|Year : 2017 | Volume
| Issue : 1 | Page : 11-17
Risk factors for ligamentum flavum hypertrophy in lumbar spinal stenosis patients from the Xinjiang Uygur Autonomous Region, China: protocol for a retrospective, single-center study
Gang Zhou, Yu-kun Zhang, Wei-min Huang
Second Department of Spine Surgery, Sixth Affiliated Hospital, Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, China
|Date of Web Publication||28-Feb-2017|
Second Department of Spine Surgery, Sixth Affiliated Hospital, Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region
Source of Support: This study was supported by the Natural Science Foundation of Xinjiang Uygur Autonomous Region of China, No. 2016D01C221., Conflict of Interest: None
Background: Ligamentum flavum hypertrophy is one important cause of spinal stenosis. Ligamentum flavum thickness of more than 4 mm measured on computed tomography (CT) and magnetic resonance imaging is considered hypertrophy, but causes of hypertrophy and distribution characteristics remain poorly understood. Previous studies showed that the ligamentum flavum thickness at the segments L2/3 , L3/4 , L4/5 and L5/S1 was positively correlated with age. It remains unclear whether ligamentum flavum thickness is associated with nationality, sex and obesity.
Methods/Design: We conducted a retrospective, single-center, case analysis at the Sixth Affiliated Hospital, Xinjiang Medical University, China. We collected lumbar CT imaging data of 104 patients diagnosed with lumbar spinal stenosis in the Sixth Affiliated Hospital, Xinjiang Medical University from May 2012 to May 2016. The primary outcome was the ligamentum flavum thickness of patients with different nationalities, sexes, heights, ages, and weights. The secondary outcomes were the morphology of lumbar vertebrae in patients with different nationalities, sexes, heights, ages, and weights; the correlation of nationality, sex, height, age, and weight with ligamentum flavum thickness; results of multiple linear regression analysis of relevant factors for ligamentum flavum hypertrophy.
Discussion: This study will determine the variations in the ligamentum flavum thickness of lumbar spinal stenosis patients of different nationalities, sexes, heights, ages, and weights in the Xinjiang Uygur Autonomous Region by measuring the ligamentum flavum thickness using CT, and analyzing risk factors for ligamentum flavum hypertrophy; the findings will provide quantitative reference data for preventing lumbar spinal stenosis induced by ligamentum flavum hypertrophy in the Xinjiang Uygur Autonomous Region.
Trial registration: ClinicalTrials.gov identifier: NCT03057353.
Ethics: The study protocol has been approved by the Ethics Committee of Sixth Affiliated Hospital, Xinjiang Medical University, China, and conducted in accordance with the Helsinki Declaration, formulated by the World Medical Association.
Informed consent: Written informed consent was obtained from all participants.
Keywords: clinical trials; lumbar spinal stenosis; spine; anatomy; computed tomography; lumbar vertebrae; ligamentum flavum thickness; nationality; sex; height; age; weight
|How to cite this article:|
Zhou G, Zhang Yk, Huang Wm. Risk factors for ligamentum flavum hypertrophy in lumbar spinal stenosis patients from the Xinjiang Uygur Autonomous Region, China: protocol for a retrospective, single-center study. Clin Trials Orthop Disord 2017;2:11-7
|How to cite this URL:|
Zhou G, Zhang Yk, Huang Wm. Risk factors for ligamentum flavum hypertrophy in lumbar spinal stenosis patients from the Xinjiang Uygur Autonomous Region, China: protocol for a retrospective, single-center study. Clin Trials Orthop Disord [serial online] 2017 [cited 2019 Feb 20];2:11-7. Available from: http://www.clinicalto.com/text.asp?2017/2/1/11/201057
| Introduction|| |
History and current related studies
The increase in human social activities has resulted in an increase in spinal degenerative disease (Chotai et al., 2016; Boissiθre et al., 2017). Lumbar vertebrae have special anatomical structures and biomechanical characteristics that can easily lead to lumbar spinal stenosis (Kreiner et al., 2014). Lumbar spinal stenosis is a medical condition in which the spinal canal narrows and compresses the spinal cord and nerves at the level of the lumbar vertebrae (Appendix 1; Schüppel and Weber, 2017; Ulrich et al., 2017). Common causes of degenerative lumbar spinal stenosis include vertebral spondylolisthesis, facet joint hyperplasia, bony spur posterior extension, intervertebral disc prolapse/protrusion, and ligamentum flavum hypertrophy.
Ligamentum flavum hypertrophy is an important cause of spinal stenosis (Gil-Salú et al., 2002; Thomé et al., 2008). When conservative treatment is ineffective, nerve compression (such as single nerve palsy or cauda equina palsy) can cause muscle paralysis or bladder symptoms, which requires surgical treatment (Shen et al., 2014; Spadaro et al., 2014). Common surgical techniques include pedicle screw fixation, flavectomy, laminectomy and facetectomy (Losiniecki et al., 2013; Seki et al., 2013; Amirouche et al., 2016; Baldawa et al., 2016; Burke et al., 2016; Ha et al., 2016). These types of surgery involve important anatomical structures, such as pedicles, ligamentum flavum, laminae, and articular processes.
Many previous studies have investigated pedicle morphology, lumbar ligamentum flavum, laminae and articular processes; important reference data are listed in [Table 1]. Safak et al. (2010) reported that ligamentum flavum thickness was not associated with sex, ligamentum flavum was markedly thicker on the left side of segments L4/5 and L5/S1 than on the right side, and ligamentum flavum thickness was not positively correlated with age. Few studies have addressed whether ligamentum flavum thickness is associated with nationality, sex and obesity.
The aim of this retrospective study is to measure the ligamentum flavum thickness on CT scans of patients of different nationalities, sexes, heights, ages, and weights from the Xinjiang Uygur Autonomous Region of China, explore the correlation between various factors and ligamentum flavum thickness, provide a reference for pedicle screw placement and lumbar decompression surgery, develop individualized surgical programs, and effectively reduce the incidence of unnecessary postoperative complications induced by misplacement.
| Methods/Design|| |
A retrospective, single-center, case analysis.
Sixth Affiliated Hospital, Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, China.
We collected lumbar CT imaging data of 104 patients with lumbar spinal stenosis who were evaluated in the Sixth Affiliated Hospital, Xinjiang Medical University from May 2012 to May 2016. We observed the incidence of ligamentum flavum hypertrophy inpatients of different nationalities, sexes, heights, ages, and weights, and explored risk factors affecting ligamentum flavum hypertrophy ([Figure 1]). Data collection began in May 2012, and data analysis is expected to be completed in May 2017.
Patients who met the inclusion criteria of this study were recruited by telephone. All patients agreed to the experiment and signed informed consent.
Patients meeting all of the following criteria were considered for admission to the trial:
- Lumbar spinal stenosis revealed by lumbar CT images
- Low back pain
- Aged 45-80 years
- Either sex
- Provided written, informed consent
Patients presenting with any of the following were excluded from the trial:
- Spinal injury
- Spinal tumor
- Spinal infection
- Congenital or acquired spine deformity
- Pulmonary tuberculosis
- Severe systemic diseases such as malignant tumor
- Inability to cooperate due to mental illness or other causes
Ligamentum flavum thickness greater than 4 mm on CT imagery is defined as ligamentum flavum hypertrophy. We hypothesized that the ligamentum flavum thickness would be increased by 1.4 mm in Hazakh patients and by 0.7 mm in Han patients. The standard deviation of ligamentum flavum thickness was predicted to be 0.9. Taking β = 0.1 and power = 90% with a significance level of α = 0.05, the final effective sample size of n = 36 Kazakh patients was calculated using PASS 11.0 software (NSCC, Kaysville, UT, USA). Assuming a patient loss rate of 20%, we required 44 patients per group, giving a total of 132 patients of three nationalities. After screening according to the inclusion and exclusion criteria, 104 patients were included in the trial.
Baseline data of 104 patients were evaluated after informed consent was obtained, including sex, age, height, nationality, weight, history of present illness, past history, family history, personal history, marital history, laboratory examination, and CT examination ([Table 2]).
|Table 2: Baseline data and general medical history of included patients |
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Patients' medical records
All data were collected from medical records. Patients were asked to fill in a questionnaire, including general information (name, sex, nationality and occupation), history of present illness (causes, accompanying symptoms, severity and treatment), past history, personal history, family history, and marital history. General physical examination and special examination for lumbar spinal stenosis were conducted. We recorded left lower limb pain, right lower limb pain, both lower limb pain, intermittent claudication (Appendix 2), straight-leg raising test (+), spinous process tenderness, unilateral lower limb radiating pain, lower limb paresthesia, abnormal muscle strength, and abnormal reflexes.
Lumbar spine CT scan
L1-5 vertebrae were scanned with a Siemens Emotion 6 CT Scanner (Siemens, Germany), and three-dimensional reconstruction was conducted. Scan parameters were collimator 0.65 mm, layer thickness 3 mm, and reconstruction increment 1.5 mm. The reconstructed image was passed to the browser. CT and three-dimensional reconstructed images were measured with the angle and length measurement tools of the browser by the same physician. Ligamentum flavum thickness (the length of C-E in [Figure 2]) was measured at the segments L2/3, L3/4, L4/5 and L5/S1.
|Figure 2: Ligamentum flavum thickness revealed by computed tomography. |
Note: The left image is a schematic drawing of the ligamentum flavum; the right image is a CT image. C-E length: ligamentum flavum thickness; A: spinous process root; B: superior articular process; C: inferior articular process; D: posterior margin of lumbar vertebral body; E: ligamentum flavum. The connection between D and E represents the distance from the posterior edge of the vertebral body to the ligamentum flavum.
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Primary outcome measure
- Ligamentum flavum thickness of patients of different nationalities, sexes, heights, ages, and weights measured on CT. That is, the changes in ligamentum flavum thickness according to different influential factors.
Secondary outcome measures
- Lumbar morphology of patients of different nationalities, sexes, heights, ages, and weights measured on CT. That is, changes in ligamentum flavum morphology.
- Correlation of nationality, sex, height, age and weight with ligamentum flavum thickness.
- Multiple linear regression analysis results of relevant factors influencing ligamentum flavum hypertrophy. Multiple linear regression analysis was performed to verify the correlation of each influential factor with ligamentum flavum hypertrophy.
Data collection, management, analysis and open-access
Written and electronic data were collected. The electronic data were stored in a specialized computer, and locked by the data manager. The written data were stored and locked in a reference room that was only accessible by the data manager and laboratory manager.
The locked database was not altered and was preserved along with the original records. The database was analyzed by a professional statistician.
Prior to any analysis of the data, the analysis plan outlined in this section was reviewed, and detailed statistical analysis plans were prepared and approved. All data regarding this trial will be preserved by the Sixth Affiliated Hospital, Xinjiang Medical University, China.
Anonymized trial data were published at www.figshare.com.
All data were analyzed using SPSS 21.0 software (IBM, Armonk, NY, USA). All measurement data were normally distributed, and were expressed as the mean ± standard deviation. Ligamentum flavum thickness was compared among groups using the two-sample t-test or one-way analysis of variance. Paired comparison between groups was conducted using the Student-Newman-Keuls test. Correlation of nationality, sex, height, age and weight with ligamentum flavum thickness was analyzed using Pearson's correlation coefficient. Risk factors for ligamentum flavum hypertrophy were analyzed using multiple linear regression analysis. Odds ratios and 95% confidence intervals were calculated. The significance level was α = 0.05.
| Trial Status|| |
Data analysis has been partially completed, and the partial results are as follows:
(1) Baseline data: Among 104 patients, there were 48 males and 56 females, with a mean age of 49.12 ± 11.06 years. There was left lower limb pain in 43 cases, right lower limb pain in 61 cases, both lower limbs pain in 43 cases, intermittent claudication in 19 cases, straight-leg raising test (+) in 34 cases, and spinous process tenderness in 32 cases; moreover, 75 cases experienced unilateral lower limb radiating pain, lower limb paresthesia, abnormal muscle strength and abnormal reflexes.
(2) Difference in ligamentum flavum thickness in patients with different nationalities and sexes: The thickness at segments L2/3, L3/4, L4/5 and L5/S1 on both sides was normally distributed. There was no significant difference between sexes in ligamentum flavum thickness at the segments L2/3, L3/4, L4/5 and L5/S1 (P > 0.05). Ligamentum flavum thickness significantly differed at the segments L2/3, L3/4, L4/5 and L5/S1 according to nationality (P < 0.01; [Table 3]).
|Table 3: Comparison of the difference in ligamentum flavum thickness in patients of different nationalities and sexes |
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(3) Correlation of age, height and weight with ligamentum flavum thickness: Ligamentum flavum thickness was positively correlated with age and weight (P < 0.05), but was not obviously associated with height ([Table 4]).
|Table 4: Correlation of age, height and weight with ligamentum flavum thickness |
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| Discussion|| |
Analysis of test results
Degenerative spinal stenosis is the most common cause of spinal stenosis. Ligamentum flavum hypertrophy is one of the most common causes of lumbar spinal stenosis. CT images revealed a strip- or V-shaped soft tissue density shadow at the posterior spinal canal along the laminae. Thickness of more than 4 mm was considered ligamentum flavum hypertrophy. CT can clearly reveal the morphology and boundaries of the ligamentum flavum. The tracer method can be used to measure ligamentum flavum thickness, sagittal diameter of the dural sac, and sagittal diameter of the lateral recess, thereby revealing the location, extent and range of hypertrophic ligamentum flavum. CT can be used to observe the morphology and width of bilateral nerve root canals in the same layer, and is of great value in the diagnosis of lateral ligamentum flavum hypertrophy.
Most previous studies have confirmed that the ligamentum flavum increases with age, mainly because of long-term fiber damage and repair (Yoshiiwa et al., 2016). Our results demonstrated that weight was also a factor affecting ligamentum flavum thickness in lumbar spinal stenosis. The increased weight increased the pressure on the lumbar vertebrae, and long-term activity led to an increased chance of ligamentum flavum injury, thereby resulting in increased ligamentum flavum thickness.
Nationality was another factor that affected the thickness of the ligamentum flavum in lumbar spinal stenosis patients in the Xinjiang Uygur Autonomous Region of China, indicating that there were some differences in ligamentum flavum development between nationalities, possibly because of genetic causes. Another possible reason is that different ethnic dietary habits lead to different probabilities of obesity. Nationalities in Xinjiang Uygur Autonomous Region eat a diet that is mostly meat-based. Long-term excess intake of nutrients leads to increased body mass, resulting in ligamentum flavum hypertrophy. The third possible reason is differences in occupation. Different nationalities may have different working habits and physical composition due to the degree of physical labor undertaken, resulting in different degrees of ligamentum flavum damage.
Limitations of this study
The sample size was small and the study area was singular. We hope to carry out a multicenter, large sample of clinical studies in subsequent trials to reduce bias (Li, 2016; Wu and Zhang, 2016; Yin et al., 2016).
Significance of this study
CT was conducted in lumbar spinal stenosis patients from the Xinjiang Uygur Autonomous Region to measure ligamentum flavum thickness, and evaluate its correlation with sex, age, nationality and weight. The results will promote the prevention and treatment of lumbar spinal stenosis caused by ligamentum flavum hypertrophy in the Xinjiang Uygur Autonomous Region.
Appendix 1 Definition for lumbar spinal stenosis
A medical condition in which the spinal canal narrows and compresses the spinal cord and nerves at the level of the lumbar vertebrae. Lumbar spinal stenosis is one of the most common causes of lumbar diseases, such as low back pain and leg pain, and mainly occurs in those aged greater than 40 years. No symptoms are seen at rest. Lower limb pain, numbness, and weakness can appear after walking. The above symptoms will be mitigated after squatting down or resting. The exacerbation of symptoms causes patients to walk shorter distances, and require longer rest periods.
Appendix 2 Definition for intermittent claudication
A symptom that describes muscle pain, including ache, cramp, numbness or sense of fatigue, classically in the calf muscle, which occurs during exercise, such as walking, and is relieved by a short period of rest. The severity of intermittent claudication is commonly judged by claudication distance and remission time. Claudication distance refers to walking distance from the beginning of the walk to the onset of pain. Obvious discomfort and pain can appear in severely affected patients after walking 50-100 m. Remission time refers to the time from pain onset to painlessness after resting. The remission time is generally 2-5 minutes. Claudication is one of the main clinical features of lumbar spinal stenosis.
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Declaration of patient consent
The authors certify that they will obtain all appropriate patient consent forms. In the form the patients will give their consent for their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Conflicts of interest
Trial concept and design, manuscript writing, critical revision, supervision, and final approval of publication: GZ. Assistance: YKZ and WMH.
This paper was screened twice using CrossCheck to verify originality before publication.
This paper was double-blinded and stringently reviewed by international expert reviewers.
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4]