Ketorolac and spinal fusion: does the perioperative use of ketorolac really inhibit spinal fusion?

STUDY DESIGN: Retrospective review. OBJECTIVE: To evaluate the effect of postoperative use of ketorolac (Toradol) on spinal fusion in humans. SUMMARY OF BACKGROUND DATA: The value of parenteral ketorolac in postoperative analgesia has been well documented across surgical specialties. However, some studies have shown that ketorolac may adversely affect osteogenic activity and fracture healing. METHODS: A total of 405 consecutive patients who underwent primary lumbar posterolateral intertransverse process fusion with pedicle screw instrumentation were included in this retrospective study. A subtotal of 228 patients received Toradol after surgery for adjunctive analgesia. Each patient received a mandatory dose of 30 mg intravenously every 6 hours for 48 hours. The same surgeon performed the fusion procedure on all of these patients. Historical controls included 177 patients who did not receive Toradol after surgery. The minimum follow-up period was 24 months. Nonunions were diagnosed by analyzing sequential radiographs, flexion-extension radiographs, and computed tomography with multiplanar reconstructions. The gold standard of surgical exploration was performed in symptomatic patients with diagnostic ambiguity or nonunions diagnosed by imaging. RESULTS: There were no smokers in the study population. Pseudarthrosis was identified in 12 of 228 patients (5.3%) who received Toradol after surgery, and in 11 of 177 patients (6.2%) who did not. There was no significant difference detected in the nonunion rates between the two groups (P > 0.05, chi2 method). CONCLUSION: Use of ketorolac after spinal fusion surgery in humans, limited to 48 hours after surgery for adjunctive analgesia, has no significant effect on ultimate fusion rates.

A comparison of commercially available demineralized bone matrix for spinal fusion.

In an effort to augment the available grafting material as well as to increase spinal fusion rates, the utilization of a demineralized bone matrix (DBM) as a graft extender or replacement is common. There are several commercially available DBM substances available for use in spinal surgery, each with different amounts of DBM containing osteoinductive proteins. Each product may have different osteoinductivity potential due to different methods of preparation, storage, and donor specifications. The purpose of this study is to prospectively compare the osteoinductive potential of three different commercially available DBM substances in an athymic rodent spinal fusion model and to discuss the reasons of the variability in osteoinductivity. A posterolateral fusion was performed in 72 mature athymic nude female rats. Three groups of 18 rats were implanted with 1 of 3 DBMs (Osteofil, Grafton, and Dynagraft). A fourth group was implanted with rodent autogenous iliac crest bone graft. The rats were sacrificed at 2, 4, 6, and 8 weeks. A dose of 0.3 cm(3) per side (0.6 cm(3)per animal) was used for each substance. Radiographs were taken at 2 weeks intervals until sacrifice. Fusion was determined by radiographs, manual palpation, and histological analysis. The Osteofil substance had the highest overall fusion rate (14/18), and the highest early 4 weeks fusion rate of (4/5). Grafton produced slightly lower fusion rates of (11/17) overall, and lower early 4 weeks fusion rate of (2/5). There was no statistically significant difference between the rate of fusion after implantation of Osteofil and Grafton. None of the sites implanted with Dynagraft fused at any time point (0/17), and there was a significantly lower fusion rate between the Dynagraft and the other two substances at the six-week-time point and for final fusion rate (P = 0.0001, Fischer's exact test). None of the autogenous iliac crest animals fused at any time point. Non-decalcified histology confirmed the presence of a pseudarthrosis or the presence of a solid fusion, and the results were highly correlated with the manual testing. Although all products claim to have significant osteoinductive capabilities, this study demonstrates that there are significant differences between some of the tested products.

Graft resorption with the use of bone morphogenetic protein: lessons from anterior lumbar interbody fusion using femoral ring allografts and recombinant human bone morphogenetic protein-2.

STUDY DESIGN: This is a prospective cohort study examining the results and radiographic characteristics of anterior lumbar interbody fusion (ALIF) using femoral ring allografts (FRAs) and recombinant human bone morphogenetic protein-2 (rhBMP-2). This was compared to a historical control ALIF using FRAs with autologous iliac crest bone graft (ICBG). OBJECTIVE: To determine whether the use of rhBMP-2 can enhance fusion ALIF with stand-alone FRAs. SUMMARY OF BACKGROUND DATA: ALIF is a well-accepted procedure in reconstructive spine surgery. Advances in spinal surgery have produced a multitude of anterior interbody implants. The rhBMP-2 has promoted fusion in patients undergoing ALIF with cages and threaded allograft dowels. The FRA still remains a traditional alternative for anterior support. However, as a stand-alone device, the FRA has fallen into disfavor because of high rates of pseudarthrosis. With the advent of rhBMP-2, the FRA may be more attractive because of its simplicity and remodeling potential. It is important to understand the implications when rhBMP-2 is used with such structural allografts. METHODS: A total of 36 consecutive patients who underwent ALIF with stand-alone FRAs by a single surgeon (E.G.D.) at 1 institute were included. A cohort of 9 consecutive patients who received FRAs filled with rhBMP-2 was followed prospectively. After noticing suboptimal results, the senior author terminated this method of lumbar fusion. A total of 27 prior consecutive patients who received FRAs filled with autogenous ICBG were used for comparison. Analyzing sequential radiographs, flexion-extension radiographs, and computerized tomography with multiplanar reconstructions determined nonunions. Minimum follow-up was 24 months. RESULTS: Pseudarthrosis was identified in 10 of 27 (36%) patients who underwent stand-alone ALIF with FRAs and ICBG. Nonunion rate was higher among patients who received FRAs with rhBMP-2 (i.e., 5 of 9 [56%]). Statistical significance was not established because of the early termination of the treatment group (P > 0.3). Of interest, radiographs and computerized tomography revealed early and aggressive resorption of the FRAs when used with rhBMP-2. This preceded graft fracture and even disintegration, resulting in instability and eventual nonunion. CONCLUSION: The use of rhBMP-2 did not enhance the fusion rate in stand-alone ALIF with FRAs. In fact, the trend was toward a higher nonunion rate with rhBMP-2, although this was not significant with the numbers available. This result appears to be caused by the aggressive resorptive phase of allograft incorporation, which occurs before the osteoinduction phase.

Intervariability and intravariability of bone morphogenetic proteins in commercially available demineralized bone matrix products.

STUDY DESIGN: Enzyme-linked immunosorbent assay was used to detect bone morphogenetic proteins (BMPs) 2, 4, and 7 in 9 commercially available ("off the shelf") demineralized bone matrix (DBM) product formulations using 3 different manufacturer's production lots of each DBM formulation. OBJECTIVES: To evaluate and compare the quantity of BMPs among several different DBM formulations (inter-product variability), as well as examine the variability of these proteins in different production lots within the same DBM formulation (intra-product variability). SUMMARY OF BACKGROUND DATA: DBMs are commonly used to augment available bone graft in spinal fusion procedures. Surgeons are presented with an ever-increasing variety of commercially available human DBMs from which to choose. Yet, there is limited information on a specific DBM product's osteoinductive efficacy, potency, and constancy. METHODS: There were protein extracts from each DBM sample separately dialyzed 4 times against distilled water at 4 degrees C for 48 hours. The amount of BMP-2, BMP-4, and BMP-7 was determined using enzyme-linked immunosorbent assay. RESULTS.: The concentrations of detected BMP-2 and BMP-7 were low for all DBM formulations, only nanograms of BMP were extracted from each gram of DBM (20.2-120.6 ng BMP-2/g DBM product; 54.2-226.8 ng BMP-7/g DBM). The variability of BMP concentrations among different lots of the same DBM formulation, intra-product variability, was higher than the variability of concentrations among different DBM formulations, inter-product variability (coefficient of variation range BMP-2 [16.34% to 76.01%], P < 0.01; BMP-7 [3.71% to 82.08%], P < 0.001). BMP-4 was undetectable. CONCLUSIONS: The relative quantities of BMPs in DBMs are low, in the order of 1 x 10(-9) g of BMP/g of DBM. There is higher variability in concentration of BMPs among 3 different lots of the same DBM formulation than among different DBM formulations. This variability questions DBM products' reliability and, possibly, efficacy in providing consistent osteoinduction.

Adjacent segment degeneration in the lumbar spine.

BACKGROUND: A primary concern after posterior lumbar spine arthrodesis is the potential for adjacent segment degeneration cephalad or caudad to the fusion segment. There is controversy regarding the subsequent degeneration of adjacent segments, and we are aware of no long-term studies that have analyzed both cephalad and caudad degeneration following posterior arthrodesis. A retrospective investigation was performed to determine the rates of degeneration and survival of the motion segments adjacent to the site of a posterior lumbar fusion. METHODS: Two hundred and fifteen patients who had undergone posterior lumbar arthrodesis were included in this study. The study group included 126 female patients and eighty-nine male patients. The average duration of follow-up was 6.7 years. Radiographs were analyzed with regard to arthritic degeneration at the adjacent levels both preoperatively and at the time of the last follow-up visit. Disc spaces were graded on a 4-point arthritic degeneration scale. Correlation analysis was used to determine the contribution of independent variables to the rate of degeneration. Survivorship analysis was performed to describe the degeneration of the adjacent motion segments. RESULTS: Fifty-nine (27.4%) of the 215 patients had evidence of degeneration at the adjacent levels and elected to have an additional decompression (fifteen patients) or arthrodesis (forty-four patients). Kaplan-Meier analysis predicted a disease-free survival rate of 83.5% (95% confidence interval, 77.5% to 89.5%) at five years and of 63.9% (95% confidence interval, 54.0% to 73.8%) at ten years after the index operation. Although there was a trend toward progression of the arthritic grade at the adjacent disc levels, there was no significant correlation, with the numbers available, between the preoperative arthritic grade and the need for additional surgery. CONCLUSIONS: The rate of symptomatic degeneration at an adjacent segment warranting either decompression or arthrodesis was predicted to be 16.5% at five years and 36.1% at ten years. There appeared to be no correlation with the length of fusion or the preoperative arthritic degeneration of the adjacent segment.

A prospective, randomized controlled clinical trial of anterior lumbar interbody fusion using a titanium cylindrical threaded fusion device.

STUDY DESIGN: A prospective, randomized, controlled clinical trial comparing a cylindrical threaded titanium cage to a femoral ring allograft control for anterior lumbar interbody fusion. OBJECTIVE: To compare these two implants with regard to arthrodesis. Secondary outcome measures included pain relief, neurological status, and general health status. SUMMARY OF BACKGROUND DATA: Anterior lumbar interbody fusion is a well-accepted procedure using trapezoidal femoral ring allografts or cylindrical titanium cages. Clinical and biomechanical studies evaluating these two distinct constructs are numerous; however, no prospective, randomized study comparing them has been done. METHODS: A multicenter trial of 140 patients: 78 were randomized to the cylindrical threaded titanium cage device treatment arm and 62 patients randomized into the control group. All had autogenous iliac crest bone graft packed into the device. All patients had a single-level stand-alone anterior lumbar interbody fusion at either the L4-L5 or L5-S1 interspace for symptomatic degenerative disc disease. Radiographic fusion data were collected as well as multiple types of outcome data, including pain/disability scores, neurologic status, and overall health. RESULTS: At 12 months, 97% of the cylindrical threaded titanium cage device group and 40% of the control group demonstrated radiographic fusion. At 24 months, 97% of the cylindrical threaded titanium cage group and 52% of the control group showed radiographic fusion. These fusion rate differences are statistically significant (P < 0.001). The Oswestry and neurologic scores were not significantly different between groups. DISCUSSION: This is the first prospective, randomized, multicenter clinical trial that compares fusion cage results to control data. CONCLUSION: Cylindrical threaded titanium cages have a higher fusion rate, comparable improvements in clinical outcome (Oswestry, Low Back Pain Questionnaire, SF-36), and fewer secondary supplemental fixation procedures compared to the femoral ring allograft control.

L5-S1 segment survivorship and clinical outcome analysis after L4-L5 isolated fusion.

STUDY DESIGN: A retrospective investigation of the L5-S1 motion segment after an isolated L4-L5 posterior lumbar fusion. OBJECTIVE: To determine the survivorship of the L5-S1 segment in patients undergoing L4-L5 fusion and to identify the correlation between radiographic degeneration and clinical outcome at this level. SUMMARY OF BACKGROUND DATA: There is current controversy regarding future degeneration of the L5-S1 segment following single-segment fusion at L4-L5. There are no long-term studies that look at L5-S1 after L4-L5 fusion to assess the rate of degeneration at this adjacent segment and the functional clinical outcome of the patient. METHODS: Thirty-two consecutive patients (average age 56.4 years, range 27-77 years) having isolated L4-L5 posterior spinal fusion for instability or stenosis by a single surgeon were included in this study. There were 25 females and 7 males with an average follow-up of 7.3 years (range 2.3-12.4 years). A survivorship analysis was performed to determine the degeneration at the adjacent L5-S1 segment. Radiographs were analyzed for arthritic degeneration at that level. At the time of the L4-L5 index procedure, the L5-S1 disc spaces were graded on a 4-point scale for degeneration. Questionnaires were submitted by mail, and telephone interviews were conducted by one of the authors to determine the current level of patient function. RESULTS: Of the total 32 patients assessed, 31 (97%) had no evidence of symptomatic degeneration at L5-S1 requiring additional decompression or fusion. One patient had clinical symptoms that required a foraminotomy and laminotomy at L5-S1, but none of the patients required any further fusion. Although there was a trend of progression of the arthritic grade at L5-S1 from preoperative to postoperative examination, there was no correlation between preoperative arthritic grade versus further degeneration. The discs showed progression of degeneration from an average score of 2.28 before surgery to a score of 2.49 after surgery at the last follow-up. CONCLUSION: There appears to be no need to routinely include the L5-S1 segment when performing a posterior lumbar fusion for patients with instability or stenosis at L4-L5 if no symptoms are attributed to the lumbosacral level. At an average of 7.3 years, there was neither increased symptomatic disc degeneration nor symptoms necessitating the need for an L5-S1 fusion.

Low back pain recollection versus concurrent accounts: outcomes analysis.

STUDY DESIGN: Patients with low back pain were asked to recall the pain and impaired functioning that they reported 5-10 years previously as part of the National Low Back Pain prospective follow-up study. In 1998, patients completed an additional follow-up. OBJECTIVES: To compare outcomes using patient-recalled data and prospectively collected data from patients with low back pain and to identify simple, symptom-specific questions that yield reliable responses over an extended period of time. SUMMARY OF BACKGROUND DATA: Outcome assessment based on patient recall may be influenced by a patient's age, gender, reporting tendency, and current health status. The impact of data collected retrospectively on outcome analyses in spinal patients has not been addressed. METHODS: Patients enrolled in the National Low Back Pain study from 1986 to 1991 completed a self-administered questionnaire at their initial visit. A sample was interviewed by telephone in 1996 and asked to recall pain characteristics and impaired functioning reported at initial examination. A 10-year follow-up (1998) on current health status was conducted by mail. The 1998 follow-up response was separately compared with recalled and initial responses, such that two patient outcome status values were calculated for each question. Agreement was evaluated using Cohen's kappa. RESULTS: The follow-up evaluation was completed by 144 patients, with a mean interval of 9.4 years. The overall simple kappa was 0.37, indicating "fair" agreement between outcomes based on initial and recalled accounts of pain. Questions on location of pain had kappa values of 0.12-0.58, radicular symptoms 0.28-0.48, and severity of pain 0.11-0.30. CONCLUSIONS: "Fair" to "moderate" agreement was found between outcomes determined by recalled versus initial reports. Accuracy was greatest for queries on frequency, location of pain, and activities affecting pain. Discrepancies were noted for queries on severity of pain, with error bias toward less pain when using the recalled data. Careful selection of questions may yield more accurate outcome measures.

Persistent low back pain and sciatica in the United States: treatment outcomes.

Patients with persistent low back pain (LBP) appear to be different in several important ways from patients who have traditionally been classified as patients with acute or chronic LBP, and data on the effectiveness of the treatments prescribed for them are lacking. The aim of the current study was to evaluate the short- and long-term effectiveness of the treatments currently prescribed for these patients. The data reported in this article were gathered as part of a multicenter, prospective, cross-sectional study of patients who were treated for persistent LBP by neurologic and orthopedic surgeons who are recognized specialists in spinal disorders. At enrollment, patients completed a baseline evaluation, and their physicians recorded relevant clinical and treatment data on standardized study forms. At 3, 6, 12, and 24 months after treatment, patients completed follow-up evaluations. Patients were divided into five treatment groups, and effectiveness was evaluated separately for each group using five patient-reported measures of outcome: pain severity, functional disability, psychologic distress, physical symptoms, and health care use. The data revealed that at the 2-year follow-up, the typical patient of the no-treatment group had improved slightly in terms of pain severity and health care use, but had experienced little or no improvement in functional disability, physical symptoms, and psychologic distress. The average patient in the conservative care group reported small improvements in pain severity, functional disability, physical symptoms, and health care use, with no change in psychologic distress. These small improvements occurred within the first 3 months after enrollment, with essentially no change thereafter. The average patient in the immediate surgical care group showed substantial improvement on all of the outcome measures. The observed improvements were evident shortly after treatment and were maintained for the duration of the study. Patients in the delayed surgical care group had outcomes that were less dramatic than those observed in the immediate surgery care group, but greater than those observed in the conservative care group. The patients who were treated surgically by physicians outside the study, outside surgical care group, did not improve over time. Patients with persistent LBP who received no treatment showed no spontaneous recovery. Conservative care treatments prescribed by surgeons who specialize in spinal disorders, did not appear to be any more effective than no treatment. The outcome of surgery for persistent LBP varied from dramatic for one subgroup of surgical patients, to poor for another subgroup of patients. Patients who were selected immediately for surgical treatment improved substantially. Those treated surgically later by study physicians or by physicians not associated with the study fared less well.