Spinal Fusion Rates Research Articles

Effects of systemically administered abaloparatide, an osteoanabolic PTHrP analog, as an adjuvant therapy for spinal fusion in rats.

BackgroundAbaloparatide is a parathyroid hormone receptor agonist that increases bone formation and reduces vertebral and nonvertebral fracture risk in women with postmenopausal osteoporosis. Animal studies indicate abaloparatide stimulates vertebral bone formation and enhances bony bridging and biomechanical stability of fracture calluses.AimsThe current study is evaluating the potential utility for abaloparatide as an adjunct therapy for spinal fusions.Material and MethodsThe effects of 14 or 28 days of daily subcutaneous injections of abaloparatide (20 μg/kg/d) or vehicle were evaluated in 32 male Sprague‐Dawley rats starting 1 day after noninstrumented posterolateral fusion (PLF) with bone autograft. Fusion mass microarchitecture was analyzed by micro‐computed tomography (micro‐CT) and serum markers of bone formation and bone resorption were evaluated. Motion segments were scored in a blinded manner as fused or unfused by postmortem radiography and manual palpation.ResultsAbaloparatide‐treated rats showed higher bone formation (serum osteocalcin) at day 14 and 28 compared with vehicle controls, without increases in the bone resorption marker serum TRACP‐5b. Micro‐CT showed greater trabecular number in fusion masses from the abaloparatide group vs vehicle controls at day 14. Manual palpation and radiography indicated no fusions in either group at day 14, whereas 25% of vehicle‐treated rats and 50% of abaloparatide‐treated rats had bilateral fusion at day 28.Discussion and ConclusionIn summary, this rat PLF model showed that abaloparatide treatment was associated with higher levels of the bone formation marker osteocalcin, improved fusion mass architecture, and a non‐ significant 2‐fold higher fusion rate compared with vehicle.

National utilization and inpatient safety measures of lumbar spinal fusion methods by race/ethnicity

Degenerative lumbar conditions are prevalent, disabling, and frequently managed with decompression and fusion. Black patients have lower spinal fusion rates than White patients. Determine whether specific lumbar fusion procedure utilization differs by race/ethnicity and whether length of stay (LOS) or inpatient complications differ by race/ethnicity after accounting for procedure performed. Large database retrospective cohort study PATIENT SAMPLE: Lumbar fusion recipients at least age 50 in the 2016 National Inpatient Sample with diagnoses of degenerative lumbar conditions. Type of fusion procedure used and inpatient safety measures including LOS, prolonged LOS, inpatient medical and surgical complications, mortality, and cost. We examined the association between race/ethnicity and the safety measures above. Covariates included several patient and hospital factors. We used multiple linear or logistic regression to determine the association between race and fusion type (PLF, P/TLIF, ALIF, PLF+P/TLIF, and PLF+ALIF [anterior-posterior fusion]) and to determine whether race was associated independently with inpatient safety measures, after adjustment for patient and hospital factors. Fusion method use did not differ among racial/ethnic groups, except for somewhat lower anterior-posterior fusion utilization in Black patients compared to White patients (crude odds ratio [OR]: 0.81 [0.67-0.97]). Inpatient safety measures differed by race/ethnicity for rates of prolonged LOS (Blacks 18.1%, Hispanics 14.5%, and Whites 11.7%), medical complications (Blacks 9.9%, Hispanics 8.7%, and Whites 7.7%), and surgical complications (Blacks 5.2%, Hispanics 6.9%, and Whites 5.4%). Differences persisted after adjustment for procedure type as well as patient and hospital factors. Blacks and Hispanics had higher risk for prolonged LOS compared to Whites (adjusted OR Blacks 1.39 [95% confidence interval {CI} 1.22-1.59]; Hispanics 1.24 [95% CI 1.02-1.52]). Blacks had higher risk for inpatient medical complications compared to Whites (adjusted OR 1.24 [95% CI 1.05-1.48]), and Hispanics had higher risk for inpatient surgical complications compared to Whites (adjusted OR 1.34 [95% CI 1.06-1.68]). Fusion method use was generally similar between racial/ethnic groups. Inpatient safety measures, adjusted for procedure type, patient and hospital factors, were worse for Blacks and Hispanics.

Role of Curcuminoids and Tricalcium Phosphate Ceramic in Rat Spinal Fusion.

Despite considerable research effort, there is a significant need for safe agents that stimulate bone formation. Treatment of large or complex bone defects remains a challenge. Implantation of small molecule-induced human bone marrow-derived mesenchymal stromal cells (hBMSCs) on an appropriate tricalcium phosphate (TCP) scaffold offers a robust system for noninvasive therapy for spinal fusion. To show the efficacy of this approach, we identified a small molecule curcuminoid that when combined with TCP ceramic in the presence of hBMSCs selectively induced growth of bone cells: after 8- or 25-day incubations, alkaline phosphatase was elevated. Treatment of hBMSCs with curcuminoid 1 and TCP ceramic increased osteogenic target gene expression (i.e., Runx2, BMP2, Osteopontin, and Osteocalcin) over time. In the presence of curcuminoid 1 and TCP ceramic, osteogenesis of hBMSCs, including proliferation, differentiation, and mineralization, was observed. No evidence of chondrogenic or adipogenic potential using this protocol was observed. Transplantation of curcuminoid 1-treated hBMSC/TCP mixtures into the spine of immunodeficient rats showed that it achieved spinal fusion and provided greater stability of the spinal column than untreated hBMSC-TCP implants or TCP alone implants. On the basis of histological analysis, greater bone formation was associated with curcuminoid 1-treated hBMSC implants manifested as contiguous growth plates with extensive hematopoietic territories. Stimulation of hBMSCs by administration of small molecule curcuminoid 1 in the presence of TCP ceramic afforded an effective noninvasive strategy that increased spinal fusion repair and provided greater stability of the spinal column after 8 weeks in immunodeficient rats. Impact statement Bone defects only slowly regenerate themselves in humans. Current procedures to restore spinal defects are not always effective. Some have side effects. In this article, a new method to produce bone growth within 8 weeks in rats is presented. In the presence of tricalcium phosphate ceramic, curcuminoid-1 small molecule-stimulated human bone marrow-derived mesenchymal stromal cells showed robust bone cell growth in vitro. Transplantation of this mixture into the spine showed efficient spinal fusion in rats. The approach presented herein provides an efficient biocompatible scaffold for delivery of a potentially clinically useful system that could be applicable in patients.

Preparation of Hydroxyapatite/Silk Fibroin Composite and Its Adoption in Posterolateral Spinal Fusion of Rats

Hydroxyapatite/silk fibroin (HAp/SF) composite was prepared and applied to the posterolateral spinal fusion model in rats to observe the effect of bone fusion. Method: Calcium chloride, diammonium phosphate, SF, and polyvinyl alcohol were used as raw materials, HAp/SF composites were prepared by chemical precipitation. The microstructure of the composite, crystal phase composition, and chemical structure were analyzed by the scanning electron microscope (SEM) and X-ray diffraction (XRD), and fourier transform infrared spectrometer (FTIR Spectrometer). Through the cultivation of osteoblasts MC3T3-E1 in vitro, the adhesion and proliferation (A&P) of cells on the face of materials were investigated. Thereby, the biocompatibility of the material was characterized. HAp/SF material was applied to the rat posterolateral spinal fusion model. The osteogenesis and spinal fusion were evaluated by the imaging observation, histological observation and manual palpation. The results showed that the rod-shaped HAp with uniform size and high purity was obtained, with a diameter of 20∼40 nm and a length of 200∼500 nm, similar to the apatite crystal in natural bone tissue (BT). In composite materials, a spatial network structure was formed by the interweaving of the SF fibers, and HAp was deposited on the face of the SF or in the middle of its network structure. In the obtained HAp/SF materials, the calcium ions of HAp and the carbonyl groups of SF were used to form thermally stable complexes through strong chemical bonds. Besides, SF was a template for the directional induction of HAp crystal growth, and the growth of HAp crystal along the C axis was regulated by SF. The growth direction was parallel to the long axis of SF fibers, and was consistent with the structure of apatite crystals deposited on the face of collagen fibers in natural BT. The results of cell culture in vitro showed that: after comparison with the control group (CG) with pure Hap, the adhesion ability of cells to HAp/SF material was significantly improved. The proliferation capacity of bone artificial bone (BAM) material and HAp/SF material was also significantly improved. The nuclear and skeletal staining results of MC3T3-E1 cells on the face of three groups of materials (HAp, BAM and HAp/SF) were combined, and the results also indicated that BAM and HAp/SF materials had good ability to promote cell A&P. The results of posterolateral spinal fusion in rats showed that HAp/SF materials group palpated the posterolateral spine for fusion. The formation of new BT on the posterolateral side of the spine was revealed by the Micro-computed tomography (Micro-CT) examination. In conclusion, HAp/SF composite had good osteoblastic compatibility and can achieve good spinal fusion effect.

Impact of sufficient contact between the autograft and endplate soon after surgery to prevent nonunion at 12 months following posterior lumbar interbody fusion.

Nonunion after posterior lumbar interbody fusion (PLIF) is associated with poor long-term outcomes in terms of health-related quality of life. Biomechanical factors in the fusion segment may influence spinal fusion rates. There are no reports on the relationship between intervertebral union and the absorption of autografts or vertebral endplates. Therefore, the purpose of this retrospective study was to evaluate the risk factors of nonunion after PLIF and identify preventive measures. The authors analyzed 138 patients who underwent 1-level PLIF between 2016 and 2018 (75 males, 63 females; mean age 67 years; minimum follow-up period 12 months). Lumbar CT images obtained soon after the surgery and at 6 and 12 months of follow-up were examined for the mean total occupancy rate of the autograft, presence of a translucent zone between the autograft and endplate (more than 50% of vertebral diameter), cage subsidence, and screw loosening. Complete intervertebral union was defined as the presence of both upper and lower complete fusion in the center cage regions on coronal and sagittal CT slices at 12 months postoperatively. Patients were classified into either union or nonunion groups. Complete union after PLIF was observed in 62 patients (45%), while nonunion was observed in 76 patients (55%). The mean total occupancy rate of the autograft immediately after the surgery was higher in the union group than in the nonunion group (59% vs 53%; p = 0.046). At 12 months postoperatively, the total occupancy rate of the autograft had decreased by 5.4% in the union group and by 11.9% in the nonunion group (p = 0.020). A translucent zone between the autograft and endplate immediately after the surgery was observed in 14 and 38 patients (23% and 50%) in the union and nonunion groups, respectively (p = 0.001). The nonunion group had a significantly higher proportion of cases with cage subsidence and screw loosening at 12 months postoperatively in comparison to the union group (p = 0.010 and p = 0.009, respectively). A lower occupancy rate of the autograft and the presence of a translucent zone between the autograft and endplate immediately after the surgery were associated with nonunion at 12 months after PLIF. It may be important to achieve sufficient contact between the autograft and endplate intraoperatively for osseous union enhancement and to avoid excessive absorption of the autograft. The achievement of complete intervertebral union may decrease the incidence of cage subsidence or screw loosening.

Assessment of the efficacy of teriparatide treatment for osteoporosis on lumbar fusion surgery outcomes: a systematic review and meta-analysis

Treatment of osteoporosis with medications like teriparatide, a parathyroid hormone, is known to improve bone density and reduce the risk of osteoporotic vertebral fractures. Anecdotal and limited surgical series have described the utility of this treatment for osteoporotic patients prior to spinal fusion surgery, but there is variability in adoption of this strategy as well as consensus regarding optimal treatment duration before and after surgery. In this study, the clinical results of the use of teriparatide for this application are reviewed and critically examined. We conducted a systematic review of electronic databases using different MeSH terms from 1980 to 2020. Pooled and subgroup analyses were performed using fixed and random effect models based upon the heterogeneity (I2). The results were reported as either mean difference (MD) or odds ratio (OR) with 95% confidence interval (CI). A total of 771 patients from 12 studies were identified. Three hundred seventy-seven patients (90.8% females) were treated with teriparatide. Lumbar spinal fusion rates were significantly higher among patients who received teriparatide compared to the non-teriparatide group (OR 2.15, 95%CI 1.56-2.97, p < 0.00001). Subgroup analysis revealed that patients receiving teriparatide demonstrated 2.12-fold and 2.23-fold higher likelihood of fusion compared to those in the bisphosphonate (OR 2.12, 95%CI 1.45-3.11, p = 0.0001) and placebo (OR 2.23, 95%CI 1.22-4.08, p = 0.009) cohorts, respectively. The treatment effect of teriparatide was associated with significantly reduced subsequent vertebral fractures (OR 0.16, 95%CI 0.06-0.41, p = 0.0002), sagittal malalignment (MD - 3.85, 95%CI: -6.49 to - 1.21, p = 0.004), limb visual analogue score (VAS) (MD - 0.36, 95%CI - 0.64 to - 0.09, p = 0.008), and spinal VAS (MD - 0.24, 95%CI - 0.44 to - 0.04, p = 0.02) compared to the non-teriparatide group. Patients using teriparatide had 30% less likelihood of screw loosening at last follow-up compared to the non-teriparatide group; however, this was not statistically significant (OR 0.70, 95%CI 0.43-1.14, p = 0.15). There did not exist any statistically significant difference between the two comparative groups in terms of pseudoarthrosis (OR 0.54, 95%CI 0.24-1.21, p = 0.13), cage subsidence (OR 1.30, 95%CI 0.38-4.52, p = 0.68), and bone mineral density (MD 0.04, 95%CI - 0.19-0.29, p = 0.74) at last follow-up examination. This meta-analysis corroborates the effectiveness of teriparatide resulting in higher fusion rates. Further study is required to determine the optimal duration of treatment and timing of surgery.

Randomized clinical trial: expanded autologous bone marrow mesenchymal cells combined with allogeneic bone tissue, compared with autologous iliac crest graft in lumbar fusion surgery

BACKGROUND CONTEXTAlthough autogenous iliac crest bone graft (AICBG) is considered the gold-standard graft material for spinal fusion, new bone substitutes are being developed to avoid associated complications and disadvantages. By combining autologous bone marrow mesenchymal stromal cells (MSCs) expanded ex vivo and allogenic cancellous bone graft, we obtain a tissue-engineered product that is osteoconductive and potentially more osteogenic and osteoinductive than AICBG, owing to the higher concentration of MSCs. PURPOSEThis study aimed to evaluate the feasibility and safety of implanting a tissue-engineered product consisting of expanded bone marrow MSCs loaded onto allograft bone (MSC+allograft) for spinal fusion in degenerative spine disease, as well as to assess its clinical and radiological efficacy. STUDY DESIGN/SETTINGA prospective, multicenter, open-label, blinded-reader, randomized, parallel, single-dose phase I-II clinical trial. PATIENT SAMPLEA total of 73 adult patients from 5 hospitals, with Meyerding grade I-II L4–L5 degenerative spondylolisthesis and/or with L4–L5 degenerative disc disease who underwent spinal fusion through transforaminal lumbar interbody fusion (TLIF). OUTCOME MEASURESSpinal fusion was assessed by plain X-ray at 3, 6, and 12 months and by computed tomography (CT) at 6 and 12 months post-treatment. An independent radiologist performed blinded assessments of all images. Clinical outcomes were measured as change from baseline value: visual analog scale for lumbar and sciatic pain at 12 days, 3, 6, and 12 months posttreatment, and Oswestry Disability Index and Short Form-36 at 3, 6, and 12 months posttreatment. METHODSPatients who underwent L4–L5 TLIF were randomized for posterior graft type only, and received either MSC+allograft (the tissue-engineered product, group A) or AICBG (standard graft material, group B). Standard graft material was used for anterior fusion in all patients. Feasibility was measured primarily as the percentage of randomized patients who underwent surgery in each treatment group. Safety was assessed by analyzing treatment-emergent adverse events (AEs) for the full experimental phase and appraising their relationship to the experimental treatment. Outcome measures, both radiological and clinical, were compared between the groups. RESULTSSeventy-three patients were randomized in this study, 36 from the MSC+allograft group and 37 from the AICBG group, and 65 were surgically treated (31 group A, 34 group B). Demographic and comorbidity data showed no difference between groups. Most patients were diagnosed with grade I or II degenerative spondylolisthesis. MSC+allograft was successfully implanted in 86.1% of randomized group A patients. Most patients suffered treatment-emergent AEs during the study (88.2% in group A and 97.1% in group B), none related to the experimental treatment. X-ray-based rates of posterior spinal fusion were significantly higher for the experimental group at 6 months (p=.012) and 12 months (p=.0003). CT-based posterior fusion rates were significantly higher for MSC+allograft at 6 months (92.3% vs 45.7%; p=.0001) and higher, but not significantly, at 12 months (76.5% vs 65.7%; p=.073). CT-based complete response (defined as the presence of both posterior intertransverse fusion and anterior interbody fusion) was significantly higher at 6 months for MSC+allograft than for AICBG (70.6% vs 40%; p=.0038), and remained so at 12 months (70.6% vs 51.4%; p=.023). Clinical results including patient-reported outcomes improved postsurgery, although there were no differences between groups. CONCLUSIONSCompared with the current gold standard, our experimental treatment achieved a higher rate of posterior spinal fusion and radiographic complete response to treatment at 6 and 12 months after surgery. The treatment clearly improved patient quality of life and decreased pain and disability at rates similar to those for the control arm. The safety profile of the tissue-engineered product was also similar to that for the standard material, and no AEs were linked to the product. Procedural AEs did not increase as a result of BM aspiration. The use of expanded bone marrow MSCs combined with cancellous allograft is a feasible and effective technique for spinal fusion, with no product-related AEs found in our study.

The temporal and spatial expression of sclerostin and Wnt signaling factors during the maturation of posterolateral lumbar spine fusions.

The bone healing environment in the posterolateral spine following arthrodesis surgery is one of the most challenging in all of orthopedics and our understanding of the molecular signaling pathways mediating osteogenesis during spinal fusion is limited. In this study, the spatial and temporal expression pattern of Wnt signaling factors and inhibitors during spinal fusion was assessed for the first time. Bilateral posterolateral spine arthrodesis with autologous iliac crest bone graft was performed on 21 New Zealand White rabbits. At 1‐, 2‐, 3‐, 4‐, and 6‐weeks, the expression of sclerostin and a variety of canonical and noncanonical Wnts signaling factors was measured by qRT‐PCR from tissue separately collected from the transverse processes, the Outer and Inner Zones of the fusion mass, and the adjancent paraspinal muscle. Immunohistochemistry for sclerostin protein was also performed. Sclerostin and many Wnt factors, especially Wnt3a and Wnt5a, were found to have distinct spatial and temporal expression patterns. For example, harvesting ICBG caused a significant increase in sclerostin expression. Furthermore, the paraspinal muscle immediately adjacent to the transplanted ICBG also had significant increases in sclerostin expression at 3 weeks, suggesting new potential mechanisms for pseudarthroses following spinal arthrodesis. The presented work is the first description of the spatial and temporal expression of sclerostin and Wnt signaling factors in the developing spine fusion, filling an important knowledge gap in the basic biology of spinal fusion and potentially aiding in the development of novel biologics to increase spinal fusion rates.

The Effects of Marijuana Use on Lumbar Spinal Fusion.

A retrospective cohort study. The purpose of this study was to evaluate marijuana usage and its effect on outcomes following transforaminal lumbar interbody fusion (TLIF). As marijuana becomes legalized throughout the United States, its medicinal and recreational usage is becoming more mainstream. Clinicians currently have little guidance regarding both short-term and long-term effects of marijuana usage on surgical interventions. While the rate of lumbar spinal fusion in the United States continues to grow, the effect of marijuana usage on fusion remains uncertain. One hundred two patients who underwent TLIF performed by the same surgeon were followed for 12 months. Patients were self-reported for marijuana usage (n = 36). Patient reported outcome measures included preoperative Oswestry disability index (ODI), 6-month ODI, and 12-month ODI, as well as length of stay (LOS), complications, return to operating room (OR), revision surgery, and confirmed fusion. Continuous variables were compared using the independent two-sample t test or analysis of variance (ANOVA), whereas categorical variables were analyzed using the chi-square or Fischer exact tests. Adjusted analysis was performed using a multivariate logistic regression model. Marijuana usage was associated with a younger population (P < 0.001), but showed no difference regarding sex or body mass index compared with the non-usage group. There was no statistically significant difference in complications, return to OR, or revision surgery between groups. When controlling for factors such as age and preoperative ODI, multivariate analysis demonstrated that marijuana usage did not limit postoperative ODI reduction. The marijuana usage group demonstrated shorter LOS (2.42 vs. 3.00 d, P = 0.020). Fusion rates at 12 months were similar between groups (96% vs. 92.3%, P = 0.678). ODI was similar between groups at all time points. Perioperative outcomes were similar in patients who underwent TLIF regardless of marijuana usage. 3.

A Comparative Evaluation of Commercially Available Cell-Based Allografts in a Rat Spinal Fusion Model.

To evaluate the comparative abilities of commercially available, viable, cellular bone allografts to promote posterolateral spinal fusion. Human allografts containing live cells were implanted in the athymic rat model of posterolateral spine fusion. Three commercially available allogeneic cellular bone matrices (Trinity Evolution, Trinity ELITE and Osteocel Plus) were compared with syngeneic iliac crest bone as the control. All spines underwent radiographs, manual palpation, and micro-computed tomography (CT) analysis after excision at 6 weeks. Histological sections of randomly selected spines were subjected to semiquantitative histopathological scoring for bone formation. By manual palpation, posterolateral fusion was detected in 40% (6/15) of spines implanted with syngeneic bone, whereas spines implanted with Trinity Evolution and Trinity ELITE allografts yielded 71% (10/14) and 77% (10/13) fusion, respectively. Only 7% (1/14) of spines implanted with Osteocel Plus allografts were judged fused by manual palpation (statistically significantly less than ELITE, P < .0007, and Evolution, P < .0013). The mineralized cancellous bone component of the allografts confounded radiographic analysis, but Trinity Evolution (0.452 ± 0.064) and Trinity ELITE (0.536 ± 0.109) allografts produced statistically significantly higher bone fusion mass volumes measured by quantitative micro-CT than did syngeneic bone (0.292 ± 0.109, P < .0001 for ELITE and P < .003 for Evolution) and Osteocel Plus (0.258 ± 0.103, P < .0001). Semiquantitative histopathological scores supported these findings because the total bone and bone marrow scores reflected significantly better new bone and marrow formation in the Trinity groups than in the Osteocel Plus group. The Trinity Evolution and Trinity ELITE cellular bone allografts were more effective at creating posterolateral fusion than either the Osteocel Plus allografts or syngeneic bone in this animal model. The superior fusion rate of Trinity cellular bone allografts may lead to better clinical outcome of spinal fusion surgeries.

Postoperative Low Back Pain after Posterior Lumbar Interbody Fusion Surgery Using Cortical Bone Trajectory Screws.

Study DesignRetrospective analysis of a case series of prospectively collected data. PurposeTo compare clinical and radiological outcomes between two posterior lumbar interbody fusion techniques: cortical bone trajectory (CBT) and traditional pedicle screw (PS).Overview of LiteratureBiomechanical studies have revealed the benefits of the CBT technique. However, clinical evidence obtained from the direct comparison of outcomes between CBT and PS is limited.MethodsWe retrospectively investigated 104 patients who had undergone posterior lumbar interbody fusion using CBT or PS. Clinical symptoms were evaluated and compared between CBT and PS using the Japanese Orthopedic Association Back Pain Evaluation Questionnaire (JOABPEQ) and Visual Analog Scale (VAS) before and 1 year after surgery. Spinal fusion status was assessed by multiplanar reconstruction computed tomography at 1 year after surgery.ResultsThe CBT and PS techniques were performed on 36 and 68 patients, respectively. Both CBT- and PS-treated patients exhibited improvement in each subdomain of the JOABPEQ and in the VAS. With regard to postoperative improvement of low back pain, the treatment effect, as assessed by the JOABPEQ, was greater for PS than for CBT. The spinal fusion rate was slightly lower for CBT than for PS, although the difference between them was not significant. The effect of treatment on postoperative low back pain was smaller for CBT than for PS, regardless of whether rigid spinal fusion was achieved.Conclusions Clinical symptoms and spinal fusion efficiency were not significantly different between CBT and PS except for postoperative improvement in low back pain. The treatment effect on postoperative low back pain was smaller for CBT than for PS.

Efficacy of Electrical Stimulation for Spinal Fusion: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Spinal fusion is one of the most common procedures performed in spine surgery. As rates of spinal fusion continue to increase, rates of complications such as nonunions continue to increase as well. Current evidence supporting the use of electrical stimulation to promote fusion is inconclusive. This review aimed to determine if postoperative electrical stimulation is more efficacious than no stimulation or placebo in promoting radiographic fusion in patients undergoing spinal fusion. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, CINAHL and MEDLINE from date of inception to current. Ongoing clinical trials were also identified and reference lists of included studies were manually searched for relevant articles. Two reviewers independently screened studies, extracted data, and assessed risk of bias. Data were pooled using the Mantel-Haenszel method. Trialists were contacted for any missing or incomplete data. Of 1184 articles screened, 7 studies were eligible for final inclusion (n = 941). A total of 487 patients received postoperative electrical stimulation and 454 patients received control or sham stimulation. All evidence was of moderate quality. Electrical stimulation (pulsed electromagnetic fields, direct current, and capacitive coupling) increased the odds of a successful fusion by 2.5-fold relative to control (OR = 2.53, 95% CI 1.86 to 3.43, p < 0.00001). A test for subgroup interaction by stimulation type, smoking status, and number of levels fused was not significant (p = 0.93, p = 0.82 and p = 0.65, respectively). This systematic review and meta-analysis found moderate-quality evidence supporting the use of postoperative electrical stimulation as an adjunct to spinal fusion surgery. Patients treated with electrical stimulation have significantly greater rates of successful fusion. The level of evidence for this study is therapeutic level I.

The effect of insulin dependent diabetes on bone metabolism and growth after spinal fusion

STUDY DESIGNExperimental animal model. OBJECTIVEThe purpose of this study was to evaluate the hypothesis that insulin dependent diabetes mellitus (IDDM) will inhibit the formation of a solid bony union after spinal fusion surgery via an alteration of the microenvironment at the fusion site in a rat model. SUMMARY OF BACKGROUND DATAPrevious studies report diabetes mellitus (DM) and specifically IDDM as a risk factor for complications and poor surgical outcomes following spinal fusion. METHODSTwenty control and 22 diabetic rats were obtained at 5 weeks of age. At 20 weeks of age, all animals underwent posterolateral lumbar fusion surgery using a tailbone autograft with diabetic rats receiving an implantable time release insulin pellet. A subset of rats was sacrificed 1-week postsurgery for growth factor (PDGF, IGF-I, TGF-β, and VEGF) and proinflammatory cytokine ELISA analysis. All other rats were sacrificed 3-months postsurgery for fusion evaluation via manual palpation and micro CT. Glycated hemoglobin (HbA1c) was measured at surgery and sacrifice on all animals. RESULTSCompared with healthy rats undergoing spinal fusion, rats with IDDM demonstrated a significant reduction in manual palpation fusion rates (16.7% vs. 43%, p<.05). Average bone mineral density, bone volume, and bone volume fraction were also significantly reduced and negatively correlated to blood glucose levels. IL-1B, IL-5, IL-10, TNF-α, and KC/GRO were significantly elevated in fusion beds of IDDM rats. CONCLUSIONSThis study demonstrates that rats with IDDM demonstrate a reduced rate and quality of spinal fusion with increased local levels of inflammatory cytokines. Targeted modalities are required to improve bone healing in this growing, high-risk population. CLINICAL SIGNIFICANCEThis is the first translational animal model of IDDM to evaluate the rate and quality of spinal fusion while controlling for other surgical and patient-related risk factors. Our findings demonstrate the complex nature by which IDDM impairs bone healing and highlight the need for additional basic science research to further elucidate this mechanism in order to develop more effective therapeutic interventions.

Low-intensity pulsed ultrasound promotes spinal fusion by regulating macrophage polarization

BackgroundSpinal fusion is considered the gold standard procedure for treating spinal degeneration, tumors, and trauma. An inflammatory response is an important part of bone repair. We investigated the polarization change of inflammatory macrophages (M1) and resident macrophages (M2) during low-intensity pulsed ultrasound (LIPUS) treatment. MethodsThirty male Sprague Dawley rats (age: 12 weeks; weight: 300 g) were used in the study. A rat spinal fusion model was established by surgical procedures. LIPUS treatment (20 min. d, 5 d/wk) was begun 3 days after surgery. The rats were randomly divided into a control group (5 subgroups, 3 rats in each subgroup) and LIPUS group (5 subgroups, 3 rats in each subgroup), and sacrificed on day 3, 5, 7, 10, and 14 after spinal fusion surgery for further evaluation. Bone volume was measured by micro-CT, fusion region was examined by histological analyses, types of macrophages in the fusion area were examined by immunohistochemical staining. Raw264.7 cells and bone marrow-derived macrophages (BMDM) were used in cell experiments. Cells were divided into a control group and LIPUS group. Flow cytometry was used to examine the rate of resident macrophages, and real-time PCR was used to examine the mRNA expression of anti-inflammation genes. ResultsLIPUS promoted spinal fusion and stimulated the transition of F4-80+/Mac-2+ (M1) to F4-80+/Mac-2− (M2), leading to the early appearance of resident macrophages. Cell experiments showed CD206+ macrophages (M2) were significantly increased after LIPUS treatment. M2-related genes and anti-inflammation factors (Arg-1, PPAR-γ, and IL-4) were increased after LIPUS treatment. ConclusionThe earlier transition from inflammatory to resident macrophage might be one reason for the positive effect of LIPUS on spinal fusion.

Percutaneous facet joints arthrodesis technology in surgical treatment of degenerative diseases of lumbar spine

Background. Minimally invasive technology of fusion broadly introduced in clinical practice represent one of modern trends in spinal surgery on the other hand those technical solutions lack to provide posterior fusion. As a consequence, patients treated with minimally invasive techniques are vulnerable in terms of pseudarthrosis and implant instability therefore measures focused on those complications’ prevention are still actual.The study objective is to evaluate efficacy and safety of suggested percutaneous facet joints arthrodesis technique as an auxiliary option to interbody fusion.Materials and methods. This is a prospective non-randomized study of 80 patients with degenerative diseases of the lumbar spine who were treated applying minimally invasive transforaminal lumbar interbody fusion, lateral lumbar interbody fusion and anterior lumbar interbody fusion. In 20 cases out of those enrolled interbody fusion was supplemented with percutaneous posterior facet joints arthrodesis. Computed tomography was administered at the period of 6 and 12 months after surgery to assess anterior and posterior fusion. The minimal follow-up period accounted for 12 months.Results. The suggested percutaneous facet joints arthrodesis fifty-fold increased the probability of posterior fusion formation compared to the rate of spontaneous spinal fusion (p &lt;0.0001, logistic regression was applied). In three cases posterior fusion formed prior to interbody fusion providing stability of segment operated on. No adverse events and no complications associated with percutaneous arthrodesis were detected.Conclusion. The suggested percutaneous facet joints arthrodesis is safe and effective minimally invasive technique that facilitates additional posterior spinal fusion formation in a short-term period herewith decreasing symptomatic pseudarthrosis development in patients operated on using minimally invasive spinal fixation and fusion.

P9. Dimethyloxaloylglycine (DMOG) preconditioning of adipose-derived mesenchymal stem cells as strategy for enhancing posterolateral lumbar fusion in a rat model

BACKGROUND CONTEXT Transplantation of adipose-derived mesenchymal stem cells (ADSCs) has become a promising approach for bone regeneration therapies, particularly in elderly patients. However, poor cell survival in vivo after implantation due to the ischemic tissue environment has been one of the major limitations of the effectiveness of this strategy. Hypoxia Inducible Factor-1α (HIF-1α) plays an important role in angiogenic-osteogenic coupling during bone regeneration, as it is a critical mediator of the adaptive cell response to hypoxia. DMOG treatment has been demonstrated to stabilize cellular expression of HIF-1α in cells, as well as enhance osteogenic and angiogenic capacity of MSCs. By therapeutically targeting both osteogenesis and vascularization via DMOG preconditioned MSCs, this tissue-engineering approach sought to yield superior bone quality and integration, thereby increasing rates of spinal fusion. PURPOSE We aimed to demonstrate that preconditioning adipose (ADSC)-derived (AD) MSCs with DMOG prior to implantation will prolong survival in vivo and improve spinal fusion outcomes in a rat model. STUDY DESIGN/SETTING In vivo study via a rat posterolateral spinal fusion model. PATIENT SAMPLE Syngeneic 6-8 week old Lewis rats. OUTCOME MEASURES Manual palpation scoring was performed by blinded researchers as follows: 0 = non-fused; 1 = partial fusion, some motion across operative joint; and, 2 = fused, no motion across the operated joint. MicroCT images were used to assess fusion mass volume (mm^3) via ImageJ software and determine CT fusion score (0 = non-fused; 1 = unilateral fusion; 2 = bilateral fusion). METHODS ADSCs were isolated from the inguinal fat pads of syngeneic 6-8 week old Lewis rats and cultured in vitro. When passage 1 (P1) ADSCs reached approximately 80% confluency they were pre-conditioned for 24 hours with 1 ng of DMOG (Fisher Scientific). After pre-conditioning, 2 × 10^6 ADSCs were seeded onto Vitoss (Stryker) bone graft substitute scaffolds for subsequent transplantation. Posterolateral spinal fusion surgery at L4-L5 was performed on 18 female Lewis rats divided into 2 experimental groups: [1] Vitoss+ADSCs pre-conditioned with DMOG; and, [2] Vitoss+non pre-conditioned ADSCs. Fusion was evaluated eight weeks post-surgery. Manual palpation scoring evaluated the motion across the operated joint, and MicroCT images were assessed for fusion mass volume and CT fusion. RESULTS Preliminary microCT imaging data suggest that DMOG pre-conditioned ADSCs (n=12) yielded significantly higher fusion mass volumes than non-preconditioned ADSCs (n=6) (23.49 mm^3 vs. 15.39 mm^3, respectively, p=.001). DMOG pre-conditioned ADSCs showed a trend towards higher rates of fusion and manual palpation scores compared to non-conditioned ADSCs (1.16 vs. 0.50, respectively, p=.06; and 1.25 vs. 0.66, respectively, p>.05). CONCLUSIONS In our rat posterolateral fusion model, DMOG pre-conditioned ADSCs displayed an increased fusion mass volume, CT fusion rates, and manual palpation score compared to non-conditioned ADSCs. Ongoing histological studies will evaluate whether there are any differences in the quality of bone formed within the fusion masses. Future studies will also compare whether these results are also similar in bone marrow-derived MSCs. FDA DEVICE/DRUG STATUS Dimethyloxaloylglycine (Investigational/Not approved)

105. Sex-based differential response in rhBMP-2-mediated spinal fusion in vivo

BACKGROUND CONTEXT Sex-based differences in clinical outcomes for spinal fusion have been investigated with conflicting results. Estrogen is well known to have a major influence on bone and interacts with the recombinant human bone morphogenetic protein-2 (rhBMP-2) pathway, yet literature investigating the potential but unsubstantiated sex-dependent differential response to rhBMP-2 spine fusion is scarce. Clarifying whethera sex-based differential bone regenerative response could improve and personalize patient care in the setting of spine and other orthopedic procedures requiring bone healing. Herein, we investigated whether there is a sex-dependent bone regenerative response to rhBMP-2 in a rat spinal fusion model. PURPOSE The purpose of this study was to assess and validate the presence and extent of the sex differences in bone response to rhBMP-2 in vivo. STUDY DESIGN/SETTING Pre-clinical. PATIENT SAMPLE Male and female Sprague-Dawley rats, ages 12-16 weeks. OUTCOME MEASURES Radiography, fusion scoring, microCT. METHODS Twenty-eight Sprague-Dawley male and female rats underwent L4-L5 posterolateral fusion with bilateral placement of an absorbable collagen sponge loaded with 10 μg of rhBMP-2/animal (INFUSE™; 5 μg/implant; N=14/group). Bone regenerative response and fusion were assessed eight weeks postoperatively via radiography and blinded manual palpation, where each specimen was assigned a score of 0 (unfused, no bridging bone), 1 (unilaterally fused, L4-L5 bridging), or 2 (bilaterally fused). MicroCT imaging (N=3/group) was used for microarchitectural analysis to evaluate new bone, the bone volume fraction, and trabecular thickness. RESULTS As expected at this dose, radiography and manual palpation showed 100% fusion rates for both sexes. Fusion scores, though, were significantly different with females having a lower fusion score (female: 1.26±0.31 vs males: 1.55±0.33, *p=0.001). Radiography showed noticeably smaller fusion mass volumes in females vs males, but the fusion mass was found to be less compressible on manual palpation in females relative to males. MicroCT evaluation showed significant differences in females vs males, with females having significantly lower new bone volumes (female: 26.591±3.871 mm3 vs male: 37.595±11.174 mm3, *p=0.046), but a significantly higher bone volume fraction (female: 0.266±0.116 vs male: 0.126±0.064, *p=0.028) and significantly greater trabecular thickness (female: 0.198±0.016 mm vs male: 0.178±0.014 mm, *p=0.041). CONCLUSIONS This study shows that there may indeed be a sex-based difference in bone regeneration induced by rhBMP-2. We showed that female rats have higher quality, but less volume of new bone formation compared to males. Future work will evaluate the extent of this distinction, especially at sub-therapeutic doses of the growth factor, and will investigate the interplay between the BMP-2 pathway and sex hormones in bone regenerative outcomes. FDA DEVICE/DRUG STATUS Unavailable from authors at time of publication.

Transforaminal lumbar interbody fusion (TLIF) versus posterior lumbar interbody fusion (PLIF) in the treatment of single-level lumbar spondylolisthesis

BackgroundVarious surgical procedures have been recommended for the treatment of lumbar spondylolisthesis, but controversy still exists regarding the optimal surgical technique. In this study, we compared the clinical and radiologic outcomes of posterior lumbar interbody fusion (PLIF) and transforaminal lumbar interbody fusion (TLIF) with pedicle screw fixation in the treatment of single-level lumbar spondylolisthesis.MethodsNinety-four patients underwent lumbar interbody fusion with pedicle screw fixation for the treatment of adult lumbar spondylolisthesis. Forty-six had PLIF with two cages and pedicle fixation (group 1), and 48 had TLIF with one cage and pedicle fixation (group 2). The follow-up was performed clinically using the visual analog scale (VAS) and Oswestry Disability Index (ODI) Questionnaires. Outcome scores were assessed 3, 6, and 12 months after surgery. Radiographs were obtained postoperatively and at regular intervals for 6 months. Perioperative outcomes such as surgery time, blood loss, length of hospital stay, and incidence of surgical complications were also recorded.ResultsEstimated blood loss and operative time in the TLIF group were significantly lower than those in the PLIF group. VAS for back pain and ODI were significantly better in the TLIF group than the PLIF group. However, at the time of the last follow-up, both groups had similar slip reduction and spinal fusion rates. More complication rate was encountered in the PLIF group compared to the TLIF group.ConclusionsOur study showed that TLIF is superior to PLIF with respect to functional outcome and complication rate in grade I/II single-level lumbar spondylolisthesis.

Locally Applied Simvastatin as an Adjunct to Promote Spinal Fusion in Rats.

Basic Science. To determine if locally delivered simvastatin can enhance bone formation in a rat spinal fusion model. The bone-anabolic properties of statins in fracture healing are well established, however, few studies have evaluated the impact of locally delivered statins in spinal fusion. We formulated poly(lactic-co-glycolic acid) (PLGA) nanoparticles by adapting previously published techniques. Two types of nanoparticles were created: simvastatin nanoparticles (SimNP) and nanoparticles without simvastatin (BlankNP). Drug elution from SimNP was characterized. Osteoblastic differentiation was analyzed using MC3T3-E1 cells cultured in differentiation medium containing SimNP or BlankNP. Forty male 12 week old outbred Wistar rats underwent uninstrumented posterolateral fusion using iliac crest bone graft and BlankNP, SimNP or simvastatin drug. X-rays to assess bone formation were obtained at 4 weeks and 9 weeks post-operatively. Spines were explanted at 9 weeks for micro-CT analysis, and a blinded manual assessment of fusion (MAF). SimNP achieved a release efficiency of 74.1% with ∼50% release occurring in the first day. Simvastatin and SimNP treated cells showed significantly greater expression of osteopontin (OPN) and osteocalcin (OCN). On micro-CT analysis, SimNP animals had higher bone volume and percent bone volume (bone volume/total volume) than control animals. SimNP rats had higher X-ray scores at 4 weeks (p=0.010) and 9 weeks (p<0.001) relative to BlankNP. MAF showed that SimNP had a higher fusion rate than BlankNP (42.9% vs. 0%, p=0.006). We were able to validate that sustained release of simvastatin via a PLGA nanoparticle. SimNP was able to induce an increase in mineralization as well as an increase in markers of bone formation. X-ray analysis, micro-CT quantification, and MAF assessment of SimNP treated rats showed significantly greater bone formation and fusion mass strength relative to vehicle treated animals. Simvastatin may be a safe, cost-effective bone anabolic agent for use in spinal fusion. N/A.

Intervertebral Disc Nucleus Repair: Hype or Hope?

Chronic back pain is a common disability, which is often accredited to intervertebral disc degeneration. Gold standard interventions such as spinal fusion, which are mainly designed to mechanically seal the defect, frequently fail to restore the native biomechanics. Moreover, artificial implants have limited success as a repair strategy, as they do not alter the underlying disease and fail to promote tissue integration and subsequent native biomechanics. The reported high rates of spinal fusion and artificial disc implant failure have pushed intervertebral disc degeneration research in recent years towards repair strategies. Intervertebral disc repair utilizing principles of tissue engineering should theoretically be successful, overcoming the inadequacies of artificial implants. For instance, advances in the development of scaffolds aided with cells and growth factors have opened up new possibilities for repair strategies. However, none has reached the stage of clinical trials in humans. In this review, we describe the hitches encountered in the musculoskeletal field and summarize recent advances in designing tissue-engineered constructs for promoting nucleus pulposus repair. Additionally, the review focuses on the effect of biomaterial aided with cells and growth factors on achieving effective functional reparative potency, highlighting the ways to enhance the efficacy of these treatments.