/pdf/chapter-4-european-guidelines-for-the-management-of-chronic-4lrtve55lo.pdf

Chapter 4. European guidelines for the management of chronic nonspecific low back pain.

http://academic.oup.com/milmed/article-pdf/146/7/506/24126715/milmed-146-7-506.pdf

Goodman and Gilman's The Pharmacological Basis of Therapeutics

Cost Effectiveness in Health and Medicine.

A critical review of recombinant human bone morphogenetic protein-2 trials in spinal surgery: emerging safety concerns and lessons learned

Biomaterials for bone tissue engineering

Study Design. A prospective randomized clinical study was conducted. Objective. To determine whether the dose and carrier that were successful in rhesus monkeys could induce consistent radiographic spine fusion in humans. of Background Data. Preclinical studies have demonstrated that recombinant human bone morphogenetic protein-2 (rhBMP-2), an osteoinductive bone morphogenetic protein, is successful at generating spine fusion in rabbits and rhesus monkeys. Methods. For this study, 25 patients undergoing lumbar arthrodesis were randomized (1:2:2 ratio) based on the arthrodesis technique: autograft/Texas Scottish Rite Hospital (TSRH) pedicle screw instrumentation (n = 5), rhBMP-2/TSRH (n = 11), and rhBMP-2 only without internal fixation (n = 9). On each side, 20 mg of rhBMP-2 were delivered on a carrier consisting of 60% hydroxyapatite and 40% tricalcium phosphate granules (10 cm 3 /side). The patients had single-level disc degeneration, Grade 1 or less spondylolisthesis, mechanical low back pain with or without leg pain, and at least 6 months failure of non-operative treatment. Results. All 25 patients were available for follow-up evaluation (mean, 17 months; range 12-27 months). The radiographic fusion rate was 40% (2/5) in the autograftl TSRH group and 100% (20/20) with rhBMP-2 group with or without TSRH internal fixation (P = 0.004). A statistically significant improvement in Oswestry score was seen at 6 weeks in the rhBMP-2 only group (-17.6; P = 0.009), and at 3 months in the rhBMP-2/TSRH group (-17.0; P = 0.003), but not until 6 months in the autograft/TSRH group (-17.3; P = 0.041). At the final follow-up assessment, Oswestry improvement was greatest in the rhBMP-2 only group (-28.7, P< 0.001). The SF-36 Pain Index and PCS subscales showed similar changes. Discussion. This pilot study is the first with at least 1 year of follow-up evaluation to demonstrate successful posterolateral spine fusion using a BMP-based bone graft substitute, with radiographs and CT scans as the determinant. Consistently, rhBMP-2 was able to induce bone in the posterolateral lumbar spine when delivered at a dose of 20 mg per side with or without the use of internal fixation. Patients with spondylolisthesis classified higher than Meyerding Grade 1 or with more than 5 mm of translational motion may still require internal fixation. Some patients did smoke during the postoperative period, and all in the rhBMP-2 groups still obtained solid fusions. Conclusions. Consistently, rhBMP-2 with the biphasic calcium phosphate granules induced radiographic posterolateral lumbar spine fusion with or without internal fixation in patients whose spondylolisthesis did not exceed Grade 1. Statistically greater and quicker improvement in patient-derived clinical outcome was measured in the rhBMP-2 groups.

Use of recombinant human bone morphogenetic protein-2 to achieve posterolateral lumbar spine fusion in humans: a prospective, randomized clinical pilot trial: 2002 Volvo Award in clinical studies.

Study design A prospective, randomized, multicenter study of surgical treatment of cervical disc disease. Objective To assess the safety and efficacy of cervical disc arthroplasty using a new arthroplasty device at 24-months follow-up. Summary of background data Cervical disc arthroplasty preserves motion in the cervical spine. It is an alternative to fusion after neurologic decompression, whereas anterior decompression and fusion provides a rigorous comparative benchmark of success. Methods We conducted a randomized controlled multicenter clinical trial enrolling patients with cervical disc disease. Ultimately 242 received the investigational device (Bryan Cervical Disc), and 221 patients underwent a single-level anterior cervical discectomy and decompression and fusion as a control group. Patients completed clinical and radiographic follow-up examinations at regular intervals for 2 years after surgery. Results Analysis of 12- and 24-month postoperative data showed improvement in all clinical outcome measures for both groups; however, 24 months after surgery, the investigational group patients treated with the artificial disc had a statistically greater improvement in the primary outcome variables: Neck disability index score (P = 0.025) and overall success (P = 0.010). With regard to implant- or implant/surgical-procedure-associated serious adverse events, the investigational group had a rate of 1.7% and the control group, 3.2%. There was no statistical difference between the 2 groups with regard to the rate of secondary surgical procedures performed subsequent to the index procedure. Patients who received the artificial cervical disc returned to work nearly 2 weeks earlier than the fusion patients (P = 0.015). Conclusion Two-year follow-up results indicate that cervical disc arthroplasty is a viable alternative to anterior cervical discectomy and fusion in patients with persistently symptomatic, single-level cervical disc disease.

Comparison of BRYAN cervical disc arthroplasty with anterior cervical decompression and fusion: clinical and radiographic results of a randomized, controlled, clinical trial.

Study design Biomechanical comparison of the pull-out strengths of lateral mass and pedicle screws in the human cervical spine. Measurements of pedicle dimensions and orientation were compiled. Objectives To determine if transpedicular screws provide greater pull-out resistance than lateral mass screws and to investigate the anatomic feasibility of pedicle screw insertion. Summary of background data Cervical pedicle screws have been reported in limited clinical and biomechanical studies, and some quantitative cervical pedicle anatomy has been reported. No direct biomechanical comparisons have been made between lateral mass and pedicle screws. Methods Fifty-six fresh disarticulated human vertebrae (C2-C7) were evaluated with computed tomography to determine morphometry and vertebral body bone density. Lateral mass and pedicle screws were randomized to left versus right. A 3.5-mm cortical screw was used for both techniques, unless a pedicle was narrower than 5.0 mm; then a 2.7-mm cortical screw was used instead. Pedicle wall violations were recorded. Screws were subjected to a uniaxial load to failure. Mean pedicle height, width, and angle with respect to the vertebral midline were tabulated for each level. Results The mean load-to-failure was 677 N for the cervical pedicle screws and 355 N for the lateral mass screws. No significant correlations for either screw type were found between pull-out strength and bone density, screw length, or vertebral level. Pedicle and lateral mass dimensions were highly variable and not predictive of pull-out strength. Seven (13%) minor pedicle wall violations were observed. Conclusions Cervical pedicle screws demonstrated a significantly higher resistance to pull-out forces than did lateral mass screws. The variability in pedicle morphometry and orientation requires careful preoperative assessment to determine the suitability of pedicle screw insertion.

Cervical pedicle screws versus lateral mass screws. Anatomic feasibility and biomechanical comparison.

Study Design/Setting. Independent, retrospective clinical record review with a concurrent control. Objective. To identify whether rhBMP-2 is associated with an increased incidence of clinically relevant postoperative prevertebral swelling problems in patients undergoing anterior cervical fusions. of Background Data. Bone Morphogenetic Protein-2 (rhBMP-2) is FDA approved as a bone graft substitute in anterior lumbar interbody fusions. rhBMP-2 has also been used "off-label" in anterior cervical fusions. We suspected that rhBMP-2 might increase the incidence of adverse swelling events. Methods. A total of 234 consecutive patients (ages 12-82 years) undergoing anterior cervical fusion with and without rhBMP-2 over a 2-year period at one institution comprised the study population. The incidence of clinically relevant prevertebral swelling was calculated. The populations were compared and statistical significance was determined. Results. A total of 234 patients met the study criteria, 69 of whom underwent anterior cervical spine fusions using rhBMP-2; 27.5% of those patients in the rhBMP-2 group had a clinically significant swelling event versus only 3.6% of patients in the non-rhBMP-2 group. This difference was statistically significant (P < 0.0001) and remained so after controlling for other significant predictors of swelling. Conclusions. Off-label use of rhBMP-2 in the anterior cervical spine is associated with an increased rate of clinically relevant swelling events.

Increased swelling complications associated with off-label usage of rhBMP-2 in the anterior cervical spine.

Study Design. This retrospective clinical study evaluates complications occurring during or immediately after surgery of posterior cervical plating. Objectives. The present study quentifies risks associated with posterior cervical plating using lateral mass screw fixation. The observed clinical compliwtions are compared with theoretical risks previously studied in cadavers. Unanticipated complications are identified. Summary of Background Data. There are many reports that describe posterior cervical plating and attempt ot describe the indications for using this type of fixation, but few studies have discussed the clinical complications incurred by application of these plates and screws. Methods. Seventy-eight consecutive patients whose treatment included posterior cervical lateral mass plating were independently reviewed to identify associated complications. The average patient age was 52.9 years, and the average follow-up period was 2 years (range, 10-47 months). Multiple indications for surgery were present, but complex reconstructive procedures were required in 70.5% of cases. Complication rates were calculated as either a precentage of the number of screws inserted or as a percentage of the number of cases performed or both. Results. Six hundred fifty-four screws were inserted-an average of 8.4 screws per patient. Complication rates as a function of the number of screws inserted included nerve root injury, 0.6%; facet violations, 0.2%; vertebral artery injury, 0%; broken screw, 0.3%; screw avulsion, 0.2%; and screw loosening 1.1%. Complications as a percentage of the number of cases performed included spinal cord injury, 2.6%; iatrogenic foraminal stenosis, 2.6%; broken plate, 1.3%; lost reduction, 2.6%; adjacent segment degeneration, 3.8%; infection, 1.3%; and pseudoarthrosis, 1.4%. Conclusions. Cadaveric work has predicted certain anatomic complication rates associated with lateral mass screw insertion. This study finds the risk of lateral mass screw insertion to be considerably less than predicted in vitro. The present study reports other complications that were not predicted in laboratory studies.

John G. Heller

Papers

Use of recombinant human bone morphogenetic protein-2 to achieve posterolateral lumbar spine fusion in humans: a prospective, randomized clinical pilot trial: 2002 Volvo Award in clinical studies.

Comparison of BRYAN cervical disc arthroplasty with anterior cervical decompression and fusion: clinical and radiographic results of a randomized, controlled, clinical trial.

Cervical pedicle screws versus lateral mass screws. Anatomic feasibility and biomechanical comparison.

Increased swelling complications associated with off-label usage of rhBMP-2 in the anterior cervical spine.

Complications of Posterior Cervical Plating