Impact of surgical risk factors for non-union on lumbar spinal fusion outcomes using cellular bone allograft at 24-months follow-up.

BACKGROUND: The current report investigates fusion rates and patient-reported outcomes following lumbar spinal surgery using cellular bone allograft (CBA) in patients with risk factors for non-union. METHODS: A prospective, open label study was conducted in subjects undergoing lumbar spinal fusion with CBA (NCT02969616) to assess fusion success rates and patient-reported outcomes in subjects with risk factors for non-union. Subjects were categorized into low-risk (≤ 1 risk factors) and high-risk (> 1 risk factors) groups. Radiographic fusion status was evaluated by an independent review of dynamic radiographs and CT scans. Patient-reported outcome measures included quality of life (EQ-5D), Oswestry Disability Index (ODI) and Visual Analog Scales (VAS) for back and leg pain. Adverse event reporting was conducted throughout 24-months of follow-up. RESULTS: A total of 274 subjects were enrolled: 140 subjects (51.1%) were categorized into the high-risk group (> 1 risk factor) and 134 subjects (48.9%) into the low-risk group (≤ 1 risk factors). The overall mean age at screening was 58.8 years (SD 12.5) with a higher distribution of females (63.1%) than males (36.9%). No statistical difference in fusion rates were observed between the low-risk (90.0%) and high-risk (93.9%) groups (p > 0.05). A statistically significant improvement in patient-reported outcomes (EQ-5D, ODI and VAS) was observed at all time points (p < 0.05) in both low and high-risk groups. The low-risk group showed enhanced improvement at multiple timepoints in EQ-5D, ODI, VAS-Back pain and VAS-Leg pain scores compared to the high-risk group (p < 0.05). The number of AEs were similar among risk groups. CONCLUSIONS: This study demonstrates high fusion rates following lumbar spinal surgery using CBA, regardless of associated risk factors. Patient reported outcomes and fusion rates were not adversely affected by risk factor profiles. TRIAL REGISTRATION: NCT02969616 (21/11/2016).

Twenty-four-month interim results from a prospective, single-arm clinical trial evaluating the performance and safety of cellular bone allograft in patients undergoing lumbar spinal fusion.

BACKGROUND: Autologous bone grafts are the gold standard for spinal fusion; however, harvesting autologous bone can result in donor site infection, hematomas, increased operative time, and prolonged pain. Cellular bone allografts (CBAs) are a viable alternative that avoids the need for bone harvesting and may increase fusion success alone or when used as an adjunct material. The present study examined the efficacy and safety of CBA when used as an adjunct graft material to lumbar arthrodesis. METHODS: A prospective, single-arm, multicenter clinical trial (NCT02969616) was conducted in adult subjects (> 18 years of age) undergoing lumbar spinal fusion with CBA graft (CBA used as primary (≥ 50% by volume), with augmentation up to 50%). Radiographic fusion status was assessed by an independent review of dynamic radiographs and CT scans. Clinical outcomes were assessed with the Oswestry Disability Index (ODI), and Visual Analog Scales (VAS) score for back and leg pain. Adverse events were assessed through the 24-month follow-up period. The presented data represents an analysis of available subjects (n = 86) who completed 24 months of postoperative follow-up at the time the data was locked for analysis. RESULTS: Postoperative 24-month fusion success was achieved in 95.3% of subjects (n = 82/86) undergoing lumbar spinal surgery. Clinical outcomes showed statistically significant improvements in ODI (46.3% improvement), VAS-Back pain (75.5% improvement), and VAS-Leg pain (85.5% improvement) (p < 0.01) scores at Month 24. No subject characteristics or surgical factors were associated with pseudoarthrosis. A favorable safety profile with a limited number of adverse events was observed. CONCLUSIONS: The use of CBA as an adjunct graft material showed high rates of successful lumbar arthrodesis and significant improvements in pain and disability scores. CBA provides an alternative to autograft with comparable fusion success rates and clinical benefits. TRIAL REGISTRATION: NCT02969616.

Twelve-Month Results from a Prospective Clinical Study Evaluating the Efficacy and Safety of Cellular Bone Allograft in Subjects Undergoing Lumbar Spinal Fusion.

BACKGROUND: While autologous bone grafts remain the gold standard for spinal fusion procedures, harvesting autologous bone is associated with significant complications, including donor site infection, hematomas, increased operative time, and prolonged pain. Cellular bone allograft (CBA) presents an alternative to autologous bone harvesting, with a favorable efficacy and safety profile. The current study further investigates CBA as an adjunct to lumbar spinal fusion procedures. METHODS: A prospective, multicenter, open-label clinical study was conducted in subjects undergoing lumbar spinal fusion with CBA (NCT02969616). Radiographic fusion status was assessed by an independent review of dynamic radiographs and CT scans. Clinical outcome measures included the Oswestry Disability Index (ODI) and visual analogue scale (VAS) for back and leg pain. Adverse-event reporting was conducted throughout 12 months of follow-up. Available subject data at 12 months were analyzed. RESULTS: A total of 274 subjects were enrolled into the study, with available data from 201 subjects (73.3%) who completed 12 months of postoperative radiographic and clinical evaluation at the time of analysis. Subjects had a mean age of 60.2 ± 11.5 years. A higher number of women (n = 124, 61.7%) than men (n = 77, 38.3%) were enrolled, with a collective mean BMI of 30.6 + 6.5 kg/m2 (range 18.0-51.4). At month 12, successful fusion was achieved in 90.5% of subjects. A significant (p < 0.001) improvement in ODI, VAS-back, and VAS-leg clinical outcomes was also observed compared to baseline scores. One adverse event related to CBA (postoperative radiculopathy) was reported, with surgical exploration demonstrating interbody extrusion of graft material. This subject reported successful fusion at month 12. CONCLUSIONS: CBA represents a viable substitute for harvesting of autograft alone with a high rate of successful fusion and significant improvements in subject-reported outcomes, such as pain and disability. Positive benefit was observed in subjects reporting single and multiple risk factors for pseudoarthrosis.

Prospective clinical and radiographic evaluation of an allogeneic bone matrix containing stem cells (Trinity Evolution® Viable Cellular Bone Matrix) in patients undergoing two-level anterior cervical discectomy and fusion.

BACKGROUND: Trinity Evolution® (TE), a viable cellular bone allograft, previously demonstrated high fusion rates and no safety-related concerns after single-level anterior cervical discectomy and fusion (ACDF) procedures. This prospective multicenter clinical study was performed to assess the radiographic and clinical outcomes of TE in subjects undergoing two-level ACDF procedures. METHODS: In a prospective, multicenter study, 40 subjects that presented with symptomatic cervical degeneration at two adjacent vertebral levels underwent instrumented ACDF using TE autograft substitute in a polyetherethereketone (PEEK) cage. At 12 months, radiographic fusion status was evaluated by dynamic motion plain radiographs and thin cut CT with multiplanar reconstruction by a panel that was blinded to clinical outcome. Fusion success was defined by angular motion (≤4°) and the presence of bridging bone across the adjacent vertebral endplates. Clinical pain and function assessments included the Neck Disability Index (NDI), neck and arm pain as evaluated by visual analog scales (VAS), and SF-36 at both 6 and 12 months. RESULTS: At both 6 and 12 months, all clinical outcome scores (SF-36, NDI, and VAS pain) improved significantly (p < 0.05) compared to baseline values. There were no adverse events or infections that were attributed to the graft material, no subjects that required revisions, and no significant decreases to mean neurological evaluations at any time as compared to baseline. At 12 months, the per subject and per level fusion rate was 89.4 and 93.4%, respectively. Subgroup analysis of subjects with risk factors for pseudoarthrosis (current or former smokers, diabetic, or obese/extremely obese) compared to those without risk factors demonstrated no significant differences in fusion rates. CONCLUSIONS: Patients undergoing two-level ACDF with TE in combination with a PEEK interbody spacer and supplemental anterior fixation had a high rate of fusion success without any serious adverse events related to the graft material. TRIAL REGISTRATION: Trinity Evolution in Anterior Cervical Disectomy and Fusion (ACDF) NCT00951938.

A prospective clinical and radiographic 12-month outcome study of patients undergoing single-level anterior cervical discectomy and fusion for symptomatic cervical degenerative disc disease utilizing a novel viable allogeneic, cancellous, bone matrix (trinity evolution™) with a comparison to historical controls.

PURPOSE: This multicenter clinical study was performed to assess the safety and effectiveness of Trinity Evolution(®) (TE), a viable cellular bone allograft, in combination with a PEEK interbody spacer and supplemental anterior fixation in patients undergoing anterior cervical discectomy and fusion (ACDF). METHODS: In a prospective, multi-center study, 31 patients that presented with symptomatic cervical degeneration at one vertebral level underwent ACDF with a PEEK interbody spacer (Orthofix, Inc., Lewisville, TX, USA) and supplemental anterior fixation. In addition all patients had the bone graft substitute, Trinity Evolution (Musculoskeletal Transplant Foundation, Edison, NJ, USA), placed within the interbody spacer. At 6 and 12 months, radiographic fusion was evaluated as determined by independent radiographic review of angular motion (≤4°) from flexion/extension X-rays combined with presence of bridging bone across the adjacent endplates on thin cut CT scans. In addition other metrics were measured including function as assessed by the Neck Disability Index (NDI), and neck and arm pain as assessed by individual Visual Analog Scales (VAS). RESULTS: The fusion rate for patients using a PEEK interbody spacer in combination with TE was 78.6 % at 6 months and 93.5 % at 12 months. When considering high risk factors, 6-month fusion rates for patients that were current or former smokers, diabetic, overweight or obese/extremely obese were 70 % (7/10), 100 % (1/1), 70 % (7/10), and 82 % (9/11), respectively. At 12 months, the fusion rates were 100 % (12/12), 100 % (2/2), 100 % (11/11) and 85 % (11/13), respectively. Neck function, and neck/arm pain were found to significantly improve at both time points. No serious allograft related adverse events occurred and none of the 31 patients had subsequent additional cervical surgeries. CONCLUSIONS: Patients undergoing single-level ACDF with TE in combination with a PEEK interbody spacer and supplemental anterior fixation had a high rate of fusion success without serious allograft-related adverse events.

Clinical experience using Cortoss for treating vertebral compression fractures with vertebroplasty and kyphoplasty: twenty four-month follow-up.

STUDY DESIGN: Forty patients were enrolled in 2 FDA-approved pilot Investigational Device Exemption (IDE) studies using Cortoss for the treatment of vertebral compression fractures (VCF). Twenty patients were treated at 3 centers, using vertebroplasty (VP) and 20 patients were treated at 5 centers, using kyphoplasty (KP). OBJECTIVE: To assess the feasibility and clinical outcomes using Cortoss to treat osteoporotic VCF. SUMMARY OF BACKGROUND DATA: Cortoss is an injectable bioactive, self-setting, radiopaque composite shown to stabilize and provide immediate weight bearing support to fractured vertebrae. Cortoss is approved for use in Europe for both screw and vertebral augmentation. METHODS.: Patient assessments were conducted before surgery and after surgery through 24 months using Visual Analog Scale (VAS), Oswestry Disability Index (ODI), and quality-of-life assessment (SF-12) questionnaires. Extravasations were evaluated using radiographs and CT scans. RESULTS: Immediate pain improvement was seen in VP patients with VAS scores decreasing from 75.7 before surgery to 35.9 at 72 hours. Continued improvement from baseline was seen out to 2 years (average VAS of 48.9). Disability improved with average ODI scores decreasing from 52.2% preoperative to 38.3% at 2 years for VP patients. Immediate pain improvement was also seen in KP patients with VAS scores decreasing from 78.1 before surgery to 42.7 at 72 hours. Continued improvement from baseline was seen out to 2 years (average VAS of 25.4). ODI scores improved from 60.5% preoperative to 34.5% at 2 years for KP patients. Average material volumes injected were 1.85 mL for VP and 4.13 mL for KP. Extravasations from both techniques were minor, anatomically close to the treated vertebrae and asymptomatic. No cardiac irregularities or pulmonary emboli were observed. CONCLUSION: These studies indicate Cortoss is safe and effective in treating osteoporotic VCF using vertebroplasty or kyphoplasty. Pain relief and restoration of function with Cortoss is comparable to results found in the literature for polymethylmethacrylate.

Results of the prospective, randomized, multicenter Food and Drug Administration investigational device exemption study of the ProDisc-L total disc replacement versus circumferential fusion for the treatment of 1-level degenerative disc disease.

STUDY DESIGN: A prospective, randomized, multicenter, Food and Drug Administration-regulated Investigational Device Exemption clinical trial. OBJECTIVE: To evaluate the safety and effectiveness of the ProDisc-L (Synthes Spine, West Chester, PA) lumbar total disc replacement compared to circumferential spinal fusion for the treatment of discogenic pain at 1 vertebral level between L3 and S1. SUMMARY OF BACKGROUND DATA: As part of the Investigational Device Exemption clinical trial, favorable single center results of lumbar total disc replacement with the ProDisc-L have been reported previously. METHODS: Two hundred eighty-six (286) patients were treated on protocol. Patients were evaluated before and after surgery, at 6 weeks, 3, 6, 12, 18, and 24 months. Evaluation at each visit included patient self-assessments, physical and neurologic examinations, and radiographic evaluation. RESULTS: Safety of ProDisc-L implantation was demonstrated with 0% major complications. At 24 months, 91.8% of investigational and 84.5% of control patients reported improvement in the Oswestry Low Back Pain Disability Questionnaire (Oswestry Disability Index [ODI]) from preoperative levels, and 77.2% of investigational and 64.8% of control patients met the > or =15% Oswestry Disability Index improvement criteria. Overall neurologic success in the investigational group was superior to the control group (91.2% investigational and 81.4% control; P = 0.0341). At 6 weeks and 3 months follow-up time points, the ProDisc-L patients recorded SF-36 Health Survey scores significantly higher than the control group (P = 0.018, P = 0.0036, respectively). The visual analog scale pain assessment showed statistically significant improvement from preoperative levels regardless of treatment (P < 0.0001). Visual analog scale patient satisfaction at 24 months showed a statistically significant difference favoring investigational patients over the control group (P = 0.015). Radiographic range of motion was maintained within a normal functional range in 93.7% of investigational patients and averaged 7.7 degrees. CONCLUSIONS: ProDisc-L has been found to be safe and efficacious. In properly chosen patients, ProDisc-L has been shown to be superior to circumferential fusion by multiple clinical criteria.

Use of an advanced formulation of beta-tricalcium phosphate as a bone extender in interbody lumbar fusion.

Despite numerous advances in the development of bone graft substitutes over the past 20 years, iliac crest autograft remains the gold standard for lumbar spinal fusion. However, donor site morbidity associated with the harvesting of iliac crest autograft remains problematic. Acute and chronic pain, prolonged operative time, bleeding, infection, deformity, and nerve and vascular injury still produce significant postoperative morbidity, even in the presence of careful surgical technique. Although allograft circumvents donor site morbidity, the growing number of spinal fusions performed in the United States and worldwide is creating a shortage of cadaver bone acceptable for use. Additionally, the extensive processing and storage of allograft is expensive. Synthetic materials, such as beta-tricalcium phosphate (beta-TCP), have been developed as alternatives to both autograft and allograft. A novel formulation of ultraporous beta-TCP (Vitoss, Orthovita, Malvern, Pa) offers interconnected microporosity, providing it with good wicking and hydrophilic properties. These properties allow the migration of nutrients, growth factors, and osteogenic cells into the ultraporous beta-TCP scaffold, thereby promoting new bone growth and concurrent scaffold resorption. This study presents a retrospective review of 7 patients who underwent anterior (ALIF) or posterior (PLIF) interbody fusion at 12 levels with a 3- to 6-month follow-up. At the patients' last radiographic examination, all 12 levels were solidly fused with interbody grafting material consisting only of allograft plus a combination of ultraporous beta-TCP and venous blood as an extender. Additionally, all 7 patients had segmental pedicle-screw fixation.