Bone Metabolism in AIS

  • Jack C. Y. ChengEmail author
  • Wayne Y. W. Lee
  • Elisa M. S. Tam
  • T. P. Lam


Adolescent idiopathic scoliosis (AIS) occurs in children during their pubertal growth spurt. Rapid skeletal growth and abnormal anthropometric parameters are associated with the development and progression of scoliotic curves, with the curves stabilized when skeletal maturity is reached. Systemic osteopenia affecting multiple skeletal sites, defined as bone mineral density (BMD) of Z-score ≤ −1 with reference to the age and ethnic-matched population, was found by dual-energy X-ray absorptiometry (DXA) in over 30% of the AIS patients. The osteopenia could persist into adulthood, thus predisposing the AIS patients to osteoporosis and other related complications in later life. Osteopenia in AIS was shown to be an important prognostic factor for curve progression. Recent studies with advanced high-resolution peripheral quantitative computed tomography (HR-pQCT) revealed significant alterations in systemic bone geometry, micro-architecture, volumetric BMD, and mechanical bone strength (finite element analysis) in addition to osteopenia in AIS. Serological and cellular functional studies supported the presence of abnormal bone formation and resorption that might have contributed to the abnormal bone qualities and bone strength which could be linked to the etiopathogenesis of AIS. Physical activities, calcium and vitamin D intake, and genetics are important factors affecting bone mass in AIS. Recent RCT studies on whole-body vibration therapy and supplement therapy with calcium and vitamin D have shown to improve low bone mass in AIS significantly. A better understanding on the possible association between bone qualities and curve progression will shed light on future development of novel prognostic biomarkers and therapeutic strategies in AIS.


Adolescent idiopathic scoliosis Bone and BMD 


  1. 1.
    Riggs BL, Khosla S, Melton LJ III. The assembly of the adult skeleton during growth and maturation: implications for senile osteoporosis. J Clin Invest. 1999;104(6):671–2.PubMedPubMedCentralCrossRefGoogle Scholar
  2. 2.
    Theintz G, Buchs B, Rizzoli R, Slosman D, Clavien H, Sizonenko PC, et al. Longitudinal monitoring of bone mass accumulation in healthy adolescents: evidence for a marked reduction after 16 years of age at the levels of lumbar spine and femoral neck in female subjects. J Clin Endocrinol Metab. 1992;75(4):1060–5.PubMedGoogle Scholar
  3. 3.
    Bailey DA, Wedge JH, McCulloch RG, Martin AD, Bernhardson SC. Epidemiology of fractures of the distal end of the radius in children as associated with growth. J Bone Joint Surg Am. 1989;71(8):1225–31.PubMedCrossRefGoogle Scholar
  4. 4.
    Wang Q, Alen M, Nicholson P, Lyytikainen A, Suuriniemi M, Helkala E, et al. Growth patterns at distal radius and tibial shaft in pubertal girls: a 2-year longitudinal study. J Bone Miner Res. 2005;20(6):954–61.PubMedCrossRefGoogle Scholar
  5. 5.
    Wang Q, Wang XF, Iuliano-Burns S, Ghasem-Zadeh A, Zebaze R, Seeman E. Rapid growth produces transient cortical weakness: a risk factor for metaphyseal fractures during puberty. J Bone Miner Res. 2010;25(7):1521–6.PubMedCrossRefGoogle Scholar
  6. 6.
    Weaver CM. Adolescence: the period of dramatic bone growth. Endocrine. 2002;17(1):43–8.PubMedCrossRefGoogle Scholar
  7. 7.
    Nishiyama KK, Macdonald HM, Moore SA, Fung T, Boyd SK, McKay HA. Cortical porosity is higher in boys compared with girls at the distal radius and distal tibia during pubertal growth: an HR-pQCT study. J Bone Miner Res. 2012;27(2):273–82.PubMedCrossRefGoogle Scholar
  8. 8.
    Hauge EM, Qvesel D, Eriksen EF, Mosekilde L, Melsen F. Cancellous bone remodeling occurs in specialized compartments lined by cells expressing osteoblastic markers. J Bone Miner Res. 2001;16(9):1575–82.PubMedCrossRefGoogle Scholar
  9. 9.
    Komori T. Regulation of osteoblast differentiation by Runx2. Adv Exp Med Biol. 2010;658:43–9.PubMedCrossRefGoogle Scholar
  10. 10.
    Boyce BF, Xing L. Functions of RANKL/RANK/OPG in bone modeling and remodeling. Arch Biochem Biophys. 2008;473(2):139–46.PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Hofbauer LC, Khosla S, Dunstan CR, Lacey DL, Boyle WJ, Riggs BL. The roles of osteoprotegerin and osteoprotegerin ligand in the paracrine regulation of bone resorption. J Bone Miner Res. 2000;15(1):2–12.PubMedCrossRefGoogle Scholar
  12. 12.
    Bellido T. Osteocyte-driven bone remodeling. Calcif Tissue Int. 2014;94(1):25–34.PubMedCrossRefGoogle Scholar
  13. 13.
    Li X, Zhang Y, Kang H, Liu W, Liu P, Zhang J, et al. Sclerostin binds to LRP5/6 and antagonizes canonical Wnt signaling. J Biol Chem. 2005;280(20):19883–7.PubMedCrossRefGoogle Scholar
  14. 14.
    Weiner S, Wagner HD. The material bone: structure mechanical function relations. Annu Rev Mater Sci. 1998;28:271–98.CrossRefGoogle Scholar
  15. 15.
    Zhang Z, Zhang YW, Gao H. On optimal hierarchy of load-bearing biological materials. Proc Biol Sci. 2011;278(1705):519–25.PubMedCrossRefGoogle Scholar
  16. 16.
    Olszta MJ, Cheng XG, Jee SS, Kumar R, Kim YY, Kaufman MJ, et al. Bone structure and formation: a new perspective. Mat Sci Eng R. 2007;58(3–5):77–116.CrossRefGoogle Scholar
  17. 17.
    Addadi L, Weiner S. Interactions between acidic proteins and crystals: stereochemical requirements in biomineralization. Proc Natl Acad Sci U S A. 1985;82(12):4110–4.PubMedPubMedCentralCrossRefGoogle Scholar
  18. 18.
    Lonstein JE, Carlson JM. The prediction of curve progression in untreated idiopathic scoliosis during growth. J Bone Joint Surg Ser A. 1984;66(7):1061–71.CrossRefGoogle Scholar
  19. 19.
    Shohat M, Shohat T, Nitzan M, Mimouni M, Kedem R, Danon YL. Growth and ethnicity in scoliosis. Acta Orthop Scand. 1988;59(3):310–3.PubMedCrossRefGoogle Scholar
  20. 20.
    Cheung CSK, Lee WTK, Tse YK, Tang SP, Lee KM, Guo X, et al. Abnormal peri-pubertal anthropometric measurements and growth pattern in adolescent idiopathic scoliosis: a study of 598 patients. Spine. 2003;28(18):2152–7.CrossRefGoogle Scholar
  21. 21.
    Goldberg CJ, Dowling FE, Fogarty EE. Adolescent idiopathic scoliosis – early menarche, normal growth. Spine. 1993;18(5):529–35.PubMedCrossRefGoogle Scholar
  22. 22.
    Cheung CSK, Lee WTK, Tse YK, Guo X, Qin L, Cheng JCY. Generalized osteopenia in adolescent idiopathic scoliosis – association with abnormal pubertal growth, bone turnover, and calcium intake? Spine. 2006;31(3):330–8.PubMedCrossRefGoogle Scholar
  23. 23.
    Ylikoski M. Height of girls with adolescent idiopathic scoliosis. Eur Spine J. 2003;12(3):288–91.PubMedPubMedCentralGoogle Scholar
  24. 24.
    Cheng JCY, Leung SSF, Lau J. Anthropometric measurements and body proportions among Chinese children. Clin Orthop Relat Res. 1996;323:22–30.CrossRefGoogle Scholar
  25. 25.
    Burwell RG, Freeman BJ, Dangerfield PH, Aujla RK, Cole AA, Kirby AS, et al. Left-right upper arm length asymmetry associated with apical vertebral rotation in subjects with thoracic scoliosis: anomaly of bilateral symmetry affecting vertebral, costal and upper arm physes? Stud Health Technol Inform. 2006;123:66–71.PubMedGoogle Scholar
  26. 26.
    Burwell RG, Aujla RK, Grevitt MP, Randell TL, Dangerfield PH, Cole AA, et al. Upper arm length model suggests transient bilateral asymmetry is associated with right thoracic adolescent idiopathic scoliosis (RT-AIS) with implications for pathogenesis and estimation of linear skeletal overgrowth. Stud Health Technol Inform. 2012;176:188–94.PubMedGoogle Scholar
  27. 27.
    Burwell RG, Aujla RK, Freeman BJ, Dangerfield PH, Cole AA, Kirby AS, et al. Patterns of extra-spinal left-right skeletal asymmetries in adolescent girls with lower spine scoliosis: relative lengthening of the ilium on the curve concavity & of right lower limb segments. Stud Health Technol Inform. 2006;123:57–65.PubMedGoogle Scholar
  28. 28.
    Schwender JD, Denis F. Coronal plane imbalance in adolescent idiopathic scoliosis with left lumbar curves exceeding 40°: the role of the lumbosacral hemicurve. Spine. 2000;25(18):2358–63.PubMedCrossRefGoogle Scholar
  29. 29.
    Goldberg CJ, Fogarty EE, Moore DP, Dowling FE. Scoliosis and developmental theory: adolescent idiopathic scoliosis. Spine. 1997;22(19):2228–38.PubMedCrossRefGoogle Scholar
  30. 30.
    Burwell RG, Aujla RK, Grevitt MP, Dangerfield PH, Moulton A, Randell TL, et al. Pathogenesis of adolescent idiopathic scoliosis in girls – a double neuro-osseous theory involving disharmony between two nervous systems, somatic and autonomic expressed in the spine and trunk: possible dependency on sympathetic nervous system and hormones with implications for medical therapy. Scoliosis. 2009;4:24.PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Weinstein SL. Natural history. Spine (Phila Pa 1976). 1999;24(24):2592–600.CrossRefGoogle Scholar
  32. 32.
    Grivas TB, Vasiliadis E, Mouzakis V, Mihas C, Koufopoulos G. Association between adolescent idiopathic scoliosis prevalence and age at menarche in different geographic latitudes. Scoliosis. 2006;1(1):9.PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Lee WTK, Cheung CSK, Tse YK, Chau WW, Qin L, Cheng JCY. Persistent osteopenia in adolescent idiopathic scoliosis (AIS) – factors predisposing to generalized osteopenia, a cross-sectional and longitudinal investigation. Int Congr Ser. 2007;1297:25–31.CrossRefGoogle Scholar
  34. 34.
    Mao SH, Jiang J, Sun X, Zhao Q, Qian BP, Liu Z, et al. Timing of menarche in Chinese girls with and without adolescent idiopathic scoliosis: current results and review of the literature. Eur Spine J. 2011;20(2):260–5.PubMedCrossRefGoogle Scholar
  35. 35.
    Grivas TB, Samelis P, Pappa AS, Stavlas P, Polyzois D. Menarche in scoliotic and nonscoliotic Mediterranean girls. Is there any relation between menarche and laterality of scoliotic curves? Stud Health Technol Inform. 2002;88:30–6.PubMedGoogle Scholar
  36. 36.
    Ramirez M, Martinez-Llorens J, Sanchez JF, Bago J, Molina A, Gea J, et al. Body composition in adolescent idiopathic scoliosis. Eur Spine J. 2013;22(2):324–9.PubMedCrossRefGoogle Scholar
  37. 37.
    Barrios C, Cortes S, Perez-Encinas C, Escriva MD, Benet I, Burgos J, et al. Anthropometry and body composition profile of girls with nonsurgically treated adolescent idiopathic scoliosis. Spine. 2011;36(18):1470–7.PubMedCrossRefGoogle Scholar
  38. 38.
    Tam EM, Liu Z, Lam TP, Ting T, Cheung G, Ng BK, et al. Lower muscle mass and body fat in adolescent idiopathic scoliosis are associated with abnormal leptin bioavailability. Spine (Phila Pa 1976). 2016;41(11):940–6.CrossRefGoogle Scholar
  39. 39.
    Clark EM, Taylor HJ, Harding I, Hutchinson J, Nelson I, Deanfield JE, et al. Association between components of body composition and scoliosis: a prospective cohort study reporting differences identifiable before the onset of scoliosis. J Bone Miner Res. 2014;29(8):1729–36.PubMedCrossRefGoogle Scholar
  40. 40.
    Witzke KA, Snow CM. Lean body mass and leg power best predict bone mineral density in adolescent girls. Med Sci Sports Exerc. 1999;31(11):1558–63.PubMedCrossRefGoogle Scholar
  41. 41.
    Schonau E. The development of the skeletal system in children and the influence of muscular strength. Horm Res. 1998;49(1):27–31.PubMedGoogle Scholar
  42. 42.
    Kaji H, Kosaka R, Yamauchi M, Kuno K, Chihara K, Sugimoto T. Effects of age, grip strength and smoking on forearm volumetric bone mineral density and bone geometry by peripheral quantitative computed tomography: comparisons between female and male. Endocr J. 2005;52(6):659–66.PubMedCrossRefGoogle Scholar
  43. 43.
    Hasegawa Y, Schneider P, Reiners C. Age, sex, and grip strength determine architectural bone parameters assessed by peripheral quantitative computed tomography (pQCT) at the human radius. J Biomech. 2001;34(4):497–503.PubMedCrossRefGoogle Scholar
  44. 44.
    Faje A, Klibanski A. Body composition and skeletal health: too heavy? Too thin? Curr Osteoporos Rep. 2012;10(3):208–16.PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Wolff J. The law of bone remodeling. New York, NY: Springer; 1986.CrossRefGoogle Scholar
  46. 46.
    Lanyon LE, Rubin CT. Static vs dynamic loads as an influence on bone remodelling. J Biomech. 1984;17(12):897–905.PubMedCrossRefGoogle Scholar
  47. 47.
    World Health Organization W. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. Report of a WHO Study Group. World Health Organ Tech Rep Ser. 1994;843:1–129.Google Scholar
  48. 48.
    Endocrinology TSo. Bone densitometry in children and adolescents. Pediatrics. 2011;127(1):189–94.CrossRefGoogle Scholar
  49. 49.
    Bacchetta J, Boutroy S, Vilayphiou N, Ranchin B, Fouque-Aubert A, Basmaison O, et al. Bone assessment in children with chronic kidney disease: data from two new bone imaging techniques in a single-center pilot study. Pediatr Nephrol. 2011;26(4):587–95.PubMedCrossRefGoogle Scholar
  50. 50.
    Fewtrell MS, Gordon I, Biassoni L, Cole TJ. Dual X-ray absorptiometry (DXA) of the lumbar spine in a clinical paediatric setting: does the method of size-adjustment matter? Bone. 2005;37(3):413–9.PubMedCrossRefGoogle Scholar
  51. 51.
    Binkovitz LA, Henwood MJ. Pediatric DXA: technique and interpretation. Pediatr Radiol. 2007;37(1):21–31.PubMedCrossRefGoogle Scholar
  52. 52.
    Adams JE. Quantitative computed tomography. Eur J Radiol. 2009;71(3):415–24.PubMedCrossRefGoogle Scholar
  53. 53.
    Adams JE, Engelke K, Zemel BS, Ward KA. Quantitative computer tomography in children and adolescents: the 2013 ISCD pediatric official positions. J Clin Densitom. 2014;17(2):258–74.PubMedCrossRefGoogle Scholar
  54. 54.
    Nishiyama KK, Shane E. Clinical imaging of bone microarchitecture with HR-pQCT. Curr Osteoporos Rep. 2013;11(2):147–55.PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Liu XS, Zhang XH, Sekhon KK, Adams MF, McMahon DJ, Bilezikian JP, et al. High-resolution peripheral quantitative computed tomography can assess microstructural and mechanical properties of human distal tibial bone. J Bone Miner Res. 2010;25(4):746–56.PubMedGoogle Scholar
  56. 56.
    Macneil JA, Boyd SK. Bone strength at the distal radius can be estimated from high-resolution peripheral quantitative computed tomography and the finite element method. Bone. 2008;42(6):1203–13.PubMedCrossRefGoogle Scholar
  57. 57.
    Liu XS, Cohen A, Shane E, Yin PT, Stein EM, Rogers H, et al. Bone density, geometry, microstructure, and stiffness: relationships between peripheral and central skeletal sites assessed by DXA, HR-pQCT, and cQCT in premenopausal women. J Bone Miner Res. 2010;25(10):2229–38.PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Cohen A, Dempster DW, Muller R, Guo XE, Nickolas TL, Liu XS, et al. Assessment of trabecular and cortical architecture and mechanical competence of bone by high-resolution peripheral computed tomography: comparison with transiliac bone biopsy. Osteoporos Int. 2010;21(2):263–73.PubMedCrossRefGoogle Scholar
  59. 59.
    Cheng JCY, Qin L, Cheung CSK, Sher AHL, Lee KM, Ng SWE, et al. Generalized low areal and volumetric bone mineral density in adolescent idiopathic scoliosis. J Bone Miner Res. 2000;15(8):1587–95.PubMedCrossRefGoogle Scholar
  60. 60.
    El Maghraoui A, Roux C. DXA scanning in clinical practice. QJM. 2008;101(8):605–17.PubMedCrossRefGoogle Scholar
  61. 61.
    Burner WL III, Badger VM, Sherman FC. Osteoporosis and acquired back deformities. J Pediatr Orthop. 1982;2(4):383–5.PubMedCrossRefGoogle Scholar
  62. 62.
    Healey JH, Lane JM. Structural scoliosis in osteoporotic women. Clin Orthop Relat Res. 1985;195:216–23.Google Scholar
  63. 63.
    Cook SD, Harding AF, Morgan EL, Nicholson RJ, Thomas KA, Whitecloud TS, et al. Trabecular bone mineral density in idiopathic scoliosis. J Pediatr Orthop. 1987;7(2):168–74.PubMedCrossRefGoogle Scholar
  64. 64.
    Lee WTK, Cheung CSK, Tse YK, Guo X, Qin L, Lam TP, et al. Association of osteopenia with curve severity in adolescent idiopathic scoliosis: a study of 919 girls. Osteoporos Int. 2005;16:1924–32.PubMedCrossRefGoogle Scholar
  65. 65.
    Yeung HY, Qin L, Hung VW, Lee KM, Guo X, Ng BW, et al. Lower degree of mineralization found in cortical bone of adolescent idiopathic scoliosis (AIS). Stud Health Technol Inform. 2006;123:599–604.PubMedGoogle Scholar
  66. 66.
    Cheng JCY, Guo X, Sher AHL. Persistent osteopenia in adolescent idiopathic scoliosis – a longitudinal follow-up study. Spine. 1999;24(12):1218–22.PubMedCrossRefGoogle Scholar
  67. 67.
    Lam TP, Hung VW, Yeung HY, Tse YK, Chu WC, Ng BK, et al. 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). 2011;36(15):1211–7.CrossRefGoogle Scholar
  68. 68.
    Thomas KA, Cook SD, Skalley TC, Renshaw SV, Makuch RS, Gross M, et al. Lumbar spine and femoral neck bone mineral density in idiopathic scoliosis: a follow-up study. J Pediatr Orthop. 1992;12(2):235–40.PubMedCrossRefGoogle Scholar
  69. 69.
    Snyder BD, Katz DA, Myers ER, Breitenbach MA, Emans JB. Bone density accumulation is not affected by brace treatment of idiopathic scoliosis in adolescent girls. J Pediatr Orthop. 2005;25(4):423–8.PubMedCrossRefGoogle Scholar
  70. 70.
    Soucacos PN, Zacharis K, Soultanis K, Gelalis J, Xenakis T, Beris AE. Risk factors for idiopathic scoliosis: review of a 6-year prospective study. Orthopedics. 2000;23(8):833–8.PubMedGoogle Scholar
  71. 71.
    Hung VWY, Qin L, Cheung CSK, Lam TP, Ng BKW, Tse YK, et al. Osteopenia: a new prognostic factor of curve progression in adolescent idiopathic scoliosis. J Bone Joint Surg. 2005;87(12):2709–16.PubMedGoogle Scholar
  72. 72.
    Lam TP, Hung VW, Yeung HY, Chu WC, Ng BK, Lee KM, et al. Quantitative ultrasound for predicting curve progression in adolescent idiopathic scoliosis: a prospective cohort study of 294 cases followed-up beyond skeletal maturity. Ultrasound Med Biol. 2013;39(3):381–7.PubMedCrossRefGoogle Scholar
  73. 73.
    Yip BH, Yu FW, Wang Z, Hung VW, Lam TP, Ng BK, et al. Prognostic value of bone mineral density on curve progression: a longitudinal cohort study of 513 girls with adolescent idiopathic scoliosis. Sci Rep. 2016;6:39220.PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    Slemenda CW, Miller JZ, Hui SL, Reister TK, Johnston CC Jr. Role of physical activity in the development of skeletal mass in children. J Bone Miner Res. 1991;6(11):1227–33.PubMedCrossRefGoogle Scholar
  75. 75.
    Rubin K, Schirduan V, Gendreau P, Sarfarazi M, Mendola R, Dalsky G. Predictors of axial and peripheral bone mineral density in healthy children and adolescents, with special attention to the role of puberty. J Pediatr. 1993;123(6):863–70.PubMedCrossRefGoogle Scholar
  76. 76.
    Lee WTK, Cheung CSK, Tse YK, Guo X, Qin L, Ho SC, et al. Generalized low bone mass of girls with adolescent idiopathic scoliosis is related to inadequate calcium intake and weight bearing physical activity in peripubertal period. Osteoporos Int. 2005;16:1024–35.PubMedCrossRefGoogle Scholar
  77. 77.
    Yu WS, Chan KY, Yu FW, Ng BK, Lee KM, Qin L, et al. Bone structural and mechanical indices in adolescent idiopathic scoliosis evaluated by high-resolution peripheral quantitative computed tomography (HR-pQCT). Bone. 2014;61C:109–15.CrossRefGoogle Scholar
  78. 78.
    Rizzoli R, Bonjour JP. Physiology of calcium and phosphate homeostases. In: Seibel MJ, Robins SP, Bilezikian JP, editors. Dynamics of bone and cartilage metabolism. London: Academic; 2006. p. 345–60.CrossRefGoogle Scholar
  79. 79.
    Society CN. Chinese dietary reference intakes. Beijing: Chinese Light Industry Press; 2000.Google Scholar
  80. 80.
    Akseer N, Kish K, Rigby WA, Greenway M, Klentrou P, Wilson PM, et al. Does bracing affect bone health in women with adolescent idiopathic scoliosis? Scoliosis. 2015;10:5.PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    Gozdzialska A, Jaskiewicz J, Knapik-Czajka M, Drag J, Gawlik M, Ciesla M, et al. Association of calcium and phosphate balance, vitamin D, PTH, and calcitonin in patients with adolescent idiopathic scoliosis. Spine (Phila Pa 1976). 2016;41(8):693–7.CrossRefGoogle Scholar
  82. 82.
    Balioglu MB, Aydin C, Kargin D, Albayrak A, Atici Y, Tas SK, et al. Vitamin-D measurement in patients with adolescent idiopathic scoliosis. J Pediatr Orthop B. 2017;26(1):48–52.PubMedCrossRefGoogle Scholar
  83. 83.
    Andrew T, Macgregor AJ. Genes and osteoporosis. Curr Osteoporos Rep. 2004;2(3):79–89.PubMedCrossRefGoogle Scholar
  84. 84.
    Sobieszczanska M, Jonkisz J, Tabin M, Laszki-Szczachor K. Osteoporosis: genetic determinants and relationship with cardiovascular disease. Adv Clin Exp Med. 2013;22(1):119–24.PubMedGoogle Scholar
  85. 85.
    Richards JB, Kavvoura FK, Rivadeneira F, Styrkarsdottir U, Estrada K, Halldorsson BV, et al. Collaborative meta-analysis: associations of 150 candidate genes with osteoporosis and osteoporotic fracture. Ann Intern Med. 2009;151(8):528–37.PubMedPubMedCentralCrossRefGoogle Scholar
  86. 86.
    Richards JB, Zheng HF, Spector TD. Genetics of osteoporosis from genome-wide association studies: advances and challenges. Nat Rev Genet. 2012;13(8):576–88.PubMedCrossRefGoogle Scholar
  87. 87.
    Pothuaud L, Van Rietbergen B, Mosekilde L, Beuf O, Levitz P, Benhamou CL, et al. Combination of topological parameters and bone volume fraction better predicts the mechanical properties of trabecular bone. J Biomech. 2002;35(8):1091–9.PubMedCrossRefGoogle Scholar
  88. 88.
    Pistoia W, van Rietbergen B, Lochmuller EM, Lill CA, Eckstein F, Ruegsegger P. Estimation of distal radius failure load with micro-finite element analysis models based on three-dimensional peripheral quantitative computed tomography images. Bone. 2002;30(6):842–8.PubMedCrossRefGoogle Scholar
  89. 89.
    Sornay-Rendu E, Boutroy S, Munoz F, Delmas PD. Alterations of cortical and trabecular architecture are associated with fractures in postmenopausal women, partially independent of decreased BMD measured by DXA: the OFELY study. J Bone Miner Res. 2007;22(3):425–33.PubMedCrossRefGoogle Scholar
  90. 90.
    NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and Therapy. Osteoporosis prevention, diagnosis, and therapy. JAMA. 2001;285(6):785–95.CrossRefGoogle Scholar
  91. 91.
    Wang Z, Chen H, Yu YE, Zhang J, Cheuk KY, Ng BK, et al. Unique local bone tissue characteristics in iliac crest bone biopsy from adolescent idiopathic scoliosis with severe spinal deformity. Sci Rep. 2017;7:40265.PubMedPubMedCentralCrossRefGoogle Scholar
  92. 92.
    Okata H, Nakamura M, Henmi A, Yamaguchi S, Mikami Y, Shimauchi H, et al. Calcification during bone healing in a standardised rat calvarial defect assessed by micro-CT and SEM-EDX. Oral Dis. 2015;21(1):74–82.PubMedCrossRefGoogle Scholar
  93. 93.
    Tzaphlidou M, Speller R, Royle G, Griffiths J, Olivo A, Pani S, et al. High resolution Ca/P maps of bone architecture in 3D synchrotron radiation microtomographic images. Appl Rad Isotopes. 2005;62(4):569–75.CrossRefGoogle Scholar
  94. 94.
    Yu W, Chan Ky YFWP, Hy Y, Ng BKW, Lee K, et al. Abnormal bone quality versus low bone mineral density in adolescent idiopathic scoliosis: a case-control study with in vivo high-resolution peripheral quantitative computed tomography. Spine J. 2013;13(11):1493–9.PubMedCrossRefGoogle Scholar
  95. 95.
    Liu XS, Sajda P, Saha PK, Wehrli FW, Bevill G, Keaveny TM, et al. Complete volumetric decomposition of individual trabecular plates and rods and its morphological correlations with anisotropic elastic moduli in human trabecular bone. J Bone Miner Res. 2008;23(2):223–35.PubMedCrossRefGoogle Scholar
  96. 96.
    Liu XS, Stein EM, Zhou B, Zhang CA, Nickolas TL, Cohen A, et al. Individual trabecula segmentation (ITS)-based morphological analyses and microfinite element analysis of HR-pQCT images discriminate postmenopausal fragility fractures independent of DXA measurements. J Bone Miner Res. 2012;27(2):263–72.PubMedPubMedCentralCrossRefGoogle Scholar
  97. 97.
    Cheung CS, Lee WT, Tse YK, Lee KM, Guo X, Qin L, et al. Generalized osteopenia in adolescent idiopathic scoliosis—association with abnormal pubertal growth, bone turnover, and calcium intake? Spine (Phila Pa 1976). 2006;31(3):330–8.CrossRefGoogle Scholar
  98. 98.
    Suh KT, Lee SS, Hwang SH, Kim SJ, Lee JS. Elevated soluble receptor activator of nuclear factor-kappaB ligand and reduced bone mineral density in patients with adolescent idiopathic scoliosis. Eur Spine J. 2007;16(10):1563–9.PubMedPubMedCentralCrossRefGoogle Scholar
  99. 99.
    Brzezinski A. Melatonin in humans. N Engl J Med. 1997;336(3):186–95.PubMedCrossRefGoogle Scholar
  100. 100.
    O'Kelly C, Wang X, Raso J, Moreau M, Mahood J, Zhao J, et al. The production of scoliosis after pinealectomy in young chickens, rats, and hamsters. Spine. 1999;24(1):35–43.PubMedCrossRefGoogle Scholar
  101. 101.
    Machida M, Saito M, Dubousset J, Yamada T, Kimura J, Shibasaki K. Pathological mechanism of idiopathic scoliosis: Experimental scoliosis in pinealectomized rats. Eur Spine J. 2005;14(9):843–8.PubMedCrossRefGoogle Scholar
  102. 102.
    Machida M, Dubousset J, Imamura Y, Iwaya T, Yamada T, Kimura J. An experimental study in chickens for the pathogenesis of idiopathic scoliosis. Spine. 1993;18(12):1609–15.PubMedCrossRefGoogle Scholar
  103. 103.
    Moreau A, Wang DS, Forget S, Azeddine B, Angeloni D, Fraschini F, et al. Melatonin signaling dysfunction in adolescent idiopathic scoliosis. Spine. 2004;29(16):1772–81.PubMedCrossRefGoogle Scholar
  104. 104.
    Moreau A, Akoumé Ndong MY, Azeddine B, Franco A, Rompré PH, Roy-Gagnon MH, et al. Molecular and genetic aspects of idiopathic scoliosis: Blood test for idiopathic scoliosis. Orthopade. 2009;38(2):114–21.PubMedCrossRefGoogle Scholar
  105. 105.
    Man G, Wang W, Yeung B, Lee S, Ng B, Hung W-Y, et al. Abnormal proliferation and differentiation of osteoblasts from girls with adolescent idiopathic scoliosis to melatonin. J Pineal Res. 2010;49:69–77.PubMedGoogle Scholar
  106. 106.
    Man GCW, Wong JH, Wang WWJ, Sun GQ, Yeung BHY, Ng TB, et al. Abnormal melatonin receptor 1B expression in osteoblasts from girls with adolescent idiopathic scoliosis. J Pineal Res. 2011;50(4):395–402.PubMedCrossRefGoogle Scholar
  107. 107.
    Yim AP, Yeung HY, Sun G, Lee KM, Ng TB, Lam TP, et al. Abnormal skeletal growth in adolescent idiopathic scoliosis is associated with abnormal quantitative expression of melatonin receptor, MT2. Int J Mol Sci. 2013;14(3):6345–58.PubMedPubMedCentralCrossRefGoogle Scholar
  108. 108.
    Qiu XS, Tang NLS, Yeung HY, Lee KM, Hung VWY, Ng BKW, et al. Melatonin receptor 1B (MTNR1B) gene polymorphism is associated with the occurrence of adolescent idiopathic scoliosis. Spine. 2007;32(16):1748–53.PubMedCrossRefGoogle Scholar
  109. 109.
    Qiu Y, Sun X, Qiu X, Li W, Zhu Z, Zhu F, et al. Decreased circulating leptin level and its association with body and bone mass in girls with adolescent idiopathic scoliosis. Spine (Phila Pa 1976). 2007;32(24):2703–10.CrossRefGoogle Scholar
  110. 110.
    Liu Z, Tam EM, Sun GQ, Lam TP, Zhu ZZ, Sun X, et al. Abnormal leptin bioavailability in adolescent idiopathic scoliosis: an important new finding. Spine (Phila Pa 1976). 2012;37(7):599–604.CrossRefGoogle Scholar
  111. 111.
    Tam EM, Yu FW, Hung VW, Liu Z, Liu KL, Ng BK, et al. Are volumetric bone mineral density and bone micro-architecture associated with leptin and soluble leptin receptor levels in adolescent idiopathic scoliosis? A case-control study. PLoS One. 2014;9(2):e87939.PubMedPubMedCentralCrossRefGoogle Scholar
  112. 112.
    Burwell RG, Dangerfield PH, Moulton A, Anderson SI. Etiologic theories of idiopathic scoliosis: autonomic nervous system and the leptin-sympathetic nervous system concept for the pathogenesis of adolescent idiopathic scoliosis. Stud Health Technol Inform. 2008;140:197–207.PubMedGoogle Scholar
  113. 113.
    Leboeuf D, Letellier K, Alos N, Edery P, Moldovan F. Do estrogens impact adolescent idiopathic scoliosis? Trends Endocrinol Metab. 2009;20(4):147–52.PubMedCrossRefGoogle Scholar
  114. 114.
    Rubin C, Turner AS, Bain S, Mallinckrodt C, McLeod K. Low mechanical signals strengthen long bones. Nature. 2001;412(6847):603–4.PubMedCrossRefGoogle Scholar
  115. 115.
    Gilsanz V, Wren TA, Sanchez M, Dorey F, Judex S, Rubin C. Low-level, high-frequency mechanical signals enhance musculoskeletal development of young women with low BMD. J Bone Miner Res. 2006;21(9):1464–74.PubMedCrossRefGoogle Scholar
  116. 116.
    Rubin C, Recker R, Cullen D, Ryaby J, McCabe J, McLeod K. Prevention of postmenopausal bone loss by a low-magnitude, high-frequency mechanical stimuli: a clinical trial assessing compliance, efficacy, and safety. J Bone Miner Res. 2004;19(3):343–51.PubMedCrossRefGoogle Scholar
  117. 117.
    Slatkovska L, Alibhai SM, Beyene J, Cheung AM. Effect of whole-body vibration on BMD: a systematic review and meta-analysis. Osteoporos Int. 2010;21(12):1969–80.PubMedPubMedCentralCrossRefGoogle Scholar
  118. 118.
    Kohrt WM. Aging and the osteogenic response to mechanical loading. Int J Sport Nutr Exerc Metab. 2001;11(Suppl):S137–42.PubMedCrossRefGoogle Scholar
  119. 119.
    Lam TP, Ng BK, Cheung LW, Lee KM, Qin L, Cheng JC. Effect of whole body vibration (WBV) therapy on bone density and bone quality in osteopenic girls with adolescent idiopathic scoliosis: a randomized, controlled trial. Osteoporos Int. 2013;24(5):1623–36.PubMedCrossRefGoogle Scholar
  120. 120.
    Lee WT, Jiang J. The resurgence of the importance of vitamin D in bone health. Asia Pac J Clin Nutr. 2008;17(Suppl 1):138–42.PubMedGoogle Scholar
  121. 121.
    Grivas TB, Vasiliadis E, Savvidou O, Mouzakis V, Koufopoulos G. Geographic latitude and prevalence of adolescent idiopathic scoliosis. Stud Health Technol Inform. 2006;123:84–9.PubMedGoogle Scholar
  122. 122.
    Lam TP, Yu WS, Mak WY, Cheung TF, Lee KM, BKW N, et al., editors. Vitamin D insufficiency and its association with low bone mass in girls with adolescent idiopathic scoliosis (AIS). 48th Scoliosis Research Society (SRS) annual meeting, Sep 2013. Lyon: Scoliosis Research Society (SRS); 2013.Google Scholar
  123. 123.
    Hung VWY, Qin L, Cheung CSK, Lam TP, Ng BKW, Tse YK, et al. Osteopenia: a new prognostic factor of curve progression in adolescent idiopathic scoliosis. J Bone Joint Surg Am. 2005;87:2709–16.PubMedGoogle Scholar
  124. 124.
    Schneider P, Meier M, Wepf R, Muller R. Towards quantitative 3D imaging of the osteocyte lacuno-canalicular network. Bone. 2010;47(5):848–58.PubMedCrossRefGoogle Scholar
  125. 125.
    Ruchon AF, Tenenhouse HS, Marcinkiewicz M, Siegfried G, Aubin JE, DesGroseillers L, et al. Developmental expression and tissue distribution of Phex protein: effect of the Hyp mutation and relationship to bone markers. J Bone Miner Res. 2000;15(8):1440–50.PubMedCrossRefGoogle Scholar
  126. 126.
    Zhao CQ, Liu D, Li H, Jiang LS, Dai LY. Expression of leptin and its functional receptor on disc cells: contribution to cell proliferation. Spine (Phila Pa 1976). 2008;33(23):E858–64.CrossRefGoogle Scholar
  127. 127.
    Jones SJ, Glorieux FH, Travers R, Boyde A. The microscopic structure of bone in normal children and patients with osteogenesis imperfecta: a survey using backscattered electron imaging. Calcif Tissue Int. 1999;64(1):8–17.PubMedCrossRefGoogle Scholar
  128. 128.
    Knothe Tate ML, Adamson JR, Tami AE, Bauer TW. The osteocyte. Int J Biochem Cell Biol. 2004;36(1):1–8.PubMedCrossRefGoogle Scholar
  129. 129.
    Cheng JC, Tang SP, Guo X, Chan CW, Qin L. Osteopenia in adolescent idiopathic scoliosis: a histomorphometric study. Spine (Phila Pa 1976). 2001;26(3):E19–23.CrossRefGoogle Scholar
  130. 130.
    Ren Y, Lin S, Jing Y, Dechow PC, Feng JQ. A novel way to statistically analyze morphologic changes in Dmp1-null osteocytes. Connect Tissue Res. 2014;55(Suppl 1):129–33.PubMedPubMedCentralCrossRefGoogle Scholar
  131. 131.
    Cejka D, Jager-Lansky A, Kieweg H, Weber M, Bieglmayer C, Haider DG, et al. Sclerostin serum levels correlate positively with bone mineral density and microarchitecture in haemodialysis patients. Nephrol Dial Transplant. 2012;27(1):226–30.PubMedCrossRefGoogle Scholar
  132. 132.
    Christen P, Ito K, Ellouz R, Boutroy S, Sornay-Rendu E, Chapurlat RD, et al. Bone remodelling in humans is load-driven but not lazy. Nat Commun. 2014;5:4855.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Japan KK 2018

Authors and Affiliations

  • Jack C. Y. Cheng
    • 1
    • 2
    Email author
  • Wayne Y. W. Lee
    • 1
    • 2
  • Elisa M. S. Tam
    • 1
    • 2
  • T. P. Lam
    • 1
    • 2
  1. 1.Department of Orthopaedics and Traumatology, SH Ho Scoliosis Research Laboratory, Prince of Wales HospitalThe Chinese University of Hong KongShatinChina
  2. 2.Joint Scoliosis Research Center of the Chinese University of Hong Kong and Nanjing UniversityHong KongChina

Personalised recommendations