Abstract
Generalized low bone mass and osteopenia in both axial and peripheral skeleton in adolescent idiopathic scoliosis (AIS) have been reported in literature. However, the exact mechanisms and causes of the bone loss in AIS are not identified yet. Therefore, this study examined the relationship between serum concentration of soluble receptor activator of nuclear factor-κB ligand (RANKL), serum level of osteoprotegerin (OPG) and bone mass in 72 patients with AIS and compared to those of 64 age- and gender-matched healthy controls. The mean lumbar spinal bone mineral density (LSBMD) and femoral neck BMD (FNBMD) in patients with AIS were decreased compared with that in control individuals, respectively (P = 0.0029 and P = 0.0192, respectively). The mean RANKL and RANKL to OPG ratio in patients with AIS were increased compared with that in control subjects, respectively (P = 0.0004 and P = 0.0032, respectively). The RANKL and RANKL to OPG ratios were negatively correlated to the LSBMD and serum OPG levels in both groups. Serum OPG levels were positively correlated to the LSBMD and FNBMD in both groups. These findings mean that the imbalance and the disturbed interaction of RANKL and OPG may be an important cause and pathogenesis in reduced BMD in AIS.
Similar content being viewed by others
References
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 31:387–395
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 39:1352–1360
Burner WL, Badger VM, Sherman FC (1982) Osteoporosis and acquired back deformities. J Pediatr Orthop 2:383–385
Capparelli C, Morony S, Warmington K, Adamu S, Lacey D, Dunstan CR, Stouch B, Martin S, Kostenuik PJ (2003) Sustained antiresorptive effects after a single treatment with human recombinant osteoprotegerin (OPG): a pharmacodynamic and pharmacokinetic analysis in rats. J Bone Miner Res 18:852–858
Cheng JC, Guo X (1997) Osteopenia in adolescent idiopathic scoliosis. A primary problem or secondary to the spinal deformity? Spine 22:1716–1721
Cheng JC, Guo X, Sher AH (1999) Persistent osteopenia in adolescent idiopathic scoliosis. A longitudinal follow up study. Spine 24:1218–1222
Cheng JC, Leung SS, Lee WT, Lau JT, Maffulli N, Cheung AY, Chan KM (1998) Determinants of axial and peripheral bone mass in Chinese adolescents. Arch Dis Child 78:524–530
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 15:1587–1595
Cheng JC, Tang SP, Guo X, Chan CW, Qin L (2001) Osteopenia in adolescent idiopathic scoliosis: a histomorphometric study. Spine 26:E19–E23
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 7:168–174
Crotti TN, Smith MD, Weedon H, Ahern MJ, Findlay DM, Kraan M, Tak PP, Haynes DR (2002) Receptor activator NF-kappaB ligand (RANKL) expression in synovial tissue from patients with rheumatoid arthritis, spondyloarthropathy, osteoarthritis, and from normal patients: semiquantitative and quantitative analysis. Ann Rheum Dis 61:1047–1054
Ford DM, Bagnall KM, Clements CA, McFadden KD (1988) Muscle spindles in the paraspinal musculature of patients with adolescent idiopathic scoliosis. Spine 13:461–465
Ford DM, Bagnall KM, McFadden KD, Greenhill BJ, Raso VJ (1984) Paraspinal muscle imbalance in adolescent idiopathic scoliosis. Spine 9:373–376
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 280:13720–13727
Haynes DR, Barg E, Crotti TN, Holding C, Weedon H, Atkins GJ, Zannetino A, Ahern MJ, Coleman M, Roberts-Thomson PJ, Kraan M, Tak PP, Smith MD (2003) Osteoprotegerin expression in synovial tissue from patients with rheumatoid arthritis, spondyloarthropathies and osteoarthritis and normal controls. Rheumatology 42:123–134
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 10:1–14
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 140:4382–4389
Ho S, Wong E, Chan SG, Lau J, Chan C, Leung PC (1997) Determinants of peak bone mass in Chinese women aged 21–40 years. III. Physical activity and bone mineral density. J Bone Miner Res 12:1262–1271
Johnston CC Jr, Miller JZ, Slemenda CW, Reister TK, Hui S, Christian JC, Peacock M (1992) Calcium supplementation and increase in bone mineral density in children. New Engl J Med 327:82–87
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:1186–1192
Kostenuik PJ, Bolon B, Morony S, Daris M, Geng Z, Carter C, Sheng J (2004) Gene therapy with human recombinant osteoprotegerin reverses established osteopenia in ovariectomized mice. Bone 34:656–664
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 14:329–335
McCarrey JR, Abbott UK, Benson DR, Riggins RS (1981) Genetics of scoliosis in chickens. J Hered 72:6–10
Nilsson BE, Westlin NE (1971) Bone density in athletes. Clin Orthop 77:179–182
Rogers A, Saleh G, Hannon RA, Greenfield D, Eastell R (2002) Circulating estradiol and osteoprotegerin as determinants of bone turnover and bone density in postmenopausal women. J Clin Endocrinol Metab 87:4470–4475
Slemenda CW, Peacock M, Hui S, Zhou L, Johnston CC (1997) Reduced rates of skeletal remodeling are associated with increased bone mineral density the development of peak skeletal mass. J Bone Miner Res 12:676–682
Smith FM, Latchford G, Hall RM, Millner PA, Dickson RA (2002) Indications of disordered eating behaviour in adolescent patients with idiopathic scoliosis. J Bone Joint Surg 84-B:392–394
Stilwell DL Jr (1962) Structural deformities of vertebrae: Bone adaptation and modeling in experimental scoliosis and kyphosis. J Bone Joint Surg 44-A:611–634
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:66–71
Thomas KA, Cook SD, Skalley TC, Renshaw SV, Makuch RS, Gross M, Whitecloud TS 3rd, Bennett JT (1992) Lumbar spine and femoral neck bone mineral density in idiopathic scoliosis: a follow up study. J Pediatr Orthop 12:235–240
Wang ED, Drummond DS, Dormans JP, Moshang T, Davidson RS, Gruccio D (1997) Scoliosis in patients treated with growth hormone. J Pediatr Orthop 17:708–711
Acknowledgments
K. T. Suh, S.-S. Lee and S. H. Hwang contributed equally to this study. This study was supported by Medical Research Institute Grant (2007-12), Pusan National University.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Suh, K.T., Lee, SS., Hwang, S.H. et al. Elevated soluble receptor activator of nuclear factor-κB ligand and reduced bone mineral density in patients with adolescent idiopathic scoliosis. Eur Spine J 16, 1563–1569 (2007). https://doi.org/10.1007/s00586-007-0390-2
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00586-007-0390-2