Does smoking increase the risk of lumbar disc prolapse in individuals aged from 20 to 40 years?

Table of Contents

Acknowledgements

Statement of Affirmation

Abstract
Introduction
Background
Methods
Results
Discussion
Conclusion

1. Introduction

2. Background
2.1 Disease overview
2.2 Anatomy of spinal disc
2.3 Diagnosis of lumbar disc prolapse
2.4 Management
2.5 Risk factors for lumbar disc prolapse
2.5.1 Age
2.5.2 Sex
2.5.3 High body mass index
2.5.4 Physical workload
2.5.5 Smoking
2.5.6 Genetic factors
2.6 Summary

3. Issues for selecting study design
3.1 Randomised/Non-Randomised controlled trial
3.2 Cohort study design (prospective/retrospective)
3.3 Case-control study design

4. Issues to be considered for a case-control study
4.1 Identifying appropriate study population
4.2 Study sample size
4.3 Data collection
4.4 Sample questionnaire
4.5 Potential sources of bias
4.6 Potential confounders

5. Statistical analysis

6. Ethical issues

7. Discussion and conclusions

8. References

Acknowledgements

I would like to show my sincere gratitude to my supervisor and mentor Dr. Gillian Dite, for acting as a sounding board as I developed this research protocol. Thanks for you guidance and encouragement

I would also like to express my gratitude to Assoc. Prof. Mark Jenkins, subject coordinator for his supervision and advice in conducting this project

Abstract

Introduction

Lumbar disc prolapse is one of the most common neurological conditions and there has been no agreement on its appropriate management. Lumbar disc prolapse is a very common cause of a clinical spectrum of symptoms including back pain, sciatica, knee pain and numbness, and in severe cases, nerve damage and loss of bladder and bowel control. Back pain is the most common symptom of lumbar disc prolapse and is one of the most common conditions for which a patient seeks medical attention. The primary aim of this research project is to design a protocol that estimates the effect of smoking on the risk of lumbar disc prolapse in individuals aged from 20 to 40 years

Background

Evidence suggests that smokers have a 3-4 times higher risk of developing disc disease and that smoking can exacerbate pre-existing disc degeneration. Nicotine and other harmful toxins in cigarette smoke prevent nucleosus pulposus and annulus fibrosus cells from up taking nutrients. This can cause significant inhibition of cell proliferation and extra cellular matrix synthesis, making disc injury more likely and recovery from an injury slow. While there is strong evidence in the literature that smoking does have a role in the pathogenesis of lumbar disc prolapse and back pain, there are no accurate estimates of the magnitude of the increased risk

Methods

Different analytical study designs were evaluated to assess their strengths, limitations and feasibility for answering the research question. Issues of subject selection, bias and measurement were assessed for case-control and cohort study designs. It was concluded that the most epidemiologically robust design would be a case-control study, which was chosen for its efficiency in time and cost

Results

Cases will be chosen from orthopaedic, neurological and physiotherapy wards from hospitals across Australia and controls will be chosen from neighbourhood of the cases. The primary outcome will be lumbar disc prolapse confirmed on either computerised tomography (CT) scan or magnetic resonance imaging (MRI). Exposure assessment will be conducted during a face-to-face interview by trained interviewers using a structured questionnaire, to minimise bias. Statistical analysis will be conducted using Stata 11, using logistic regression techniques and adjusting for potential confounders

Discussion

Considering the relative rarity of lumbar disc prolapse and number of true cases, the study has to be conducted all across Australian hospitals to recruit the high number of cases required for the study to have sufficient power to detect an odds ratio of 1.5. Controls could have been recruited from the same hospitals but might have introduced selection bias

Conclusion

A case-control study is the best design to realise the primary aim of this research protocol. Conducting the study across Australia will enable enough cases to be identified and recruiting controls from the neighborhood of the cases with simple enrolment requirements will increase the response rate and minimise the bias. Exposure measurement through face-to-face interview by trained interviewers using a structured questionnaire is cost efficient, and the use of trained interviewers ensures that participants understand the questions clearly

Table of Figures

Figure 1 Diagrammatic representation of prolapsed disc and compression of nerve root

Figure 2 Diagrammatic coronal views of vertebral bodies and disc

Figure 3 Diagrammatic sagittal view of a vertebral disc

Figure 4 Magnetic resonance image (MRI) of lumbar disc prolapse (transverse and sagittal views)

1. Introduction

Lumbar disc prolapse is one of the most common neurological conditions (Broetz, Hahn et al. 2008) and has a vast spectrum of symptoms including back pain, pain and numbness around the knees, sciatica, severe nerve damage and loss of bladder and bowel control (Heliovaara, Impivaara et al. 1987) (Weber 1994). These symptoms can cause severe disability, and back pain as a result of lumbar disc prolapse is one of the most common conditions for which a patient seeks medical attention (Manek and MacGregor 2005). There is little agreement on the appropriate management of lumbar disc prolapse (Broetz, Hahn et al. 2008).

The known risk factors for lumbar disc prolapse include age, sex, high body mass index (BMI), and occupations such as night shift workers, athletes, drivers and heavy weight lifters. Some studies have shown that smoking is associated with a higher incidence of lumbar disc prolapse (Akmal, Kesani et al. 2004). In-vitro studies of non-human spinal disc showed that smoking does have detrimental effect on nucleolus pulposus cells (Akmal, Kesani et al. 2004). Recent studies have shown that there is a genetic component to the risk of lumbar disc prolapse and back pain (Manek and MacGregor 2005).

The widely accepted explanation for the effect of smoking on spinal disc cells is that the nutritional uptake by disc cells is hampered by carboxy-hemoglobin present in the blood of smokers (Gullihorn, Karpman et al. 2005), vasoconstriction (Miller, Clouse et al. 2000) and changes in blood flow (Ernst 1993).

Of the general population, 60% to 80% experience back pain during their lifetime (Riihimaki 1991). Lumbar disc prolapse and associated back pain pose huge economic and public health burden (Hootman, Helmick et al. 2003). In Finland in 1980, around 3.7% of disability pensions granted to people aged from 30 to 64 years was due to lumbar disc prolapse, and 6% of work place disability could be attributed to lumbar disc prolapses (Heliovaara, Impivaara et al. 1987). In people with lumbar disc prolapse, the ability to perform routine daily work has been shown to be slightly limited in 56%, at least markedly limited in 21% and severely limited in 5% (Heliovaara, Impivaara et al. 1987). Additionally, around 51% of patients with lumbar disc prolapse need long-term medical care including more than 10 visits to physicians, hospitals, surgical or neurosurgical specialists within 12 months (Heliovaara, Impivaara et al. 1987). This recurrent use of medical assistance was specifically common in patients with lumbar disc prolapse, and 5% was directly attributed to lumbar disc prolapse related back pain (Heliovaara, Impivaara et al. 1987).

2. Background

2.1 Disease overview

Lumbar disc prolapse occurs when the soft gelatinous nucleus pulposus of vertebral disc extrudes though weakened walls of the annulus fibrosus resulting in compression of the adjacent nerve roots (Figure 1) (Heliovaara, Impivaara et al. 1987). The association between the extent of lumbar disc prolapse and clinical signs and symptoms is not properly understood (Masui, Yukawa et al. 2005) (Komori, Okawa et al. 1998) but common symptoms due to compression of nerve roots range from back pain, knee pain, numbness around the knees, sciatica to loss of bladder and bowel control in cases of severe spinal cord compression (Heliovaara, Impivaara et al. 1987) (Weber 1994).

Figure 1 Diagrammatic representation of prolapsed disc and compression of nerve root *

illustration not visible in this excerpt

*Image source: http://www.patient.co.uk/pdf/pilsL762.pdf#

In Australia, in 1998, back problems affected 5.4% of the total population, making it one of the most common musculoskeletal conditions following arthritis (AIHW 2006). In 1995, the National Health Survey of Australia estimated the disease burden due to musculoskeletal conditions of the back to be 2,065 years lived with disability (YLD) for males and 1,903 YLD for females, and the overall incidence of back problems to be 65,938 per 100,000 individuals (Mathers, Vos et al. 2001). The 1995 National Health Survey also showed that around 2.2% of the population self-reported disorders of vertebral disc (Mathers, Vos et al. 2001). These estimates may be unreliable as they were calculated from self-reported data and therefore the accurate estimates of incidence and prevalence of lumbar disc prolapse are not available.

2.2 Anatomy of spinal disc

The intervertebral disc is a fibro-cartilagenous structure enclosed between hyaline cartilagenous end plates of the adjacent vertebral bodies (Figure 2) (Cassinelli and Kang 2000).

Figure 2 Diagrammatic coronal views of vertebral bodies and disc*

illustration not visible in this excerpt

*Image source: http://www.iupui.edu/~anatd502/Labs.f04/cartilage%20&%20bone%20lab/Bone%20&%20Cartilage%20%20Lab.html

The intervertebral disc is composed of concentrically arranged tissue layers (Cassinelli and Kang 2000). The outer part is the annulus fibrosus and is made of dense, highly oriented collagen lamellae and the inner part is soft gelatinous nucleus pulposus (Figure 3) (Cassinelli and Kang 2000).

Figure 3 Diagrammatic sagittal view of a vertebral disc

illustration not visible in this excerpt

Outer annulus fibrosus and centrally located gelatinous nucleus pulposus are separated by a thin fibrous tissue called as the transition zone (Trout, Buckwalter et al. 1982).

Intervertebral discs have limited vessel innervations and are relatively hypo-vascular (Cassinelli and Kang 2000). The primary mechanism for the nutrition of the inner disc is through diffusion of nutrients and metabolites across the end plates of their adjacent vertebral bodies (Cassinelli and Kang 2000). Inner regions of the disc are without innervations as free nerve endings penetrate only a short distance into the annulus fibrosus (Jackson, Winkelmann et al. 1966) (Ashton, Ashton et al. 1992).

Special arrangement of the collagen in the outer layers of annulus fibrosus provide tensile strength of the intervertebral disc, stability between vertebrae and prevents bulging of disc in response to load (Ostrum, Romy et al. 1993).

2.3 Diagnosis of lumbar disc prolapse

The usual presenting complaint to a physician is back pain, which can be accompanied by pain radiating along the buttock to the back of one or both legs and numbness around the knees (Heliovaara, Impivaara et al. 1987). In severe cases of lumbar disc prolapse, the patient can present with a loss of bladder and bowel control, due to nerve root compression (Weber 1994). The diagnosis is usually made on clinical history and examination, but can only be confirmed only through computerised tomography (CT) or Magnetic resonance imaging (MRI) (Figures 4 & 5) (Deyo, Loeser et al. 1990).

Figure 4 Magnetic resonance image (MRI) of lumbar disc prolapse (transverse and sagittal views) *

illustration not visible in this excerpt

*Image source: http://www.vbsc.org.au/lumb_prolapse.htm

2.4 Management

The usual management of lumbar disc prolapse is complete bed rest for few weeks, analgesics, skeletal muscle relaxants and mechanical traction (Deyo, Loeser et al. 1990). It is known that the prolapsed portion of disc tends to decrease in size with time (Bush, Cowan et al. 1992) which can be confirmed by MRI (Broetz, Hahn et al. 2008). Physiotherapy and exercises to strengthen back muscles are advised to prevent relapses (Broetz, Hahn et al. 2008). In severe cases of nerve compression or compromised bladder or bowel control, immediate surgery is required to release compression on the spinal cord (Deyo, Loeser et al. 1990).

2.5 Risk factors for lumbar disc prolapse

2.5.1 Age

Disc degeneration is a normal ageing process and usually begins in the second decade of life (Powell, Szypryt et al. 1986). Disc degeneration is a common occurrence in the second and third decades of life, and this degeneration of annulus fibrosus and nucleus pulposus can reduce disc strength, making nucleus pulposus more likely to prolapse (Powell, Szypryt et al. 1986).

One study demonstrated that the prevalence of degenerative disc disease increases progressively with age from 6% under 20 years to 79% over 60 years, with over one third aged 21 to 40 years showing abnormal disc on MRI (Powell, Szypryt et al. 1986). The same study found that 60% of subjects aged less than 40 years had some degree of lumbar disc prolapse (Powell, Szypryt et al. 1986).

Another study found the mean age at the diagnosis of lumbar disc prolapse to be 40 years (Seidler, Bolm-Audorff et al. 2003). Another study of adolescents and young adults found the prevalence of back pain to be 7% in subjects aged 12 to 22 years, and suggested that there is a strong statistical association between back pain and age (Hestbaek, Leboeuf-Yde et al. 2004). One study found that there was decline in hospitalisations due to lumbar disc prolapse after the age of 49 years (Heliovaara, Knekt et al. 1987).

The widely accepted explanation for lumbar disc prolapse becoming less common in older age is that there is a change in the consistency of the nucleus pulposus with advancing age (Ostrum, Romy et al. 1993). It becomes less gelatinous and more fibrous and there is nothing to bulge out (Ostrum, Romy et al. 1993).

2.5.2 Sex

Many studies have shown that the risk and prevalence of lumbar disc prolapse is higher for males. In one study conducted in Finland, the prevalence of lumbar disc prolapse was found to be higher in men 5.1% compared with women 3.7% (p<0.005) (Heliovaara, Impivaara et al. 1987). Another study found that men had a 1.6 times higher chance of lumbar disc prolapse than women (Heliovaara, Knekt et al. 1987).

2.5.3 High body mass index

Being overweight (body mass index (BMI) >= 25 kg/m2) is strongly associated with an increased risk of disc degeneration and detrimental effects on the nucleus pulposus, changes which can be seen on MRI (adjusted odds ratio (OR) = 4.3, 95% confidence interval (95% CI) 1.3-14.3) and being overweight at young age (risk ratio (RR) 3.8, 95 % CI 1.4-10.4) was more strongly associated with disc degeneration than being overweight in middle age (RR 1.3, 95 % CI 0.7-2.7) (Liuke, Solovieva et al. 2005).

2.5.4 Physical workload

There is a strong statistical association between lumbar disc prolapse and physical workload in the form of extreme forward bending, weight lifting or carrying heavy objects (Seidler, Bolm-Audorff et al. 2003). Another study has shown that there is an increased frequency of lumbar disc prolapse in foundry workers as compared to general population (Lawrence, Molyneux et al. 1966). Heavy lifting at work by agriculturalists, bricklayers, road menders, welders and heavy work done by miners, blacksmiths, carpenters and dock workers has also been shown to be associated with a higher incidence of lumbar disc prolapse (Braun 1969).

It has been found that there is increased risk of lumbar disc prolapse and hospitalisation in occupations requiring heavy physical workload such as wood, metal and construction workers (Heliovaara 1987). A case-control study showed that metal workers, construction workers who held their jobs for than 10 years had higher incidence of lumbar disc prolapse (Hofmann, Bolm-Audorff et al. 1997). Another case-control study has shown an increased incidence of lumbar disc prolapse in people lifting objects weighing more than 11.3 kg more than 25 times per day (Kelsey 1975).

2.5.5 Smoking

In an experimental study on rabbits, where 5000ng/kg nicotine was injected daily to two groups of 6 rabbits, for 4 weeks in the first group and 8 weeks in the second group, there were marked histological changes in spinal disc structures, such as the presence of spaces within the nucleus pulposus and separation from the adjacent annulus fibrosus (Afifi and Hafez 2007). The study also showed a dose-dependent relationship of these changes with amount of nicotine; “disc degeneration was more marked in rabbits injected with nicotine for 8 weeks than in those injected for 4 weeks” (Afifi and Hafez 2007). Nicotine has also been demonstrated to cause adverse morphologic changes in chick vertebral chondrocytes (Khan, Provenza et al. 1981), delayed bone healing (Hollinger, Schmitt et al. 1999) and higher failure rates of spinal vertebral fusion (Silcox III, Boden et al. 1998).

Many retrospective and prospective studies have shown that smokers do have higher incidence of back conditions (Ernst 1993). It has also been shown that back problems are positively associated with smoking history and number of packs smoked (Frymoyer, Pope et al. 1983). Another study has shown that, compared to non-smokers, the age and sex-adjusted OR for back symptoms increased in order for non-smokers, ex-smokers, pipe or cigar smokers and current smokers (Heliovaara, Makela et al. 1991).

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