European Spine Journal

, 18:1936 | Cite as

Association between osteoprotegerin gene polymorphism and bone mineral density in patients with adolescent idiopathic scoliosis

  • Il-Soo Eun
  • Weon Wook Park
  • Kuen Tak Suh
  • Jeung Il Kim
  • Jung Sub Lee
Original Article


Generalized low bone mass and osteopenia have been reported in the axial and peripheral skeleton of adolescent idiopathic scoliosis (AIS) patients. Recently, many studies have shown that gene polymorphisms are related to osteoporosis. However, no studies have linked the association between gene polymorphisms and bone mass of AIS. Therefore, this study examined the association between the bone mass and RANKL, RANK, and OPG gene polymorphisms in 198 girls diagnosed with AIS. OPG 163 A → G, 209 G → A, 245 T → G, and 1181 G → C polymorphisms; RANK 421 C → T and 575 C → T polymorphisms; and RANKL rs12721445 and rs2277438 polymorphisms, as well as the bone mineral density at the lumbar spine (LSBMD) and femoral neck (FNBMD) were analyzed. The 163 A → G, 209 G → A, and 245 T → G polymorphisms in the OPG gene were in complete linkage. No RANK 421 C → T and 575 C → T polymorphisms or RANKL rs12711445 polymorphism were observed. There was a significant association between the OPG gene 1181 G → C polymorphism and LSBMD. LSBMD in AIS with the CC genotype was found to be significantly higher than in AIS with the GC (P < 0.05) or GG (P < 0.01) genotype. However, there was no significant association between LSBMD or FNBMD and the OPG gene 245 T → G polymorphism or the RANKL rs2277438 polymorphism. These results suggest that the OPG gene 1181 G → C polymorphism is associated with LSBMD in girls with AIS.


Adolescent idiopathic scoliosis Bone mineral density OPG RANKL Polymorphism 


  1. 1.
    Ahn UM, Ahn NU, Nallamshetty L, Buchowski JM, Rose PS, Miller NH, Kostuik JP, Sponseller PD (2002) The etiology of adolescent idiopathic scoliosis. Am J Orthop 31:387–395PubMedGoogle Scholar
  2. 2.
    Arko B, Prezelj J, Kocijancic A, Komel R, Marc J (2005) Association of the osteoprotegerin gene polymorphisms with bone mineral density in postmenopausal women. Maturitas 51:270–279CrossRefPubMedGoogle Scholar
  3. 3.
    Arko B, Prezelj J, Komel R, Kocijancic A, Hudler P, Marc J (2002) Sequence variations in the osteoprotegerin gene promoter in patients with postmenopausal osteoporosis. J Clin Endocrinol Metab 87:4080–4084CrossRefPubMedGoogle Scholar
  4. 4.
    Arnold A, Horst SA, Gardella TJ, Baba H, Levine MA, Kronenberg HM (1990) Mutation of the signal peptide encoding region of the preproparathyroid hormone gene in familial isolated hypoparathyroidism. J Clin Invest 86:1084–1087CrossRefPubMedGoogle Scholar
  5. 5.
    Baek KH, Oh KW, Lee WY, Tae HJ, Rhee EJ, Han JH, Cha BY, Kim YJ, Lee KW, Son HY, Kang SK, Kim CC, Kang MI (2006) Changes in the serum sex steroids, IL-7 and RANKL-OPG system after bone marrow transplantation: influences on bone and mineral metabolism. Bone 39:1352–1360CrossRefPubMedGoogle Scholar
  6. 6.
    Burner WL, Badger VM, Sherman FC (1982) Osteoporosis and acquired back deformities. J Pediatr Orthop 2:383–385PubMedGoogle Scholar
  7. 7.
    Cheng JC, Guo X (1997) Osteopenia in adolescent idiopathic scoliosis. A primary problem or secondary to the spinal deformity? Spine 22:1716–1721CrossRefPubMedGoogle Scholar
  8. 8.
    Cheng JC, Guo X, Sher AH (1999) Persistent osteopenia in adolescent idiopathic scoliosis. A longitudinal follow up study. Spine 24:1218–1222CrossRefPubMedGoogle Scholar
  9. 9.
    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 15:1587–1595CrossRefPubMedGoogle Scholar
  10. 10.
    Cheng JC, Tang SP, Guo X, Chan CW, Qin L (2001) Osteopenia in adolescent idiopathic scoliosis: a histomorphometric study. Spine 26:E19–E23CrossRefPubMedGoogle Scholar
  11. 11.
    Choi JY, Shin A, Park SK, Chung HW, Cho SI, Shin CS, Kim H, Lee KM, Lee KH, Kang C, Cho DY, Kang D (2005) Genetic polymorphisms of OPG, RANK, and ESR1 and bone mineral density in Korean postmenopausal women. Calcif Tissue Int 77:152–159CrossRefPubMedGoogle Scholar
  12. 12.
    Cook SD, Harding AF, Morgan EL, Nicholson RJ, Thomas KA, Whitecloud TS, Ratner ES (1987) Trabecular bone mineral density in idiopathic scoliosis. J Pediatr Orthop 7:168–174PubMedGoogle Scholar
  13. 13.
    Ford DM, Bagnall KM, Clements CA, McFadden KD (1988) Muscle spindles in the paraspinal musculature of patients with adolescent idiopathic scoliosis. Spine 13:461–465CrossRefPubMedGoogle Scholar
  14. 14.
    Ford DM, Bagnall KM, McFadden KD, Greenhill BJ, Raso VJ (1984) Paraspinal muscle imbalance in adolescent idiopathic scoliosis. Spine 9:373–376CrossRefPubMedGoogle Scholar
  15. 15.
    Garcia Palacios V, Robinson LJ, Borysenko CW, Lehmann T, Kalla SE, Blair HC (2005) Negative regulation of RANKL-induced osteoclastic differentiation in RAW264.7 Cells by estrogen and phytoestrogens. J Biol Chem 280:13720–13727CrossRefPubMedGoogle Scholar
  16. 16.
    Herman R, Mixon J, Fisher A, Maulucci R, Stuyck J (1985) Idiopathic scoliosis and the central nervous system: a motor control problem [The Harrington lecture 1983]. Scoliosis Research Society. Spine 10:1–14CrossRefPubMedGoogle Scholar
  17. 17.
    Hofbauer LC, Gori F, Riggs BL, Lacey DL, Dunstan CR, Spelsberg TC, Khosla S (1999) Stimulation of osteoprotegerin ligand and inhibition of osteoprotegerin production by glucocorticoids in human osteoblastic lineage cells: potential paracrine mechanisms of glucocorticoid-induced osteoporosis. Endocrinology 140:4382–4389CrossRefPubMedGoogle Scholar
  18. 18.
    Hsu YH, Niu T, Terwedow HA, Xu X, Feng Y, Li Z, Brain JD, Rosen CJ, Laird N, Xu X (2006) Variation in genes involved in the RANKL/RANK/OPG bone remodeling pathway are associated with bone mineral density at different skeletal sites in men. Hum Genet 118:568–577CrossRefPubMedGoogle Scholar
  19. 19.
    Kim JG, Kim JH, Kim JY, Ku SY, Jee BC, Suh CS, Kim SH, Choi YM (2007) Association between osteoprotegerin (OPG), receptor activator of nuclear factor-κB (RANK), and RANK ligand (RANKL) gene polymorphisms and circulating OPG, soluble RANKL levels, and bone mineral density in Korean postmenopausal women. Menopause 14:913–918CrossRefPubMedGoogle Scholar
  20. 20.
    Kindsfater K, Lowe T, Lawellin D, Weinstein D, Akmakjian J (1994) Levels of platelet calmodulin for the prediction of progression and severity of adolescent idiopathic scoliosis. J Bone Joint Surg 76-A:1186–1192Google Scholar
  21. 21.
    Langdahl BL, Carstens M, Stenkjaer L, Eriksen EF (2002) Polymorphisms in the osteoprotegerin gene are associated with osteoporotic fractures. J Bone Miner Res 17:1245–1255CrossRefPubMedGoogle Scholar
  22. 22.
    Machida M, Dubousset J, Imamura Y, Iwaya T, Yamada T, Kimura J, Toriyama S (1994) Pathogenesis of idiopathic scoliosis: SEPs in chicken with experimentally induced scoliosis and in patients with idiopathic scoliosis. J Pediatr Orthop 14:329–335PubMedGoogle Scholar
  23. 23.
    McCarrey JR, Abbott UK, Benson DR, Riggins RS (1981) Genetics of scoliosis in chickens. J Hered 72:6–10PubMedGoogle Scholar
  24. 24.
    Ohmori H, Makita Y, Funamizu M, Hirooka K, Hosoi T, Orimo H, Suzuki T, Ikari K, Nakajima T, Inoue I, Hata A (2002) Linkage and association analyses of the osteoprotegerin gene locus with human osteoporosis. J Hum Genet 47:400–406CrossRefPubMedGoogle Scholar
  25. 25.
    Stilwell DL Jr (1962) Structural deformities of vertebrae: bone adaptation and modeling in experimental scoliosis and kyphosis. J Bone Joint Surg 44-A:611–634PubMedGoogle Scholar
  26. 26.
    Suh KT, Lee SS, Hwang SH, Kim SJ, Lee JS (2007) Elevated soluble receptor activator of nuclear factor-κB ligand and reduced bone mineral density in patients with adolescent idiopathic scoliosis. Eur Spine J 16:1563–1569CrossRefPubMedGoogle Scholar
  27. 27.
    Suh KT, Lee SS, Kim SJ, Kim YK, Lee JS (2007) Pineal gland metabolism in patients with adolescent idiopathic scoliosis. J Bone Joint Surg 89-B:66–71CrossRefGoogle Scholar
  28. 28.
    Thomas KA, Cook SD, Skalley TC, Renshaw SV, Makuch RS, Gross M, Whitecloud TS III, Bennett JT (1992) Lumbar spine and femoral neck bone mineral density in idiopathic scoliosis: a follow up study. J Pediatr Orthop 12:235–240PubMedGoogle Scholar
  29. 29.
    Vidal C, Brincat M, Xuereb Anastasi A (2006) TNFRSF11B gene variants and bone mineral density in postmenopausal women in Malta. Maturitas 53:386–395CrossRefPubMedGoogle Scholar
  30. 30.
    Wang ED, Drummond DS, Dormans JP, Moshang T, Davidson RS, Gruccio D (1997) Scoliosis in patients treated with growth hormone. J Pediatr Orthop 17:708–711CrossRefPubMedGoogle Scholar
  31. 31.
    Wuyts W, Van Wesenbeeck L, Morales-Piga A, Ralston S, Hocking L, Vanhoenacker F, Westhovens R, Verbruggen L, Anderson D, Hughes A, Van Hul W (2001) Evaluation of the role of RANK and OPG genes in Paget’s disease of bone. Bone 28:104–107CrossRefPubMedGoogle Scholar
  32. 32.
    Yamada Y, Ando F, Niino N, Shimokata H (2003) Association of polymorphisms of the osteoprotegerin gene with bone mineral density in Japanese women but not men. Mol Genet Metab 80:344–349CrossRefPubMedGoogle Scholar
  33. 33.
    Zhao HY, Liu JM, Ning G, Zhang LZ, Sun LH, Xu MY, Uitterlinden AG, Chen JL (2005) The influence of Lys3Asn polymorphism in the osteoprotegerin gene on bone mineral density in Chinese postmenopausal women. Osteoporos Int 16:1519–1524CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Il-Soo Eun
    • 1
  • Weon Wook Park
    • 2
  • Kuen Tak Suh
    • 3
  • Jeung Il Kim
    • 3
  • Jung Sub Lee
    • 3
  1. 1.Department of Orthopaedic SurgeryBusan Medical centerBusanKorea
  2. 2.Department of Orthopaedic SurgeryKorea HospitalBusanKorea
  3. 3.Department of Orthopaedic Surgery, Medical Research InstitutePusan National University School of MedicineBusanKorea

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