ProDisc-C Total Disc Replacement Versus Anterior Cervical Discectomy and Fusion for Single-Level Symptomatic Cervical Disc Disease: Seven-Year Follow-up of the Prospective Randomized U.S. Food and Drug Administration Investigational Device Exemption Study.

BACKGROUND: In patients with single-level cervical degenerative disc disease, total disc arthroplasty can relieve radicular pain and preserve functional motion between two vertebrae. We compared the efficacy and safety of cervical total disc arthroplasty with that of anterior cervical discectomy and fusion (ACDF) for the treatment of single-level cervical degenerative disc disease between C3-C4 and C6-C7. METHODS: Two hundred and nine patients at thirteen sites were randomly treated with either total disc arthroplasty with ProDisc-C (n = 103) or with ACDF (n = 106). Patients were assessed preoperatively; at six weeks and three, six, twelve, eighteen, and twenty-four months postoperatively; and then annually until seven years postoperatively. Outcome measures included the Neck Disability Index (NDI), the Short Form-36 (SF-36), postoperative neurologic parameters, secondary surgical procedures, adverse events, neck and arm pain, and satisfaction scores. RESULTS: At seven years, the overall follow-up rate was 92% (152 of 165). There were no significant differences in demographic factors, follow-up rate, or patient-reported outcomes between groups. Both procedures were effective in reducing neck and arm pain and improving and maintaining function and health-related quality of life. Neurologic status was improved or maintained in 88% and 89% of the patients in the ProDisc-C and ACDF groups, respectively. After seven years of follow-up, thirty secondary surgical procedures had been performed in nineteen (18%) of 106 patients in the ACDF group compared with seven secondary surgical procedures in seven (7%) of 103 patients in the ProDisc-C group (p = 0.0099). There were no significant differences in the rates of any device-related adverse events between the groups. CONCLUSIONS: Total disc arthroplasty with ProDisc-C is a safe and effective surgical treatment of single-level symptomatic cervical degenerative disc disease. Clinical outcomes after total disc arthroplasty with ProDisc-C were similar to those after ACDF. Patients treated with ProDisc-C had a lower probability of subsequent surgery, suggesting that total disc arthroplasty provides durable results and has the potential to slow the rate of adjacent-level disease. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

The relationship between serum vitamin D levels and spinal fusion success: a quantitative analysis.

STUDY DESIGN: An in vivo dosing study of vitamin D in a rat posterolateral spinal fusion model with autogenous bone grafting. Rats randomized to 4 levels of vitamin D-adjusted rat chow, longitudinal serum validation, surgeons/observers blinded to dietary conditions, and rats followed prospectively for fusion endpoint. OBJECTIVE: To assess the impact of dietary and serum levels of vitamin D on fusion success, consolidation of fusion mass, and biomechanical stiffness after posterolateral spinal fusion procedure. SUMMARY OF BACKGROUND DATA: Metabolic risk factors, including vitamin D insufficiency, are often overlooked by spine surgeons. Currently, there are no published data on the causal effect of insufficient or deficient vitamin D levels on the success of establishing solid bony union after a spinal fusion procedure. METHODS: Fifty rats were randomized to 4 experimentally controlled rat chow diets: normal control, vitamin D-deficient, vitamin D-insufficient, and a nontoxic high dose of vitamin D, 4 weeks prior to surgery and maintained postsurgery until sacrifice. Serum levels of 25(OH)D were determined at surgery and sacrifice using radioimmunoassay. Posterolateral fusion surgery with tail autograft was performed. Rats were sacrificed 12 weeks postoperatively, and fusion was evaluated via manual palpation, high-resolution radiographs, micro-computed tomographic scans, and biomechanical testing. RESULTS: Serum 25(OH)D and calcium levels were significantly correlated with vitamin D-adjusted chow (P < 0.001). There was a dose-dependent relationship between vitamin D-adjusted chow and manual palpation fusion, with greatest differences found in measures of radiographical density between high and deficient vitamin D (P < 0.05). Adequate levels of vitamin D (high and normal control) yielded stiffer fusion than inadequate levels (insufficient and deficient) (P < 0.05). CONCLUSION: Manual palpation fusion rates increased with supplementation of dietary vitamin D. Biomechanical stiffness, bone volume, and density were also positively related to vitamin D and calcium. LEVEL OF EVIDENCE: N/A.

Health state utility of patients with single-level cervical degenerative disc disease: comparison of anterior cervical discectomy and fusion with cervical disc arthroplasty.

OBJECT: Cost-effectiveness analysis (CEA) of medical interventions has become increasingly relevant to the discussion of optimization of care. The use of utility scales in CEA permits a quantitative assessment of effectiveness of a given intervention. There are no published utility values for degenerative disc disease (DDD) of the cervical spine, anterior cervical discectomy and fusion (ACDF), or cervical disc replacement (CDR). The purpose of this study was to define health utility values for those health states. METHODS: The 36-Item Short Form Health Survey data from the ProDisc-C investigational device exemption study were obtained for single-level DDD at baseline and 24 months postoperatively after ACDF or CDR procedures. Patients in the original study were randomized to either ACDF or CDR. Utilizing a commercially available Short Form-6 dimensions program, utility scores were calculated for each health state using a set of parametric preference weights obtained from a sample of the general population using the recognized valuation technique of standard gamble. RESULTS: The baseline health state utility (HSU) value for a patient with single-level DDD was 0.54 in both the ACDF and CDR groups. Postoperative changes in HSU values were seen in both intervention groups at 24 months. Cervical disc replacement had a HSU value of 0.72. Anterior cervical discectomy and fusion was found to have a postoperative utility state of 0.71. No statistically significant difference was found in the HSU for ACDF and CDR at 24 months of follow-up. CONCLUSIONS: This study represents the first calculated HSU value for a patient with single-level cervical DDD. Additionally, 2 common treatment interventions for this disease state were assessed. Both treatments were found to have significant impact on the HSU values. These values are integral to future CEA of ACDF and CDR.

Bone marrow enhances the performance of rhBMP-2 in spinal fusion: a rodent model.

BACKGROUND: Reliable and rapid bone formation is the goal of biologics and cell-based spinal fusion technologies. While no cell-based therapy alone has been successful, recombinant human bone morphogenetic protein-2 (rhBMP-2) has been successfully used in a wide spectrum of patients undergoing a variety of spinal fusion procedures since its approval by the United States Food and Drug Administration (FDA) in 2002. However, the question remains how to improve the biologic efficiency, or osteoinductivity, of rhBMP-2 for successful application in the most challenging patients undergoing spinal fusion or to reduce the doses currently required. The present study investigated how varying the cellular environments through the addition of freshly harvested bone marrow aspirate (BMA) modulates rhBMP-2 efficiency. METHODS: An L4-L5 posterolateral intertransverse process spinal fusion procedure was performed in Lewis rats. The implants were a subeffective concentration of 0.006 mg/mL of rhBMP-2/two absorbable collagen sponges (ACS) plus directly applied fresh syngeneic BMA transplants (n = 18), 0.006-mg/mL rhBMP-2/two ACS/side (n = 12), 0.006-mg/mL rhBMP-2/one ACS/side (n = 12), or BMA/one ACS/side (n = 6). Rats were killed at eight weeks and were evaluated with use of manual palpation, radiographs, and biomechanical testing. RESULTS: BMA plus 0.006-mg/mL rhBMP-2/ACS significantly increased the L4-L5 fusion rate to 89% (sixteen of eighteen) compared with a base fusion rate of 33% (four of twelve) to 50% (six of twelve) for rats implanted with rhBMP-2/ACS (p < 0.05), with no difference in strength or stiffness between conditions. No fusion or bone formation was observed in the six rats that received BMA/ACS alone. CONCLUSIONS: Less rhBMP-2 was needed for effect when mixed with BMA. A nearly twofold increase in the fusion rate was found when BMA was mixed with a deliberate subeffective concentration of rhBMP-2. There was no improvement in terms of fusion strength or stiffness.

Five-year reoperation rates, cervical total disc replacement versus fusion, results of a prospective randomized clinical trial.

STUDY DESIGN: Prospective randomized clinical trial. OBJECTIVE: Determine the reasons for, and rates of, secondary surgical intervention up to 5 years at both the index and adjacent levels in patients treated with cervical total disc replacement (TDR) or anterior cervical discectomy and fusion (ACDF). Patients undergoing TDR received ProDisc-C. SUMMARY OF BACKGROUND DATA: Several outcome-based prospective, randomized clinical trials have shown cervical TDR to be equivalent, if not superior, to fusion. The ability of TDR to allow decompression while maintaining motion has led many to suggest that adjacent-level degeneration and reoperation rates may be decreased when compared with fusion. METHODS: A total of 209 patients were treated and randomized (TDR, n = 103; ACDF, n = 106) at 13 sites. A secondary surgical intervention at any level was considered a reoperation. RESULTS: At 5 years, patients who received ProDisc-C had statistically significant higher probability of no secondary surgery at the index and adjacent levels than patients who underwent ACDF (97.1% vs. 85.5%, P = 0.0079). No reoperations in patients who received ProDisc-C were performed for implant breakages or device failures. For patients who underwent ACDF, the most common reason for reoperation at the index level was pseudarthrosis, and for patients who underwent both ACDF and TDR, the most common reason for adjacent-level surgery was recurrent neck and/or arm pain. CONCLUSION: Five-year follow-up of a prospective randomized clinical trial revealed 5-fold difference in reoperation rates when comparing patients who underwent ACDF (14.5%) with patients who underwent TDR (2.9%). These findings suggest the durability of TDR and its potential to slow the rate of adjacent-level disease.

Does 360° lumbar spinal fusion improve long-term clinical outcomes after failure of conservative treatment in patients with functionally disabling single-level degenerative lumbar disc disease? Results of 5-year follow-up in 75 postoperative patients.

BACKGROUND: Surgical treatment of patients with mechanical degenerative disc disease has been controversial, but improvements in clinical outcomes have been shown in properly selected patients with disease-specific diagnoses, with fusion arguably now becoming the "gold standard" for surgical management of these patients. No published study thus far has been designed for prospective enrollment of patients with specific inclusion/exclusion criteria in whom at least 6 months of conservative therapy has failed and who are then offered a standardized surgical procedure and are followed up for 5 years. METHODS: The study group was composed of the patients in the prospective, randomized Food and Drug Administration Investigational Device Exemption trial comparing ProDisc-L (Synthes Spine, West Chester, Pennsylvania) with 360° fusion for the treatment of single-level symptomatic disc degeneration. Of 80 patients randomized to 360° fusion after failure of non-operative care, 75 were treated on protocol with single-level fusions. Follow-up of this treatment cohort was 97% at 2 years and 75% at 5 years and serves as the basis for this report. Patients in the trial were required to have failure of at least 6 months of nonoperative care and in fact had failure of an average of 9 months of nonoperative treatment. The mean Oswestry Disability Index score indicated greater than 60% impairment. The mean entry-level pain score on a visual analog scale was greater than 8 of 10. RESULTS: After fusion, not only did patients have significant improvements in measurable clinical outcomes such as the Oswestry Disability Index score and pain score on a visual analog scale but there were also substantial improvements in their functional status and quality of life. Specifically, over 80% of patients in this study had improvements in recreational status that was maintained 5 years after index surgery, indicating substantial improvements in life quality that were not afforded by months of conservative care. The percentage of patients using narcotics at the 5-year follow-up visit was less than half the percentage of patients who had used narcotics as part of their prior conservative treatment. CONCLUSIONS: The 5-year results of this post hoc analysis of 75 patients involved in a multicenter, multi-surgeon trial support 360° fusion surgery as a predictable and lasting treatment option to improve pain and function in properly selected patients with mechanical degenerative disc disease. These improvements occurred dramatically immediately after surgery and have been maintained through the scope of this follow-up period, with 98% follow-up at 2 years and 75% of patients available at 5 years.

Five-year results of the prospective, randomized, multicenter, Food and Drug Administration investigational device exemption study of the ProDisc-L total disc replacement versus circumferential arthrodesis for the treatment of single-level degenerative disc disease.

OBJECT: The purpose of this study was to evaluate the long-term safety and effectiveness of the ProDisc-L total disc replacement (TDR) as part of an FDA-mandated postmarket approval study. This report summarizes the clinical findings after 5 years of follow-up. METHODS: Two hundred thirty-six patients were treated and followed up for 5 years; 161 TDRs and 75 fusions had been performed in these patients. The primary outcome was a 10-component success end point. Secondary outcome measures included neurological status, secondary surgery, Oswestry Disability Index (ODI), 36-Item Short Form Health Survey (SF-36), visual analog scale (VAS) assessing pain and satisfaction, radiographic data, narcotic use, activity, and recreation status. Patients were monitored through their 5-year postoperative visits under the FDA postmarket surveillance provisions in the original investigational device exemption approval. RESULTS: The overall follow-up rate at 5 years was 81.8%. Study success demonstrated that TDR was noninferior to fusion with a 12.5% margin (p = 0.0099). Both TDR and fusion treatment groups maintained significant improvement on the ODI at 5 years compared with baseline (p < 0.0001). Secondary surgeries at the index level were performed in 12% of fusion patients and 8% of TDR patients. Radiographically, none of the TDRs developed spontaneous fusion. The segmental range of motion following TDR remained within normal range, although it decreased by approximately 0.5° in years 3 to 5. The VAS pain scores decreased from preoperative values by 48% in both treatment groups at 5 years. Patient satisfaction remained high in both groups (77%), while the percentage of patients indicating that they would have the surgery again was higher in TDR patients (82.5%) than in fusion patients (68.0%). CONCLUSIONS: Patients in both groups maintained significant improvement during the 5-year follow-up. The TDR group had significantly better improvement on some scales. Although TDR patients avoid the stiffness of fusion and are more satisfied than fusion patients, both fusion and TDR are reasonable surgical options in this specific patient population.

Five-year adjacent-level degenerative changes in patients with single-level disease treated using lumbar total disc replacement with ProDisc-L versus circumferential fusion.

OBJECT: The authors report the 5-year results for radiographically demonstrated adjacent-level degenerative changes from a prospective multicenter study in which patients were randomized to either total disc replacement (TDR) or circumferential fusion for single-level lumbar degenerative disc disease (DDD). METHODS: Two hundred thirty-six patients with single-level lumbar DDD were enrolled and randomly assigned to 2 treatment groups: 161 patients in the TDR group were treated using the ProDisc-L (Synthes Spine, Inc.), and 75 patients were treated with circumferential fusion. Radiographic follow-up data 5 years after treatment were available for 123 TDR patients and 43 fusion patients. To characterize adjacent-level degeneration (ALD), radiologists at an independent facility read the radiographic films. Adjacent-level degeneration was characterized by a composite score including disc height loss, endplate sclerosis, osteophytes, and spondylolisthesis. At 5 years, changes in ALD (ΔALDs) compared with the preoperative assessment were reported. RESULTS: Changes in ALD at 5 years were observed in 9.2% of TDR patients and 28.6% of fusion patients (p = 0.004). Among the patients without adjacent-level disease preoperatively, new findings of ALD at 5 years posttreatment were apparent in only 6.7% of TDR patients and 23.8% of fusion patients (p = 0.008). Adjacent-level surgery leading to secondary surgery was reported for 1.9% of TDR patients and 4.0% of fusion patients (p = 0.6819). The TDR patients had a mean preoperative index-level range of motion ([ROM] of 7.3°) that decreased slightly (to 6.0°) at 5 years after treatment (p = 0.0198). Neither treatment group had significant changes in either ROM or translation at the superior adjacent level at 5 years posttreatment compared with baseline. CONCLUSIONS: At 5 years after the index surgery, ProDisc-L maintained ROM and was associated with a significantly lower rate of ΔALDs than in the patients treated with circumferential fusion. In fact, the fusion patients were greater than 3 times more likely to experience ΔALDs than were the TDR patients. Clinical trial registration no.: NCT00295009.

Spinal fusion in the United States: analysis of trends from 1998 to 2008.

STUDY DESIGN: Epidemiological study using national administrative data. OBJECTIVE: To provide a complete analysis of national trends in spinal fusion from 1998 to 2008 and compare with trends in laminectomy, hip replacement, knee arthroplasty, percutaneous transluminal coronary angioplasty, and coronary artery bypass graft. SUMMARY OF BACKGROUND DATA: Previous studies have reported a rapid increase in volume of spinal fusions in the United States prior to 2001, but limited reports exist beyond this point, analyzing all spinal fusion procedures collectively. METHODS: Data were obtained from the Healthcare Cost and Utilization Project Nationwide Inpatient Sample for the years 1998 to 2008. Discharges were identified using International Classification of Diseases, Ninth Revision, Clinical Modification procedure codes for the following procedures: spinal fusion, laminectomy, hip replacement, knee arthroplasty, percutaneous transluminal coronary angioplasty, and coronary artery bypass graft. Population-based utilization rates were calculated from the US census data. RESULTS: Between 1998 and 2008, the annual number of spinal fusion discharges increased 2.4-fold (137%) from 174,223 to 413,171 (P < 0.001). In contrast, during the same time period, laminectomy, hip replacement, knee arthroplasty, and percutaneous coronary angioplasty yielded relative increases of only 11.3%, 49.1%, 126.8%, and 38.8% in discharges, while coronary artery bypass graft experienced a decrease of 40.1%. Between 1998 and 2008, mean age for spinal fusion increased from 48.8 to 54.2 years (P < 0.001), in-hospital mortality rate decreased from 0.29% to 0.25% (P < 0.01), and mean total hospital charges associated with spinal fusion increased 3.3-fold (P < 0.001). The national bill for spinal fusion increased 7.9-fold (P < 0.001). CONCLUSION: Frequency, utilization, and hospital charges of spinal fusion have increased at a higher rate than other notable inpatient procedures, as seen in this study from 1998 to 2008. In addition, patient demographics and hospital characteristics changed significantly; in particular, whereas the average age for spinal fusion increased, the in-hospital mortality rate decreased.

Lumbar plexus anatomy within the psoas muscle: implications for the transpsoas lateral approach to the L4-L5 disc.

BACKGROUND: The transpsoas lateral surgical approach has been advocated as an alternative to direct anterior approaches for less invasive or minimally invasive access to the spine. Postoperative thigh pain, paresthesia, and/or weakness have been described after the use of this surgical approach. The purpose of this cadaveric anatomic study is to provide a description of the lumbar plexus as it relates to the transpsoas lateral surgical approach. METHODS: Dissection of the lumbar plexus was performed in eighteen cadaveric specimens. Needle markers were placed in the L2-L3, L3-L4, and L4-L5 discs in the midcoronal plane. The anatomic structures were surveyed, and the proximity of the needle to the neural structures was observed. RESULTS: In thirteen of the eighteen specimens, the femoral nerve received its contributions from the L2 to L4 nerve roots and was formed at the L4-L5 disc space. In all specimens, the femoral nerve passed dorsal to or directly at the midpoint of the disc. In three specimens, the needle displaced or was immediately adjacent to the femoral nerve. The femoral nerve was found between the needle and the posterior aspect of the L4-L5 disc space in thirteen of the eighteen specimens. CONCLUSIONS: Because of the proximity of the neural elements, in particular the femoral nerve, to the center of the disc space, the transpsoas lateral surgical approach to the L4-L5 disc space will likely cause intraoperative displacement of neural structures from their anatomic course during retractor dilation. Careful attention should be paid to retractor placement and dilation time during transpsoas lateral access surgery, particularly at the L4-L5 disc.

Variability across ten production lots of a single demineralized bone matrix product.

BACKGROUND: Demineralized bone matrix is an osteoinductive allograft derived from processed bone that is commonly mixed with autogenous bone in fusion procedures to treat diseases of the spine. An increasing number of demineralized bone matrix-based products are commercially available for spinal fusion procedures, but osteoinductive variability has been found not only across different products but also among production lots from the same demineralized bone matrix formulation. The purpose of this study was to assess the lot-to-lot variability across a single demineralized bone matrix-based product in terms of both extracted bone morphogenetic protein (BMP) concentrations (in vitro) and fusion performance in rats (in vivo). The goal was also to determine whether the in vitro measures could sufficiently and accurately predict the in vivo fusion performance of different demineralized bone matrix-based product lots. METHODS: BMP-2 and BMP-7 were extracted from ten production lots of InterGro DBM Putty and quantified with use of ELISA (enzyme-linked immunosorbent assay). A posterolateral lumbar spinal fusion was performed on forty athymic rats with implantation of a demineralized bone matrix-based product. Fusion success was determined at eight weeks with use of radiographs and manual palpation of the segments. Logistic regression was used to determine the predictive abilities of BMPs. RESULTS: Significant lot-to-lot variability was found in terms of both BMP concentrations (22 to 110 pg of BMP-2 per milligram of product and 44 to 125 pg of BMP-7 per milligram of product) and in vivo rates of fusion (0% to 75%; p < 0.04 for all). BMP-2 and BMP-7 concentrations correlated positively with each other across lots (r = 0.77, p < 0.0001). Most notably, extracted amounts of BMP-2 and BMP-7 each predicted in a dose-dependent manner the in vivo fusion performance in rats (R(2) = 0.32, p < 0.01 for BMP-2, and R(2) = 0.22, p < 0.009 for BMP-7). CONCLUSIONS: Assays for demineralized bone matrix-extracted BMP-2 and BMP-7 levels may be feasible and sufficient for predicting spinal fusion performance of individual production lots from the same demineralized bone matrix-based product.

Cost comparison of patients with 3-level artificial total lumbar disc replacements versus 360° fusion at 3 contiguous lumbar vertebral levels: an analysis of compassionate use at 1 site of the US investigational device exemption clinical trial.

BACKGROUND: We sought to evaluate the difference between hospital service costs of 2 treatment options for patients diagnosed with 3-level degenerative disc disease (DDD) in the lumbar spine. In this retrospective analysis, itemized billing records of hospital stay for patients with 3-level DDD treated with artificial disc replacement (ADR) were compared with those treated with circumferential fusion (standard of care). METHODS: Sequential 3-level DDD patients treated with either ADR (ProDisc-L; Synthes, West Chester, Pennsylvania) or circumferential fusion during the period from January 2004 to October 2005 were included. Surgeries were performed at the same hospital for all patients. The ADR-treated patients were participating in the investigational device exemption clinical trial as part of the compassionate-use arm. Patients treated with fusion at the same institution during this same time interval were evaluated. Itemized billing records were collected at least 1 year after the index surgery. Costs according to hospital service categories were compared between ADR-treated and fusion-treated patients by use of analysis of variance and multivariate statistical techniques. RESULTS: There were 43 consecutive patients treated for 3-level DDD between January 2004 and October 2005. Of these, 21 underwent 3-level ADR and 22 had a 3-level fusion procedure. There was a mean of 3 fewer hospital days for patients treated with ADR (4.77 ± 1.11 days) than for those treated with fusion (8.00 ± 1.82 days) (P < .0001). The cost of hospital services for ADR-treated patients was 49% less excluding instrumentation costs and 54% less when accounting for instrumentation. The pattern of cost was similar when workers' compensation patients were analyzed separately. CONCLUSIONS: ADR-treated 3-level patients benefited from significantly lower costs from their in-hospital stay compared with those treated by fusion. Hospital service costs were 49% (54% when instrumentation was included in the costs) less for ADR patients than for fusion patients.

Results at 24 months from the prospective, randomized, multicenter Investigational Device Exemption trial of ProDisc-C versus anterior cervical discectomy and fusion with 4-year follow-up and continued access patients.

BACKGROUND: Cervical total disk replacement (TDR) is intended to address pain and preserve motion between vertebral bodies in patients with symptomatic cervical disk disease. Two-year follow-up for the ProDisc-C (Synthes USA Products, LLC, West Chester, Pennsylvania) TDR clinical trial showed non-inferiority versus anterior cervical discectomy and fusion (ACDF), showing superiority in many clinical outcomes. We present the 4-year interim follow-up results. METHODS: Patients were randomized (1:1) to ProDisc-C (PDC-R) or ACDF. Patients were assessed preoperatively, and postoperatively at 6 weeks and 3, 6, 12, 18, 24, 36, and 48 months. After the randomized portion, continued access (CA) patients also underwent ProDisc-C implantation, with follow-up visits up to 24 months. Evaluations included Neck Disability Index (NDI), Visual Analog Scale (VAS) for pain/satisfaction, and radiographic and physical/neurologic examinations. RESULTS: Randomized patients (103 PDC-R and 106 ACDF) and 136 CA patients were treated at 13 sites. VAS pain and NDI score improvements from baseline were significant for all patients (P < .0001) but did not differ among groups. VAS satisfaction was higher at all time points for PDC-R versus ACDF patients (P = .0499 at 48 months). The percentage of patients who responded yes to surgery again was 85.6% at 24 months and 88.9% at 48 months in the PDC-R group, 80.9% at 24 months and 81.0% at 48 months in the ACDF group, and 86.3% at 24 months in the CA group. Five PDC-R patients (48 months) and no CA patients (24 months) had index-level bridging bone. By 48 months, approximately 4-fold more ACDF patients required secondary surgery (3 of 103 PDC-R patients [2.9%] vs 12 of 106 ACDF patients [11.3%], P = .0292). Of these, 6 ACDF patients (5.6%) required procedures at adjacent levels. Three CA patients required secondary procedures (24 months). CONCLUSIONS: Our 4-year data support that ProDisc-C TDR and ACDF are viable surgical options for symptomatic cervical disk disease. Although ACDF patients may be at higher risk for additional surgical intervention, patients in both groups show good clinical results at longer-term follow-up.

Access strategies for revision in anterior lumbar surgery.

STUDY DESIGN: Sixty-two consecutive patients undergoing anterior lumbar revision surgery from February 2000 to September 2007 were evaluated for approach strategies and complications. OBJECTIVE: To determine the incidence of complications in these patients and to make recommendations on future revisions based on the results obtained. SUMMARY OF BACKGROUND DATA: Only 2 articles exist in the literature that address this situation and they have widely varying results in a small number of patients. This larger series may help give more certainty to the expectations for complications in patients undergoing revision anterior lumbar surgery. METHODS: A concurrent database was maintained on these 62 consecutive patients. Preoperative strategies were evaluated and complications were tabulated as they occurred and later analyzed to arrive at recommendations for future similar cases. RESULTS: Twenty-three patients had the same level revised and 39 patients had adjacent levels operated on. There were 3 venous injuries (4.8%), 3 arterial injuries (4.8%), and 1 ureteral injury (1.6%). All 3 arterial injuries occurred while approaching L3-L4 after L4 to S1 prior fusion or disc replacement. All 3 venous injuries and the ureteral injury occurred while approaching a previously operated level or levels. Six of these patients had the injuries repaired and the procedures completed with full recovery. One L5-S1 revision had the procedure aborted after a venous injury. There were no deaths. CONCLUSION: Although the incidence of complications in revisions is much greater than for index cases, the actual percentage of venous, arterial, and ureteral complications is certainly acceptable for patients who must have this type of surgery. Only very experienced access surgeons should attempt revision surgery.

An in vitro and in vivo analysis of fibrin glue use to control bone morphogenetic protein diffusion and bone morphogenetic protein-stimulated bone growth.

BACKGROUND CONTEXT: Recombinant human bone morphogenetic protein-2 (rh-BMP2) has become popular for augmenting spine fusion in the lumbar and cervical spine. Concerns exist, however, over bone morphogenetic protein (BMP)-stimulated soft-tissue swelling and bone growth stimulation in areas where bone is not desired, especially as the material "leaks" into such spaces. The most detrimental effects of such leakage might be airway compromise, while heterotopic bone formation into the spinal canal has been reported in animal and human studies. Fibrin glue has been used as a carrier of many osteoinductive materials; however, its efficacy at modulating the clinical effects of BMP are not known. The amorphous nature of fibrin glue makes it a candidate to control diffusion of BMP and possibly limit bone formation by limiting BMP diffusion to areas where such bone is not desired. PURPOSE: To evaluate the use of fibrin glue to limit BMP diffusion and BMP-stimulated bone growth. STUDY DESIGN/SETTING: This is an in vitro basic science study and an in vivo prospective randomized animal study. STUDY SAMPLE: Eighteen Lewis rats. OUTCOME MEASURES: In vitro study: Enzyme-linked immunosorbent assay measurement of rh-BMP2 concentration in saline. In vivo study: At day 60, rats were evaluated for neurologic deficits before sacrifice. Spines were harvested, and the following studies were performed: 1) manual testing for fusion and bone growth; 2) X-ray evaluation; 3) Micro-computed tomography (micro-CT) scans. METHODS: In vitro study: Collagen sponges soaked with BMP at two different concentrations were incubated in saline solution with and without encapsulation by fibrin glue. Saline BMP concentrations were measured at consecutive time points. In vivo study: A rat fusion model using rh-BMP2 for fusion has been developed and tested with resultant100% fusion in over 100 rats. Lewis rats were divided into two groups and treated as follows: I: Exposure of L4-L5 transverse processes, decortication, and placement of BMP sponge in the lateral intertransverse space. II: Exposure and decortication as above and placement of fibrin glue before BMP sponge placement. RESULTS: In vitro study: Peak rh-BMP2 concentrations in saline were 20% and 45% of the maximum possible for fibrin glue encapsulated sponges and controls, respectively, with a more gradual increase to peak concentration in samples encapsulated in fibrin glue. In vivo study: No rats exhibited any neurologic deficits. X-rays revealed at least partial bone formation in all rats. Manual testing of intertransverse fusion spines revealed 100% fusion in rats treated with BMP only, whereas rats treated with fibrin glue before placement of BMP sponges revealed only one possible fusion. Posterior-lateral bone formation was present on X-ray in both groups, and micro-CT imaging revealed bridging bone from transverse processes to the BMP-stimulated bone in the control groups. In spines treated with fibrin glue before rh-BMP2 placement, bone formation could still be seen within the soft tissues; however, bridging bone connecting to the transverse processes was either significantly decreased or not present. CONCLUSIONS: Fibrin glue can limit rh-BMP2 diffusion. Also, because it limited bone formation at the transverse processes, it can be inferred that fibrin glue can limit bone formation when used to separate areas of desired bone formation from areas where bone formation is not desired.

Controlling bone morphogenetic protein diffusion and bone morphogenetic protein-stimulated bone growth using fibrin glue.

STUDY DESIGN: An in vitro and in vivo study. OBJECTIVE: To evaluate the ability of fibrin glue to limit diffusion of recombinant human bone morphogenetic protein (rhBMP)-2 and its ability to protect spinal nerves from rhBMP-2 stimulated bone growth. SUMMARY OF BACKGROUND DATA: Studies have shown bone morphogenetic protein (rhBMP-2) stimulated bone growth can encroach on the spinal canal and nerves, causing neural compression. More recently, rhBMP-2 use in the cervical spine has been associated with life-threatening swelling. Fibrin glue has been used as a biologic carrier but has not been evaluated for its ability to limit rhBMP-2. METHODS: In phase 1 of the study, rhBMP-2 soaked absorbable collagen sponges (ACS) were encapsulated in fibrin glue and immediately incubated in physiologic lactated ringers solution at 38 degrees C. Samples of solution were tested for rhBMP-2 concentration. In phase 2 of the study, rats were surgically treated with laminectomy and placement of rhBMP-2/ACS versus laminectomy and placement of fibrin glue before placement of rhBMP-2/ACS. After 8 weeks, animals were euthanized and imaged using micro-computerized tomography. RESULTS: The diffusion study showed a significant limitation in rhBMP-2 diffusion when encapsulated in fibrin glue. The laminectomy study revealed blockage of bone formation by fibrin glue and protection of the spinal canal. CONCLUSIONS: Fibrin glue can limit the diffusion of rhBMP-2, and, thus, it can be used to help protect the spinal canal and nerve roots from rhBMP-2 stimulated bone growth.

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.

Computed tomography assessment of the accuracy of in vivo placement of artificial discs in the lumbar spine including radiographic and clinical consequences.

STUDY DESIGN: Prospective cohort study of 52 patients who had undergone artificial lumbar disc replacement. OBJECTIVES: To evaluate the implantation accuracy of prosthesis positioning, subsequent facet joint changes and prosthesis migration, and the clinical consequences of implant position. SUMMARY OF BACKGROUND DATA: Accuracy of spinal prosthesis implantation has not been evaluated rigorously, especially with a mini-incision approach. It is unknown if the inexact placement of a mobile device in the spine has any biomechanical, radiographic, or clinical repercussions. METHODS: A total of 52 consecutive patients were treated using standard methods of disc implantation with an intervertebral prosthesis. Computed tomography scans were performed within 3 days and again at 6 to 24 months. An independent radiologist analyzed the images for prosthesis position, rotation, migration, and facet changes. Results were compared with clinical outcome, measured by the Visual Analog Scale and Oswestry Disability Index. RESULTS: Deviation of the prosthesis from the center position was under 1.2 mm, and rotation off of midline was under 12 degrees. Follow-up CT scans showed no migration or facet changes. Regression analysis showed no correlation of prosthesis position with clinical outcome. CONCLUSIONS: Current prosthetic disc implantation methods, with minimally invasive access techniques, are relatively accurate. Although there can be deviation of the prosthesis from ideal placement, no repercussions were attributable.