The Longitudinal Effects of Posterior Spinal Fusion with Derotation on Axial Deformity in Adolescent Idiopathic Scoliosis.

STUDY DESIGN: Retrospective case series. OBJECTIVE: To characterize the change in angle of trunk rotation (ATR), axial vertebral rotation (AVR), and body surface rotation (BSR) in patients with adolescent idiopathic scoliosis (AIS) undergoing posterior spinal fusion (PSF) with en-bloc derotation across multiple postoperative visits. SUMMARY OF BACKGROUND DATA: Previous research has documented ATR, AVR, and BSR correction for AIS patients after surgery. However, there is a lack of evidence on the sustainability of this correction over time. METHODS: This was a retrospective study from a single-center prospective surface topographic registry of patients with AIS, age 11-20 at time of surgery, who underwent PSF with en-bloc derotation. Patients with previous spine surgery were excluded. ATR was measured with a scoliometer, AVR through EOS radiographic imaging, and BSR via surface topographic scanning, Data collection occurred at: preoperative, six-week, three-month, six-month, one-year, and two-year postoperative visits. BSR and AVR were tracked at the preoperative apical vertebral level, and the level with maximum deformity, at each respective timepoint. Generalized estimating equations models were used for statistical analysis. Covariates included age, sex, and body mass index. RESULTS: 49 patients (73.4% female, mean age 14.6±2.2 years, mean preoperative coronal curve angle 57.9°±8.5, and 67% major thoracic) were evaluated. ATR correction was significantly improved at all postoperative timepoints and there was no significant loss of correction. AVR Max and AVR Apex were significantly improved at all timepoints but there was a significant loss of correction for AVR Apex between the six-week and one-year visit (P=0.032). BSR Max achieved significant improvement at the three-month visit. BSR Apex was significantly improved at the three-month and one-year visit. CONCLUSION: ATR and AVR demonstrated significant axial plane correction at two-years postoperative in patients undergoing PSF for AIS. BSR did not maintain significant improvement by the two-year visit.

Novel Surface Topographic Assessment of Lung Volume and Pulmonary Function Tests in Idiopathic Scoliosis: A Preliminary Study.

OBJECTIVE: Severe spinal deformity results in restrictive pulmonary disease from thoracic distortions and lung-volume limitations. Though spirometry and body plethysmography are widely accepted tests for pulmonary function tests (PFTs), they are time-consuming and require patient compliance. This study investigates whether surface topographic [surface topography (ST)] measurements of body volume difference (BVD) and torso volume difference between maximum inhale and exhale correlate to values determined on PFTs. METHODS: This study included patients with idiopathic scoliosis and thoracic/thoracolumbar curves ≥40 degrees. Patients received ST scans, clinical examinations, and EOS biplanar radiographs on the same day. PFTs were performed within 3 months of ST/radiographic analysis. Univariate linear regression analysis was used to examine relationships between BVD, PFT values, and mean curves. RESULTS: Sixteen patients (14.6 ± 2.2 y, 69% females) with idiopathic scoliosis and mean thoracic/thoracolumbar curves of 62 degrees ± 15˚ degrees (45 degrees to 93 degrees) were assessed. BVD displayed statistically high-positive positive correlations with forced vital capacity ( R = 0.863, P < 0.0001), forced expiratory volume in 1 second ( R = 0.870, P < 0.001), vital capacity ( R = 0.802, P < 0.0001), and TLC ( R = 0.831, P < 0.0001. Torso volume difference showed similarly high positive correlations to forced vital capacity, forced expiratory volume in 1 second, vital capacity, and TLC, but not residual volume. No correlations emerged between the mean thoracic/thoracolumbar curve and BVD or PFT values. CONCLUSION: This study strongly endorses further investigation into ST scanning as an alternative to traditional PFTs for assessing pulmonary volumes. The noncontact and noninvasive nature of ST scanning presents a valuable alternative method for analyzing thoracic volume, particularly beneficial for patients unable to cooperate with standard PFTs. LEVEL OF EVIDENCE: Level II-prognostic.

Decisional regret following corrective adult spinal deformity surgery: a single institution study of incidence and risk factors.

PURPOSE: To assess the characteristics and risk factors for decisional regret following corrective adult spinal deformity (ASD) surgery at our hospital. METHODS: This is a retrospective cohort study of a single-surgeon ASD database. Adult patients (> 40 years) who underwent ASD surgery from May 2016 to December 2020 with minimum 2-year follow-up were included (posterior-only, ≥ 4 levels fused to the pelvis) (n = 120). Ottawa decision regret questionnaires, a validated and reliable 5-item Likert scale, were sent to patients postoperatively. Regret scores were defined as (1) low regret: 0-39 (2) medium to high regret: 40-100. Risk factors for medium or high decisional regret were identified using multivariate models. RESULTS: Ninety patients were successfully contacted and 77 patients consented to participate. Nonparticipants were older, had a higher incidence of anxiety, and higher ASA class. There were 7 patients that reported medium or high decisional regret (9%). Ninety percentage of patients believed that surgery was the right decision, 86% believed that surgery was a wise choice, and 87% would do it again. 8% of patients regretted the surgery and 14% believed that surgery did them harm. 88% of patients felt better after surgery. On multivariate analysis, revision fusion surgery was independently associated with an increased risk of medium or high decisional regret (adjusted odds ratio: 6.000, 95% confidence interval: 1.074-33.534, p = 0.041). CONCLUSIONS: At our institution, we found a 9% incidence of decisional regret. Revision fusion was associated with increased decisional regret. Estimates for decisional regret should be based on single-institution experiences given differences in patient populations.

Pre-operative bone quality deficits and risk of complications following spine fusion surgery among postmenopausal women.

Poor bone quality is a risk factor for complications after spinal fusion surgery. This study investigated pre-operative bone quality in postmenopausal women undergoing spine fusion and found that those with small bones, thinner cortices and surgeries involving more vertebral levels were at highest risk for complications. PURPOSE: Spinal fusion is one of the most common surgeries performed worldwide. While skeletal complications are common, underlying skeletal deficits are often missed by pre-operative DXA due to artifact from spinal pathology. This prospective cohort study investigated pre-operative bone quality using high resolution peripheral CT (HRpQCT) and its relation to post-operative outcomes in postmenopausal women, a population that may be at particular risk for skeletal complications. We hypothesized that women with low volumetric BMD (vBMD) and abnormal microarchitecture would have higher rates of post-operative complications. METHODS: Pre-operative imaging included areal BMD (aBMD) by DXA, cortical and trabecular vBMD and microarchitecture of the radius and tibia by high resolution peripheral CT. Intra-operative bone quality was subjectively graded based on resistance to pedicle screw insertion. Post-operative complications were assessed by radiographs and CTs. RESULTS: Among 50 women enrolled (age 65 years), mean spine aBMD was normal and 35% had osteoporosis by DXA at any site. Low aBMD and vBMD were associated with "poor" subjective intra-operative quality. Skeletal complications occurred in 46% over a median follow-up of 15 months. In Cox proportional models, complications were associated with greater number of surgical levels (HR 1.19 95% CI 1.06-1.34), smaller tibia total area (HR 1.67 95% CI1.16-2.44) and lower tibial cortical thickness (HR 1.35 95% CI 1.05-1.75; model p < 0.01). CONCLUSION: Women with smaller bones, thinner cortices and procedures involving a greater number of vertebrae were at highest risk for post-operative complications, providing insights into surgical and skeletal risk factors for complications in this population.

Intravenous Ketorolac Substantially Reduces Opioid Use and Length of Stay After Lumbar Fusion: A Randomized Controlled Trial.

STUDY DESIGN: A randomized, double-blinded, placebo-controlled trial. OBJECTIVE: To examine the effect of intravenous ketorolac (IV-K) on hospital opioid use compared with IV-placebo (IV-P) and IV acetaminophen (IV-A). SUMMARY OF BACKGROUND DATA: Controlling postoperative pain while minimizing opioid use after lumbar spinal fusion is an important area of study. PATIENTS AND METHODS: Patients aged 18 to 75 years undergoing 1 to 2 level lumbar fusions between April 2016 and December 2019 were included. Patients with chronic opioid use, smokers, and those on systemic glucocorticoids or contraindications to study medications were excluded. A block randomization scheme was used, and study personnel, hospital staff, and subjects were blinded to the assignment. Patients were randomized postoperatively. The IV-K group received 15 mg (age > 65) or 30 mg (age < 65) every six hours (q6h) for 48 hours, IV-A received 1000 mg q6h, and IV-P received normal saline q6h for 48 hours. Demographic and surgical details, opioid use in morphine milliequivalents, opioid-related adverse events, and length of stay (LOS) were recorded. The primary outcome was in-hospital opioid use up to 72 hours. RESULTS: A total of 171 patients were included (58 IV-K, 55 IV-A, and 58 IV-P) in the intent-to-treat (ITT) analysis, with a mean age of 57.1 years. The IV-K group had lower opioid use at 72 hours (173 ± 157 mg) versus IV-A (255 ± 179 mg) and IV-P (299 ± 179 mg; P = 0.000). In terms of opiate use, IV-K was superior to IV-A ( P = 0.025) and IV-P ( P = 0.000) on ITT analysis, although on per-protocol analysis, the difference with IV-A did not reach significance ( P = 0.063). When compared with IV-P, IV-K patients reported significantly lower worst ( P = 0.004), best ( P = 0.001), average ( P = 0.001), and current pain ( P = 0.002) on postoperative day 1, and significantly shorter LOS ( P = 0.009) on ITT analysis. There were no differences in opioid-related adverse events, drain output, clinical outcomes, transfusion rates, or fusion rates. CONCLUSIONS: By reducing opioid use, improving pain control on postoperative day 1, and decreasing LOS without increases in complications or pseudarthrosis, IV-K may be an important component of "enhanced recovery after surgery" protocols.

Trans-sacral interbody fixation in long fusions to the sacrum for adult spinal deformity: complications and fusion rates at minimum two years follow-up.

PURPOSE: This study aims to investigate the fusion rate and complications associated with trans-sacral interbody fusion (TSIF) in long fusions to the sacrum for adult spinal deformity (ASD) over a two year follow-up period. Potential predictor variables associated with pseudarthrosis were also examined. METHODS: A retrospective clinical review was conducted on a consecutive series of ASD patients who underwent long fusions to the sacrum, with TSIF performed as a same-day or staged procedure. Patient demographics, bone mineral density, operative details, perioperative and late complications, and fusion rates were reviewed. Univariate analysis was used to identify the risk factors associated with pseudarthrosis. RESULTS: The study included 43 patients with an average age of 55.3 ± 8.9 years. The perioperative complication rate was 28%, with 12% of the complications directly related to TSIF. The late complication rate was 33%, with 16% related to TSIF. The most common complications were pseudarthrosis (14%) and postoperative ileus (7%). The overall radiographic fusion rate at two years was 86%. Univariate analysis revealed that revision surgery was significantly associated with pseudarthrosis (p = 0.027). Over the follow-up period, patients who underwent TSIF during long posterior fusions to the sacrum showed improvement in overall SRS scores, ODI scores, and SF-36 physical health and mental health (p < 0.05). CONCLUSION: TSIF is a relatively safe and minimally invasive method for achieving interbody fusion at the lumbosacral junction in the treatment of ASD, with acceptable fusion rates and a low complication rate. However, TSIF is not recommended for revision reconstruction in ASD.

Inducing Angiogenesis in the Nucleus Pulposus.

Bone morphogenetic protein (BMP) gene delivery to Lewis rat lumbar intervertebral discs (IVDs) drives bone formation anterior and external to the IVD, suggesting the IVD is inhospitable to osteogenesis. This study was designed to determine if IVD destruction with a proteoglycanase, and/or generating an IVD blood supply by gene delivery of an angiogenic growth factor, could render the IVD permissive to intra-discal BMP-driven osteogenesis and fusion. Surgical intra-discal delivery of naïve or gene-programmed cells (BMP2/BMP7 co-expressing or VEGF165 expressing) +/- purified chondroitinase-ABC (chABC) in all permutations was performed between lumbar 4/5 and L5/6 vertebrae, and radiographic, histology, and biomechanics endpoints were collected. Follow-up anti-sFlt Western blotting was performed. BMP and VEGF/BMP treatments had the highest stiffness, bone production and fusion. Bone was induced anterior to the IVD, and was not intra-discal from any treatment. chABC impaired BMP-driven osteogenesis, decreased histological staining for IVD proteoglycans, and made the IVD permissive to angiogenesis. A soluble fragment of VEGF Receptor-1 (sFlt) was liberated from the IVD matrix by incubation with chABC, suggesting dysregulation of the sFlt matrix attachment is a possible mechanism for the chABC-mediated IVD angiogenesis we observed. Based on these results, the IVD can be manipulated to foster vascular invasion, and by extension, possibly osteogenesis.

Exploring Correlations Between Pain and Deformity in Idiopathic Scoliosis With Validated Self-reported Pain Scores, Radiographic Measurements, and Trunk Surface Topographic Measurements.

BACKGROUND: Up to 75% of patients with idiopathic scoliosis (IS) report back pain, but the exact contributors are unclear. This study seeks to assess how pain correlates with demographics, radiographic and surface topographic (ST) measurements, and patient-reported outcome measures (PROMs) in patients with IS. METHODS: Patient-Reported Outcome Measurement Information System (PROMIS) Pain Interference (PI) and Scoliosis Research Society revised (SRS-22r) pain domain from an IRB approved prospectively collected registry containing patients 11 to 21 years old with IS were correlated (Spearman coefficients) with measurements from whole-body EOS radiography and ST scanning, PROMIS 1.0 PROMs, Trunk Appearance Perception Scale (TAPS), and SRS-22r domains. SRS-22r and PROMIS-PI were also compared between different sex, scoliosis severities, and primary curve locations with Mann-Whitney U or Kruskal-Wallis tests, and if significant differences were found, included with the 5 highest univariate correlated variables into stepwise multivariate linear regression models ( P <0.05 to enter, P >0.1 to remove) predicting SRS-22r pain and PROMIS-PI. RESULTS: One hundred and forty-nine patients (14.5 ± 2.0 y, body mass index 20.6 ± 4.1 kg/m 2 , 96 (64%) female, mean major coronal curve 40 ± 19 deg, range: 10 deg, 83 deg) reported mean PROMIS-PI of 42.2 ± 10.0 and SRS-22r pain of 4.4 ± 0.6. SRS-22r self-image was the most correlated variable with both SRS-22r pain (rho=0.519) and PROMIS-PI (rho=-0.594). Five variables, none of which were ST or radiographic measures, strongly predicted SRS pain domain (R=0.711, R2=0.505, N=138). Two variables (SRS-22r self-image and SRS-22r function) were utilized by a model correlated with PROMIS-PI (R=0.687, R2=0.463, N=124). CONCLUSIONS: SRS-22r function and self-image domains were more strongly correlated with SRS-22r pain and PROMIS-PI than any radiographic or ST measurements. LEVEL OF EVIDENCE: Level II-retrospective study.

3D surface topographic measurements for idiopathic scoliosis are highly correlative to patient self-image questionnaires.

PURPOSE: Adolescent idiopathic scoliosis (AIS) is a deformity of the spine that results in external asymmetry of the torso in the shoulder, waist, and rib hump. Several patient reported outcome measures (PROMS) including the Trunk Appearance Perception Scale (TAPS) and SRS-22r self-image domain are used to measure the patient's self-perception. The purpose of this study is to investigate the relationship between objective surface topographic measurements of the torso to subjective patient self-perception. METHODS: 131 AIS subjects and 37 controls participated in this study. All subjects completed TAPS and SRS-22r PROMS followed by whole body 3d surface topographic scanning. An automated analysis pipeline was used to compute 57 measurements. Multivariate linear models were developed to predict TAPS and SRS-22r self-image using each unique combination of 3 parameters and leave one out validation where the best combinations were selected. RESULTS: Back surface rotation, waist crease vertical asymmetry and rib prominence volume were most predictive of TAPS. The final predicted TAPS values from leave one out cross validation was correlated to ground truth TAPS scores with an R value of 0.65. Back surface rotation, silhouette centroid deviation, and shoulder normal asymmetry were most predictive of SRS-22r self-image with a correlation of R = 0.48. CONCLUSION: Surface topographic measurements of the torso are correlated to TAPS and SRS-22r self-image scores in AIS patients and controls, with TAPS exhibiting a stronger relationship, better reflecting the patient's external asymmetries.

Identification of Novel Genetic Markers for the Risk of Spinal Pathologies: A Genome-Wide Association Study of 2 Biobanks.

BACKGROUND: Identifying genetic risk factors for spinal disorders may lead to knowledge regarding underlying molecular mechanisms and the development of new treatments. METHODS: Cases of lumbar spondylolisthesis, spinal stenosis, degenerative disc disease, and pseudarthrosis after spinal fusion were identified from the UK Biobank. Controls were patients without the diagnosis. Whole-genome regressions were used to test for genetic variants potentially implicated in the occurrence of each phenotype. External validation was performed in FinnGen. RESULTS: A total of 389,413 participants were identified from the UK Biobank. A locus on chromosome 2 spanning GFPT1, NFU1, AAK1, and LOC124906020 was implicated in lumbar spondylolisthesis. Two loci on chromosomes 2 and 12 spanning genes GFPT1, NFU1, and PDE3A were implicated in spinal stenosis. Three loci on chromosomes 6, 10, and 15 spanning genes CHST3, LOC102723493, and SMAD3 were implicated in degenerative disc disease. Finally, 2 novel loci on chromosomes 5 and 9, with the latter corresponding to the LOC105376270 gene, were implicated in pseudarthrosis. Some of these variants associated with spinal stenosis and degenerative disc disease were also replicated in FinnGen. CONCLUSIONS: This study revealed nucleotide variations in select genetic loci that were potentially implicated in 4 different spinal pathologies, providing potential insights into the pathological mechanisms. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

3D Surface Topographic Optical Scans Yield Highly Reliable Global Spine Range of Motion Measurements in Scoliotic and Non-Scoliotic Adolescents.

Background: Adolescent idiopathic scoliosis results in three dimensional changes to a patient's body, which may change a patient's range of motion. Surface topography is an emerging technology to evaluate three dimensional parameters in patients with scoliosis. The goal of this paper is to introduce novel and reliable surface topographic measurements for the assessment of global coronal and sagittal range of motion of the spine in adolescents, and to determine if these measurements can distinguish between adolescents with lumbar scoliosis and those without scoliosis. Methods: This study is a retrospective cohort study of a prospectively collected registry. Using a surface topographic scanner, a finger to floor and lateral bending scans were performed on each subject. Inter- and intra-rater reliabilities were assessed for each measurement. ANOVA analysis was used to test comparative hypotheses. Results: Inter-rater reliability for lateral bending fingertip asymmetry (LBFA) and lateral bending acromia asymmetry (LBAA) displayed poor reliability, while the coronal angle asymmetry (CAA), coronal angle range of motion (CAR), forward bending finger to floor (FBFF), forward bending acromia to floor (FBAF), sagittal angle (SA), and sagittal angle normalized (SAN) demonstrated good to excellent reliability. There was a significant difference between controls and lumbar scoliosis patients for LBFA, LBAA, CAA and FBAF (p-values < 0.01). Conclusion: Surface topography yields a reliable and rapid process for measuring global spine range of motion in the coronal and sagittal planes. Using these tools, there was a significant difference in measurements between patients with lumbar scoliosis and controls. In the future, we hope to be able to assess and predict perioperative spinal mobility changes.

Lumbar spine intervertebral disc gene delivery of BMPs induces anterior spine fusion in lewis rats.

Minimally invasive techniques and biological autograft alternatives such as the bone morphogenetic proteins (BMPs) can reduce morbidity associated with spinal fusions. This study was a proof-of-concept for gene-therapy-mediated anterior spine fusion that could be adapted to percutaneous technique for clinical use. Isogeneic bone marrow stromal cells genetically programmed to express b-galactosidase (LACZ, a marker gene), BMP2, BMP7, a mixture of BMP2 and BMP7 infected cells (homodimers, HM), or BMP2/7 heterodimers (HT) were implanted into the discs between lumbar vertebrae 4 and 5 (L4/5) and L5/6 of male Lewis rats. Spine stiffening was monitored at 4, 8 and 12 weeks using noninvasive-induced angular displacement (NIAD) testing. At 12 weeks isolated spines were assessed for fusion and bone formation by palpation, biomechanical testing [four-point bending stiffness, moment to failure in extension, and in vitro angular displacement (IVAD)], faxitron x-rays, microCT, and histology. Progressive loss of NIAD occurred in only the HT group (p < 0.001), and biomechanical tests correlated with the NIAD results. Significant fusion occurred only in the HT group (94% of animals with one or both levels) as assessed by palpation (p < 0.001), which predicted HT bone production assessed by faxitron (p ≤ 0.001) or microCT (p < 0.023). Intervertebral bridging bone was consistently observed only in HT-treated specimens. Induced bone was located anterior and lateral to the disc space, with no bone formation noted within the disc. Percutaneous anterior spine fusions may be possible clinically, but induction of bone inside the disc space remains a challenge.

Classification system for cervical spine deformity morphology: a validation study.

OBJECTIVE: The objective of this study was to initially validate a recent morphological classification of cervical spine deformity pathology. METHODS: The records of 10 patients for each of the 3 classification subgroups (flat neck, focal deformity, and cervicothoracic), as well as for 8 patients with coronal deformity only, were extracted from a prospective multicenter database of patients with cervical deformity (CD). A panel of 15 physicians of various training and professional levels (i.e., residents, fellows, and surgeons) categorized each patient into one of the 4 groups. The Fleiss kappa coefficient was utilized to evaluate intra- and interrater reliability. Accuracy, defined as properly selecting the main driver of deformity, was reported overall, by morphotype, and by reviewer experience. RESULTS: The overall classification demonstrated a moderate to substantial agreement (round 1: interrater Fleiss kappa = 0.563, 95% CI 0.559-0.568; round 2: interrater Fleiss kappa = 0.612, 95% CI 0.606-0.619). Stratification by level of training demonstrated similar mean interrater coefficients (residents 0.547, fellows 0.600, surgeons 0.524). The mean intrarater score was 0.686 (range 0.531-0.823). A substantial agreement between rounds 1 and 2 was demonstrated in 81.8% of the raters, with a kappa score > 0.61. Stratification by level of training demonstrated similar mean intrarater coefficients (residents 0.715, fellows 0.640, surgeons 0.682). Of 570 possible questions, reviewers provided 419 correct answers (73.5%). When considering the true answer as being selected by at least one of the two main drivers of deformity, the overall accuracy increased to 86.0%. CONCLUSIONS: This initial validation of a CD morphological classification system reiterates the importance of dynamic plain radiographs for the evaluation of patients with CD. The overall reliability of this CD morphological classification has been demonstrated. The overall accuracy of the classification system was not impacted by rater experience, demonstrating its simplicity.

The Effects of Adolescent Idiopathic Scoliosis on Axial Rotation of the Spine: A Study of Twisting Using Surface Topography.

Axial twisting of the spine has been previously shown to be affected by scoliosis with decreased motion and asymmetric twisting. Existing methods for evaluating twisting may be cumbersome, unreliable, or require radiation exposure. In this study, we present an automated surface topographic measurement tool to evaluate global axial rotation of the spine, along with two measurements: twisting range of motion (TROM) and twisting asymmetry index (TASI). The aim of this study is to evaluate the impact of scoliosis on axial range of motion. Adolescent idiopathic scoliosis (AIS) patients and asymptomatic controls were scanned in a topographic scanner while twisting maximally to the left and right. TROM was significantly lower for AIS patients compared to control patients (69.1° vs. 78.5°, p = 0.020). TASI was significantly higher for AIS patients compared to control patients (29.6 vs. 19.8, p = 0.023). After stratifying by scoliosis severity, both TROM and TASI were significantly different only between control and severe scoliosis patients (Cobb angle > 40°). AIS patients were then divided by their major curve region (thoracic, thoracolumbar, or lumbar). ANOVA and post hoc tests showed that only TROM is significantly different between thoracic AIS patients and control patients. Thus, we demonstrate that surface topographic scanning can be used to evaluate twisting in AIS patients.

Activation of nuclear factor-kappa B by TNF promotes nucleus pulposus mineralization through inhibition of ANKH and ENPP1.

Spontaneous mineralization of the nucleus pulposus (NP) has been observed in cases of intervertebral disc degeneration (IDD). Inflammatory cytokines have been implicated in mineralization of multiple tissues through their modulation of expression of factors that enable or inhibit mineralization, including TNAP, ANKH or ENPP1. This study examines the underlying factors leading to NP mineralization, focusing on the contribution of the inflammatory cytokine, TNF, to this pathologic event. We show that human and bovine primary NP cells express high levels of ANKH and ENPP1, and low or undetectable levels of TNAP. Bovine NPs transduced to express TNAP were capable of matrix mineralization, which was further enhanced by ANKH knockdown. TNF treatment or overexpression promoted a greater increase in mineralization of TNAP-expressing cells by downregulating the expression of ANKH and ENPP1 via NF-κB activation. The increased mineralization was accompanied by phenotypic changes that resemble chondrocyte hypertrophy, including increased RUNX2 and COL10A1 mRNA; mirroring the cellular alterations typical of samples from IDD patients. Disc organ explants injected with TNAP/TNF- or TNAP/shANKH-overexpressing cells showed increased mineral content inside the NP. Together, our results confirm interactions between TNF and downstream regulators of matrix mineralization in NP cells, providing evidence to suggest their participation in NP calcification during IDD.

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

STUDY DESIGN: Basic Science. OBJECTIVE: To determine if locally delivered simvastatin can enhance bone formation in a rat spinal fusion model. SUMMARY OF BACKGROUND DATA: 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. METHODS: 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). RESULTS: 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). CONCLUSION: 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. LEVEL OF EVIDENCE: N/A.

Erratum to Surgical Risk Stratification Based on Preoperative Risk Factors in Severe Pediatric Spinal Deformity Surgery [Spine Deformity 2 (2014) 340-349].

The corresponding author regret that co-author name was incorrectly published as "Elias C. Papadopoulus" in the article. The correct name of the author should be displayed as "Elias C. Papadopoulos".

Erratum to Incidence and Risk Factors for Major Surgical Complications in Patients With Complex Spinal Deformity: A Report From an SRS GOP Site [Spine Deformity 3 (2015) 57-64].

The corresponding author regret that co-author name was incorrectly published as "Elias C. Papadopoulus" in the article. The correct name of the author should be displayed as "Elias C. Papadopoulos".