Top

Published in:

Open Access 01-10-2016 | Review Article

Adolescent idiopathic scoliosis: evidence for intrinsic factors driving aetiology and progression

Authors: Matthew M. P. Newton Ede, Simon W. Jones

Published in: International Orthopaedics | Issue 10/2016

Abstract

Adolescent idiopathic scoliosis (AIS) is now considered to be a multifactorial heterogeneous disease, with recent genomic studies supporting the role of intrinsic factors in contributing to the onset of disease pathology and curve progression. Understanding the key molecular signalling pathways by which these intrinsic factors mediate AIS pathology may facilitate the development of pharmacological therapeutics and the identification of predictive markers of progression. The heterogenic nature of AIS has implicated multiple tissue types in the disease pathophysiology, including spinal bone, intervertebral disc and paraspinal muscles. In this review, we highlight some of the mechanisms and intrinsic molecular regulators within these different tissue types and review the evidence for their involvement in AIS pathology.

Acaroglu E, Bobe R, Enouf J, Marcucio R, Moldovan F, Moreau A (2012) The metabolic basis of adolescent idiopathic scoliosis: 2011 report of the “metabolic” workgroup of the Fondation Yves Cotrel. Eur Spine J 21:1033–1042CrossRefPubMedPubMedCentral

Avikainen VJ, Rezasoltani A, Kauhanen HA (1999) Asymmetry of paraspinal EMG-time characteristics in idiopathic scoliosis. J Spinal Disord 12:61–67CrossRefPubMed

Azeddine B, Letellier K, Wang DS, Moldovan F, Moreau A (2007) Molecular determinants of melatonin signaling dysfunction in adolescent idiopathic scoliosis. Clin Orthop Relat Res 462:45–52CrossRefPubMed

Behan WM, Longman C, Petty RK, Comeglio P, Child AH, Boxer M, Foskett P, Harriman DG (2003) Muscle fibrillin deficiency in Marfan’s syndrome myopathy. J Neurol Neurosurg Psychiatry 74:633–638CrossRefPubMedPubMedCentral

Brodner W, Krepler P, Nicolakis M, Langer M, Kaider A, Lack W, Waldhauser F (2000) Melatonin and adolescent idiopathic scoliosis. J Bone Joint Surg Br 82:399–403CrossRefPubMed

Buchan JG, Alvarado DM, Haller GE, Cruchaga C, Harms MB, Zhang T, Willing MC, Grange DK, Braverman AC, Miller NH, Morcuende JA, Tang NL, Lam TP, Ng BK, Cheng JC, Dobbs MB, Gurnett CA (2014) Rare variants in FBN1 and FBN2 are associated with severe adolescent idiopathic scoliosis. Hum Mol Genet 23:5271–5282CrossRefPubMedPubMedCentral

Bushell GR, Ghosh P, Taylor TK (1978) Collagen defect in idiopathic scoliosis. Lancet 2:94–95CrossRefPubMed

Busscher I, Wapstra FH, Veldhuizen AG (2010) Predicting growth and curve progression in the individual patient with adolescent idiopathic scoliosis: design of a prospective longitudinal cohort study. BMC Musculoskelet Disord 11:93CrossRefPubMedPubMedCentral

Cheng JC, Qin L, Cheung CS, Sher AH, Lee KM, Ng SW, Guo X (2000) Generalized low areal and volumetric bone mineral density in adolescent idiopathic scoliosis. J Bone Miner Res 15:1587–1595CrossRefPubMed

10.

Cheng JC, Tang SP, Guo X, Chan CW, Qin L (2001) Osteopenia in adolescent idiopathic scoliosis: a histomorphometric study. Spine (Phila Pa 1976) 26:E19–E23CrossRef

11.

Cheung J, Veldhuizen AG, Halbertsma JP, Maurits NM, Sluiter WJ, Cool JC, Van Horn JR (2004) The relation between electromyography and growth velocity of the spine in the evaluation of curve progression in idiopathic scoliosis. Spine (Phila Pa 1976) 29:1011–1016CrossRef

12.

Cheung KM, Wang T, Qiu GX, Luk KD (2008) Recent advances in the aetiology of adolescent idiopathic scoliosis. Int Orthop 32:729–734CrossRefPubMed

13.

Cholewicki J, Panjabi MM, Khachatryan A (1997) Stabilizing function of trunk flexor-extensor muscles around a neutral spine posture. Spine (Phila Pa 1976) 22:2207–2212CrossRef

14.

Day G, Frawley K, Phillips G, McPhee IB, LaBrom R, Askin G, Mueller P (2008) The vertebral body growth plate in scoliosis: a primary disturbance of growth? Scoliosis 3:3CrossRefPubMedPubMedCentral

15.

Dickson RA (1988) The aetiology of spinal deformities. Lancet 1:1151–1155CrossRefPubMed

16.

Eun IS, Park WW, Suh KT, Kim JI, Lee JS (2009) Association between osteoprotegerin gene polymorphism and bone mineral density in patients with adolescent idiopathic scoliosis. Eur Spine J 18:1936–1940CrossRefPubMedPubMedCentral

17.

Gervais J, Perie D, Parent S, Labelle H, Aubin CE (2012) MRI signal distribution within the intervertebral disc as a biomarker of adolescent idiopathic scoliosis and spondylolisthesis. BMC Musculoskelet Disord 13:239CrossRefPubMedPubMedCentral

18.

Gibson JN, McMaster MJ, Scrimgeour CM, Stoward PJ, Rennie MJ (1988) Rates of muscle protein synthesis in paraspinal muscles: lateral disparity in children with idiopathic scoliosis. Clin Sci (Lond) 75:79–83CrossRef

19.

Gumucio JP, Mendias CL (2013) Atrogin-1, MuRF-1, and sarcopenia. Endocrine 43:12–21CrossRefPubMed

20.

Guttman M, Amit I, Garber M, French C, Lin MF, Feldser D, Huarte M, Zuk O, Carey BW, Cassady JP, Cabili MN, Jaenisch R, Mikkelsen TS, Jacks T, Hacohen N, Bernstein BE, Kellis M, Regev A, Rinn JL, Lander ES (2009) Chromatin signature reveals over a thousand highly conserved large noncoding RNAs in mammals. Nature 458:223–227CrossRefPubMedPubMedCentral

21.

Hefti F (2013) Pathogenesis and biomechanics of adolescent idiopathic scoliosis (AIS). J Child Orthop 7:17–24CrossRefPubMedPubMedCentral

22.

Heindel JJ, Balbus J, Birnbaum L, Brune-Drisse MN, Grandjean P, Gray K, Landrigan PJ, Sly PD, Suk W, Cory SD, Thompson C, Hanson M (2015) Developmental origins of health and disease: integrating environmental influences. Endocrinology 156:3416–3421CrossRefPubMedPubMedCentral

23.

Hung VW, Qin L, Cheung CS, Lam TP, Ng BK, Tse YK, Guo X, Lee KM, Cheng JC (2005) Osteopenia: a new prognostic factor of curve progression in adolescent idiopathic scoliosis. J Bone Joint Surg Am 87:2709–2716CrossRefPubMed

24.

Jones SW, Brockbank SM, Clements KM, Le GN, Campbell D, Read SJ, Needham MR, Newham P (2009) Mitogen-activated protein kinase-activated protein kinase 2 (MK2) modulates key biological pathways associated with OA disease pathology. Osteoarthritis Cartilage 17:124–131CrossRefPubMed

25.

Jones SW, Lindsay MA (2004) Overview of target validation and the impact of oligonucleotides. Curr Opin Mol Ther 6:546–550PubMed

26.

Kesling KL, Reinker KA (1997) Scoliosis in twins. A meta-analysis of the literature and report of six cases. Spine (Phila Pa 1976) 22:2009–2014CrossRef

27.

Khalil AM, Guttman M, Huarte M, Garber M, Raj A, Rivea MD, Thomas K, Presser A, Bernstein BE, Van OA, Regev A, Lander ES, Rinn JL (2009) Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression. Proc Natl Acad Sci U S A 106:11667–11672CrossRefPubMedPubMedCentral

28.

Koyama H, Nakade O, Takada Y, Kaku T, Lau KH (2002) Melatonin at pharmacologic doses increases bone mass by suppressing resorption through down-regulation of the RANKL-mediated osteoclast formation and activation. J Bone Miner Res 17:1219–1229CrossRefPubMed

29.

Lam TP, Hung VW, Yeung HY, Tse YK, Chu WC, Ng BK, Lee KM, Qin L, Cheng JC (2011) Abnormal bone quality in adolescent idiopathic scoliosis: a case–control study on 635 subjects and 269 normal controls with bone densitometry and quantitative ultrasound. Spine (Phila Pa 1976) 36:1211–1217CrossRef

30.

Lemaire V, Tobin FL, Greller LD, Cho CR, Suva LJ (2004) Modeling the interactions between osteoblast and osteoclast activities in bone remodeling. J Theor Biol 229:293–309CrossRefPubMed

31.

Little JP, Pearcy MJ, Izatt MT, Boom K, Labrom RD, Askin GN, Adam CJ (2015) Understanding how axial loads on the spine influence segmental biomechanics for idiopathic scoliosis patients: A magnetic resonance imaging study. Clin Biomech (Bristol, Avon) 32:220–8

32.

Liu H, Huang X, Liu X, Xiao S, Zhang Y, Xiang T, Shen X, Wang G, Sheng B (2014) miR-21 promotes human nucleus pulposus cell proliferation through PTEN/AKT signaling. Int J Mol Sci 15:4007–4018CrossRefPubMedPubMedCentral

33.

Liu XY, Wang L, Yu B, Zhuang QY, Wang YP (2015) Expression signatures of long noncoding RNAs in adolescent idiopathic scoliosis. Biomed Res Int 2015:276049. doi:10.1155/2015/276049

34.

Londono D, Kou I, Johnson TA, Sharma S, Ogura Y, Tsunoda T, Takahashi A, Matsumoto M, Herring JA, Lam TP, Wang X, Tam EM, Song YQ, Fan YH, Chan D, Cheah KS, Qiu X, Jiang H, Huang D, TSRHC IS Clinical Group, International Consortium for Scoliosis Genetics, Su P, Sham P, Cheung KM, Luk KD, Gordon D, Qiu Y, Cheng J, Tang N, Ikegawa S, Wise CA (2014) A meta-analysis identifies adolescent idiopathic scoliosis association with LBX1 locus in multiple ethnic groups. J Med Genet 51:401–406CrossRefPubMed

35.

Machida M, Dubousset J, Satoh T, Murai I, Wood KB, Yamada T, Ryu J (2001) Pathologic mechanism of experimental scoliosis in pinealectomized chickens. Spine (Phila Pa 1976) 26:E385–E391CrossRef

36.

Machida M, Murai I, Miyashita Y, Dubousset J, Yamada T, Kimura J (1999) Pathogenesis of idiopathic scoliosis. Experimental study in rats. Spine (Phila Pa 1976) 24:1985–1989CrossRef

37.

Man GC, Wang WW, Yeung BH, Lee SK, Ng BK, Hung WY, Wong JH, Ng TB, Qiu Y, Cheng JC (2010) Abnormal proliferation and differentiation of osteoblasts from girls with adolescent idiopathic scoliosis to melatonin. J Pineal Res 49:69–77PubMed

38.

Mannion AF, Meier M, Grob D, Muntener M (1998) Paraspinal muscle fibre type alterations associated with scoliosis: an old problem revisited with new evidence. Eur Spine J 7:289–293CrossRefPubMedPubMedCentral

39.

McMaster ME, Lee AJ, Burwell RG (2015) Physical activities of Patients with adolescent idiopathic scoliosis (AIS): preliminary longitudinal case–control study historical evaluation of possible risk factors. Scoliosis 10:6CrossRefPubMedPubMedCentral

40.

Nakade O, Koyama H, Ariji H, Yajima A, Kaku T (1999) Melatonin stimulates proliferation and type I collagen synthesis in human bone cells in vitro. J Pineal Res 27:106–110CrossRefPubMed

41.

Nakamura T (1980) Histopathological study on the intervertebral discs of idiopathic scoliosis (author’s transl). Nihon Seikeigeka Gakkai Zasshi 54:523–538PubMed

42.

Negrini S, De Mauroy JC, Grivas TB, Knott P, Kotwicki T, Maruyama T, O’Brien JP, Rigo M, Zaina F (2014) Actual evidence in the medical approach to adolescents with idiopathic scoliosis. Eur J Phys Rehabil Med 50:87–92PubMed

43.

Nikolova S, Dikova M, Dikov D, Djerov A, Dzhebir G, Atanasov V, Savov A, Kremensky I (2015) Role of the IL-6 gene in the etiopathogenesis of idiopathic scoliosis. Anal Cell Pathol (Amst) 2015:621893. doi:10.1155/2015/621893

44.

Nowak R, Kwiecien M, Tkacz M, Mazurek U (2014) Transforming growth factor-beta (TGF- beta) signaling in paravertebral muscles in juvenile and adolescent idiopathic scoliosis. Biomed Res Int 2014:594287. doi:10.1155/2014/594287

45.

Peng Y, Liang G, Pei Y, Ye W, Liang A, Su P (2012) Genomic polymorphisms of G-protein estrogen receptor 1 are associated with severity of adolescent idiopathic scoliosis. Int Orthop 36:671–677CrossRefPubMed

46.

Qiu XS, Tang NL, Yeung HY, Lee KM, Hung VW, Ng BK, Ma SL, Kwok RH, Qin L, Qiu Y, Cheng JC (2007) Melatonin receptor 1B (MTNR1B) gene polymorphism is associated with the occurrence of adolescent idiopathic scoliosis. Spine (Phila Pa 1976) 32:1748–1753CrossRef

47.

Qiu XS, Tang NL, Yeung HY, Qiu Y, Qin L, Lee KM, Cheng JC (2006) The role of melatonin receptor 1B gene (MTNR1B) in adolescent idiopathic scoliosis—A genetic association study. Stud Health Technol Inform 123:3–8PubMed

48.

Raczkowski JW (2007) The concentrations of testosterone and estradiol in girls with adolescent idiopathic scoliosis. Neuro Endocrinol Lett 28:302–304PubMed

49.

Rainoldi L, Zaina F, Villafane JH, Donzelli S, Negrini S (2015) Quality of life in normal and idiopathic scoliosis adolescents before diagnosis: reference values and discriminative validity of the SRS-22. A cross-sectional study of 1,205 pupils. Spine J 15:662–667CrossRefPubMed

50.

Roberts S, Menage J, Eisenstein SM (1993) The cartilage end-plate and intervertebral disc in scoliosis: calcification and other sequelae. J Orthop Res 11:747–757CrossRefPubMed

51.

Ruegg UT (2013) Pharmacological prospects in the treatment of Duchenne muscular dystrophy. Curr Opin Neurol 26:577–584CrossRefPubMed

52.

Rusova TV, Rykova VI, Korel AV, Zaidman AM, Tkachev DS (2005) Glycosaminoglycans of the vertebral body growth plate in patients with idiopathic scoliosis. Bull Exp Biol Med 139:738–740CrossRefPubMed

53.

Ryzhkov II, Borzilov EE, Churnosov MI, Ataman AV, Dedkov AA, Polonikov AV (2013) Transforming growth factor beta 1 is a novel susceptibility gene for adolescent idiopathic scoliosis. Spine (Phila Pa 1976) 38:E699–E704CrossRef

54.

Satomura K, Tobiume S, Tokuyama R, Yamasaki Y, Kudoh K, Maeda E, Nagayama M (2007) Melatonin at pharmacological doses enhances human osteoblastic differentiation in vitro and promotes mouse cortical bone formation in vivo. J Pineal Res 42:231–239CrossRefPubMed

55.

Suh KT, Lee SS, Hwang SH, Kim SJ, Lee JS (2007) Elevated soluble receptor activator of nuclear factor-kappaB ligand and reduced bone mineral density in patients with adolescent idiopathic scoliosis. Eur Spine J 16:1563–1569CrossRefPubMedPubMedCentral

56.

Suh KT, Lee SS, Kim SJ, Kim YK, Lee JS (2007) Pineal gland metabolism in patients with adolescent idiopathic scoliosis. J Bone Joint Surg Br 89:66–71CrossRefPubMed

57.

Sun X, Wu T, Liu Z, Zhu Z, Qian B, Zhu F, Ma W, Yu Y, Wang B, Qiu Y (2013) Osteopenia predicts curve progression of adolescent idiopathic scoliosis in girls treated with brace treatment. J Pediatr Orthop 33:366–371CrossRefPubMed

58.

Trontelj JV, Fernandez JM (1988) Single fiber EMG in juvenile idiopathic scoliosis. Muscle Nerve 11:297–300CrossRefPubMed

59.

van der Kraan PM, van den Berg WB (2012) Chondrocyte hypertrophy and osteoarthritis: role in initiation and progression of cartilage degeneration? Osteoarthritis Cartilage 20:223–232CrossRefPubMed

60.

Wajchenberg M, Martins DE, Luciano RP, Puertas EB, Del CD, Schmidt B, Oliveira AB, Faloppa F (2015) Histochemical analysis of paraspinal rotator muscles from patients with adolescent idiopathic scoliosis: a cross-sectional study. Medicine (Baltimore) 94:e598

61.

Wang S, Qiu Y, Ma Z, Xia C, Zhu F, Zhu Z (2010) Expression of Runx2 and type X collagen in vertebral growth plate of patients with adolescent idiopathic scoliosis. Connect Tissue Res 51:188–196CrossRefPubMed

62.

Wang S, Qiu Y, Zhu Z, Ma Z, Xia C, Zhu F (2007) Histomorphological study of the spinal growth plates from the convex side and the concave side in adolescent idiopathic scoliosis. J Orthop Surg Res 2:19CrossRefPubMedPubMedCentral

63.

Wang WW, Man GC, Wong JH, Ng TB, Lee KM, Ng BK, Yeung HY, Qiu Y, Cheng JC (2014) Abnormal response of the proliferation and differentiation of growth plate chondrocytes to melatonin in adolescent idiopathic scoliosis. Int J Mol Sci 15:17100–17114CrossRefPubMedPubMedCentral

64.

Worthington V, Shambaugh P (1993) Nutrition as an environmental factor in the etiology of idiopathic scoliosis. J Manipulative Physiol Ther 16:169–173PubMed

65.

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

66.

Yoshihara H, Kawakami N, Matsuyama Y, Inoh H, Imagama S, Ishiguro N (2005) A histomorphologic study of scoliosis in pinealectomized chickens. Spine (Phila Pa 1976) 30:2244–2251CrossRef

67.

Yu X, Li Z, Shen J, Wu WK, Liang J, Weng X, Qiu G (2013) MicroRNA-10b promotes nucleus pulposus cell proliferation through RhoC-Akt pathway by targeting HOXD10 in intervetebral disc degeneration. PLoS One 8:e83080

68.

Zaina F, De Mauroy JC, Grivas T, Hresko MT, Kotwizki T, Maruyama T, Price N, Rigo M, Stikeleather L, Wynne J, Negrini S (2014) Bracing for scoliosis in 2014: state of the art. Eur J Phys Rehabil Med 50:93–110PubMed

69.

Zhang HQ, Lu SJ, Tang MX, Chen LQ, Liu SH, Guo CF, Wang XY, Chen J, Xie L (2009) Association of estrogen receptor beta gene polymorphisms with susceptibility to adolescent idiopathic scoliosis. Spine (Phila Pa 1976) 34:760–764CrossRef

70.

Zhu F, Qiu Y, Yeung HY, Lee KM, Cheng JC (2006) Histomorphometric study of the spinal growth plates in idiopathic scoliosis and congenital scoliosis. Pediatr Int 48:591–598CrossRefPubMed

Title: Adolescent idiopathic scoliosis: evidence for intrinsic factors driving aetiology and progression
Authors: Matthew M. P. Newton Ede
Simon W. Jones
Publication date: 01-10-2016
Publisher: Springer Berlin Heidelberg
Published in: International Orthopaedics / Issue 10/2016
Print ISSN: 0341-2695
Electronic ISSN: 1432-5195
DOI: https://doi.org/10.1007/s00264-016-3132-4

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Adolescent idiopathic scoliosis: evidence for intrinsic factors driving aetiology and progression

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 10/2016

Minimally invasive plate osteosynthesis of acetabular anterior column fractures using the two-incision minimally invasive approach and a preshaped three dimension plate

Erratum to: Is the use of thin, highly cross-linked polyethylene liners safe in total hip arthroplasty?

Reply to comments on Chang et al.: Meta-analysis shows that highly comminuted bicondylar tibial plateau fractures treated by single lateral locking plate give similar outcomes as dual plate fixation

Displaced intra-articular calcaneal fractures: is there a consensus on treatment in Germany?

Comment on Özcan. et al.: prospective comparative study of two methods for fixation after distal femur corrective osteotomy for valgus deformity; retrograde intramedullary nailing versus less invasive stabilization system plating

No differences between direct anterior and lateral approach for primary total hip arthroplasty related to muscle damage or functional outcome