Smoking and intervertebral disc degeneration

Smoking and intervertebral disc degeneration

Medical Hypotheses (2001) 56(4), 537–539 © 2001 Harcourt Publishers Ltd doi: 10.1054/mehy.2000.1253, available online at on...

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Medical Hypotheses (2001) 56(4), 537–539 © 2001 Harcourt Publishers Ltd doi: 10.1054/mehy.2000.1253, available online at on

Smoking and intervertebral disc degeneration R. R. Fogelholm,1 A. V. Alho (deceased)2 1

Department of Neurology, University of Helsinki, Helsinki, Finland Orton Othopaedic Hospital, Invalid Foundation, Helsinki, Finland


Summary Cigarette smokers have an increased risk of low back pain which may be caused by disc degeneration and spinal instability, for example. Ischemia, apoptosis, faulty synthesis of disc macromolecules, and an imbalance between disc matrix proteinases and their inhibitors may be involved in the pathogenesis of disc degeneration. Along with degeneration, the primary avascular disc turns vascular. There is some evidence that disc degeneration of cigarette smokers is of more severe degree than that of non-smokers. Cigarette-smoking increases serum proteolytic activity by releasing proteolytic enzymes from neutrophils in alveolar capillaries, and by inhibiting the activity of alpha-1-antiprotease, the most potent protease inhibitor. We hypothesize that the high serum proteolytic activity of cigarette-smokers gets access to a previously degenerated neovascularized disc and speeds up the degerative process. The increased proteolytic activity may also weaken the spinal ligaments resulting in spinal instability. These processes may explain the increased risk of low back pain of cigarette smokers. © 2001 Harcourt Publishers Ltd

INTRODUCTION Low back pain (LBP) is one of the leading public health problems in developed countries. In theory, it may be caused by any disease that involves pain-sensitive parts of the spine, e.g. lumbar disc degeneration (1,2). The pathogenesis of disc degeneration is not completely understood. Lately, the importance of disc ischemia caused by abdominal aortic atherosclerosis stenosing the arteries feeding the lumbar spine and other structures of the back (3), and the imbalance between disc matrix proteases and their inhibitors (4) have been stressed. It is likely that both mechanisms operate together. The increased risk of LBP among cigarette-smokers has been known for 20 years (5) and the odds ratio compared with non-smokers has been 1.3 to 2.5 (5–10). This association seems to be dose-dependent (11). Several explanations for causality have been proposed (12). Received 24 July 2000 Accepted 16 October 2000 Correspondence to: Rainer R. Fogelholm MD, PhD, Pappilantie 10 B 8, 02400 Kirkkonummi, Finland. Phone & Fax: +358 9 221 3731; E-mail: [email protected]

Nicotine may cause vasoconstriction and reduce the blood flow of vertebral bodies and thus impair disc metabolism (11). Nicotine may also lower the central nervous system pain threshold (7). High CO-hemoglobin content of the smokers may disturb the oxydative metabolism, and chronic cough frequent among smokers is supposed to damage mechanically the discs by increasing the intradiscal pressure (5). Smoking is also indirectly involved by accelerating aortic atherosclerosis and stenosis of the orifices of the arteries feeding the spine (13–15).

STRUCTURE OF THE INTERVERTEBRAL DISC The disc consists of a gelatinous central nucleus pulposus surrounded by annulus fibrosus formed of concentric collagen fibres interconnected with the adjoining vertebral bodies. The cartilaginous end plate separates the highly vascular cancellous bone of the vertebral body from the avascular intervertebral disc (16). The nutrition of the disc occurs by diffusion, mainly from the adjacent vertebral bodies through the end plates, and to a lesser extent, from the arteries of the longitudinal ligaments (17). The nucleus contains 80–90% water, and of the dry weight 65% are proteoglycans, 25% collagens mainly of 537


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type II, and a small proportion consists of elastic fibres and other minor components. Annulus fibrosus is composed mainly of collagen fibres of types I and II (60% of the dry weight), 20% of the dry weight are proteoglycans, and the remaining consists of elastic fibers and other non-collagen proteins (18,19). Only 1–5% of the disc volume is comprised of cells, mainly of fibroblasts and chondrocytes. It has been presumed that these cells synthetize the macromolecules of disc matrix, including the proteolytic enzymes and their inhibitors (16) present in small amounts in a normal disc. Kang et al. (20) measured low levels of matrix metalloproteinase (MMP), gelatinase and caseinase but not of collagenase activity in non-degenerated disc culture media. Similarly, Crean et al. (21) obtained only small MMP-2 and MMP-3 activities in mildly degenerated discs compared with more severely degenerated ones. Sedowofia et al. (19) measured from homogenates of both nucleus and annulus collagenolytic, gelatinolytic and elastolytic activities. Whether the discs were normal or degenerated was not stated. DISC DEGENERATION With advancing disc degeneration, the boundary between nucleus and annulus becomes blurred, the nucleus loses fluid, becomes more fibrous and begins to fissure. The disc loses height, and osteophytes begin to grow from adjacent vertebral bodies above and below the disc. Simultaneously, the vascularity of the disc increases. New arteries emerge between the outer layers of the annulus fibrosus and later penetrate even into the nucleus. The number and depth of the vascular channels increases with advancing disc degeneration (17). These new vessels originate from arteries of the longitudinal ligaments, periosteum of the vertebral bodies and cancellous bone beneath the end plate (22). Eventually, the initially avascular disc turns into a vascular one. The pathogenetic mechanisms behind disc degeneration are not fully understood. Poor nutrition due to atheromatous stenosis of the feeding arteries emerging from the abdominal aorta seems to be one of the underlying factors (3). Another factor is an imbalance between the synthesis and breakdown of matrix components. The synthesis may be impaired because of poor nutrition of the disc cells. Apoptosis diminishes the number of functioning cells which, in addition, may produce faulty matrix molecules (23). All the time the proteolytic enzymes continue to break down matrix macromolecules. As mentioned earlier, normal discs contain several MMPs and neutral collagenolytic, gelatinolytic and elastolytic enzymes (19). Studies on degenerated discs have shown that the activities of proteolytic enzymes are Medical Hypotheses (2001) 56(4), 537–539

much higher than in normal discs, and that the activity increases along with the grade of degeneration (20,21). An interesting observation is the absence of polymorphonuclear neutrophil elastase from normal discs and its high activity in degenerated and vascularized ones (24). The balance between MMPs and their tissue inhibitors is regulated by numerous inhibitory and stimulating factors (4). Neutrophile elastase and the other serine proteases disturb this balance by inactivating the tissue MMP inhibitors (25). CIGARETTE SMOKING AND SERUM PROTEOLYTIC ACTIVITY The toxic action of cigarette-smoke on the neutrophile white cells in pulmonary capillaries induces them to release elastase and other proteases into the circulation (26). Serum proteolytic activity is still accentuated because cigarette smoke inhibits alpha-1-antiprotease, the most potent protease inhibitor (27,28), and the high white blood cell count and the tendency of these cells to retain in lung capillaries of smokers (26,29). Peak serum proteolytic activity occurs usually one to two hours after intensive smoking (30), after which it diminishes but remains on average higher than that of non-and exsmokers (31). OUR HYPOTHESIS Among the factors determining disc degeneration are: (1) disc ischemia due to stenosis and occlusion of the feeding arteries; (2) apoptosis of disc cells; (3) faulty and insufficient synthesis of matrix macromolecules, and (4) disturbed equilibrium between matrix proteolytic enzymes and their inhibitors. Ischemia activates body’s healing processes and collateral vascular channels are formed between adjacent vertebral bodies and blood vessels grow in the intervening disc. This neovascularization gives access for the increased serum proteolytic enzyme activity of cigarette smokers to enter the disc matrix and this speeds up the degenerative process. It is, however, quite evident that the neutrophile proteases are only one of several factors in disc degeneration. In identical twins, discordant with respect to smoking habits, the smokers showed only 18% greater mean disc degeneration scores than the non-smoking twins (32). Another study showed that patients who needed surgical treatment for hemiated lumbar or cervical discs were more often smokers than the controls (33). In addition to speeding up disc degeneration, it seems very plausible that the increased proteolytic activity attacks also other connective tissue structures of the spine which increases the instability caused by disc degeneration. These two mechanisms could well explain © 2001 Harcourt Publishers Ltd

Smoking and intervertebral disc degeneration

the increased risk of low back pain among both current and ex-smokers. ACKNOWLEDGMENT The authors thank Leena I. Kauppila for her constructive review of the manuscript.

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Medical Hypotheses (2001) 56(4), 537–539