Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ASCO Annual Meeting 2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

2024 ASCO Annual Meeting

Keep up to date with all the top stories and latest evidence with our hub page, including official congress videos and expert takeaways.
ADVANCED SEARCH
Log in
Top
European Spine Journal
Published in: European Spine Journal 1/2011

Open Access 01-05-2011 | Original Article

The role of melatonin in the pathogenesis of adolescent idiopathic scoliosis (AIS)

Authors: M. Girardo, N. Bettini, E. Dema, S. Cervellati

Published in: European Spine Journal | Special Issue 1/2011

Login to get access

Abstract

The cause of adolescent idiopathic scoliosis (AIS) in humans remains obscure and probably multifactorial. At present, there is no proven method or test available to identify children or adolescent at risk of developing AIS or identify which of the affected individuals are at risk of progression. Reported associations are linked in pathogenesis rather than etiologic factors. Melatonin may play a role in the pathogenesis of scoliosis (neuroendocrine hypothesis), but at present, the data available cannot clearly show the role of melatonin in producing scoliosis in humans. The data regarding human melatonin levels are mixed at best, and the melatonin deficiency as a causative factor in the etiology of scoliosis cannot be supported. It will be an important issue of future research to investigate the role of melatonin in human biology, the clinical efficacy, and safety of melatonin under different pathological situations. Research is needed to better define the role of all factors in AIS development.
Literature
1.
Alexander MA, Bunch WH, Ebbesson SOE (1972) Can experimental dorsal rhizotomy produce scoliosis? J Bone Joint Surg [Am] 54-A:1509–1513
2.
Arendt J (1998) Melatonin and the pineal gland: influence on mammalian seasonal and circadian physiology. Rev Reprod 3:13–22PubMedCrossRef
3.
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 462:45–52PubMedCrossRef
4.
Bagnall KM, Raso VJ, Hill DL, Moreau M, Mahood JK, Jiang H, Russell G, Bering M, Buzzell GR (1997) Melatonin levels in idiopathic scoliosis. Spine 21:1974–1978CrossRef
5.
Bagnall KM, Raso VJ, Hill DL, Moreau M, Mahood JK, Jiang H, Russell G, Bering M, Buzzell GR (1996) Melatonin levels in idiopathic scoliosis. Diurnal and nocturnal serum melatonin levels in girls with adolescent idiopathic scoliosis. Spine 21:1974–1978PubMedCrossRef
6.
Bagnall K, Raso VJ, Moreau M, Mahood J, Wang X, Zhao J (1999) The effects of melatonin therapy on the development of scoliosis after pinealectomy in the chicken. J Bone Joint Surg Am 81:191–199PubMed
7.
Barrios C, Tuñón MT, DeSalis JA, Beguiristain JL, Canadell J (1987) Scoliosis induced by medullary damage: an experimental study in rabbits. Spine 12:433–439PubMedCrossRef
8.
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] 82:399–403CrossRef
9.
Brydon L, Roka F, Petit L, de Coppet P, Tissot M, Barrett P, Morgan PJ, Nanoff C, Strosberg AD, Jockers R (1999) Dual signaling of human Mel1a melatonin receptors via G(i2), G(i3), and G(q/11) proteins. Mol Endocrinol 13:2025–2038PubMedCrossRef
10.
11.
Cheung KM, Lu DS, Poon AM, Wang T, Luk KD, Leong JC (2003) Effect of melatonin suppression on scoliosis development in chickens by either constant light or surgical pinealectomy. Spine 28:1941–1944PubMedCrossRef
12.
Cheung KM, Wang T, Poon AM, Carl A, Tranmer B, Hu Y, Luk KD, Leong JC (2005) The effect of pinealectomy on scoliosis development in young nonhuman primates. Spine 30(18):2009–2013PubMedCrossRef
13.
Cheung KM, Wang T, Hu YG, Leong JC (2003) Primary thoracolumbar scoliosis in pinealectomized chickens. Spine 28:2499–2504PubMedCrossRef
14.
Day GA, McPhee IB, Tuffley J, Tomlinson F, Chaseling R, Kellie S, Torode I, Sherwood M, Cutbush K, Geddes AJ, Brankoff B (2007) Idiopathic scoliosis and pineal lesions in Australian children. J Orthop Surg (Hong Kong) 15(3):327–333
15.
Dubousset J, Queneau P, Thillard Mi (1983) Experimental scoliosis induced by pineal and diencephalic lesions in young chickens: its relation with clinical findings. Orthop Trans 7:7–12
16.
Fagan AB, Kennaway DJ, Sutherland AD (1998) Total 24-hour melatonin secretion in adolescent idiopathic scoliosis: a case–control study. Spine 23(1):41–46PubMedCrossRef
17.
Fautick JD, Lershl A, Bergmann M, Moller M, Fraschini F, Wittkowski W, Stankov B (1994) The adult human cerebellum is a target of the neuro endocrine system involved in the circadian timing. Neurosci Lett 179:60–64CrossRef
18.
Ford DM, Bagnall KM, Clements CA, McFadden KD (1988) Muscle spindles in the paraspinal musculature of patients with adolescent idiopathic scoliosis. Spine 13:461–465PubMedCrossRef
19.
Ford DM, Bagnall KM, McFadden KD, Greenhill BJ, Raso VJ (1984) Paraspinal muscle imbalance in adolescent idiopathic scoliosis. Spine 9:373–376PubMedCrossRef
20.
Gauer F, Masson-Pevet M, Pevet P (1992) Effect of constant light, pinealectomy and guanosine triphosphate gamma-S on the density of melatonin receptors in the rat suprachiasmatic nucleus: a possible implication on melatonin action. J Neuroendocrinol 4:455–459CrossRef
21.
Gerdin MJ, Mseeh F, Dubocovich ML (2003) Mutagenesis studies of the human MT2 melatonin receptor. Biochem Pharmacol 66:315–320PubMedCrossRef
22.
Gorman KF, Breden F (2009) Idiopathic-type scoliosis is not exclusive to bipedalism. Med Hypotheses 72(3):348–352PubMedCrossRef
23.
Green RJL (1981) Histochemistry and ultrastructure of the paraspinal muscles in idiopathic scoliosis and in control subjects. Med Lab Sci 38:197–216PubMed
24.
25.
Herman R, Mixon J, Fisher A, Maulucci R, Stuyck J (1985) Idiopathic scoliosis and the central nervous system: a motor control problem: the Hamngton Lecture, 1983 Scoliosis Society. Spine 10:1–14PubMedCrossRef
26.
Hilibrand AS, Blakemore LC, Loder RT, Greenfield ML, Farley FA, Hensinger RN, Hariharan M (1996) The role of melatonin in the pathogenesis of adolescent idiopathic scoliosis. Spine 21:1140–1146PubMedCrossRef
27.
Kitay JI (1954) Pineal lesions and precocious puberty: a review. J Clin Endocrinol Metab 14:622–625PubMedCrossRef
28.
29.
30.
Ldhauser F, Weiszenbacher G, Frisch H, Zetlhuber U, Waldhauser M, Wurtman RJ (1984) Fall in nocturnal serum melatonin during prepuberty and pubescence. Lancet 1:362–365CrossRef
31.
Lowe TG, Edgar M, Margulies JY (2000) Etiology of idiopathic scoliosis: current trends in research. J Bone Joint Surg Am 82:1157–1168PubMed
32.
Lowe TG, Edgar M, Margulies JY, Miller NH, Raso VJ, Reinker KA, Rivard CH (2000) Etiology of idiopathic scoliosis: current trends in research. J Bone Joint Surg Am 82-A(8):1157–1168PubMed
33.
Lynch HJ, Wurtman RJ, Moskowitz MA, Archer MC, Ho MH (1975) Daily rhythm in human urinary melatonin. Science 187:169–171PubMedCrossRef
34.
Machida M, Dubousset J, Imamura Y, Iwaya T, Yamada T, Kimura J (1995) Role of melatonin deficiency in the development of scoliosis in pinealectomised chickens. J Bone Joint Surg (Br) 77-B:134–138
35.
Machida M, Dubousset J, Imamura Y, Iwaya T, Yamada T, Kimura J (1993) An experimental study in chickens for the pathogenesis of idiopathic scoliosis. Spine 18:1609–1615PubMedCrossRef
36.
Machida M, Dubousset J, Imamura Y, Iwaya T, Yamada T, Kimura J (1994) Pathogenesis of idiopathic scoliosis: SEPs in chickens with experimentally induced scoliosis and in patients with idiopathic scoliosis. J Pediatr Orthop 14:329–335PubMedCrossRef
37.
Machida M, Dubousset J, Imamura Y, Miyashita Y, Yamada T, Kimura J (1996) Melatonin: a possible role in pathogenesis of adolescent idiopathic scoliosis. Spine 21:1147–1152PubMedCrossRef
38.
Machida M, Murai H, Miyashita Y, Dubousset J, Yamada T, Kimura J (1999) Pathogenesis of idiopathic scoliosis. Spine 24:1985–1989PubMedCrossRef
39.
Machida M, Saito S, Dubousset J, Yamada T, Kimura J, Shibasaki K (2005) Pathological mechanism of idiopathic scoliosis: experimental scoliosis in pinealectomized rats. Eur Spine J 14:843–848PubMedCrossRef
40.
41.
Mannion AF, Meier M, Grob D, Müntener M (1998) Paraspinal muscle fiber type alterations associated with scoliosis: an old problem revisited with new evidence. Eur Spine J 7:289–293PubMedCrossRef
42.
Meier MP, Klein MP, Krebs D, Grob D, Müntener M (1997) Fiber transformation in multifidus muscle of young patients with idiopathic scoliosis. Spine 22:2357–2364PubMedCrossRef
43.
Morcuende JAMR, Dolan L, Stevens J, Beck J, Wang K, Weinstein SL, Sheffield V (2003) Allelic variants of human melatonin 1A receptor in patients with familial adolescent idiopathic scoliosis. Spine 28:2025–2029PubMedCrossRef
44.
Moreau A, Wang DS, Forget S, Azeddine B, Angeloni D, Fraschini F, Labelle H, Poitras B, Rivard Gh, Grimard G (2004) Melatonin signaling dysfunction in adolescent idiopathic scoliosis. Spine 29:1772–1781PubMedCrossRef
45.
Morgan PJ, Barrett P, Howell HE, Helliwell R (1994) Melatonin receptors: localization, molecular pharmacology and physiological significance. Neurochem Int 24:101–146PubMedCrossRef
46.
Murata J, Sawamura Y, Ikeda J, Hashimoto S, Honma K (1998) Twenty four hour rhythm of melatonin in patients with a history of pineal and/or hypothalamo-neurohypophyseal germinoma. J Pineal Res 25:159–166PubMedCrossRef
47.
Nogueira K, Liberman B, Pimentel-Filho FR, Goldman J, Silva ME, Vieira JO, Buratini JA, Cukiert A (2002) hCG-secreting pineal teratoma causing precocious puberty: report of two patients and review of the literature. J Pediatr Endocrinol Metab 15:1195–1201PubMedCrossRef
48.
O’Kelly C, Wang X, Raso J, Moreau M, Mahood J, Zhao J, Bagnall K (1999) The production of scoliosis following pinealectomy in young chickens, rats and hamsters. Spine 24:35–43PubMedCrossRef
49.
Oyama J, Murai I, Kanazawa K, Machida M (2006) Bipedal ambulation induces experimental scoliosis in C57BL/6J mice with reduced plasma and pineal melatonin levels. J Pineal Res 40:219–224PubMedCrossRef
50.
Petit L, Lacroix I, de Coppet P (1999) Differential signaling of human Mel1a and Mel1b melatonin receptors through the cyclic guanosine 3′-5′-monophosphate pathway. Biochem Pharmacol 58:633–639PubMedCrossRef
51.
Pincott JR, Davies IS, Tails LF (1984) Scoliosis caused by section of dorsal spinal nerve roots. J Bone Joint Surg [Br] 66B:27–29
52.
Pincott JR, Tails LF (1982) Experimental scoliosis in primates: a neurological cause. J Bone Joint Surg [Br] 64B:503–507
53.
Qiu XU, Tang NLS, Yeung HY, Cheng JCY, Qiu Y (2008) Lack of association between the promoter polymorphism of the MTNR1A gene and adolescent idiopathic scoliosis. Spine 33(20):2204–2207PubMedCrossRef
54.
Qiu XU, Tang NLS, Yeung HY, Lee KM, Hung VWY, Ng WK, Suk Ling Ma, Kwok RHK, Lin Qin, Yong Qiu, Cheng JCY (2007) Melatonin receptor 1B (MTNR1B) gene polymorphism is associated with the occurrence of adolescent idiopathic scoliosis. Spine 32(16): 1748–1753
55.
Qiu Y, Wu L, Wang B, Yu Y, Zhu Z (2007) Asymmetric expression of melatonin receptor mRNA in bilateral paravertebral muscles in adolescent idiopathic scoliosis. Spine 32(6):667–672PubMedCrossRef
56.
57.
Reppert SM, Godson C, Mahle CD, Weaver DR, Slaugenhaupt SA, Gusella JF (1995) Molecular characterization of a second melatonin receptor expressed in human retina and brain: the Mel 1b melatonin receptor. Proc Natl Acad Sci USA 92:8734–8738PubMedCrossRef
58.
Reppert SM, Weaver DR, Rivkees SA, Stopa EG (1988) Putative melatonin receptors in human biological clock. Science 242:78–81PubMedCrossRef
59.
Rivarola, Belgorosky A, Mendilaharzu H, Vidal G (2001) Precocious puberty in children with tumours of the suprasellar and pineal areas: organic central precocious puberty. Acta Paediatr 90:751–756
60.
Roka F, Brydon L, Waldhoer M (1999) Tight association of the human Mel(1a)-melatonin receptor and G(i): precoupling and constitutive activity. Mol Pharmacol 56:1014–1024PubMed
61.
Sklar CA, Conte FA, Kaplan SL, Grumbach MM (1981) Human chorionic gonadotropin-secreting pineal tumor: relation to pathogenesis and sex limitation of sexual precocity. J Clin Endocrinol Metab 53:656–660PubMedCrossRef
62.
Turek FW, Gillette MU (2004) Melatonin, sleep, and circadian rhythms: rationale for development of specific melatonin agonists. Sleep Med 5:523–532PubMedCrossRef
63.
Turgut M, Yenisey C, Uysal A, Bozkurt M, Yurtseven ME (2003) The effects of pineal gland transplantation on the production of spinal deformity and serum melatonin level following pinealectomy in the chicken. Eur Spine J 12:487–494PubMedCrossRef
64.
Vanecek J (1998) Cellular mechanisms of melatonin action. Physiol Rev 78:687–721PubMed
65.
von Gall C, Stehle JH, Weaver DR (2002) Mammalian melatonin receptors: molecular biology and signal transduction. Cell Tissue Res 309:151–162CrossRef
66.
Wang H, Wu Z, Zhuang Q, Fei Q, Zhang J, Liu Y, Wang Y, Ding Y, Qiu G (2008) Association study of tryptophan hydroxylase 1 and arylalkylamine N-acetyltransferase polymorphisms with adolescent idiopathic scoliosis in Han Chinese. Spine 33(20):2199–2203PubMedCrossRef
67.
Witt-Enderby PA, Bennett J, Jarzynka MJ, Firestine S, Melan MA (2003) Melatonin receptors and their regulation: biochemical and structural mechanisms. Life Sci 72:2183–2198PubMedCrossRef
68.
Yamada K, Yamamoto H, Nakagawa Y, Tezuka A, Tamura T, Kawata S (1984) Etiology of idiopathic scoliosis. Clin Orthop I 84:50–57
Metadata
Title
The role of melatonin in the pathogenesis of adolescent idiopathic scoliosis (AIS)
Authors
M. Girardo
N. Bettini
E. Dema
S. Cervellati
Publication date
01-05-2011
Publisher
Springer-Verlag
Published in
European Spine Journal / Issue Special Issue 1/2011
Print ISSN: 0940-6719
Electronic ISSN: 1432-0932
DOI
https://doi.org/10.1007/s00586-011-1750-5

Other articles of this Special Issue 1/2011

European Spine Journal 1/2011 Go to the issue

Original Article

TLIF for symptomatic disc degeneration: a retrospective study of 100 patients

Original Article

A minimally invasive posterior lumbar interbody fusion for degenerative lumbar spine instabilities

Original Article

Critical analysis of lumbar interspinous devices failures: a retrospective study

Original Article

Nucleus disc arthroplasty with the NUBAC™ device: 2-year clinical experience

Editorial

Contribution of Italian spine research to peer reviewed publications

Original Article

Role of rod diameter in comparison between only screws versus hooks and screws in posterior instrumentation of thoracic curve in idiopathic scoliosis