorial condition with both genetic predisposition and environmental factors combining to produce the disease named "Scoliosis". Certain individuals have greater genetic pre-disposition than others and certain individuals are exposed to more environmental factors than others. A mixture of too much of one or the other spells trouble.
However, not all it lost. When one applies this understanding of scoliosis as multi-factorial condition it becomes clear that we can alter the natural course of the condition by simply altering one or both of the components that actually cause the condition (genetic predisposition and environmental factors).....Especially now, since scoliosis genetic testing (Scoliscore) for predisposition is now available.
For the first time in human history we can now predict whom is most at risk for developing severe scoliosis and implement a personalized and customized scoliosis treatment plan that is intended not to reduce the spinal curvature (which is the intended goal), but to reduce and minimize the environmental factors that are engaging the genetic predisposition that is causing the condition. That's right folks, we're talking about a pathway to a potential cure for scoliosis! It's truly an amazing breakthrough in both thought and technology.
Scoliosis brace treatment fails to alter the natural course of the condition simply because it fails to reduce or eliminate ANY of the environmental factors that combine with the genetic pre-disposition that cause the condition. Scoliosis surgery completely disregards any attempt to even treat the cause of idiopathic scoliosis at all and relies on brute forced correction to artificially hold the spine straight(er).
None of the current “main-stream” scoliosis spine treatment (scoliosis brace treatment or scoliosis surgery) approaches will ever lead us to a cure or a better way to treat scoliosis....ever. So why do we continue to do it? Well, new ideas (even when they are good ones) aren’t always readily accepted at first…..especially when they contradict the conventional wisdom that many fortunes and academic reputations have be built and based upon. How do we break the cycle of failed scoliosis treatment? It has been said that no system can reform itself and that is probably true. Asking the orthopedic community to cut their financial throats and admit complete and utter incompetence in the field of scoliosis treatment isn’t likely to happen anytime soon, so a change in the future of scoliosis treatment will most likely come from grass roots efforts in articles like this one and technological breakthroughs like Scoliscore genetic testing and the upcoming scoliosis blood test which will allow researchers to test and demonstrate the effectiveness (or lack thereof in the case of scoliosis brace treatment and scoliosis surgery) of a scoliosis treatment’s ability to bend the natural course of the condition towards a cure. Please click here to receive a FREE SCOLIOSIS TREATMENT INFORMATION KIT.
Scoliosis genetic and blood tests pave the way for early stage scoliosis intervention in the future.
The treatment of idiopathic scoliosis, particularly brace and surgical treatment, has been controversial. It has been difficult to determine which patients were going to progress, and who would benefit from conservative treatment (scoliosis exercise, bracing, etc.) or "require" surgery.
The eagerly awaited scoliosis blood test which measures level of osteopontin (OPN) will hopefully we used in conjunction with the patient's genetic risk analysis and can be used to determine how effective a conservative treatment approach may be for any given patient before they fail therapeutic trial. Please click here to receive a FREE SCOLIOSIS TREATMENT INFORMATION KIT.
From the patent for the soon-to-be-released (hopefully) scoliosis blood test......
"The present invention also encompasses the monitoring of the biomarkers disclosed herein to assess the efficacy of numerous approaches to prevent scoliosis and curve progression such as any physical therapies (e.g. postural exercises, physiotherapies, biomechanical stimulations by manipulation or using specific devices e.g. vibrant plates); the monitoring of bracing efficacy or development of novel braces; the monitoring of new surgical devices with or without fusion of vertebras, and the monitoring of the efficacy of specific diet, nutraceutical and/or pharmacological scoliosis spine treatments.
Without being so limited, the first measure after the braces have been applied could be performed 1 month later to determine for instance whether the braces are well adjusted and determine whether the patient is compliant to the treatment. Thereafter, the monitoring could be performed every three to six months depending on whether high OPN levels are detected or not. This method of the present invention may advantageously reduces the requirement for x-rays. X-rays could be performed for instance only at visits where OPN levels detected are too high.
Any amount of a pharmaceutical and/or nutraceutical and/or dietary supplement compositions can be administered to a subject. The dosages will depend on many factors including the mode of administration. Typically, the amount of anti-scoliosis composition (e.g. osteopontin inhibitor or selenium compound) contained within a single dose will be an amount that effectively prevents, delays or reduces scoliosis without inducing significant toxicity "therapeutically effective amount".
The effective amount of the osteopontin inhibitor or selenium compound may also be measured directly. The effective amount may be given daily or weekly or fractions thereof. Typically, a pharmaceutical and/or nutraceutical and/or dietary supplement composition of the invention can be administered in an amount from about 0.001 mg up to about 500 mg per kg of body weight per day (e.g., 10 mg, 50 mg, 100 mg, or 250 mg).
Plasma selenium concentration was thus measured in pediatric populations (AIS vs. healthy controls) to determine whether or not low selenium levels correlate with higher OPN concentrations in AIS. Results show a correlation between high OPN levels and low selenium levels in scoliotic and asymptomatic at risk children." Please click here to receive a FREE SCOLIOSIS TREATMENT INFORMATION KIT ASAP.
The long awaited scoliosis blood test will hopefully be available soon. It was suppose to be out several years ago and no one knows why it has been delayed. There is some speculation around the campfire that the problem lies in the CD-44 receptor blocker medication the could be offered in conjunction with the blood test if it indicates high levels of osteopontin (OPN), but no one knows for sure.
Here is a copy of the blood test patent. It is pretty long and dry lawyer type language, but it does have some pearls of knowledge sprinkled through out and it mentions that high levels of selenium may be effective in naturally driving down high leves of osteopontin (OPN). I have left the entire document unedited since it is technically a legal document and some folks may want to sort through the raw data themselves.
(WO/2008/119170) METHOD OF DETERMINING RISK OF SCOLIOSIS Biblio. DataDescriptionClaimsNational PhaseNoticesDocuments Note: OCR Text Note: Text based on automatic Optical WO 2008119170 20081009 -->METHOD OF DETERMINING RISK OF SCOLIOSIS TITLE OF THE INVENTION CROSS REFERENCE TO RELATED APPLICATIONS [0001] This application claims priority, under 35 U. S. C. § 119(e), of U.S. provisional application serial No. 60/909,408, filed on March 30, 2007 and on U.S. provisional application serial No. 61/025,571 , filed on February 1, 2008. All documents above are incorporated herein in their entirety by reference. STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT [0002] N/A. FIELD OF THE INVENTION [0003] The present invention relates to methods of determining the risk of developing scoliosis, methods of stratifying a subject having a scoliosis, methods for assessing the efficacy of a brace on a subject having a scoliosis, and kits therefor. BACKGROUND OF THE INVENTION [0004] Spinal deformities and scoliosis in particular, represent the most prevalent type of orthopedic deformities in children and adolescents, while adolescent idiopathic scoliosis (AIS) represents the most common form of scoliosis. [0005] The etiology of adolescent idiopathic scoliosis (AIS) remains poorly understood resulting in the traditional paradigm that AIS is a multi-factorial disease with a genetic predisposition.(1'7)The occurrence of a melatonin signaling dysfunction in cells derived from biopsies obtained intraoperatively from affected AIS patients has been reported.8 [0006] Unfortunately, there is no proven method or test available to identify children or adolescents at risk of developing AIS or to identify, which of the affected individuals may require treatment due to the risk of progression. Consequently, the application of current -->treatments, such as bracing or surgical correction, is delayed until a significant deformity is detected or until a significant progression is clearly demonstrated, resulting in a delayed and less optimal treatment.29 [0007] The present description refers to a number of documents, the content of which is herein incorporated by reference in their entirety. SUMMARY OF THE INVENTION [0008] More specifically, in accordance with the present invention, there is provided a method for determining the risk for developing a scoliosis comprising monitoring osteopontin (OPN) expression in a sample from a subject over time; wherein an OPN expression that increases in the subject sample over time is indicative that the subject is at risk for developing a scoliosis. [0009] In a specific embodiment, the monitoring begins when the subject is about three years old. In another specific embodiment, the monitoring is performed by measuring OPN expression at a frequency of at least about once per month. In another specific embodiment, the monitoring is performed by measuring OPN expression at a frequency of at least about once per six month. In another specific embodiment, the method further comprises measuring sCD44 expression in a sample from the subject. In another specific embodiment, the monitoring OPN expression is performed using an enzyme- linked immunosorbent assay (ELISA) or radioimmunoassay (RIA). [0010] In accordance with the present invention, there is provided a method for determining the risk for developing a scoliosis comprising measuring osteopontin (OPN) expression in a sample from a subject; wherein an OPN expression that is higher in the subject sample than that in a control sample is indicative that the subject is at risk for developing a scoliosis. [0011] In another specific embodiment, the subject is a likely candidate for developing a scoliosis. In another specific embodiment, the subject is a likely candidate for developing adolescent idiopathic scoliosis. In another specific embodiment, the subject is pre- diagnosed as having a scoliosis. [0012] In another specific embodiment, the subject is pre-diagnosed with adolescent idiopathic scoliosis. -->[0013] In accordance with another aspect of the present invention, there is provided a method of stratifying a subject having a scoliosis comprising measuring osteopontin (OPN) expression in a sample from the subject; whereby the measuring step enables the stratification of the subject into a scoliosis subgroup. [0014] In accordance with another aspect of the present invention, there is provided a method for assessing the efficacy of a brace on a subject having a scoliosis comprising measuring osteopontin (OPN) expression in a sample from the subject prior to and at least once after bracing the subject, wherein an increase in the OPN expression after as compared to prior to bracing the subject is indicative that the brace is ineffective. [0015] In a specific embodiment, the determining the OPN expression after the bracing is performed at least one month after the bracing. In another specific embodiment, the determining the OPN expression after bracing the subject is performed at least 2 months hours after the bracing. In another specific embodiment, the determining the OPN expression after bracing the subject is performed at least three months after the bracing. In another specific embodiment, the determining the OPN expression after bracing the subject is performed at least six months after the bracing. [0016] In another specific embodiment, the method further comprises measuring soluble CD44 receptor (sCD44) expression in the sample from the subject. [0017] In another specific embodiment, the sample from the subject is a biological fluid from the subject. In another specific embodiment, the biological fluid is selected from the group consisting of blood, urine, tear and saliva. In another specific embodiment, the biological fluid is plasma. [0018] In another specific embodiment, the OPN expression is OPN protein. In another specific embodiment, the determining of the OPN expression is performed with an antibody that specifically binds to OPN. In another specific embodiment, the measuring OPN expression is performed using an enzyme-linked immunosorbent assay (ELISA). In another specific embodiment, the sample is a plasma sample and an OPN expression that is higher than 700 nanograms per milliliter of plasma is indicative that the subject is at risk for developing a scoliosis. In another specific embodiment, the sample is a plasma sample and an OPN expression that is higher than 800 nanograms per milliliter of plasma is indicative that the subject is at risk for developing a scoliosis. -->[0019] In another specific embodiment, the OPN expression is OPN RNA. In another specific embodiment, the sample from the subject is a paraspinal muscle biopsy and the OPN expression is OPN RNA. [0020] In accordance with another aspect of the present invention, there is provided a method of selecting an agent as a potential candidate for the reduction or prevention of scoliosis comprising contacting a candidate agent with a cell expressing osteopontin (OPN), and detecting the expression of OPN, wherein when the expression of OPN is lower in the presence of the candidate agent as compared to in the absence thereof, the candidate agent is selected. [0021] In accordance with another aspect of the present invention, there is provided a method of selecting an agent as a potential candidate for the reduction or prevention of scoliosis comprising contacting a candidate agent with a cell expressing sCD44, and detecting the expression of sCD44, wherein when the expression of OPN is higher in the presence of the candidate agent as compared to in the absence thereof, the candidate agent is selected. [0022] In another specific embodiment, the cell is a cell derived from a scoliotic patient. [0023] In accordance with another aspect of the present invention, there is provided a method of selecting an agent as a potential candidate for the prevention or reduction of scoliosis comprising administering a candidate agent to a scoliosis model animal before scoliosis has developed in the animal, whereby the candidate is selected when the scoliosis is prevented or reduced in the model animal as compared to in a control animal who was not administered the candidate agent. [0024] In accordance with another aspect of the present invention, there is provided a method of preventing or reducing scoliosis comprising administering to a subject having scoliosis a therapeutically effective amount of an osteopontin inhibitor (OPN) or a selenium rich diet, whereby scoliosis is thereby prevented or treated. [0025] In accordance with another aspect of the present invention, there is provided a method of preventing or reducing scoliosis comprising administering to a subject having scoliosis a therapeutically effective amount of a CD44 inhibitor, whereby scoliosis is thereby prevented or treated. -->[0026] In accordance with another aspect of the present invention, there is provided a method of preventing or reducing scoliosis comprising administering to a subject having scoliosis a therapeutically effective amount of a sCD44 stimulator, whereby scoliosis is thereby prevented or treated. [0027] In a specific embodiment of the methods of the present invention, the subject is human. In another specific embodiment of the methods of the present invention, the subject is human female. In another specific embodiment of the methods of the present invention, the subject is human male. [0028] In accordance with another aspect of the present invention, there is provided an osteopontin inhibitor for use in the treatment or prevention of scoliosis. [0029] In accordance with another aspect of the present invention, there is provided a CD44 inhibitor for use in the treatment or prevention of scoliosis. [0030] In accordance with another aspect of the present invention, there is provided a sCD44 stimulator for use in the treatment or prevention of scoliosis. [0031] In accordance with another aspect of the present invention, there is provided a use of an osteopontin inhibitor in the manufacture of a medicament for the prevention or the treatment of scoliosis. [0032] In accordance with another aspect of the present invention, there is provided a use of an osteopontin inhibitor for the prevention or the treatment of scoliosis. [0033] In accordance with another aspect of the present invention, there is provided a use of a CD44 inhibitor in the manufacture of a medicament for the prevention or the treatment of scoliosis. [0034] In accordance with another aspect of the present invention, there is provided a use of a CD44 inhibitor for the prevention or the treatment of scoliosis. [0035] In accordance with another aspect of the present invention, there is provided a use of a sCD44 stimulator in the manufacture of a medicament for the prevention or the treatment of scoliosis. [0036] In accordance with another aspect of the present invention, there is provided a -->use of a sCD44 stimulator for the prevention or the treatment of scoliosis. [0037] In a specific embodiment of the uses of the present invention, the scoliosis is adolescent idiopathic scoliosis. [0038] In accordance with another aspect of the present invention, there is provided a kit for predicting the risk of developing a scoliosis comprising a ligand specific to osteopontin (OPN) and instructions to use the kit for predicting the risk of developing a scoliosis. In a specific embodiment, the kit further comprises a ligand specific to soluble CD44 (SCD44). [0039] Other objects, advantages and features of the present invention will become more apparent upon reading of the following non-restrictive description of specific embodiments thereof, given by way of example only with reference to the accompanying drawings. BRIEF DESCRIPTION OF THE DRAWINGS [0040] In the appended drawings: [0041] Figure 1 presents OPN detection in pinealectomized chicken and corresponding scoliosis. Upper and lower panels illustrates the up regulation of OPN expression detected in paraspinal muscles of pinealectomized chicken developing a scoliosis (S) vs. those remaining unaffected (NS) at the mRNA and protein levels respectively.; [0042] Figure 2 graphically presents in the left panel the dynamic variation of circulating OPN levels in scoliotic bipedal C57BI/6J mice after surgery, and in the right panel presents typical x-rays of scoliotic deformities observed in bipedal C57BI/6J mice, where females (708) are more severely affected than males (907); [0043] Figure 3 shows a variation in plasma melatonin concentrations in different mouse strains. S = scoliotic; NS = non-scoliotic; [0044] Figure 4 shows the effect of the pharmacological inhibition of OPN transcription on scoliotic pinealectomized chicken; [0045] Figure 5 graphically presents the sensitivity and specificity of plasma -->osteopontin in healthy control subjects, AIS patients and at risk asymptomatic subjects. In Panel A, an analysis that included 33 healthy control subjects and 32 AIS patients with severe Cobb's Angle ( ≥45°) revealed an area under the curve (AUC) of 0.94 with a standard error of 0.03 (95 percent confidence interval [Cl], 0.88 to 1.000). In Panel B, the use of a cut-off value of 700 nanograms per ml of osteopontin showed a high sensitivity (90.6%) and a very good specificity (81.8%) for the early detection of AIS and for detecting the risk of scoliosis progression. In Panel C, the use of a cut-off value of 800 nanograms/ml of osteopontin also showed a high sensitivity (84.9%) and a higher specificity (90.9%) for the early detection of AIS and for detecting the risk of scoliosis progression. In Panel D, a clear correlation between the levels of plasma osteopontin and the Cobb's angle is demonstrated using all AIS patients, yielding a p-value 0.001 and 1^=0.26; [0046] Figure 6 presents graphs showing the distribution of age in the different groups for male and female combined (control, at risk, AIS <45 and AIS >45) (Panel A), and separated by sex female (Panel B) and male (Panel C); [0047] Figure 7 shows profiles of change in OPN levels, sCD44 levels, and Cobb's angle over follow up time in 4 selected AIS female patients (not under brace treatment) aged 12 (red), 14 (green and blue), and 17 (yellow) at baseline visit; [0048] Figure 8 shows the distribution of total change in OPN (left panel) and sCD44 (left panel) levels over follow-up time in AIS patients with worsened curve deformity (total increase in Cobb's angle greater than 3°; n=14) and in those without significant change in curve (no change in Cobb's angle, decrease, or increase smaller than 3°; n=36); [0049] Figure 9 presents graphs showing OPN progression correlated with Cobb's angle progression in AIS patients; [0050] Figure 10 presents graphs showing OPN regression or stabilization correlated with Cobb's angle regression or stabilization in AIS patients; [0051] Figure 11 shows profiles of change in OPN and sCD44 levels over follow up time in 4 selected at risk subjects without scoliosis: one male aged 13 (green), and 3 female aged 5 (gold), 11 (blue), and 9 (red) at baseline visit; -->[0052] Figure 12 compares OPN, sCD44 and HA levels in non AIS scoliotic patients (NAIS) (OPN (n=28), sCD44 (n=18), HA (n=24)), healthy controls (n=35) and AIS patients (n=252); [0053] Figure 13 presents a histogram comparison of circulating levels of OPN change in function of spine biomechanics in pre-operated AIS patients (n=79) vs. post- operated AIS patients (n=28); [0054] Figure 14 presents a histogram comparison of circulating levels of OPN and sCD44 of in pre-operated AIS female (OPN (n=10); sCD44 (n=15)) vs. post- operated AIS female (OPN (n=10); sCD44 (n=12)); [0055] Figure 15 presents charts distributing AIS patients across the predefined cut-off zones pre-operation (Panel A) and post-operation (Panel B); [0056] Figure 16 presents charts distributing AIS patients across the predefined cut-off zones prior to being treated with bracing (Panel A) and after bracing (Panel B); [0057] Figure 17 illustrates a hypothetic molecular concept underlying spinal deformity progression in AIS; [0058] Figure 18 presents a graph that correlates selenium levels in AIS patients with OPN levels; [0059] Figure 19 presents a histogram comparing selenium levels in three categories of subjects : controls, low OPN producers and high OPN producers; [0060] Figure 20 presents the nucleotide sequences of the three human OPN isoforms (transcript variant 1 , mRNA N M_001040058 (SEQ ID NO: 1); transcript variant 2, mRNA NM_000582 (SEQ ID NO: 2); transcript variant 3, mRNA N M_001040060 (SEQ ID NO: 3) and the amino acid sequences of the three human OPN isoforms (isoform a NP_001035147 (SEQ ID NO: 4); isoform b NP_000573 (SEQ ID NO: 5); and isoform c NP_001035149 (SEQ ID NO: 6)); [0061] Figure 21 presents the nucleotide sequences (mRNA) of six isoforms of human CD44 (NM_000610 transcript variant 1 (SEQ ID NO : 7); NM_001001389 transcript variant 2 (SEQ ID NO: 8); NM_001001390 transcript variant 3 (SEQ ID NO: 9); NM_001001391 transcript variant 4 (SEQ ID NO: 10); NM_001001392 transcript variant -->5 (SEQ ID NO: 11 ); X62739 lsoform identified in tumour cells (SEQ ID NO: 12)) and amino acid sequences of six isoforms of human sCD44 (NP_000601 isoform 1 precursor (SEQ ID NO : 13); NP_001001389 isoform 2 precursor (SEQ ID NO: 14); NP_001001390 isoform 3 precursor (SEQ ID NO: 15); NP_001001391 isoform 4 precursor (SEQ ID NO: 16); NP_001001392 isoform 5 precursor (SEQ ID NO: 17); and CAA44602 Isoform identified in tumour cells (SEQ ID NO: 18)); and [0062] Figure 22 shows the structure of sCD44 (Panel A), the origin of the various CD44 isoforms (Panel B) and the cleavage site in one sCD44 isoform (SEQ ID NO: 23). DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS [0063] The involvement of osteopontin (OPN) (also called secreted phosphoprotein 1 , bone sialoprotein I, early T-lymphocyte activation 1), a multifunctional cytokine, was investigated in adolescent idiopathic scoliosis (AIS) and plasma OPN concentrations were determined in three populations: patients with AIS, healthy controls without any family antecedent for scoliosis and asymptomatic offspring, born from at least one scoliotic parent, who are considered as at risk ("children at risk"). [0064] A group of 252 consecutive patients with AIS were compared with 35 healthy control subjects without any family history of scoliosis and 70 asymptomatic at risk subjects. All subjects were Caucasians and demographic characteristics are shown in Table 2 below. Plasma OPN, soluble CD44 receptor (sCD44), and hyaluronan (HA) levels were measured by enzyme-linked immunosorbent assays. Pinealectomized chicken and genetically modified bipedal C57BI/6J mice devoid of either OPN or CD44 receptor, a known OPN receptor, were also studied. [0065] Mean plasma OPN concentration in patients with AIS were significantly higher (p-value <0.001) in patients with AIS having a Cobb's angle >45° (965 ± 414 nanograms per milliliter) than that in healthy controls (570 ± 156 nanograms per milliliter) and than that in AIS patients with a Cobb's angle <45° (799 ± 284 nanograms per milliliter). Diagnostic sensitivity and specificity of OPN for AIS was 84.4 percent and 90.6 percent respectively (cut-off value > 800 nanograms per milliliter). Subgroup analysis showed that 47.9 percent of children at risk had OPN values higher than 800 nanograms per milliliter as opposed to only 8.6 percent for the controls indicating that elevated plasma OPN levels precede scoliosis formation. There were no significant differences in mean plasma sCD44 levels and HA levels between all groups. In respect -->to pathophysiology of scoliosis, the bipedal C57BI/6J mouse model demonstrated that the development of scoliosis requires OPN interactions with CD44 receptors since none of the genetically modified bipedal mice developed a scoliosis. Cut-off values for OPN disclosed herein were calculated using the commercial Elisa kit specific to human OPN from IBL. They may vary when a OPN expression (mRNA or protein) is measured differently (e.g. measuring OPN expression in a different biological sample through OPN RNA or OPN protein but using a different antibody). [0066] OPN (also called secreted phosphoprotein-1 , minopontin, or Eta-1) is a phosphorylated glycoprotein containing an arginine-glycine-aspartate (RGD) sequence present in mineralized tissues such as extracellular matrices. This multifunctional cytokine is involved in many pathological conditions.9'10 The presence of OPN transcripts and proteins in postural control centers such as the cerebellum, skeletal muscle proprioceptive sensory organs, and inner ear structures that control of equilibrium(11) is of interest, since AIS patients also exhibit defects in postural control, proprioception and equilibrium.(12;13) High plasma OPN levels have been found in different adult cancers and inflammatory conditions30"33. [0067] OPN signaling action: The OPN signaling pathways are not well understood, although it is known that aside from interacting with integrins, OPN can interact with CD44 receptor at the cell surface.14'15 Although CD44 is a major receptor for hyaluronan (HA), it also acts as a receptor for OPN and has multiple RGD binding sites. All human isoforms of the CD44 family of adhesion molecules are encoded by a single gene. Alternate splicing of 12 of the 19 exons in the human CD44 gene leads to the production of multiple variant isoforms16'17 and such structural heterogeneity is responsible of the ligand repertoire of CD44, which includes fibronectin18, chondroitin sulphate19, osteopontin20, at least two heparin binding growth hormones and hyaluronan.21'22 Soluble variant isoforms of sCD44 (sCD44var) have been associated with several pathological conditions.16'18'2324 It has been proposed that sCD44 isoforms are either generated through proteolytic cleavage of cell surface CD44 or by de novo synthesis due to alternative splicing. Functional diversity among CD44 molecules, unrelated to variant exon usage, is demonstrated by observations that CD44H, or any particular splice-variant, can be active for hyaluronan (HA) binding when expressed in some cell types but inactive in others. Many CD44 isoforms are tissue specific, but the full range of soluble variant isoform(s) of sCD44 has been -->associated with some pathological conditions. Indeed, circulating levels of total sCD44 and specific soluble CD44 isoforms have been shown to correlate with tumor metastasis in some malignancies, including non-Hodgkin's lymphoma and breast, gastric, and colon carcinomas. The level of soluble CD44 is also known to be higher in the body fluids of subjects with particular inflammatory conditions, such as rheumatoid arthritis, pouchitis and colitis, and bronchitis. Hyaluronan (HA), also called hyaluronate or hyaluronic acid, is a mucopolysaccharide widely distributed throughout the body and produced by a variety of cells including fibroblasts and other specialized connective tissue cells. [0068] As used herein the term "subject" is meant to refer to any mammal including human, mice, rat, dog, cat, pig, monkey, horse, etc. In a particular embodiment, it refers to a human. [0069] As used herein the term "brace" is meant to include dental and orthopedic brace and "bracing" thus refers to the action of placing the braces on the subject. In a specific embodiment, it is meant to refer to braces for scoliotic subjects. [0070] As used herein the terminology "spinal disorders and disorders causing scoliosis" refers to disorders that may involve development of a scoliosis. Without so limited, it includes AIS, congenital scoliosis, congenital cyphose scoliosis, neurological scoliosis, dysplasic scoliosis, neurofibromatosis, cerebral palsy, muscular dystrophies, neuromuscular scoliosis, spondylolesthesis and Noonan syndrome. Scoliosis that may be stratified or predicted excludes those caused by an accident and certain congenital malformations. [0071] As used herein the terms "likely candidate for developing adolescent idiopathic scoliosis" include children of which a least one parent has adolescent idiopathic scoliosis. Among other factors, age (adolescence), gender and heredity (i.e. born from a mother or father having a scoliosis) are factors that are known to contribute to the risk of developing a scoliosis and are used to a certain degree to assess the risk of developing AIS. In certain subjects, scoliosis develops rapidly over a short period of time to the point of requiring a corrective surgery. Current courses of action available -->from the moment AIS is diagnosed (when scoliosis is apparent) include observation (when Cobb's angle is around 10-25°), orthopaedic devices (when Cobb's angle is around 25-30°), and surgery (over 45°). The more reliable methods of determining the risk of progression and of monitoring treatment efficiency in accordance of the present invention may assist in 1 ) selecting an appropriate diet to remove certain food products identified as contributors to scoliosis; 2) selecting the best therapeutic agent; 3) selecting the least invasive preventive action and/or available treatment such as postural exercises, orthopaedic device, and/or less invasive surgeries or surgeries without fusions (a surgery that does not fuse vertebra and preserves column mobility). [0072] As used herein, the terms "severe AIS" refers to a scoliosis characterized by Cobb's angle of 45° or more. [0073] As used herein the terms "risk of developing scoliosis" refer to a genetic or metabolic predisposition of a subject to develop a scoliosis (i.e. spinal deformity) and/or to develop a more severe scoliosis at a future time. For instance, an increase of the Cobb's angle of a subject (e.g. from 40° to 50°, or from 18° to 25°) is a "development" of scoliosis. [0074] As used herein the terminology "biological sample" refers to any solid or liquid sample isolated from a living being. In a particular embodiment, it refers to any solid or liquid sample isolated from a human. Without being so limited it includes a biopsy material, blood, tears (48), saliva, maternal milk, synovial fluid, urine, ear fluid, amniotic fluid and cerebrospinal fluid. In a specific embodiment it refers to a blood sample. [0075] As used herein the terminology "blood sample" is meant to refer to blood, plasma or serum. In a preferred embodiment, plasma is used. In a more specific embodiment it refers to a plasma sample. [0076] As used herein the terminology "control sample" is meant to refer to a sample that does not come from a subject known to have scoliosis or known to be a likely candidate for developing a scoliosis. In methods for determining the risk of -->developing scoliosis in a subject that is pre-diagnosed with scoliosis, the sample may however also come from the subject under scrutiny at an earlier stage of the disease or disorder. [0077] As used herein the term "treating" or "treatment" in reference to scoliosis is meant to refer to at least one of a reduction of Cobb's angle in a preexisting spinal deformity, improvement of column mobility, preservation/maintenance of column mobility, improvement of equilibrium and balance in a specific plan; maintenance/preservation of equilibrium and balance in a specific plan; improvement of functionality in a specific plan, preservation/maintenance of functionality in a specific plan, cosmetic improvement, and combination of any of the above. [0078] As used herein the term "preventing" or "prevention" in reference to scoliosis is meant to refer to a at least one of a reduction in the progression of a Cobb's angle in a patient having a scoliosis or in an asymptomatic patient, a complete prevention of apparition of a spinal deformity, including changes affecting the rib cage and pelvis in 3D, and a combination of any of the above. [0079] As used herein the term "osteopontin inhibitor" refers to an agent able to reduce or block expression (transcription or translation) of OPN (gene called sspM), an agent able to reduce or block OPN secretion or an agent able to reduce or block OPN binding to its receptor CD44. Without being so limited, the agent can be natural or synthetic and can be a protein such as but not limited to an antibody that specifically binds to OPN, a peptide, a small molecule, a nucleotide such as but not limited to an antisense or a si RNA specific to OPN. [0080] As used herein the term "CD44 inhibitor" refers to an agent able to reduce expression (transcription or translation) of CD44, or an agent able to reduce CD44 localization at the cellular membrane. Without being so limited, the agent can be natural or synthetic and can be a protein such as but not limited to an antibody that specifically binds to CD44, a peptide, a small molecule, a nucleotide such as but not limited to an antisense or a siRNA specific to CD44. -->[0081] As used herein the term "sCD44 stimulator" refers to an agent able to increase expression (transcription or translation) of sCD44, an agent able to increase sCD44 secretion or an agent able to increase sCD44 affinity toward OPN. Without being so limited, the agent can be a protein, a peptide, a small molecule or a nucleotide. [0082] The articles "a," "an" and "the" are used herein to refer to one or to more than one (i.e., to at least one) of the grammatical object of the article. [0083] The term "including" and "comprising" are used herein to mean, and re used interchangeably with, the phrases "including but not limited to" and "comprising but not limited to". [0084] The terms "such as" are used herein to mean, and is used interchangeably with, the phrase "such as but not limited to". [0085] The present invention also relates to methods for the determination of the level of expression (i.e. transcript or translation product) of OPN, HA or sCD44. The present invention therefore encompasses any known method for such determination including Elisa (Enzyme Linked Immunosorbent Assay), RIA (Radioimmunoassay), real time PCR and competitive PCR, Northern blots, nuclease protection, plaque hybridization and slot blots. [0086] The present invention also concerns isolated nucleic acid molecules including probes and primers to detect OPN, sCD44 or CD44. In specific embodiments, the isolated nucleic acid molecules have no more than 300, or no more than 200, or no more than 100, or no more than 90, or no more than 80, or no more than 70, or no more than 60, or no more than 50, or no more than 40 or no more than 30 nucleotides. In specific embodiments, the isolated nucleic acid molecules have at least 17, or at least 18, or at least 19, or at least 20, or at least 30, or at least 40 nucleotides. In other specific embodiments, the isolated nucleic acid molecules have at least 20 and no more than 300 nucleotides. In other specific embodiments, the isolated nucleic acid molecules have at least 20 and no more than 200 nucleotides. In other specific embodiments, the isolated nucleic acid molecules have at least 20 and no more than 100 nucleotides. In -->other specific embodiments, the isolated nucleic acid molecules have at least 20 and no more than 90 nucleotides. In other specific embodiments, the isolated nucleic acid molecules have at least 20 and no more than 80 nucleotides. In other specific embodiments, the isolated nucleic acid molecules have at least 20 and no more than 70 nucleotides. In other specific embodiments, the isolated nucleic acid molecules have at least 20 and no more than 60 nucleotides. In other specific embodiments, the isolated nucleic acid molecules have at least 20 and no more than 50 nucleotides. In other specific embodiments, the isolated nucleic acid molecules have at least 20 and no more than 40 nucleotides. In other specific embodiments, the isolated nucleic acid molecules have at least 17 and no more than 40 nucleotides. In other specific embodiments, the isolated nucleic acid molecules have at least 20 and no more than 30 nucleotides. In other specific embodiments, the isolated nucleic acid molecules have at least 17 and no more than 30 nucleotides. In other specific embodiments, the isolated nucleic acid molecules have at least 30 and no more than 300 nucleotides. In other specific embodiments, the isolated nucleic acid molecules have at least 30 and no more than 200 nucleotides. In other specific embodiments, the isolated nucleic acid molecules have at least 30 and no more than 100 nucleotides. In other specific embodiments, the isolated nucleic acid molecules have at least 30 and no more than 90 nucleotides. In other specific embodiments, the isolated nucleic acid molecules have at least 30 and no more than 80 nucleotides. In other specific embodiments, the isolated nucleic acid molecules have at least 30 and no more than 70 nucleotides. In other specific embodiments, the isolated nucleic acid molecules have at least 30 and no more than 60 nucleotides. In other specific embodiments, the isolated nucleic acid molecules have at least 30 and no more than 50 nucleotides. In other specific embodiments, the isolated nucleic acid molecules have at least 30 and no more than 40 nucleotides. It should be understood that in real-time PCR, primers also constitute probe without the traditional meaning of this term. Primers or probes appropriate to detect OPN sCD44 and CD44 in the methods of the present invention can be designed with known methods using sequences distributed across their respective nucleotide sequence (49). [0087] Probes of the invention can be utilized with naturally occurring sugar-phosphate backbones as well as modified backbones including phosphorothioates, dithionates, alkyl phosphonates and α-nucleotides and the like. Modified sugar-phosphate backbones are generally known. Probes of the invention can -->be constructed of either ribonucleic acid (RNA) or deoxyribonucleic acid (DNA), and preferably of DNA. [0088] The types of detection methods in which probes can be used include Southern blots (DNA detection), dot or slot blots (DNA, RNA), and Northern blots (RNA detection). Although less preferred, labeled proteins could also be used to detect a particular nucleic acid sequence to which it binds. Other detection methods include kits containing probes on a dipstick setup and the like. [0089] As used herein the terms "detectably labeled" refer to a marking of a probe or an antibody in accordance with the presence invention that will allow the detection of OPN, HA and/or sCD44 in accordance with the present invention. Although the present invention is not specifically dependent on the use of a label for the detection of a particular nucleic acid sequence, such a label might be beneficial, by increasing the sensitivity of the detection. Furthermore, it enables automation. Probes can be labeled according to numerous well known methods. Non-limiting examples of labels include 3H, 14C, 32P, and 35S. Non-limiting examples of detectable markers include ligands, fluorophores, chemiluminescent agents, enzymes, and antibodies. Other detectable markers for use with probes, which can enable an increase in sensitivity of the method of the invention, include biotin and radionucleotides. It will become evident to the person of ordinary skill that the choice of a particular label dictates the manner in which it is bound to the probe. [0090] As commonly known, radioactive nucleotides can be incorporated into probes of the invention by several methods. Non-limiting examples thereof include kinasing the 5' ends of the probes using gamma 32P ATP and polynucleotide kinase, using the Klenow fragment of Pol I of E. coli in the presence of radioactive dNTP (e.g. uniformly labeled DNA probe using random oligonucleotide primers in low-melt gels), using the SP6/T7 system to transcribe a DNA segment in the presence of one or more radioactive NTP, and the like. [0091] The present invention also relates to methods of selecting compounds. As used herein the term "compound" is meant to encompass natural, synthetic or semi-synthetic compounds, including without being so limited chemicals, -->macromolecules, cell or tissue extracts (from plants or animals), nucleic acid molecules, peptides, antibodies and proteins. [0092] The present invention also relates to arrays. As used herein, an "array" is an intentionally created collection of molecules which can be prepared either synthetically or biosynthetically. The molecules in the array can be identical or different from each other. The array can assume a variety of formats, e.g., libraries of soluble molecules; libraries of compounds tethered to resin beads, silica chips, or other solid supports. [0093] As used herein "array of nucleic acid molecules" is an intentionally created collection of nucleic acids which can be prepared either synthetically or biosynthetically in a variety of different formats (e.g., libraries of soluble molecules; and libraries of oligonucleotides tethered to resin beads, silica chips, or other solid supports). Additionally, the term "array" is meant to include those libraries of nucleic acids which can be prepared by spotting nucleic acids of essentially any length (e.g., from 1 to about 1000 nucleotide monomers in length) onto a substrate. The term "nucleic acid" as used herein refers to a polymeric form of nucleotides of any length, either ribonucleotides, deoxyribonucleotides or peptide nucleic acids (PNAs), that comprise purine and pyrimidine bases, or other natural, chemically or biochemically modified, non-natural, or derivatized nucleotide bases. The backbone of the polynucleotide can comprise sugars and phosphate groups, as may typically be found in RNA or DNA, or modified or substituted sugar or phosphate groups. A polynucleotide may comprise modified nucleotides, such as methylated nucleotides and nucleotide analogs. The sequence of nucleotides may be interrupted by non-nucleotide components. Thus the terms nucleoside, nucleotide, deoxynucleoside and deoxynudeotide generally include analogs such as those described herein. These analogs are those molecules having some structural features in common with a naturally occurring nucleoside or nucleotide such that when incorporated into a nucleic acid or oligonucleotide sequence, they allow hybridization with a naturally occurring nucleic acid sequence in solution. Typically, these analogs are derived from naturally occurring nucleosides and nucleotides by replacing and/or modifying the base, the ribose or the phosphodiester moiety. The changes can be tailor made to stabilize or destabilize hybrid formation or enhance the specificity of hybridization with a complementary nucleic acid sequence as desired. -->[0094] As used herein "solid support", "support", and "substrate" are used interchangeably and refer to a material or group of materials having a rigid or semi-rigid surface or surfaces. In many embodiments, at least one surface of the solid support will be substantially flat, although in some embodiments it may be desirable to physically separate synthesis regions for different compounds with, for example, wells, raised regions, pins, etched trenches, or the like. According to other embodiments, the solid support(s) will take the form of beads, resins, gels, microspheres, or other geometric configurations. [0095] Any known nucleic acid arrays can be used in accordance with the present invention. For instance, such arrays include those based on short or longer oligonucleotide probes as well as cDNAs or polymerase chain reaction (PCR) products. Other methods include serial analysis of gene expression (SAGE), differential display, as well as subtractive hybridization methods, differential screening (DS), RNA arbitrarily primer (RAP)-PCR, restriction endonucleolytic analysis of differentially expressed sequences (READS), amplified restriction fragment-length polymorphisms (AFLP). Antibodies [0096] The present invention encompasses using antibodies for detecting or determining OPN, sCD44 or CD44 levels for instance in the samples of a subject and for including in kits of the present invention. Antibodies that specifically bind to these biological markers can be produced routinely with methods further described below. The present invention also encompasses using antibodies commercially available. Without being so limited antibodies that specifically bind to OPN include those listed in Table 1 below. [0097] Table 1 commercially available human OPN Elisa kits. --> [0098] Both monoclonal and polyclonal antibodies directed to OPN are included within the scope of this invention as they can be produced by well established procedures known to those of skill in the art. Additionally, any secondary antibodies, either monoclonal or polyclonal, directed to the first antibodies would also be included within the scope of this invention. [0099] As used herein, the term "anti-OPN antibody" or "immunologically specific anti- OPN antibody" refers to an antibody that specifically binds to (interacts with) an OPN protein and displays no substantial binding to other naturally occurring proteins other than the ones sharing the same antigenic determinants as the OPN protein. The term antibody or immunoglobulin is used in the broadest sense, and covers monoclonal antibodies (including full length monoclonal antibodies), polyclonal antibodies, multispecific antibodies, and antibody fragments so long as they exhibit the desired biological activity. Antibody fragments comprise a portion of a full length antibody, -->generally an antigen binding or variable region thereof. Examples of antibody fragments include Fab, Fab1, F(ab')2, and Fv fragments, diabodies, linear antibodies, single-chain antibody molecules, single domain antibodies (e.g., from camelids), shark NAR single domain antibodies, and multispecific antibodies formed from antibody fragments. Antibody fragments can also refer to binding moieties comprising CDRs or antigen binding domains including, but not limited to, VH regions (VH, VH-VH), anticalins, PepBodies™, antibody-T-cell epitope fusions (Troybodies) or Peptibodies. Additionally, any secondary antibodies, either monoclonal or polyclonal, directed to the first antibodies would also be included within the scope of this invention. [00100] In general, techniques for preparing antibodies (including monoclonal antibodies and hybridomas) and for detecting antigens using antibodies are well known in the art (Campbell, 1984, In "Monoclonal Antibody Technology: Laboratory Techniques in Biochemistry and Molecular Biology", Elsevier Science Publisher, Amsterdam, The Netherlands) and in Harlow et al., 1988 (in: Antibody A Laboratory Manual, CSH Laboratories). The term antibody encompasses herein polyclonal, monoclonal antibodies and antibody variants such as single-chain antibodies, humanized antibodies, chimeric antibodies and immunologically active fragments of antibodies (e.g. Fab and Fab1 fragments) which inhibit or neutralize their respective interaction domains in Hyphen and/or are specific thereto. [00101] Polyclonal antibodies are preferably raised in animals by multiple subcutaneous (sc), intravenous (iv) or intraperitoneal (ip) injections of the relevant antigen with or without an adjuvant. It may be useful to conjugate the relevant antigen to a protein that is immunogenic in the species to be immunized, e.g., keyhole limpet hemocyanin, serum albumin, bovine thyroglobulin, or soybean trypsin inhibitor using a bifunctional or derivatizing agent, for example, maleimidobenzoyl sulfosuccinimide ester (conjugation through cysteine residues), N-hydroxysuccinimide (through lysine residues), glutaraldehyde, succinic anhydride, SOCI2, or R1N=C=NR, where R and R1 are different alkyl groups. [00102] Animals may be immunized against the antigen, immunogenic conjugates, or derivatives by combining the antigen or conjugate (e.g., 100 μg for rabbits or 5 μg for mice) with 3 volumes of Freund's complete adjuvant and injecting the solution -->intradermally at multiple sites. One month later the animals are boosted with the antigen or conjugate (e.g., with 1/5 to 1/10 of the original amount used to immunize) in Freund's complete adjuvant by subcutaneous injection at multiple sites. Seven to 14 days later the animals are bled and the serum is assayed for antibody titer. Animals are boosted until the titer plateaus. Preferably, for conjugate immunizations, the animal is boosted with the conjugate of the same antigen, but conjugated to a different protein and/or through a different cross-linking reagent. Conjugates also can be made in recombinant cell culture as protein fusions. Also, aggregating agents such as alum are suitably used to enhance the immune response. [00103] Monoclonal antibodies may be made using the hybridoma method first described by Kohler et al., Nature, 256: 495 (1975), or may be made by recombinant DNA methods (e.g., U.S. Patent No. 6,204,023). Monoclonal antibodies may also be made using the techniques described in U.S. Patent Nos. 6,025,155 and 6,077,677 as well as U.S. Patent Application Publication Nos. 2002/0160970 and 2003/0083293 (see also, e.g., Lindenbaum et al., 2004). [00104] In the hybridoma method, a mouse or other appropriate host animal, such as a rat, hamster or monkey, is immunized (e.g., as hereinabove described) to elicit lymphocytes that produce or are capable of producing antibodies that will specifically bind to the antigen used for immunization. Alternatively, lymphocytes may be immunized in vitro. Lymphocytes then are fused with myeloma cells using a suitable fusing agent, such as polyethylene glycol, to form a hybridoma cell. [00105] The hybridoma cells thus prepared are seeded and grown in a suitable culture medium that preferably contains one or more substances that inhibit the growth or survival of the unfused, parental myeloma cells. For example, if the parental myeloma cells lack the enzyme hypoxanthine guanine phosphoribosyl transferase (HGPRT or HPRT), the culture medium for the hybridomas typically will include hypoxanthine, aminopterin, and thymidine (HAT medium), which substances prevent the growth of HGPRT-deficient cells. [00106] As used herein, the term "purified" in the expression "purified antibody" is simply meant to distinguish man-made antibody from an antibody that may -->naturally be produced by an animal against its own antigens. Hence, raw serum and hybridoma culture medium containing anti-OPN antibody are "purified antibodies" within the meaning of the present invention. [00107] The present invention also encompasses arrays to detect and/or quantify the translation products of OPN, HA or sCD44. Such arrays include protein micro- or macroarrays, gel technologies including high-resolution 2D-gel methodologies, possibly coupled with mass spectrometry imaging system at the cellular level such as microscopy combined with a fluorescent labeling system. [00108] The present invention also encompasses methods for identifying specific mutation(s) directly or indirectly affecting the transcription, translation, post- translational modification or activity of OPN. Without being so limited, mutations of interest include any mutation affecting the interactions between OPN and any soluble or non soluble isoform of CD44 or the binding of HA to any soluble or non soluble isoform of CD44. [00109] The present invention also encompasses the monitoring of the biomarkers disclosed herein to assess the efficacy of numerous approaches to prevent scoliosis and curve progression such as any physical therapies (e.g. postural exercises, physiotherapies, biomechanical stimulations by manipulation or using specific devices e.g. vibrant plates); the monitoring of bracing efficacy or development of novel braces; the monitoring of new surgical devices with or without fusion of vertebras, and the monitoring of the efficacy of specific diet, nutraceutical and/or pharmacological treatments. Without being so limited, the first measure after the braces have been applied could be performed 1 month later to determine for instance whether the braces are well adjusted and determine whether the patient is compliant to the treatment. Thereafter, the monitoring could be performed every three to six months depending on whether high OPN levels are detected or not. This method of the present invention may advantageously reduces the requirement for x-rays. X-rays could be performed for instance only at visits where OPN levels detected are too high. [00110] The present invention also encompasses the monitoring of the biomarkers disclosed herein identify patients having a risk of progression for early -->bracing or for less-invasive surgeries with novel fusionless devices, for pharmacological treatments and to monitor responses to treatment in patients with AIS. Of note, fusionless devices are particularly useful for patients still possessing a growth potential so that identification of the risk of developing a scoliosis as early as possible in the life of the subject is beneficial. In a specific embodiment, monitoring begins when the subject is about 5 years old or less in subjects having a scoliosis family antecedent/history. The frequency of the testing could typically be every six months. In case where OPN values are above the cut-off value (i.e. > 800 ng/ml when the OPN IBL ELISA kit code No. 27158 is used), the frequency would be advantageously significantly increased (e.g. every month, every two months, every three months...). [00111] The present invention also encompasses methods to screen/select for potential useful therapeutic agents using whole cells assays, the therapeutic compound being able to repress the transcription and/or synthesis of OPN (encoded by ssp1 gene), and/or able to increase the production of sCD44 which could sequester circulating OPN, and/or able to interfere with OPN liaison with the CD44 receptor, and/ or able to block CD44 receptor. Cells for use in such methods includes cells of any source (including in house or commercially available cell lines) and type (any tissue). In house cell lines could be made for instance by immortalizing cells from AIS subjects. In specific embodiments, methods of screening of the invention seek to identify agents that inhibit OPN expression (transcription and/or translation) and agents that increase sCD44 expression (transcription and/or translation). Useful cell lines for these embodiments include those producing high levels of OPN and/or low levels of sCD44. Such useful cell lines are described in references 43-56. [00112] In a particular embodiment, it includes cells of any cell type derived from a scoliotic patient, (whole cell assay). In specific embodiments, it includes osteoblasts, chondrocytes, myoblasts or blood cells including lymphocytes. As used herein, the term "cell derived from a scoliotic patient" refers to cells isolated directly from scoliotic patients, or immortalized cell lines originating from cells isolated directly from scoliotic patients. In specific embodiments, the cells are paraspinal muscle cells. Such cells may be isolated by a subject through needle biopsies for instance. [00113] Pharmaceutical compositions can also be administered by routes -->such as nasally, intravenously, intramuscularly, subcutaneously, sublingually, intrathecal^, or intrademnally. The route of administration can depend on a variety of factors, such as the environment and therapeutic goals. Dosage [00114] Any amount of a pharmaceutical and/or nutraceutical and/or dietary supplement compositions can be administered to a subject. The dosages will depend on many factors including the mode of administration. Typically, the amount of anti-scoliosis composition (e.g. osteopontin inhibitor or selenium compound) contained within a single dose will be an amount that effectively prevents, delays or reduces scoliosis without inducing significant toxicity "therapeutically effective amount". [00115] In some embodiments, the therapeutically effective amount of the neutraceutical anti-scoliosis composition (e.g. selenium supplement) can be altered. Useful effective amount concentrations include amounts ranging from about 0.01% to about 10% of a total diet on a weight by weight basis, from about 1% to about 6% of a total diet on a weight by weight basis, or from about 02% to about 6% of a total diet on a weight by weight basis. [00116] The effective amount of the osteopontin inhibitor or selenium compound may also be measured directly. The effective amount may be given daily or weekly or fractions thereof. Typically, a pharmaceutical and/or nutraceutical and/or dietary supplement composition of the invention can be administered in an amount from about 0.001 mg up to about 500 mg per kg of body weight per day (e.g., 10 mg, 50 mg, 100 mg, or 250 mg). Dosages may be provided in either a single or multiple dosage regimen. For example, in some embodiments the effective amount is a dose that ranges from about 1 mg to about 25 grams of the anti-scoliose preparation per day, about 50 mg to about 10 grams of the anti-scoliose preparation per day, from about 100 mg to about 5 grams of the anti-scoliose preparation per day, about 1 gram of the anti-scoliose preparation per day, about 1 mg to about 25 grams of the anti-scoliose preparation per week, about 50 mg to about 10 grams of the anti-scoliose preparation per week, about 100 mg to about 5 grams of the anti-scoliose preparation every other day, and about 1 gram of the anti-scoliose preparation once a week. -->[00117] By way of example, a pharmaceutical (e.g. containing an osteopontin inhibitor) and/or nutraceutical (e.g. containing selenium) and/or dietary supplement (e.g. containing selenium) composition of the invention can be in the form of a liquid, solution, suspension, pill, capsule, tablet, gelcap, powder, gel, ointment, cream, nebulae, mist, atomized vapor, aerosol, or phytosome. For oral administration, tablets or capsules can be prepared by conventional means with at least one pharmaceutically acceptable excipient such as binding agents, fillers, lubricants, disintegrants, or wetting agents. The tablets can be coated by methods known in the art. Liquid preparations for oral administration can take the form of, for example, solutions, syrups, or suspension, or they can be presented as a dry product for constitution with saline or other suitable liquid vehicle before use. Dietary supplements of the invention also can contain pharmaceutically acceptable additives such as suspending agents, emulsifying agents, non-aqueous vehicles, preservatives, buffer salts, flavoring, coloring, and sweetening agents as appropriate. Preparations for oral administration also can be suitably formulated to give controlled release of the active ingredients. [00118] In addition, a pharmaceutical (e.g. containing an osteopontin inhibitor) and/or nutraceutical (e.g. containing selenium) and/or dietary supplement (e.g. containing selenium) composition of the invention can contain a pharmaceutically acceptable carrier for administration to a mammal, including, without limitation, sterile aqueous or non-aqueous solutions, suspensions, and emulsions. Examples of nonaqueous solvents include, without limitation, propylene glycol, polyethylene glycol, vegetable oils, and injectable organic esters. Aqueous carriers include, without limitation, water, alcohol, saline, and buffered solutions. Pharmaceutically acceptable carriers also can include physiologically acceptable aqueous vehicles (e.g., physiological saline) or other known carriers appropriate to specific routes of administration. [00119] An osteopontin inhibitor or selenium may be incorporated into dosage forms in conjunction with any of the vehicles which are commonly employed in pharmaceutical preparations, e.g. talc, gum arabic, lactose, starch, magnesium searate, cocoa butter, aqueous or non-aqueous solvents, oils, paraffin derivatives or glycols. Emulsions such as those described in U.S. Pat. No. 5,434,183, may also be used in which vegetable oil (e.g., soybean oil or safflower oil), emulsifying agent (e.g., egg yolk phospholipid) and water are combined with glycerol. Methods for preparing appropriate -->formulations are well known in the art (see e.g., Remington's Pharmaceutical Sciences, 16th Ed., 1980, A. Oslo Ed., Easton, Pa.). [00120] In cases where parenteral administration is elected as the route of administration, preparations containing osteopontin inhibitor or selenium may be provided to patients in combination with pharmaceutically acceptable sterile aqueous or non-aqueous solvents, suspensions or emulsions. Examples of non-aqueous solvents are propylene glycol, polyethylene glycol, vegetable oil, fish oil, and injectable organic esters. Aqueous carriers include water, water-alcohol solutions, emulsions or suspensions, including saline and buffered medical parenteral vehicles including sodium chloride solution, Ringer's dextrose solution, dextrose plus sodium chloride solution, Ringer's solution containing lactose, or fixed oils. Intravenous vehicles may include fluid and nutrient replenishers, electrolyte replenishers, such as those based upon Ringer's dextrose, and the like. [00121] These are simply guidelines since the actual dose must be carefully selected and titrated by the attending physician based upon clinical factors unique to each patient or by a nutritionist. The optimal daily dose will be determined by methods known in the art and will be influenced by factors such as the age of the patient and other clinically relevant factors. In addition, patients may be taking medications for other diseases or conditions. The other medications may be continued during the time that the osteopontin inhibitor or selenium compound is given to the patient, but it is particularly advisable in such cases to begin with low doses to determine if adverse side effects are experienced. [00122] The present invention also relates to kits. Without bei 200 micrograms of selenium (L-selenomethionine to be exact) may turn out to be a key factor in slowing or eliminating the risk of rapid progression in adolescents with scoliotic curves. Yet-to-be-released research has found the high levels of a cytokine called osteopontin (OPN) is very highly correlated with rapid curve progression. I'm not sure if they have been able to determine if the increased OPN is a trigger or a signal, but in either case, therapeutic doses of selenium (200 micrograms) a day may have a significant effect on naturally driving down levels of OPN.
Please click here to receive a FREE SCOLIOSIS TREATMENT INFORMATION KIT ASAP. |
