What is Intervertebral Disc Degeneration, and What Causes It?

Department of Anatomy, University of Bristol, Bristol, United Kingdom.
Spine (Impact Factor: 2.3). 09/2006; 31(18):2151-61. DOI: 10.1097/01.brs.0000231761.73859.2c
Source: PubMed


STUDY DESIGN: Review and reinterpretation of existing literature. OBJECTIVE: To suggest how intervertebral disc degeneration might be distinguished from the physiologic processes of growth, aging, healing, and adaptive remodeling. SUMMARY OF BACKGROUND DATA: The research literature concerning disc degeneration is particularly diverse, and there are no accepted definitions to guide biomedical research, or medicolegal practice. DEFINITIONS: The process of disc degeneration is an aberrant, cell-mediated response to progressive structural failure. A degenerate disc is one with structural failure combined with accelerated or advanced signs of aging. Early degenerative changes should refer to accelerated age-related changes in a structurally intact disc. Degenerative disc disease should be applied to a degenerate disc that is also painful. JUSTIFICATION: Structural defects such as endplate fracture, radial fissures, and herniation are easily detected, unambiguous markers of impaired disc function. They are not inevitable with age and are more closely related to pain than any other feature of aging discs. Structural failure is irreversible because adult discs have limited healing potential. It also progresses by physical and biologic mechanisms, and, therefore, is a suitable marker for a degenerative process. Biologic progression occurs because structural failure uncouples the local mechanical environment of disc cells from the overall loading of the disc, so that disc cell responses can be inappropriate or "aberrant." Animal models confirm that cell-mediated changes always follow structural failure caused by trauma. This definition of disc degeneration simplifies the issue of causality: excessive mechanical loading disrupts a disc's structure and precipitates a cascade of cell-mediated responses, leading to further disruption. Underlying causes of disc degeneration include genetic inheritance, age, inadequate metabolite transport, and loading history, all of which can weaken discs to such an extent that structural failure occurs during the activities of daily living. The other closely related definitions help to distinguish between degenerate and injured discs, and between discs that are and are not painful.

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    • "The intervertebral disc (IVD), often referred to as a hydrodynamic pad, is a specialised tissue situated between adjacent vertebrae within the spinal column , and is crucial for providing structure and function to the spine[1]. One of the main functions of the IVD is to transmit mechanical load as well as permitting movement and flexibility of the spine. "
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    • "This phenomenon was also previously described in a rabbit model, in which osteophyte formation was induced by intradiscal injection of labelled mesenchymal stem cells[40]. Diffusion of rhBMP-7 out of the IVD may have been enhanced by biomechanical forces and/or disorganization of the lamellar structure of the AF that are part of the early IVD degeneration process[2]. Various dosages of rhBMP-7, ranging from 0.005 μg to 2 mg, with or without a carrier, have been reported to induce endochondral bone formation in extraskeletal sites (muscle, subcutis, tendon, thyroid cartilage, and subdural space) and in several species (for example, baboons, rats, and dogs)[6,41424344. "
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    ABSTRACT: Low back pain is a major cause of disability and is heavily associated with intervertebral disc degeneration. Osteogenic protein 1 (OP-1) is a growth factor that has shown potential to regenerate the intervertebral disc in human cells and animal models. However, high doses are required, presumably due to clearance from the tissue; controlled release may be a solution to this problem. In this study, we developed a preclinical, pathophysiological human tissue explant culture model of degenerated nucleus pulposus (NP). The NP explants were cultured for 28 days and injected with 100 µg OP-1 as a bolus, or with sustained-release biodegradable microspheres loaded with 16 or 1.6 µg OP-1. After culture, the tissue explants were analysed for biochemical content [water, sulphated glycosaminoglycans (GAGs), hydroxyproline and DNA], histology, cell viability and gene expression (disc matrix anabolic and catabolic markers). Untreated degenerated NP explants lost some of their GAG content when cultured for 4 weeks, but maintained other tissue constituents. Gene expression levels were close to native values. A bolus injection of OP-1 partially restored GAG content to the native level in half of the donors, while the sustained release of OP-1 did not affect the NP explants. No effect of treatment was observed on anabolic or catabolic gene expression at day 28. These results demonstrated that the regenerative potential of OP-1 is donor dependent, and only at very high doses. This questions the clinical use of OP-1 as a regenerative agent, as these high doses may increase the incidence of complications. Copyright © 2015 John Wiley & Sons, Ltd.
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