Platelet Calmodulin Levels in Adolescent Idiopathic Scoliosis

Lowe, Thomas G.; Lawellin, David; Smith, David C.; Price, Charles T.; Häher, Thomas R.; Merola, Andrew A.; O’Brien, Michael F.

doi:10.1097/00007632-200204010-00016

Cited by 59 publications

(23 citation statements)

References 14 publications

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“…Calmodulin, a calcium-binding receptor protein, regulates contractile properties in platelets and muscles, and interacts with melatonin. Increased levels of calmodulin in platelets and an asymmetrical distribution of calmodulin in paraspinal muscles compared to healthy controls have been described in IS patients [18, 19]. …”

Section: Aetiology and Pathogenesismentioning

confidence: 99%

Genetics and pathogenesis of idiopathic scoliosis

2016

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Idiopathic scoliosis (IS), the most common spinal deformity, affects otherwise healthy children and adolescents during growth. The aetiology is still unknown, although genetic factors are believed to be important. The present review corroborates the understanding of IS as a complex disease with a polygenic background. Presumably IS can be due to a spectrum of genetic risk variants, ranging from very rare or even private to very common. The most promising candidate genes are highlighted.

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Section: Aetiology and Pathogenesismentioning

confidence: 99%

Genetics and pathogenesis of idiopathic scoliosis

2016

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“…There is evidence that genetic factors such as estrogen receptor genotype may predict curve progression in IS [122]. There is also evidence that elevated calmodulin levels contribute to curve progression in IS, possibly through interference with estrogen binding to the estrogen receptor [123]. SNPs have been used to develop an AIS-Prognostic Test (AIS-PT) to identify the curves that will not require bracing or surgery and curves that will fail bracing.…”

Section: Idiopathic Scoliosismentioning

confidence: 99%

“…A higher risk for operative treatment was observed among patients with genotype XX and Xx, compared to patients with genotype xx. There is also evidence that elevated calmodulin levels contribute to curve progression in IS, possibly through interference with estrogen binding to the estrogen receptor [123]. …”

Section: Idiopathic Scoliosismentioning

confidence: 99%

Genetic Aspects of Congenital and Idiopathic Scoliosis

Giampietro

2012

Scientifica

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Congenital and idiopathic scoliosis represent disabling conditions of the spine. While congenital scoliosis (CS) is caused by morphogenic abnormalities in vertebral development, the cause(s) for idiopathic scoliosis is (are) likely to be varied, representing alterations in skeletal growth, neuromuscular imbalances, disturbances involving communication between the brain and spine, and others. Both conditions are characterized by phenotypic and genetic heterogeneities, which contribute to the difficulties in understanding their genetic basis that investigators face. Despite the differences between these two conditions there is observational and experimental evidence supporting common genetic mechanisms. This paper focuses on the clinical features of both CS and IS and highlights genetic and environmental factors which contribute to their occurrence. It is anticipated that emerging genetic technologies and improvements in phenotypic stratification of both conditions will facilitate improved understanding of the genetic basis for these conditions and enable targeted prevention and treatment strategies.

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“…Melatonin [7-13] and its signaling pathway dysfunction [14-20] and platelet-calmodulin dysfunction [21,22] detected in AIS subjects involve the autonomic nervous system. In AIS girls, autonomic nervous system activity was reported to be higher than controls [23].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2009

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Anthropometric data from three groups of adolescent girls - preoperative adolescent idiopathic scoliosis (AIS), screened for scoliosis and normals were analysed by comparing skeletal data between higher and lower body mass index subsets. Unexpected findings for each of skeletal maturation, asymmetries and overgrowth are not explained by prevailing theories of AIS pathogenesis. A speculative pathogenetic theory for girls is formulated after surveying evidence including: (1) the thoracospinal concept for right thoracic AIS in girls; (2) the new neuroskeletal biology relating the sympathetic nervous system to bone formation/resorption and bone growth; (3) white adipose tissue storing triglycerides and the adiposity hormone leptin which functions as satiety hormone and sentinel of energy balance to the hypothalamus for long-term adiposity; and (4) central leptin resistance in obesity and possibly in healthy females. The new theory states that AIS in girls results from developmental disharmony expressed in spine and trunk between autonomic and somatic nervous systems. The autonomic component of this double neuro-osseous theory for AIS pathogenesis in girls involves selectively increased sensitivity of the hypothalamus to circulating leptin (genetically-determined up-regulation possibly involving inhibitory or sensitizing intracellular molecules, such as SOC3, PTP-1B and SH2B1 respectively), with asymmetry as an adverse response (hormesis); this asymmetry is routed bilaterally via the sympathetic nervous system to the growing axial skeleton where it may initiate the scoliosis deformity (leptin-hypothalamic-sympathetic nervous system concept = LHS concept). In some younger preoperative AIS girls, the hypothalamic up-regulation to circulating leptin also involves the somatotropic (growth hormone/IGF) axis which exaggerates the sympathetically-induced asymmetric skeletal effects and contributes to curve progression, a concept with therapeutic implications. In the somatic nervous system, dysfunction of a postural mechanism involving the CNS body schema fails to control, or may induce, the spinal deformity of AIS in girls (escalator concept). Biomechanical factors affecting ribs and/or vertebrae and spinal cord during growth may localize AIS to the thoracic spine and contribute to sagittal spinal shape alterations. The developmental disharmony in spine and trunk is compounded by any osteopenia, biomechanical spinal growth modulation, disc degeneration and platelet calmodulin dysfunction. Methods for testing the theory are outlined. Implications are discussed for neuroendocrine dysfunctions, osteopontin, sympathoactivation, medical therapy, Rett and Prader-Willi syndromes, infantile idiopathic scoliosis, and human evolution. AIS pathogenesis in girls is predicated on two putative normal mechanisms involved in trunk growth, each acquired in evolution and unique to humans.

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Platelet Calmodulin Levels in Adolescent Idiopathic Scoliosis

Cited by 59 publications

References 14 publications

Genetics and pathogenesis of idiopathic scoliosis

Genetics and pathogenesis of idiopathic scoliosis

Genetic Aspects of Congenital and Idiopathic Scoliosis

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

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