Genetic influences on cervical and lumbar disc degeneration: A magnetic resonance imaging study in twins

Abstract

Objective. Degenerative intervertebral disc disease is common; however, the importance of genetic factors is unknown. This study sought to determine the extent of genetic influences on disc degeneration by classic twin study methods using magnetic resonance imaging (MRI).Methods. We compared MRI features of degenerative disc disease in the cervical and lumbar spine of 172 monozygotic and 154 dizygotic twins (mean age 51.7 and 54.4, respectively) who were unselected for back pain or disc disease. An overall score for disc degeneration was calculated as the sum of the grades for disc height, bulge, osteophytosis, and signal intensity at each level. A "severe disease" score (excluding minor grades) and an "extent of disease" score (number of levels affected) were also calculated.Results. For the overall score, heritability was 74% (95% confidence interval [95% CI] 64-81%) at the lumbar spine and 73% (95% CI 64-80%) at the cervical spine. For "severe disease," heritability was 64% and 79% at the lumbar and cervical spine, respectively, and for "extent of disease," heritability was 63% and 63%, respectively. These results were adjusted for age, weight, height, smoking, occupational manual work, and exercise. Examination of individual features revealed that disc height and bulge were highly heritable at both sites, and osteophytes were heritable in the lumbar spine. Conclusion.These results suggest an important genetic influence on variation in intervertebral disc degeneration. However, variation in disc signal is largely influenced by environmental factors shared by twins. The use of MRI scans to determine the phenotype in family and population studies should allow a better understanding of disease mechanisms and the identification of the genes involved.Degenerative intervertebral disc disease is common with aging and is thought to be a contributing factor to pain, disability, and time lost from work in Western countries. Despite this, little is known about the pathogenesis of degenerative disc disease and the relative importance of genetic and environmental factors. Degenerative disease of the cervical and lumbar spine increases in prevalence with age, such that by the age of 60 years, most individuals have some radiographic evidence of disc narrowing and/or apophyseal osteoarthritis (OA); however, the degree of change varies considerably between individuals (1-4).Clinical observations have long supported the concept that there is some genetic or familial contribution to OA in peripheral and axial joints. Early studies by Stecher (5) demonstrated that distal interphalangeal OA, as manifested by Heberden's nodes, was 3 times as common in the sisters of affected subjects as in the general population. Generalized OA is associated with multiple joint involvement at a rate higher than that expected by age alone (6) and is also associated with cervical and lumbar disc disease. Family studies have indicated that first-degree relatives are twice as likely as population controls to have generalized OA (7). In a recent twin s...

Intervertebral disc degeneration: New insights based on “skipped” level disc pathology

“…variety of additional potential etiologic factors have been reported, suggesting that the impetus for disc degeneration may be a complex, multifactorial process (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22). Nonetheless, the effects of such degeneration, if progressive, may lead to the development of low back pain with or without sciatica.…”

“…Although addressing genetic, developmental, or other potential etiologic factors (e.g., environmental, systematic diseases, hormonal) (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22) that have been suggested to be associated with disc degeneration goes beyond the nature of our study design, one should not dismiss the possibility that such factors may play a role in the manifestation of SLDD. Although a biomechanical component is suggested as contributing to disc degeneration in this context, the suggestion requires further investigation.…”

Association between the -1306C/T polymorphism of matrix metalloproteinase-2 gene and lumbar disc disease in Chinese young adults

“…Epidemiologic studies suggest that heredity is the largest single determinant of disc degeneration [16]. According to the hypothesis that persons with earlier age of disease onset are more likely to have a genetic predisposition, the association of the MMP-2 -1306C/T polymorphism with the susceptibility to LDD was investigated in young adults.…”

Genetic and environmental influences on non-specific low back pain in children: a twin study

“…Some studies have primarily investigated the genetic role in the pathophysiology of intervertebral disc degeneration [4,35]. Degenerative disc pathology is believed to be an intermediate finding in the causal pathway of LBP in some, but not all, cases of LBP.…”