Randall F. Dryer

Lumbar disc arthroplasty with Maverick disc versus stand-alone interbody fusion: a prospective, randomized, controlled, multicenter investigational device exemption trial.

Study Design. Randomized, controlled, multicenter, investigational device exemption trial. Objective. To investigate the safety and effectiveness of the first two-piece, metal-on-metal lumbar disc prosthesis for treating patients with single-level degenerative disc disease. Summary of Background Data. For patients with degenerative disc disease unresponsive to conservative measures, lumbar disc arthroplasty provides an alternative to fusion designed to relieve persistent discogenic pain and maintain motion. Methods. After 2:1 randomization, 577 patients were treated in either the investigational group (405), receiving lumbar disc arthroplasty, or the control group (172), receiving anterior lumbar interbody fusion. Patients were evaluated preoperatively, at surgery/discharge, and at 1.5, 3, 6, 12, and 24 months after surgery. The primary study endpoint was overall success, a composite measure of safety and effectiveness as recommended by the Food and Drug Administration and defined in the protocol. Results. Both treatment groups demonstrated significant improvements compared with preoperative status. The investigational group had statistically superior outcomes (P < 0.05) at all postoperative evaluations in Oswestry Disability Index, back pain, and Short Form-36 Physical Component Summary scores as well as patient satisfaction. Investigational patients had longer surgical times (P < 0.001) and greater blood loss (P < 0.001) than did control patients; however, hospitalization stays were similar for both groups. Investigational patients had fewer implant or implant/surgical procedure-related adverse events (P < 0.001). Return-to-work intervals were reduced for investigational patients. Disc height and segmental angular motion were maintained throughout the study in the investigational group. In the investigational group, overall success superiority was found when compared to the control group as defined by the Food and Drug Administration Investigational Device Exemption protocol. Conclusion. The investigational group consistently demonstrated statistical superiority versus fusion on key clinical outcomes including improved physical function, reduced pain, and earlier return to work.

Retrograde ejaculation following single-level anterior lumbar surgery with or without recombinant human bone morphogenetic protein-2 in 5 randomized controlled trials: clinical article.

OBJECT The aim of this study was to determine the incidence and assess specific risk factors in the postoperative development of retrograde ejaculation (RE) in men treated for degenerative lumbar disc disease at the L4-5 or L5-S1 level with stand-alone anterior interbody implants with or without recombinant human bone morphogenetic protein-2 (rhBMP-2). METHODS Patients enrolled in 5 prospective, randomized, multicenter FDA-approved investigational device exemption studies were observed for a minimum of 2 years to assess the rate of RE. Five hundred eight men with symptomatic single-level lumbar degenerative disc disease with up to Grade 1 spondylolisthesis underwent anterior lumbar interbody surgery with stand-alone anterior implants at either L4-5 or L5-S1. All patient self-reported and physician-documented adverse events were recorded over the entire course of follow-up. In the investigational groups, 207 patients were treated with an open surgical procedure using dual paired constructs and rhBMP-2 on an absorbable collagen sponge. The control groups (n = 301) were treated with lumbar fusion cage implants and iliac crest autograft or a metal-on-metal disc arthroplasty device. Multivariate analyses of RE were performed to assess the influence of treatment (rhBMP-2), surgical approach, and treated level. Data were analyzed for each trial individually and for the data pooled from the 5 trials. RESULTS Retrograde ejaculation occurred at the highest rates in the earliest clinical trial. Of the 146 men, 6 (4.1%) developed RE postoperatively. In subsequent studies, the rates of RE ranged from 0% to 2.1%. Combining the data from the 5 trials, RE was reported in 7 (3.4%) of the 207 patients who received the rhBMP-2 treatment compared with 5 (1.7%) of the 301 patients who received the autograft or lumbar disc treatment (p = 0.242, Fisher exact test). Cases of RE were reported in 7 (1.6%) of 445 patients who underwent a retroperitoneal spinal exposure; 5 RE cases were reported in 58 patients (8.6%) who underwent a transperitoneal approach. The difference in surgical approaches was significant (p = 0.007, Fisher exact test). There was no difference in the rate of RE based on the lumbar level exposed (p = 0.739). Multivariate analyses were consistent with the conclusions from Fisher exact tests. In the initial rhBMP-2 trial, after adjusting for effects of surgical approach and treated level, the difference in RE between the treatment groups (rhBMP-2 vs autograft or disc arthroplasty) was not significant (p = 0.177); however, the difference in RE between the retroperitoneal and transperitoneal approaches was significant (p = 0.029). CONCLUSIONS In these 5 prospective randomized trials involving anterior lumbar interbody surgery, the use of rhBMP-2 was associated with a higher incidence of RE (3.4% vs 1.7%) but did not reach statistical significance. Based on surgical approach, the difference in rates of RE was statistically significant. This study reports on the outcomes of 5 prospective randomized FDA-approved investigational device exemption trials. Registration for studies became law in 2007. Four of these trials were completed before the law went into effect. The registration number for the lumbar disc arthroplasty trial is NCT00635843.

Cervical disc arthroplasty with the Prestige LP disc versus anterior cervical discectomy and fusion, at 2 levels: results of a prospective, multicenter randomized controlled clinical trial at 24 months

OBJECTIVE The authors compared the efficacy and safety of arthroplasty using the Prestige LP cervical disc with those of anterior cervical discectomy and fusion (ACDF) for the treatment of degenerative disc disease (DDD) at 2 adjacent levels. METHODS Patients from 30 investigational sites were randomized to 1 of 2 groups: investigational patients (209) underwent arthroplasty using a Prestige LP artificial disc, and control patients (188) underwent ACDF with a cortical ring allograft and anterior cervical plate. Patients were evaluated preoperatively, intraoperatively, and at 1.5, 3, 6, 12, and 24 months postoperatively. Efficacy and safety outcomes were measured according to the Neck Disability Index (NDI), Numeric Rating Scales for neck and arm pain, 36-Item Short-Form Health Survey (SF-36), gait abnormality, disc height, range of motion (investigational) or fusion (control), adverse events (AEs), additional surgeries, and neurological status. Treatment was considered an overall success when all 4 of the following criteria were met: 1) NDI score improvement of ≥ 15 points over the preoperative score, 2) maintenance or improvement in neurological status compared with preoperatively, 3) no serious AE caused by the implant or by the implant and surgical procedure, and 4) no additional surgery (supplemental fixation, revision, or nonelective implant removal). Independent statisticians performed Bayesian statistical analyses. RESULTS The 24-month rates of overall success were 81.4% for the investigational group and 69.4% for the control group. The posterior mean for overall success in the investigational group exceeded that in the control group by 0.112 (95% highest posterior density interval = 0.023 to 0.201) with a posterior probability of 1 for noninferiority and 0.993 for superiority, demonstrating the superiority of the investigational group for overall success. Noninferiority of the investigational group was demonstrated for all individual components of overall success and individual effectiveness end points, except for the SF-36 Mental Component Summary. The investigational group was superior to the control group for NDI success. The proportion of patients experiencing any AE was 93.3% (195/209) in the investigational group and 92.0% (173/188) in the control group, which were not statistically different. The rate of patients who reported any serious AE (Grade 3 or 4) was significantly higher in the control group (90 [47.9%] of 188) than in the investigational group (72 [34.4%] of 209) with a posterior probability of superiority of 0.996. Radiographic success was achieved in 51.0% (100/196) of the investigational patients (maintenance of motion without evidence of bridging bone) and 82.1% (119/145) of the control patients (fusion). At 24 months, heterotopic ossification was identified in 27.8% (55/198) of the superior levels and 36.4% (72/198) of the inferior levels of investigational patients. CONCLUSIONS Arthroplasty with the Prestige LP cervical disc is as effective and safe as ACDF for the treatment of cervical DDD at 2 contiguous levels and is an alternative treatment for intractable radiculopathy or myelopathy at 2 adjacent levels. Clinical trial registration no.: NCT00637156 ( clinicaltrials.gov ).

Allogeneic mesenchymal precursor cells (MPCs) combined with an osteoconductive scaffold to promote lumbar interbody spine fusion in an ovine model

BACKGROUND Advances in immunomagnetic cell sorting have enabled isolation and purification of pleuripotent stem cells from marrow aspirates and have expanded stem cell therapies to include allogeneic sources. PURPOSE This study aimed to determine the safety and efficacy of allogeneic mesenchymal precursor cells (MPCs) combined with an osteoconductive scaffold in lumbar interbody spinal fusion using an ovine model. STUDY DESIGN Thirty-two skeletally mature ewes underwent a single-level interbody fusion procedure using a Polyetheretherketone fusion cage supplemented with either iliac crest autograft (AG) or an osteconductive scaffold (Mastergraft Matrix, Medtronic, Memphis, TN, USA) with 2.5×10(6) MPCs, 6.25×10(6) MPCs, or 12.5×10(6) MPCs. METHODS Plain radiographs and computed tomography scans were scored for bridging bone at multiple points during healing and at necropsy. The biomechanical competency of fusion was scored by manual palpation and quantified using functional radiographs at necropsy. Postnecropsy histopathology and histomorphometric analysis assessed the local response to MPC treatment and quantified the volume and connectivity of newly formed bridging bone. Safety was assessed by serum biochemistry, hematology, and organ histopathology. RESULTS Mesenchymal precursor cell treatment caused no adverse systemic or local tissue responses. All analyses indicated MPCs combined with an osteoconductive scaffold achieved similar or better fusion success as AG treatment after 16 weeks, and increasing the MPC dose did not enhance fusion. Manual palpation of the fusion site indicated more than 75% of MPC-treated and 65% of AG-treated animals achieved rigid fusion, which was corroborated with functional radiography. Computed tomography fusion scores indicated all animals in the MPC- and AG-treatment groups were fused at 16 weeks, yet X-ray scores indicated only 67% of the AG-treated animals were fused. Histomorphometry analyses showed equivalent outcomes for fusion connectivity and bony fusion area for MPC- and AG-treated groups. Approximately 6% residual graft material remained in the MPC-treated fusion sites at 16 weeks. CONCLUSIONS Adult allogeneic MPCs delivered using an osteoconductive scaffold were both safe and efficacious in this ovine spine interbody fusion model. These results support the use ofallogeneic MPCs as an alternative to AG for lumbar interbody spinal fusion procedures.

Clinical and Radiographic Outcomes in Patients Undergoing Single-level Anterior Cervical Arthrodesis: A Prospective Trial Comparing Allograft to a Reduced Dose of rhBMP-2.

Study Design: A prospective study with historical controls. Objectives: To evaluate and compare the safety and effectiveness of recombinant human bone morphogenetic protein-2 (rhBMP-2) with allograft for anterior cervical discectomy and fusion (ACDF) in patients with symptomatic single-level cervical degenerative disk disease. Summary of Background Data: rhBMP-2 is an osteoinductive protein that has been shown to induce fusion when used as an implant with a suitable carrier in spine surgery. However, some previous studies have shown rhBMP-2 use to be associated with a higher complication rate. Methods: Investigational patients (224) with single-level cervical degenerative disk disease underwent ACDF with rhBMP-2 at a dose of 0.6 or 1.05 mg and were compared with historical control patients (486) treated with allograft spacer and cervical plate. Results: At 24 months, improvement was significantly greater in the investigational group (37.1 points) than in the control group for Neck Disability Index (P=0.002) and arm pain (P=0.031). The overall neurological success rate was higher in the investigational group (P<0.001). Neck pain and general health status (SF-36 PCS and MCS) were similar. Fusion rate in the investigational group was higher than in the control group (99.4% vs. 87.2%, P=0.002). Cumulative adverse event rates at 24 months were similar; however, higher rates of dysphagia (P=0.001), local swelling (P=0.024), oropharyngeal pain (P=0.013), neck pain (P=0.019), and foraminal stenosis (P=0.002) were observed in the investigational group. Heterotopic ossification was also higher in the investigational group. Conclusions: At doses of 0.6 or 1.05 mg in a PEEK interbody cage, rhBMP-2 was effective in inducing fusion and improving Neck Disability Index and arm pain in single-level ACDF patients; however, higher rates of certain adverse events were observed in the investigational group. Level of Evidence: Level 2.