Coverage Policy Manual
Policy #: 2011059
Category: Laboratory
Initiated: August 2011
Last Review: July 2018
  Genetic Test: Adolescent Idiopathic Scoliosis; Prediction of Disease Progression

Description:
The ScoliScore™ AIS (adolescent idiopathic scoliosis) prognostic DNA-based test (Axial Biotech, Salt Lake City, UT) is a saliva-based genetic test designed to predict the risk of progression of scoliosis in patients with AIS. The test uses an algorithm incorporating results of testing for 53 single nucleotide polymorphisms (SNPs), along with the patient’s presenting spinal curve (Cobb angle) to generate a risk score (ranging from 1 to 200), which can be used qualitatively or quantitatively to predict the likelihood of spinal curve progression. The test is intended for white (Caucasian) patients with a primary diagnosis of AIS between the ages of 9 and 13 years-old with a mild scoliotic curve (defined as <25º).
 
Background
Adolescent idiopathic scoliosis (AIS) is the most common pediatric spinal deformity affecting 1 to 3% of adolescents (Weinstein, 2008). This disease, of unknown etiology, occurs in otherwise healthy children with the onset highly correlated with the adolescent growth spurt. The vertebrae become misaligned such that the spine deviates from the midline laterally and becomes rotated axially. Deviation can occur anteriorly (a lordotic deviation) or posteriorly (a kyphotic deviation). Although AIS affects females and males in a nearly 1:1 ratio, progression to severe deformity occurs more often in females. Because the disease can have rapid onset and produce considerable morbidity, school screenings have been recommended. However, screening remains somewhat controversial, with conflicting guidelines supporting this practice or alternatively suggesting insufficient evidence for this.
 
Diagnosis is established by radiologic observation in adolescents (age 10 years until the age of skeletal maturity) of a lateral spine curvature of 10 degrees or more as measured using the Cobb angle (Ward, 2010). The Cobb angle is defined as the angulation measured between the maximally tilted proximal and distal vertebrae of the curve. Curvature is considered mild (less than 25º), moderate (25º to 40º), or severe (more than 40º) in an individual still growing. Once diagnosed, patients must be monitored over several years, usually with serial radiographs for curve progression. If the curve progresses, spinal bracing is the generally accepted first-line treatment. If the curve progresses in spite of bracing, spinal fusion may be recommended.
 
Curve progression has been linked to a number of factors, including sex, curve magnitude, patient age and skeletal maturity. Risk tables have been published by Lonstein and Carlson (Lonstein, 1984) and Peterson and Nachemson (Peterson, 1995) to help in triage and treatment decision making about patients with AIS. Tan et al. (Tan, 2009) have recently compared a broad array of factors and concluded that using 30º as an endpoint, initial Cobb angle magnitude produces the best prediction of progression outcome.
 
The familial nature of this disease was noted as early as 1968 (Wynne-Davies, 1968).  About one-quarter of patients report a positive family history of disease and twin studies have consistently supported shared genetic factors (Weinstein, 2008). Genome-wide linkage studies have reported multiple chromosomal regions of interest, often not replicated. Ogilvie has recently suggested AIS is a complex polygenic trait (Ogilvie, 2010). He and colleagues at Axial Diagnostics have published a study evaluating an algorithm using 53 SNP markers identified from unpublished genome-wide association studies (GWAS) to identify patients unlikely to exhibit severe progression in curvature versus those at considerable risk for severe progression. The clinical validity of this assay has recently been reported in a retrospective case control cohort study using this algorithm (Ward, 2010).  
 
Regulatory Status
The ScoliScore™ AIS (adolescent idiopathic scoliosis) prognostic DNA-based test (Axial Biotech, Salt Lake City, UT) has not been approved or cleared by the U.S Food and Drug Administration (FDA) but is being offered as a laboratory-developed test. The laboratory performing this test is accredited by the Centers for Medicare and Medicaid (CMS) under the Clinical Laboratory Improvement Amendments of 1988 (CLIA).
 
FDA has indicated an interest in changing its policy for use of enforcement discretion in the oversight of laboratory-developed tests, but the status of this proposed change in policy and the impact of any particular laboratory-developed test are currently unknown.
 
Coding
The ScoliScore™ AIS (adolescent idiopathic scoliosis) prognostic DNA-based test (Axial Biotech, Salt Lake City, UT) does not have a specific CPT code. The manufacturer website suggests use of a combination of molecular analysis CPT codes (two of them with multiple units), including:
 
83891 Molecular diagnostics; isolation or extraction of highly purified nucleic acid, each nucleic acid type (i.e., DNA or RNA)
83898 Molecular diagnostics; amplification, target, each nucleic acid sequence
83903 Molecular diagnostics; mutation scanning, by physical properties (e.g., single strand conformational polymorphisms [SSCP], heteroduplex, denaturing gradient gel electrophoresis [DGGE], RNA’ase A), single segment, each
83012 Molecular diagnostics; interpretation and report
 

Policy/
Coverage:
The use of prognostic DNA-based testing (ScoliScore ™ AIS) to predict the risk of progression of scoliosis in patients with adolescent idiopathic scoliosis does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
 
For contracts without primary coverage criteria, the use of prognostic DNA-based testing (ScoliScore ™ AIS) to predict the risk of progression of scoliosis in patients with adolescent idiopathic scoliosis is considered investigational.  Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 

Rationale:
Introduction
Validation of genotyping to improve treatment outcomes is a multistep process. In general, important steps in the validation process address the following:
 
Analytic validity: measures technical performance, i.e., whether the test accurately and reproducibly detects the gene markers of interest
  
Clinical validity: measures the strength of the associations between the selected genetic markers and clinical status.
 
 Clinical utility: determines whether the use of genotyping for specific genetic markers to guide treatment decisions improves patient outcomes such as survival or adverse event rate compared to standard treatment without
 
Literature Review
 
Analytical validity: There are no published reports on analytical performance of this test. It is offered by a CLIA-accredited laboratory and requirements for analytical performance and quality control are components of this process.
 
Clinical validity: Ward et al. have recently described a company-sponsored clinical validation study of a DNA-based prognostic test to predict spinal curve progression in adolescent idiopathic scoliosis (Ward, 2010). This test involves use of a proprietary algorithm to integrate information from 53 single nucleotide polymorphisms (SNPs) identified as exhibiting an association with AIS in a case-controlled GWAS study of 2,750 patients. The GWAS was used to develop a 1 to 200 scoring system. A cut-point of 40 or less was selected during the GWAS to identify patients at low risk (less than 1%) of developing severe curvatures requiring surgical intervention. Following generation of data, an analysis of patients with scores of 190 or greater was performed to determine risk for developing severe curves.
 
Clinical validation of this test (Ward, 2010) was performed in a retrospective analysis of cases preselected by curvature severity (mild, moderate, or severe) and assigned into 3 cohorts identified as: 1) a screening cohort of white females; 2) a spinal surgery practice cohort of white females; and 3) a male cohort. Inclusion/exclusion criteria were cited as being used, but not explicitly provided, although a component of cohort development was matching of prevalence of disease by severity according to that expected from review of the literature or survey of clinical practices. There is minimal information provided about the demographics of patients assigned to each cohort.
 
Assignment of curvature severity was performed using expert opinion of a single orthopedic spine surgeon and was supplemented by external blinded review of the spinal surgery practice patients using an outside panel of 3 independent scoliosis experts.
 
The screening cohort was composed of patients (n=176) recruited to ensure 85% exhibited mild or improved curves, 12% moderate curve progression, and 3% severe curve progression. Using a risk score cut-off of 41 or less, the predictive value of a negative test (defined as identification of patients without severe curve progression) was 100% (95% confidence intervals [CI]: 98.6 to100%). No analysis was performed to demonstrate whether this was a statistically significant improvement in prediction of negatives, given the low initial prevalence of patients expected to exhibit severe progression.
 
The spine surgery practice cohort was composed of patients (n=133) recruited to ensure 68% exhibited mild or improved curves, 21% moderate curve progression, and 11% severe curve progression. Using the risk score cut-off of 41 or less, the predictive value of a negative test (defined as identification of patients without severe curve progression) was 99% (95% CI: 95.4 to 99.6%). No analysis was performed to demonstrate whether this was a statistically significant improvement in prediction of negatives.
 
In the male cohort (n=163), the prevalence of patients with progression to severe curvature is 11% before testing. The negative predictive value after testing was 97% (95% CI: 93.3 to 99%).
 
Although there is a description of positive predictive value in patients exhibiting high risk score values, recruitment of patients into this category appear to be derived from patients pooled from different and undescribed sources making interpretation difficult.
 
A subsequent genome-wide association study (GWAS) evaluating 327,000 SNPs in 419 families with AIS (Sharma, 2011) failed to duplicate the associations reported in the study by Ward et al.
 
Clinical utility: No studies have been performed examining the impact of testing on health care outcomes.
 
Current practice includes careful follow-up of patients. Those with progressive disease are frequently treated with bracing, or in severe cases, with surgical intervention. Careful follow-up and treatment of patients with scoliosis would be expected to have an impact on the gold standard endpoint being used to evaluate this test in this study – severe curvature. Test-induced changes in outcome will provide insight into the clinical utility of the test. Because treatment outcome is used as the endpoint of interest in characterizing the test, changes in outcome may also produce changes in the test’s clinical validity.
 
Summary
Idiopathic adolescent scoliosis is a disease of unknown etiology that causes mild to severe spinal deformity in approximately 1 to 3% of adolescents. While there is controversy about the value of both screening and treatment, patients once diagnosed are frequently closely followed. In cases with significant progression of curvature, both medical (bracing) and surgical (spinal fusion) interventions are considered. Classification tables for likelihood of progressive disease have been constructed to assist in managing patients, but these have not proven to be highly reliable and the impact of their use on outcomes is unknown.
 
Investigators affiliated with Axial Biotec have recently reported on use of a test based on an algorithm incorporating results of 53 SNPs along with the Cobb angle to predict progression of scoliosis. Preliminary clinical validity results for the ScoliScoreAIS (adolescent idiopathic scoliosis) prognostic DNA-based test are available, indicating a high negative predictive value and an uncertain positive predictive value. A single study has been published reporting a high negative predictive value in ruling out the possibility of progression to severe curvature, in a population with a low baseline likelihood of progression. It is not clear if the increase in certainty provided by testing is statistically or clinically meaningful. Furthermore, a similar recently published GWAS study has failed to identify overlapping SNPs for identification of disease progression (prognosis).
 
The clinical utility of the test remains unknown. There is no direct evidence demonstrating that use of this test results in changes in management that improve outcomes. The value of early identification and intervention(s) for individuals at risk for progression of disease is unclear.  Further research on both clinical validity and utility are needed.
 
2012 Update
A literature search was conducted through September 2012.  There was no new randomized trials, practice guidelines, position statements or other publications identified that would prompt a change in the coverage statement.
 
Roye et al. have recently reported results in 91 patients evaluated using ScoliScore (Roye, 2012). Although they noted a positive correlation between Cobb angle and ScoliScore results (r-.581, p<0.001), ScoliScore appeared to be providing information very different from that observed using standard risk score with a marked increase in low risk patients and decrease in high risk patients. However, no clinical endpoints were examined in association with classification results and so the interpretation of results observed remains unclear.
 
 
2013 Update
A literature search was conducted using the MEDLINE database through September 2013.  No new information was identified that would prompt a change in the coverage statement.   
 
2014 Update
A literature search conducted through June 2014 did not reveal any new information that would prompt a change in the coverage statement. The key identified literature is summarized below.
 
Bohl et al reported results from a small retrospective cohort study comparing ScoliScore results among patients with AIS undergoing bracing whose scoliosis progressed to those undergoing bracing who did not have progression (Bohl, 2014). The authors contacted 25 patients with AIS treated at a single institution that underwent nighttime bracing; 16 subjects provided saliva samples to allow ScoliScore testing. The authors report that the 8 patients whose curves progressed to greater than 45 degrees had a higher mean ScoliScore than those whose curves did not progress (176 vs 112, respectively; p=0.03). No patient with a ScoliScore below 135 progressed to greater than 45 degrees. The interpretation of these results is unclear due to the study’s small size and potential for selective response bias.
 
 Clinical validity of other genetic testing for scoliosis prognosis: In 2013, Fendri et al reported results from a case-control GWAS study of 6 AIS patients and 6 non-AIS controls evaluating differential gene expression profiling in AIS (Fendri, 2013). Gene expression profiles from primary osteoblasts derived from spinal vertebrae of AIS patients (n=6) were compared with profiles from the same cells collected from age and sex-matched previously-healthy patients who underwent spinal surgery for trauma (n=6). One hundred forty-five genes displayed significant gene expression changes in AIS osteoblasts compared with non-AIS osteoblasts. After hierarchical clustering gene ontology analysis, the authors identified 5 groups based on molecular function and biological process that fell into 4 pathways: developmental/growth differentiation of skeletal elements (ie, HOXB8, HOXB2, MEOX2, PITX1), cellular signaling (ie, HOXA11 BARX1), connecting structural integrity of the extracellular matrix to the structural integrity of a bone or a muscle fiber (ie, COMP, HOXA2, HOXA11), and cellular signaling and cartilage damage (GDF15).
 
Studies have also associated polymorphisms in the promoter regions of tissue inhibitor of metalloproteinase-2 and neurotrophin 3 with AIS severity in Chinese populations (Jiang, 2012; Qiu, 2012) Replication of these genetic associations is needed.
 
Clinical utility: No studies have been performed examining the impact of DNA-based predictive testing for scoliosis on health care outcomes.
 
Ongoing Clinical Trials
A search of online database ClinicalTrials.gov in June 2014 identified the following studies that use DNAbased testing in the evaluation of scoliosis:
  • Genetic Evaluation for the Scoliosis Gene(s) in Patients With Neurofibromatosis 1 and Scoliosis
(NCT01776125) – This is a retrospective observational cohort study designed to compare genetic profiles on the ScoliScore among patients with neurofibromatosis with dystrophic scoliosis with those with nondystrophic scoliosis. Enrollment is planned for 100 subjects; the study completion date is listed as August 2013, but no published results were identified.
 
In 2004, the U.S. Preventive Services Task Force (USPSTF) recommended against the routine screening of asymptomatic adolescents for idiopathic scoliosis (Grade D Recommendation) (USPSFT, 2004). No USPSTF recommendations for DNA-based testing for adolescent idiopathic scoliosis were identified.
 
2015 Update
A literature search conducted through May 2015 did not reveal any new information that would prompt a change in the coverage statement.  The key identified literature is summarized below.
 
A 2011 Cochrane review, updated in 2014, identified 2 small studies with a total of 57 patients that met the review’s inclusion criteria for local intramuscular transplantation of autologous mononuclear cells (monocytes) for critical limb ischemia (CLI) (Moazzami, 2011; 2014).  Studies were excluded that used mesenchymal stem cells (MSCs) or bone marrow aspirate. In one of the studies, intramuscular injection of bone marrow-derived mononuclear cells (BM-MNCs) was compared with standard conservative treatment. In the second study, peripheral blood-derived mononuclear cells were collected following injections of granulocyte-macrophage colony-stimulating factor (GM-CSF) and transplanted by intramuscular injections. Both studies showed a significant reduction in amputations with treatment with monocytes, but larger randomized controlled trials (RCTs) are needed to adequately evaluate the effect of treatment with greater certainty. No additional studies were found for the 2014 update of this systematic review.
 
Intra-Arterial Injection
JUVENTAS (Rejuvenating Endothelial Progenitor Cells via Transcutaneous Intra-arterial Supplementation) is a randomized double-blind, placebo-controlled trial from Europe (NCT00371371) (Teraa, 2015). This foundation-supported trial evaluated the clinical effects of repeated intra-arterial infusion of BMMNCs in 160 patients with non-revascularizable critical limb ischemia. Patients received repeated intraarterial infusion of BM-MNCs or placebo (autologous peripheral blood erythrocytes) into the common femoral artery. The primary outcome measure, the rate of major amputation after 6 months, was not significantly different between the two groups (19% for BM-MNCs vs 13% controls). Secondary outcomes of quality of life, rest pain, ABI, and transcutaneous oxygen pressure improved to a similar extent in both groups, reinforcing the need for a placebo control in this type of trial.
 
Practice Guidelines and Position Statements
The European Society of Cardiology published 2011 guidelines on the diagnosis and treatment of PADs (Tendera, 2011). The guidelines did not recommend for or against stem cell therapy for PAD. The guidelines provided the following information: Stem cell and gene therapy for revascularization is a novel therapy that is currently being evaluated to stimulate neovascularization. For autologous cell transplantation, bone marrow and peripheral blood are rich sources of stem and progenitor cells. At this time, it is unclear which of the many different cell types is the most promising. At present, angiogenic gene and stem cell therapy are still being investigated, and it is too early to make firm recommendations.
 
2016 Update
A literature search conducted through April 2016 did not reveal any new information that would prompt a change in the coverage statement. The key identified literature is summarized below.
 
A number of GWASs have attempted to identify genetic loci with associations with AIS progression. Sharma and colleagues reported results of a GWAS evaluating 327,000 SNPs in 419 families with AIS that found 3 loci significantly associated with scoliosis progression, which did not include any of the 53 SNPs included in the Ward and colleagues study previously described (Sharma, 2011).  Tang and colleagues evaluated the association between the 53 SNPs used in the Ward et al study previously described and severe scoliosis in a case control study involving 450 AIS patients of French-Canadian background (Tang, 2015).
 
2017 Update
A literature search conducted through June 2017 did not reveal any new information that would prompt a change in the coverage statement. The key identified literature is summarized below.
 
In 2015, Roye and colleagues reported on an independent validation of the ScoliScore algorithm in a sample of 126 patients with AIS who were enrolled at 2 centers using a retrospective cohort design (Roye, 2015). Eligible patients had AIS with an initial Cobb angle of 10° to 25° and were white with skeletal immaturity. ScoliScore results were provided as continuous and categoric variables; categories were low (1-50 points), intermediate (51-179 points), or high (180-200 points) risk for progression. Outcomes were defined as progression (curve progression to >40° or requirement for spinal fusion) or nonprogression (reached skeletal maturity without curve progression >40°). The mean ScoliScore overall was 103 (SD=60). In unadjusted analysis, the continuous ScoliScore value was not significantly associated with curve progression (odds ratio [OR], 0.999; 95% CI, 0.991 to 1.006; p=0.664). The proportion of patients with curve progression did not differ significantly by ScoliScore risk group. The ScoliScore test PPV and NPV were 0.27 (95% CI, 0.09 to 0.55) and 0.87 (95% CI, 0.69 to 0.96), respectively.
 
In 2012, Roye and colleagues reported retrospective results for 91 patients evaluated using ScoliScore (Roye, 2012). Although they noted a positive correlation between Cobb angle and ScoliScore results (r=0.581, p<0.001), ScoliScore appeared to be providing information very different from that observed using a standard risk score, with a marked increase in low-risk patients and a decrease in high-risk patients. However, no clinical end points were examined in association with classification results, and so interpretation of results observed remains unclear.
 
Bohl and colleagues reported results from a small retrospective cohort study comparing ScoliScore results among patients with AIS undergoing bracing whose scoliosis progressed to those undergoing bracing who did not have progression (Bohl, 2016). Authors contacted 25 patients with AIS treated at a single institution who underwent nighttime bracing; 16 subjects provided saliva samples to allow ScoliScore testing. Authors reported that the 8 patients whose curves progressed to greater than 45° had a higher mean ScoliScore than those whose curves did not progress (176 vs 112, respectively; p=0.03). No patient with a ScoliScore below 135 progressed to greater than 45°. The interpretation of these results is unclear due to the study’s small size and potential for selective response bias.
 
Xu and colleagues reported on the association between the 53 SNVs in the ScoliScore panel with scoliosis progression in a retrospective case-control study of 670 female Han Chinese patients with AIS (Xu, 2016). Patients were identified from a set of patients who visited trialists’ scoliosis center for a time period that overlapped with that for the patients in the 2015 Xu study, but it is not specified whether the data overlap. Of the 670 patients, 313 were assigned to the nonprogression group (defined as a Cobb angle <25° at final follow-up) and 357 were assigned to the progression group (defined as a Cobb angle of >40° at final follow-up). The overall follow-up duration was not specified. At 2 loci, allele frequencies differed between groups: the progression group had a significantly higher frequency of allele A at rs9945359 (25.7% vs 19.5%; OR=1.42; 95% CI, 1.09 to 1.88; p=0.01) and a significantly lower frequency of allele A at rs17044552 (11.5% vs 16.4%; OR=0.65; 95% CI, 0.47 to 0.91; p=0.01).
 
2018 Update
A literature search was conducted through June 2018.  There was no new information identified that would prompt a change in the coverage statement.  

CPT/HCPCS:
81479Unlisted molecular pathology procedure
83012Haptoglobin; phenotypes

References: Tan KJ, Moe MM, Vaithinathan R et al.(2009) Curve progression in idiopathic scoliosis: follow-up study to skeletal maturity. Spine (Phila Pa 1976) 2009; 34(7):697-700.

. Xu L, Qin X, Sun W, et al.(2016) Replication of association between 53 single-nucleotide polymorphisms in a DNA-based diagnostic test and AIS progression in Chinese Han population. Spine (Phila Pa 1976). Feb 2016;41(4):306-310. PMID 26579958

BLL Partners LLC.(2017) Transgenomic Finalizes Divestment of its Genetic Assays & Platforms Business Unit. 2015; https://www.sec.gov/Archives/edgar/data/1043961/000114420415068699/v425907_ex99-1.htm. Accessed December 15, 2017.

Bloomberg.(2017) Life Sciences Tools and Services: Company Overview of Transgenomic, Inc. 2017; https://www.bloomberg.com/research/stocks/private/snapshot.asp?privcapId=416660. Accessed December 15, 2017.

Bohl DD, Telles CJ, Ruiz FK et al.(2014) A Genetic Test Predicts Providence Brace Success for Adolescent Idiopathic Scoliosis When Failure is Defined as Progression to Greater Than 45 Degrees. J Spinal Disord Tech 2014.

Bohl DD, Telles CJ, Ruiz FK, et al.(2016) A genetic test predicts providence brace success for adolescent idiopathic scoliosis when failure is defined as progression to >45 degrees. Clin Spine Surg. Apr 2016;29(3):E146-150. PMID 27007790

Fendri K, Patten SA, Kaufman GN et al.(2013) Microarray expression profiling identifies genes with altered expression in Adolescent Idiopathic Scoliosis. Eur. Spine J. 2013; 22(6):1300-11.

Lonstein JE, Carlson JM.(1984) The prediction of curve progression in untreated idiopathic scoliosis during growth. J Bone Joint Surg Am 1984; 66(7):1061-71.

Moazzami K, Moazzami B, Roohi A, et al.(2014) Local intramuscular transplantation of autologous mononuclear cells for critical lower limb ischaemia. Cochrane Database Syst Rev. 2014;12:CD008347. PMID 25525690

Ogilvie J.(2010) Adolescent idiopathic scoliosis and genetic testing. Curr Opin Pediatr 2010; 22(1):67-70.

Peterson LE, Nachemson AL.(1995) Prediction of progression of the curve in girls who have adolescent idiopathic scoliosis of moderate severity. Logistic regression analysis based on data from The Brace Study of the Scoliosis Research Society. J Bone Joint Surg Am 1995; 77(6):823-7.

Roye BD, Wright ML, Matsumoto H, et al.(2015) An independent evaluation of the validity of a DNA-based prognostic test for adolescent idiopathic scoliosis. J Bone Joint Surg Am. Dec 16 2015;97(24):1994-1998. PMID 26677232

Roye BD, Wright ML, Williams BA et al.(2012) Does ScoliScore provide more information than traditional clinical estimates of curve progression? Spine (Phila Pa 1976) 2012 [Epub ahead of print].

Roye BD, Wright ML, Williams BA, et al.(2012) Does ScoliScore provide more information than traditional clinical estimates of curve progression? Spine (Phila Pa 1976). Dec 1 2012;37(25):2099-2103. PMID 22614798

Sharma S, Gao X, Londono D et al.(2011) Genome-wide association studies of adolescent idiopathic scoliosis suggest candidate susceptibility genes. Hum Mol Genet 2011; 20(7):1456-66.

Tang QL, Julien C, Eveleigh R, et al.(2015) A Replication Study for Association of 53 Single Nucleotide Polymorphisms in ScoliScore Test With Adolescent Idiopathic Scoliosis in French-Canadian Population. Spine (Phila Pa 1976). Apr 15 2015;40(8):537-543. PMID 25646748

Tendera M, Aboyans V, Bartelink M, et al.(2011) ESC Guidelines on the Diagnosis and Treatment of Peripheral Artery Diseases. Eur Heart J. 2011; 32(22):2851-2906. PMID 21873417

Teraa M, Sprengers RW, Schutgens RE, et al.(2015) Effect of Repetitive Intra-Arterial Infusion of Bone Marrow Mononuclear Cells in Patients With No-Option Limb Ischemia: The Randomized, Double-Blind, Placebo- Controlled Rejuvenating Endothelial Progenitor Cells via Transcutaneous Intra-arterial Supplementation (JUVENTAS) Trial. Circulation. Mar 10 2015;131(10):851-860. PMID 25567765

U.S. Preventive Services Task Force.(2004) Screening for Idiopathic Scoliosis in Adolescents. 2004. Available online at: http://www.uspreventiveservicestaskforce.org/uspstf/uspsaisc.htm. Last accessed June, 2014.

Ward K, Ogilvie JW, Singleton MV et al.(2010) Validation of DNA-based prognostic testing to predict spinal curve progression in adolescent idiopathic scoliosis. Spine (Phila Pa 1976) 2010; 35(25):E1455-64.

Weinstein SL, Dolan LA, Cheng JC et al.(2008) Adolescent idiopathic scoliosis. Lancet 2008; 371(9623):1527-37.

Wynne-Davies R.(1968) Familial (idiopathic) scoliosis. A family survey. J Bone Joint Surg Br 1968; 50(1):24-30.

Xu L, Huang S, Qin X, et al.(2015) Investigation of the 53 markers in a DNA-based prognostic test revealing new predisposition genes for adolescent idiopathic scoliosis. Spine (Phila Pa 1976). Jul 15 2015;40(14):1086-1091. PMID 25811265


Group specific policy will supersede this policy when applicable. This policy does not apply to the Wal-Mart Associates Group Health Plan participants or to the Tyson Group Health Plan participants.
CPT Codes Copyright © 2019 American Medical Association.