|Year : 2018 | Volume
| Issue : 1 | Page : 8-14
Modified posterior lumbar interbody fusion augmented with bone cement in the treatment of senile degenerative lumbar spondylolisthesis: study protocol for a self-controlled trial
Rong Ren, Qi-Fa Guo, Zhao-Wei Li, Ze-Qing Li, Bao-Ming Tang
Department of Orthopedics, Affiliated Hospital of Qinghai University, Xining, Qinghai Province, China
|Date of Web Publication||9-Apr-2018|
Department of Orthopedics, Affiliated Hospital of Qinghai University, Xining, Qinghai Province
Source of Support: None, Conflict of Interest: None
Background and objectives: Posterior lumbar interbody fusion is the main repair method for senile degenerative lumbar spondylolisthesis. For elderly patients with osteoporosis, single screw rod system fixation regularly results in dislocation. The incidence of implant loosening is high, and therefore, effective internal fixation is not achieved. Thus, this study will use the modified posterior lumbar interbody fusion procedure combined with bone cement augmentation for the treatment of senile degenerative lumbar spondylolisthesis so as to increase the stability of the vertebral body, make the fixator firm, and to maximize the recovery of postoperative motor function.
Design: This is a prospective, single-center, self-controlled trial.
Methods: 113 patients with senile degenerative lumbar spondylolisthesis, aged 65–70 years, irrespective of sex, will be recruited from the Department of Orthopedics of Affiliated Hospital of Qinghai University of China. The patients will be treated with modified posterior lumbar interbody fusion combined with bone cement augmentation. Follow-up will be performed at 3 and 12 months.
Outcome measures: The primary outcome measure is recovery of motor function as indicated by the postoperative Oswestry Disability Index score at 12 months. The secondary outcome measures are the change in the rate of excellent and good Oswestry Disability Index scores (comparing preoperative scores with the 4-month postoperative scores), Visual Analogue Scale scores, intervertebral space height, foraminal height, the preoperative and 4 and 14 months postoperative slip distance and slip angle, incidence of adverse reactions, success rate of vertebral fusion, and incidence of secondary slip 4 and 14 months postoperatively.
Discussion: This trial aims to observe the efficacy of modified posterior lumbar interbody fusion combined with bone cement augmentation in the treatment of senile degenerative lumbar spondylolisthesis and to validate whether the procedure is safe and reliable.
Ethics and dissemination: This trial has been approved by the Medical Ethics Committee of Affiliated Hospital of Qinghai University of China (approval number: QHY023G). The study protocol will be proformed in accordance with the Declaration of Helsinki, formulated by the World Medical Association. Written informed consent will be obtained from all participants. This trial was designed in October 2017. The recruitment of subjects and data collection will begin in June 2018. The recruitment will be finished in December 2018. Outcome measures will be analyzed in January 2020. This trial will be completed in February 2020. The results of the trial will be reported in a scientific conference or disseminated in a peer-reviewed journal.
Trial registration: This trial had been registered in the Chinese Clinical Trial Registry (registration number: ChiCTR1800015335). Protocol version (1.0).
Keywords: lumbar spondylolisthesis; senile; modified posterior lumbar interbody fusion; bone cement; Oswestry Disability Index; foraminal height; intervertebral space height; incidence of secondary slip; adverse reactions; clinical trial
|How to cite this article:|
Ren R, Guo QF, Li ZW, Li ZQ, Tang BM. Modified posterior lumbar interbody fusion augmented with bone cement in the treatment of senile degenerative lumbar spondylolisthesis: study protocol for a self-controlled trial. Clin Trials Degener Dis 2018;3:8-14
|How to cite this URL:|
Ren R, Guo QF, Li ZW, Li ZQ, Tang BM. Modified posterior lumbar interbody fusion augmented with bone cement in the treatment of senile degenerative lumbar spondylolisthesis: study protocol for a self-controlled trial. Clin Trials Degener Dis [serial online] 2018 [cited 2018 Jun 24];3:8-14. Available from: http://www.clinicaltdd.com/text.asp?2018/3/1/8/228986
| Introduction|| |
Due to degenerative changes and the low elastin content in the posterior longitudinal ligament of the spinal column in patients with osteoporosis, the bearing capacity of the trunk and back muscles decreases, and the incidence of senile degenerative lumbar spondylolisthesis increases, which leads to limb dysfunction and impacts the quality of life of patients.,,, Studies addressing senile degenerative lumbar spondylolisthesis in the past two years are shown in [Table 1].,,
|Table 1: Three clinical studies published from 2017 to 2018 on senile degenerative lumbar spondylolisthesis|
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Posterior lumbar interbody fusion (PLIF) is a classic method for the treatment of lumbar spondylolisthesis used inside and outside China. PLIF can achieve good therapeutic benefits for patients with lumbar spondylolisthesis.,, In PLIF, a pedicle fixation system is used to reduce and fix the sliding vertebra, and then interbody fusion is conducted. For elderly patients with osteoporosis, severe spondylolisthesis and intervertebral space stenosis occur easily. The single screw rod system fixation easily induces dislocation and implant loosening. If the body is fixed directly, the vertebral body is easily damaged or even cracked by screws. Thus, when using a pedicle fixation system for the reduction and fixation of the sliding vertebra, it is difficult to achieve a good effect, and eventually this ends in failure.,,
Novelty of this study
This trial aims to modify and refine the classic PLIF procedure. After laminectomy for decompression, a fusion cage is inserted for intervertebral distraction and reduction. Afterwards, a pedicle screw rod system augmented with bone cement is utilized for supplementary reduction and fixation.
The aim of this prospective, single-center, self-controlled, clinical trial is to validate the safety and efficacy of modified PLIF combined with bone cement augmentation for treating senile degenerative lumbar spondylolisthesis.
| Methods/Design|| |
This is a prospective, single-center, self-controlled trial. Trial flow chart is displayed in [Figure 1].
Department of Orthopedics of Affiliated Hospital of Qinghai University, Qinghai Province, China.
The study plan leaflets, containing trial information, and inclusion and exclusion criteria, will be dispatched in the Affiliated Hospital of Qinghai University. According to the requirements of the trial scheme, the researcher will further screen the recruits who are interested in participating in the trial. After provision of informed consent, these patients will be enrolled in our study.
Patients who meet all of the following criteria will be considered for study inclusion:
- Diagnostic criteria of senile degenerative lumbar spondylolisthesis: (1) Intractable low back pain, sometimes accompanied by radiating pain in the lower limbs, affecting motor functions such as walking and (2) lumbar X-ray films, computed tomography, and magnetic resonance imaging images reveal single-level lumbar spondylolisthesis with lumbar spondylolysis
- Dual-energy X-ray bone densitometer reveals a bone density of 0.6–0.8 g/cm2; T value of < −2.5
- Age from 65 to 70 years
- Bone density of the lumbar spine determined by quantitative computed tomography less than 80 mg/cm3 recommended by the International Society for Clinical Densitometry and American College of Radiology serves as a diagnostic criterion for osteoporosis
- Provision of informed consent
Patients who meet one or more of the following conditions will be excluded from the study:
- History of thoracic and lumbar surgeries
- Lumbar tumor, fracture, and lumbar tuberculosis
- Those with severe hypertension, diabetes, kidney disease, and other diseases indicating that surgery cannot be tolerated
Randomization and blinding
In this self-controlled trial, no randomization or blinding method will be used.
This trial aims to modify the classic PLIF procedure. After laminectomy for decompression, a fusion cage is inserted for intervertebral distraction and reduction. Afterwards, a pedicle screw rod system and bone cement augmentation will be utilized for supplementary reduction and fixation.
Senior physicians from the medical and surgical departments of the hospital will consult to assess surgical risks and provide guided treatment and perioperative treatment for patients with basic diseases. Ceftezole will be administered for preventive anti-infective treatment 2 days preoperatively.
Modified PLIF augmented with bone cement
Specific steps are exhibited in [Figure 2].
|Figure 2: Specific steps of modified posterior lumbar interbody fusion augmented with bone cement.|
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Ceftezole will be administered for anti-infective treatment for 1 week, and ganglioside will be administered for 1 week. At postoperative 24 hours, the drainage tube will be removed when the drainage volume is less than 30 mL. At postoperative day 2, 4, and 6, conventional dressing will be carried out. Rehabilitation physicians will consult to perform waist and lower limb functional rehabilitation training for the patient.
Suspension or modification of intervention standards allocated to participants
When the researchers have concluded that the operation is safe and effective and need to suspend or terminate the clinical trial, we will notify the subjects, and ensure that the patients are properly treated and followed up. Simultaneously, we will immediately notify the sponsor and the ethics committee and provide a detailed written explanation of the termination or suspension of the trial.
Primary outcome measure
Twelve months postoperatively, the achievement of an excellent or good rate on the Oswestry Disability Index score will be used to indicate recovery of motor function. The questionnaire contains 10 topics concerning intensity of pain, lifting, ability to care for oneself, ability to walk, ability to sit, sexual function, ability to stand, social life, sleep quality, and ability to travel. Each topic category comprises six statements and each statement is scored on a scale of 0–5. Score 5 indicates a most severe disability, affecting quality of life. Oswestry Disability Index scores will be defined as: (preoperative score – postoperative score) / preoperative score × 100%. A score of more than 15% will be considered an excellent or good effect.
Secondary outcome measures
- The Oswestry Disability Index scores will be assessed preoperatively and 4 months postoperatively: The scoring criteria will be the same as above.
- Visual Analogue Scale will be used preoperatively, and 4 and 14 months postoperatively: It is on a scale of 0–10. The higher the score, the more severe the pain in the patient’s waist.
- Foraminal height will be assessed preoperatively, and 4 and 14 months postoperatively: The measurement method is shown in [Figure 3]
. The higher the value, the worse the stability of the lumbar spine.
|Figure 3: Measurement of foraminal height, slip distance, and slip angle.|
Note: h: Foraminal height; H: slip distance; a: slip angle.
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- Intervertebral space height will be assessed preoperatively, and 4 and 14 months postoperatively: The intervertebral space height is expressed by the mean value of the height of the anterior, middle, and posterior margins of the intervertebral space using the Quint method.
- The slip distance will be measured preoperatively, and 4 and 14 months postoperatively: The measurement method is shown in [Figure 3]. The higher the value, the worse the stability of the lumbar spine.
- The slip angle will be measured preoperatively, and 4 and 14 months postoperatively: The measurement method is shown in [Figure 3]. The higher the value, the worse the stability of the lumbar spine.
- The incidence of secondary slip will be measured 4 and 14 months postoperatively: The incidence is measured according to the Taillard index.
- The success rate of vertebral fusion will be measured 4 and 14 months postoperatively: Evaluation criteria for postoperative fusion are as follows:
- Continuous trabeculae in the fusion zone and range of motion < 5° in hyperextension and hyperflexion indicate fusion success.
- Displacement and loosening of the fusion cage, translucent zone at the contact surface between the vertebral body and the fusion cage > 2 mm or range of motion > 5° in hyperextension and hyperflexion indicate fusion failure.
- The success rate of vertebral fusion is defined as: number of patients with successful fusion/total number of patients × 100%.
- The incidence of adverse reactions 4 and 14 months postoperatively: The paravertebral tissue structure may be damaged due to leakage of bone cement and may cause adverse reactions, such as spinal compression, intercostal neuralgia, filling of paravertebral vein, arterial embolism, infection, and secondary nerve injury. The incidence of adverse reactions will be defined as the number of patients with adverse reactions/total number of patients × 100%.
The schedule of outcome measurement assessments is listed in [Table 2].
Once a patient has signed the informed consent form and is selected for the trial, events that have a causal relationship with the surgical treatment during the trial will be considered adverse events. Adverse events may include spinal compression, intercostal neuralgia, leakage of bone cement into the intervertebral space, filling of paravertebral vein, arterial embolism, infection, secondary nerve injury, and height loss of the anterior margin of the injured vertebra. During follow-up, the investigators will report the details, including the date and type of occurrence and the measures taken to treat the adverse events, to the trial leader and the ethics committee within 24 hours.
In accordance with previous results and our experience, we hypothesize that the excellent and good rate of Oswestry Disability Index score at postoperative 12 months will be 90%. Taking β = 0.2 and power = 80% with a significance level of α = 0.05, the final effective sample size of n = 94 patients per group will be calculated using PASS 11.0 software (PASS, Kaysville, UT, USA). If we assume a loss rate of 20%, we will totally require 113 patients.
All data will be analyzed using SPSS 20.0 software (IBM, Armonk, NY, USA), according to the intention-to-treat principle. Normally distributed measurement data will be expressed as the mean ± SD. Non-normally distributed measurement data will be expressed as the lower quartile (q1) and median and upper quartiles (q3). Enumeration data will be presented as percentages.
Selection of statistical methods
The excellent and good rate of Oswestry Disability Index score, incidence of secondary slip, success rate of vertebral fusion and incidence of adverse reactions at various time points will be compared using McNemar test. Foraminal height, intervertebral space height, slip distance and slip angle will be compared using repeated measures analysis of variance. The significance level will be α = 0.05.
Included subjects will be assigned to the per protocol set. Per protocol set refers to the set of subjects who meet inclusion and exclusion criteria, complete the study without major protocol deviations, provide tight enough compliance and fulfill the case report form.
Data collection and management
Case report forms will be recorded, collected and summarized. The data will include demographic information, disease type, concomitant diseases, and adverse events. Above data will be recorded electronically using a double-data entry strategy.
The electronic database will be accessible only by the project manager. This arrangement will not be altered. The Affiliated Hospital of Qinghai University of China will preserve all of the data regarding this trial. Two staff members will transcribe the trial outcomes. An investigator will schedule, check, and lock up the data.
Data monitoring committee composition
The data monitoring committee needs to be equipped with members who are properly qualified to perform their duties independently and play a guiding role in the data monitoring committee to ensure the integrity of the research and protect the safety of the participants.
All surgeons participating in this study and serving as at least senior associate chief physician have a wealth of orthopedic surgery experience.
During the trial, implementation of the trial protocol will be monitored. Prior to trial commencement, informed consent will be obtained from all patients. The patient enrollment rate and trial progression will be monitored to ensure eligible enrollment. Inspectors will confirm the integrity and authenticity of all data records, and confirm that all adverse events are reported within the allotted time and recorded.
Compensation to study participants
Patients participating in the trial will receive free laboratory examinations and imaging examinations included in the study protocol during follow-up. The hospital will allow professional doctors to closely follow up each patient’s condition, and reimburse each patient’s travel expenses.
Ethics and dissemination
This trial has been approved by the Medical Ethics Committee of Affiliated Hospital of Qinghai University of China (approval number: QHY023G). The writing and editing of the article were performed in accordance with the Standard Protocol Item: Recommendations for Interventional Trail (SPIRIT) (Additional file 1 [Additional file 1]). The study protocol will be conducted in accordance with the Declaration of Helsinki, formulated by the World Medical Association. Written informed consent will be obtained from all participants. If and when any unexpected risk occurs during the clinical trial, informed consent-related content will be modified in accordance with the sponsor. After receiving agreement by the ethics committee, informed consent will be obtained again by the involved subjects or their guardians. Results will be disseminated through presentations at scientific meetings and/or by publication in a peer-reviewed journal. Anonymized trial data will be published at www.figshare.com.
| Trial Status|| |
The authors are preparing for the recruitment at the time of submission of this study protocol, and the recruitment of subjects will begin in June 2018.
| Discussion|| |
Contributions and problems of previous studies in this field
As China enters an aging society, aging and fatigue induce spinal degenerative changes, especially the decreased elastin content in the posterior longitudinal ligament of the spinal column. Thus, the bearing capacity of the trunk and back muscles decreases. Osteoporosis aggravates the decrease of bone density in the spine, which eventually leads to the rupture of the fibrous ring and the prolapse of the nucleus pulposus. The incidence of senile degenerative lumbar spondylolisthesis gradually increases, which leads to limb dysfunction and impacts the quality of life of patients. However, the surgical procedures for treating senile degenerative lumbar spondylolisthesis are diversified. PLIF is currently a classic surgical procedure for lumbar spondylolisthesis, but for elderly patients, PLIF results in poor fixation effects and poor recovery of motor function. Therefore, it is necessary to study new therapies.
Features of this study protocol
Compared with a previous study, this prospective, single-center, self-controlled, clinical trial will enlarge the sample size (n = 113) and modify the classical PLIF so as to observe the efficacy and safety of modified PLIF augmented with bone cement for treating senile degenerative lumbar spondylolisthesis.
Limitations of this study
Randomization will not be used for group assignment, and the follow-up time is short. The results are relatively simple. These will affect the accuracy of the results and will continuously improve in the future research.
Significance of this study
This trial will validate whether modified PLIF augmented with bone cement can effectively promote the recovery of motor function in patients with senile degenerative spondylolisthesis, and confirm whether this method is worthy of more extensive use in the clinic.
Additional file 1: SPIRIT checklist.
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Study design: RR. Subject recruitment: QFG and ZWL. Data collection and analysis: ZQL and BMT. All authors approve the final version of the manuscript.
Conflicts of interest
We declare that we have no conflicts of interest in project research and manuscript writing.
The study receives no specific funding agency in the public, commercial, or not-for-profit sectors.
This trial has been approved by the Medical Ethics Committee of Affiliated Hospital of Qinghai University of China (approval number: QHY023G). The study will be performed in accordance with the Declaration of Helsinki and relevant ethical principles.
Declaration of patient consent
The authors certify that they will obtain all patient consent forms. In the form, patients will give their consent for their images and other clinical information to be reported in the journal. The patients will 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.
Data sharing statement
Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices) will be in particular shared. Study protocol and informed consent form will be available. The data will be available immediately following publication without end date. Results will be disseminated through presentations at scientific meetings and/or by publication in a peer-reviewed journal. Anonymized trial data will be available indefinitely at www.figshare.com.
Checked twice by iThenticate.
Externally peer reviewed.
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2]