transforming-growth-factor-beta and Scoliosis

Topics: Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Cervical Vertebrae; Humans; Lumbar Vertebrae; Orthopedic Procedures; Recombinant Proteins; Scoliosis; Spinal Cord Injuries; Spine; Transforming Growth Factor beta

In adults, symptomatic scoliosis is usually a de novo primary degenerative deformity that develops in the fifth or sixth decade or an unrecognized or untreated idiopathic deformity with superimposed degeneration. The evaluation and treatment of adult scoliosis must focus on addressing patient symptoms while limiting the consequences of the treatment. The presence of neurological deficits, the flexibility of the deformity, the coronal and sagittal balance, and status of spinal segments outside of the main deformity are all important considerations when planning surgery. The complication rate of deformity surgery in adults is potentially high; but excellent functional outcome and patient satisfaction can occur with thorough preoperative patient education and meticulous surgical technique.

Topics: Adult; Biological Factors; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Humans; Internal Fixators; Intervertebral Disc; Lumbar Vertebrae; Orthopedic Procedures; Scoliosis; Transforming Growth Factor beta

Prospective, single center, nonblinded radiographic analysis of anterior and posterior adult spinal deformity fusions performed with bone morphogenetic protein (rhBMP-2).. To determine the ability of rhBMP-2 to achieve multilevel spinal fusion in the deformity patient.. No previous study has evaluated rhBMP-2 for multilevel adult spinal deformity fusion with 2-year results. We postulated fusion could be achieved without distant autogenous graft harvest.. Prospective analysis was performed for 98 patients (308 levels; mean age, 51.4 years) who underwent multilevel anterior or posterior spinal fusion (PSF) with minimum 2-year follow-up (average, 2.6 years). Group 1 (10 mg/level) contained 47 patients (109 levels; 2.33 levels/patient) who underwent anterior spinal fusion (ASF): BMP on an absorbable collagen sponge (ACS) with a titanium mesh cage. Group 2 (20 mg/level) included 43 patients (156 levels; 3.63 levels/patient) with PSF: BMP on an ACS with local bone graft (LBG) and bulking agent [tricalcium phosphate/hydroxyapatite (TCP-HA)]. Group 3 (40 mg/level) contained 8 patients (43 levels; 5.38 levels/patient) with PSF: rhBMP-2 and TCP-HA with no autologous bone. Confounding negative factors were present in the study population: medical comorbidities (26%), tobacco use (17%), revision surgery (34%), previous laminectomy (51%), and preoperative pseudarthrosis (27%). Postoperative films (AP, lateral, oblique) were evaluated by independent observers. Average fusion grade was based on a published scale.. Overall fusion rate was 95%. (group 1 91%, group 2 97%, group 3 100%). No confounding factor demonstrated a detrimental statistical significance to fusion.. In multilevel ASF, BMP (10 mg/level) generates fusion without autogenous bone. In multilevel PSF, BMP (20 mg/level) with LBG and TCP-HA produced fusion. BMP (40 mg/level) and TCP-HA without LBG achieved fusion. In multilevel spinal fusion, rhBMP-2 eliminated the necessity for iliac crest bone graft and yielded an excellent fusion rate.

Topics: Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Bone Regeneration; Bone Transplantation; Dose-Response Relationship, Drug; Female; Humans; Ilium; Male; Middle Aged; Osseointegration; Osteogenesis; Prospective Studies; Pseudarthrosis; Radiography; Recombinant Proteins; Scoliosis; Spinal Fusion; Transforming Growth Factor beta; Treatment Outcome

Prospective, single-center, nonblinded clinical and radiographic analysis of consecutive adult deformity patients treated with recombinant human bone morphogenetic protein-2 (rhBMP-2) without iliac or rib bone graft supplementation.. To determine the ability of rhBMP-2 to achieve both anterior and posterior spinal fusion in patients undergoing multilevel fusions for adult spinal deformity.. The literature concerning one-level anterior fusions, and potentially one-level posterior fusions, using rhBMP-2 has demonstrated clinical efficacy. No published data exist on the use of rhBMP-2 in multilevel spine fusions.. Prospective analysis of patients treated with rhBMP-2 in multilevel anterior and posterior fusions with a minimum 1-year follow-up. There were a total of 95 patient samples (70 total patients; 25 patients had rhBMP-2 used circumferentially): 46 anterior fusions (Group 1), 41 posterior fusions (Group 2), and 8 patients were "compassionate use" fusions (Group 3). In the anterior fusion group (n = 46), mean rhBMP-2/level was 10.8 mg in titanium mesh cages without any bone graft or other substance. The posterior fusion group had only local bone graft, no harvested rib or iliac bone graft (n = 41). The mean rhBMP-2/level was 13.7 mg. The "compassionate use" group (n = 8 patients) consisted of patients who had prior surgeries, prior iliac harvesting, and substantial comorbidities and therefore a higher concentration and different carrier was used. No local bone graft, no harvested bone was used. The mean rhBMP-2/level was 28.6 mg. The median dose was 40 mg for Group 3.. For the anterior fusion group (n = 46), operative levels were deemed fused in 89 of the 93 (96%) levels. For the posterior fusion group (n = 41), a solid fusion was assessed in 110 of the 118 (93%) operative levels. For the "compassionate-use" patients, the overall fusion rate was 100% (52 of 52 operative levels).. With the use of rhBMP-2, a high rate of apparent fusion was observed for anterior (96%) and posterior (93%) fusions in adult spinal deformity patients. Use of rhBMP-2 results in a promising early fusion rate without the graft harvest site morbidity.

Topics: Adult; Aged; Aged, 80 and over; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Bone Regeneration; Female; Humans; Lumbar Vertebrae; Male; Middle Aged; Osteogenesis; Prospective Studies; Radiography; Recombinant Proteins; Scoliosis; Spinal Fusion; Transforming Growth Factor beta; Treatment Outcome

Congenital scoliosis (CS) is a form of scoliosis caused by congenital vertebral malformations. Genetic predisposition has been demonstrated in CS. We previously reported that TBX6 loss-of-function causes CS in a compound heterozygous model; however, this model can explain only 10% of CS. Many monogenic and polygenic CS genes remain to be elucidated. In this study, we analyzed exome sequencing (ES) data of 615 Chinese CS from the Deciphering Disorders Involving Scoliosis and COmorbidities (DISCO) project. Cosegregation studies for 103 familial CS identified a novel heterozygous nonsense variant, c.2649G>A (p.Trp883Ter) in FBN1. The association between FBN1 and CS was then analyzed by extracting FBN1 variants from ES data of 574 sporadic CS and 828 controls; 30 novel variants were identified and prioritized for further analyses. A mutational burden test showed that the deleterious FBN1 variants were significantly enriched in CS subjects (OR = 3.9, P = 0.03 by Fisher's exact test). One missense variant, c.2613A>C (p.Leu871Phe) was recurrent in two unrelated CS subjects, and in vitro functional experiments for the variant suggest that FBN1 may contribute to CS by upregulating the transforming growth factor beta (TGF-β) signaling. Our study expanded the phenotypic spectrum of FBN1, and provided nove insights into the genetic etiology of CS.

Topics: Child; Child, Preschool; Codon, Nonsense; Congenital Abnormalities; Exome; Female; Fibrillin-1; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Infant; Male; Mutation; Mutation, Missense; Pedigree; Scoliosis; Spine; Transforming Growth Factor beta

Congenital scoliosis is defined by the presence of structural anatomical malformations that arise from failures of vertebral formation or segmentation before and after birth. The understanding of genetic background and key genes for congenital scoliosis is still poor. We herein report that the excess expression of plasminogen activator inhibitor-1 (Pai-1) induced by the upregulation of miR-224-5p is involved in the pathogenesis of congenital kyphoscoliosis through impaired osteoblast differentiation. We first investigated the variety and progression of abnormalities of the lumbar spines in Ishibashi (IS) rats, a rat model of congenital kyphoscoliosis. The rats had already shown fusion and division of the primary ossification center at postnatal day 4. Over time, the rats showed various abnormalities of the lumbar spine, including the fusion of the annular epiphyseal nucleus. At postnatal day 42, spinal curvature was clearly observed due to the fusion of the vertebral bodies. Using a microRNA array, we found that the expression of miR-224-5p was increased in the lumbar spine of the rats at postnatal day 4. The expression of Pai-1, which is involved in osteoblast differentiation regulated by miR-224-5p, was also increased, while the levels of type I collagen, a marker of osteoblast differentiation, were decreased in the lumbar spine. These results indicate that the aberrant expression of miRNA-224-5p and its target genes is involved in the impaired osteoblast differentiation and may provide a partial molecular explanation for the pathogenesis of congenital scoliosis.

Topics: Animals; Cell Differentiation; Disease Models, Animal; Kyphosis; Lumbar Vertebrae; Male; MicroRNAs; Osteogenesis; Plasminogen Activator Inhibitor 1; Rats; Rats, Wistar; Scoliosis; Signal Transduction; Transforming Growth Factor beta; Up-Regulation

Spondylocarpotarsal synostosis (SCT) is a skeletal disorder characterized by progressive vertebral, carpal and tarsal fusions, and mild short stature. The majority of affected individuals have an autosomal recessive form of SCT and are homozygous or compound heterozygous for nonsense mutations in the gene that encodes the cytoskeletal protein filamin B (FLNB), but a subset do not have FLNB mutations. Exome sequence analysis of three SCT patients negative for FLNB mutations identified an autosomal dominant form of the disease due to heterozygosity for missense or nonsense mutations in MYH3, which encodes embryonic myosin. Cells transfected with the MYH3 missense mutations had reduced TGFβ signaling, revealing a regulatory role for embryonic myosin in the TGFβ signaling pathway. In wild-type mice, there was persistent postnatal expression of embryonic myosin in the small muscles joining the neural arches of the spine suggesting that loss of myosin function in these muscles contribute to the disease. Our findings demonstrate that dominant mutations in MYH3 underlie autosomal dominant SCT, identify a postnatal role for embryonic myosin and suggest that altered regulation of signal transduction in the muscles within the spine may lead to the development of vertebral fusions.

Topics: Abnormalities, Multiple; Alleles; Bone Morphogenetic Proteins; Cytoskeletal Proteins; Exome Sequencing; Female; Genes, Dominant; Genotype; Humans; Lumbar Vertebrae; Male; Musculoskeletal Diseases; Mutation; Myosins; Phenotype; Radiography; Scoliosis; Signal Transduction; Synostosis; Thoracic Vertebrae; Transforming Growth Factor beta

Retrospective review.. This study follows the inpatient-stay administrative data that were collected for a cohort of thousands of patients who had spine fusion surgery in the state of New York. We sought to examine adult spinal deformity (ASD) for reoperation events with and without the use of bone morphogenetic protein-2 (BMP).. Randomized controlled trials have suggested that BMP may increase the likelihood of solid arthrodesis in spinal surgery. This would imply fewer reoperations for pseudarthrosis, but small cohort sizes are inadequate to monitor these events.. The 2008-2011 New York State Inpatient Database was queried using International Classification of Diseases, Ninth Revision, Clinical Modification codes. Patients age 21 years and older with a diagnosis of scoliosis and an index fusion of greater than 2 spinal motion segments were included. Patient identifiers and linkage variables were used to identify revisits. The relative risk of reoperation was calculated. The use of BMP at the initial inpatient stay was used to define the 2 cohorts for relative risk assessment.. A total of 3751 patients of ASD were identified in 2008. The use of BMP at the initial visit was performed at a rate of 37.6% for ASD. For posterior fusion cases longer than 8 levels, the rate of reoperation for a pseudarthrosis was 23.4%. For ASD fusions greater than 8 levels, the rate of reoperation for pseudarthrosis after using BMP at the index surgery was 5% and 33.9% when BMP was not used, a relative risk of 7.5 (P < 0.001).. Using relevant inhospital patient records from the New York State Inpatient Sample, we found a 7.5-fold decrease in the risk of reoperation for pseudarthrosis after long fusions when using BMP. Decreased reoperation rates are caused by the improved fusion with the use of BMP. If subsequent unnecessary hospitals stays can be avoided, the economics of BMP use should be reexamined.

Topics: Adult; Aged; Aged, 80 and over; Arthrodesis; Bone Morphogenetic Protein 2; Female; Humans; Male; Middle Aged; Recombinant Proteins; Reoperation; Retrospective Studies; Scoliosis; Transforming Growth Factor beta

Spondylocarpotarsal synostosis (SCT) is an autosomal recessive disorder characterized by progressive vertebral fusions and caused by loss of function mutations in Filamin B (FLNB). FLNB acts as a signaling scaffold by linking the actin cytoskleteon to signal transduction systems, yet the disease mechanisms for SCT remain unclear. Employing a Flnb knockout mouse, we found morphologic and molecular evidence that the intervertebral discs (IVDs) of Flnb-/-mice undergo rapid and progressive degeneration during postnatal development as a result of abnormal cell fate changes in the IVD, particularly the annulus fibrosus (AF). In Flnb-/-mice, the AF cells lose their typical fibroblast-like characteristics and acquire the molecular and phenotypic signature of hypertrophic chondrocytes. This change is characterized by hallmarks of endochondral-like ossification including alterations in collagen matrix, expression of Collagen X, increased apoptosis, and inappropriate ossification of the disc tissue. We show that conversion of the AF cells into chondrocytes is coincident with upregulated TGFβ signaling via Smad2/3 and BMP induced p38 signaling as well as sustained activation of canonical and noncanonical target genes p21 and Ctgf. These findings indicate that FLNB is involved in attenuation of TGFβ/BMP signaling and influences AF cell fate. Furthermore, we demonstrate that the IVD disruptions in Flnb-/-mice resemble aging degenerative discs and reveal new insights into the molecular causes of vertebral fusions and disc degeneration.

Topics: Abnormalities, Multiple; Actin Cytoskeleton; Animals; Bone Morphogenetic Proteins; Chondrocytes; Connective Tissue Growth Factor; Disease Models, Animal; Filamins; Growth Plate; Humans; Intervertebral Disc Degeneration; Lumbar Vertebrae; Mice; Mice, Knockout; Musculoskeletal Diseases; Scoliosis; Signal Transduction; Smad Proteins; Spine; Synostosis; Thoracic Vertebrae; Transforming Growth Factor beta

The authors have previously reported on their early experience with sublaminar polyester bands in spine surgery. In this paper, the authors describe the use of sublaminar polyester bands in long-segment posterior instrumented spinal fusions from the upper thoracic spine to the ilium in 21 children and transitional adults with progressive neuromuscular scoliosis. Transitional adults were patients older than 18 years of age with a spinal disorder of pediatric onset, such as spina bifida. This dedicated study represents the first reported use of polyester bands in spine surgery for neuromuscular scoliosis in this patient population in the US.. The authors retrospectively reviewed the demographics and procedural data of patients who underwent posterior instrumented fusion using sublaminar polyester bands for neuromuscular scoliosis.. Twenty-one pediatric and adult transitional patients, ranging in age from 10 to 20 years (mean 14 years), underwent posterior instrumented fusion for progressive neuromuscular scoliosis. The average coronal Cobb angle measured 66° before surgery (range 37°-125°). Immediately after surgery, the mean coronal Cobb angle was 40° (range 13°-85°). At last follow-up, the average coronal Cobb angle was maintained at 42° (range 5°-112°). Regarding sagittal parameters, thoracic kyphosis was restored by 8%, and lumbar lordosis improved by 20% after surgery. Mean follow-up duration was 17 months (range 2-54 months). One patient with an aborted procedure due to loss of intraoperative evoked potentials was excluded from the analysis of radiographic outcomes. Mean surgical time was 7 hours 43 minutes (range 3 hours 59 minutes to 10 hours 23 minutes). All patients received either a 12- or 24-mg dose of recombinant human bone morphogenetic protein-2. Average estimated blood loss was 976 ml (range 300-2700 ml). Complications directly related to the use of sublaminar instrumentation included transient proprioceptive deficit (1 patient) and prolonged paraparesis (1 patient). Other complications noted in this series included disengagement of the rod from an iliac screw (1 patient), proximal junctional kyphosis (1 patient), noninfected wound drainage (2 patients), and perioperative death (1 patient). The lessons learned from these complications are discussed.. Pedicle screws, laminar/pedicle/transverse process hooks, and sublaminar metal wires have been incorporated into posterior spinal constructs and widely reported and used in the thoracic and lumbar spines and sacrum with varying success. This report demonstrates the satisfactory radiological outcomes of hybrid posterior spinal constructs in pediatric and adult neuromuscular scoliosis that include sublaminar polyester bands that promise the technical ease of passing sublaminar instrumentation with the immediate biomechanical rigidity of pedicle screws and hooks. However, the high neurological complication rate associated with this technique (2/21, or 10%) tempers the acceptable radiographic outcomes.

Topics: Adolescent; Bone Morphogenetic Protein 2; Child; Child, Preschool; Feasibility Studies; Female; Humans; Kyphosis; Lordosis; Lumbar Vertebrae; Male; Paraparesis; Polyesters; Radiography; Recombinant Proteins; Retrospective Studies; Safety; Scoliosis; Spinal Fusion; Thoracic Vertebrae; Transforming Growth Factor beta; Treatment Outcome; Young Adult

Neuromuscular scoliosis is a challenging pathology to treat with high incidence of complications and failure of surgical fusion. Surgical correction can entail long fusion constructs extending to the pelvis. We report our experience in the use of bone morphogenetic protein (BMP) to augment L5-S1 arthrodesis in long segment fusions in pediatric patients with neuromuscular scoliosis.. Retrospective review of 11 pediatric patients with neuromuscular spinal deformity (mean, age 13.7 years; range, 10-20 years) who underwent long (mean, 15 levels; range, 10-18 levels) spinal instrumentation and fusion to the pelvis at a single institution from 2007 to 2012 with an average follow-up of 34 months (range, 11-62 months).. Of the 11 patients, one had pseudoarthrosis at L5-S1. The average coronal Cobb angle measured 59° before surgery and 42° immediately after surgery. The average preoperative thoracic kyphosis and lumbar sagittal lordosis measured 34 and 59°, respectively. Immediately after surgery, the thoracic and lumbar angles measured 28 and 39°, respectively. At last follow-up, the average coronal Cobb angle was maintained at 43° and the thoracic and lumbar sagittal angles were 28 and 44°, respectively. An average of 14.2 mg of recombinant human bone morphogenetic protein-2 (rh-BMP-2) was used for each case.. L5-S1 arthrodesis may be effectively achieved in long fusions for pediatric neuromuscular spinal deformity with posterolateral fusion supplemented with rh-BMP-2. This surgical strategy may be associated with lower complication rates, decreased blood loss, and shorter operative times than circumferential fusion, which is particularly important in this complex fragile patient population.

Topics: Adolescent; Bone Morphogenetic Protein 2; Child; Female; Humans; Lumbosacral Region; Male; Recombinant Proteins; Retrospective Studies; Scoliosis; Spinal Fusion; Transforming Growth Factor beta; Treatment Outcome; Young Adult

We develop a sheep thoracic spine interbody fusion model to study the suitability of polycaprolactone-based scaffold and recombinant human bone morphogenetic protein-2 (rhBMP-2) as a bone graft substitute within the thoracic spine. The surgical approach is a mini-open thoracotomy with relevance to minimally invasive deformity correction surgery for adolescent idiopathic scoliosis. To date there are no studies examining the use of this biodegradable implant in combination with biologics in a sheep thoracic spine model.. In the present study, six sheep underwent a 3-level (T6/7, T8/9 and T10/11) discectomy with randomly allocated implantation of a different graft substitute at each of the three levels: (a) calcium phosphate (CaP) coated polycaprolactone-based scaffold plus 0.54 μg rhBMP-2 (b) CaP-coated PCL-based scaffold alone or (c) autograft (mulched rib head). Fusion was assessed at 6 months post-surgery.. Computed Tomographic scanning demonstrated higher fusion grades in the rhBMP-2 plus PCL-based scaffold group in comparison with either PCL-based scaffold alone or autograft. These results were supported by histological evaluations of the respective groups. Biomechanical testing revealed significantly higher stiffness for the rhBMP-2 plus PCL-based scaffold group in all loading directions in comparison with the other two groups.. The results of this study demonstrate that rhBMP-2 plus PCL-based scaffold is a viable bone graft substitute, providing an optimal environment for thoracic interbody spinal fusion in a large animal model.

Topics: Absorbable Implants; Animals; Bone Morphogenetic Protein 2; Bone Substitutes; Calcium Phosphates; Diskectomy; Humans; Male; Polyesters; Recombinant Proteins; Scoliosis; Sheep; Spinal Fusion; Thoracic Vertebrae; Tissue Scaffolds; Transforming Growth Factor beta; Transplantation, Autologous

Multicenter, prospective analysis of consecutive patients with adult spinal deformity (ASD).. Evaluate complications associated with recombinant human bone morphogenetic protein-2 (rhBMP-2) use in ASD.. Off-label rhBMP-2 use is common; however, underreporting of rhBMP-2 associated complications has been recently scrutinized.. Patients with ASD consecutively enrolled into a prospective, multicenter database were evaluated for type and timing of acute perioperative complications.. age 18 years and older, ASD, spinal arthrodesis of more than 4 levels, and 3 or more months of follow-up. Patients were divided into those receiving rhBMP-2 (BMP) or no rhBMP-2 (NOBMP). BMP divided into location of use: posterior (PBMP), interbody (IBMP), and interbody + posterior spine (I + PBMP). Correlations between acute perioperative complications and rhBMP-2 use including total dose, dose/level, and location of use were evaluated.. A total of 279 patients (mean age: 57 yr; mean spinal levels fused: 12.0; and mean follow-up: 28.8 mo) met inclusion criteria. BMP (n = 172; average posterior dose = 2.5 mg/level, average interbody dose = 5 mg/level) had similar age, smoking history, previous spine surgery, total spinal levels fused, estimated blood loss, and duration of hospital stay as NOBMP (n = 107; P > 0.05). BMP had greater Charlson Comorbidity Index (1.9 vs. 1.2), greater scoliosis (43° vs. 38°), longer operative time (488.2 vs. 414.6 min), more osteotomies per patient (4.0 vs. 1.6), and greater percentage of anteroposterior fusion (APSF; 20.9% vs. 8.4%) than NOBMP, respectively (P < 0.05). BMP had more total complications per patient (1.4 vs. 0.6) and more minor complications per patient (0.9 vs. 0.2) than NOBMP, respectively (P < 0.05). NOBMP had more complications requiring surgery per patient than BMP (0.3 vs. 0.2; P < 0.05). Major, neurological, wound, and infectious complications were similar for NOBMP, BMP, PBMP, IBMP, and I + PBMP (P > 0.05). Multivariate analysis demonstrated small to nonexistent correlations between rhBMP-2 use and complications.. RhBMP-2 use and location of rhBMP-2 use in ASD surgery, at reported doses, do not increase acute major, neurological, or wound complications. Research is needed for higher rhBMP-2 dosing and long-term follow-up.. 2.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bone Morphogenetic Protein 2; Female; Follow-Up Studies; Humans; Male; Middle Aged; Postoperative Complications; Prospective Studies; Recombinant Proteins; Scoliosis; Spinal Fusion; Transforming Growth Factor beta; Young Adult

Most researchers agree that idiopathic scoliosis (IS) is a multifactorial disease influenced by complex genetic and environmental factors. The onset of the spinal deformity that determines the natural course of the disease, usually occurs in the juvenile or adolescent period. Transforming growth factors β (TGF-βs) and their receptors, TGFBRs, may be considered as candidate genes related to IS susceptibility and natural history. This study explores the transcriptional profile of TGF-βs, TGFBRs, and TGF-β responsive genes in the paravertebral muscles of patients with juvenile and adolescent idiopathic scoliosis (JIS and AIS, resp.). Muscle specimens were harvested intraoperatively and grouped according to the side of the curve and the age of scoliosis onset. The results of microarray and qRT-PCR analysis confirmed significantly higher transcript abundances of TGF-β2, TGF-β3, and TGFBR2 in samples from the curve concavity of AIS patients, suggesting a difference in TGF-β signaling in the pathogenesis of juvenile and adolescent curves. Analysis of TGF-β responsive genes in the transcriptomes of patients with AIS suggested overrepresentation of the genes localized in the extracellular region of curve concavity: LTBP3, LTBP4, ITGB4, and ITGB5. This finding suggests the extracellular region of paravertebral muscles as an interesting target for future molecular research into AIS pathogenesis.

Topics: Adolescent; Adult; Analysis of Variance; Female; Fluorescence; Gene Expression Profiling; Gene Ontology; Humans; Muscle, Skeletal; Oligonucleotide Array Sequence Analysis; Receptors, Transforming Growth Factor beta; RNA, Messenger; Scoliosis; Signal Transduction; Transcription, Genetic; Transcriptome; Transforming Growth Factor beta; Up-Regulation; Young Adult

Comparvative case series. Data was prospectively entered and retrospectively analyzed.. To evaluate the need for distal lumbar interbody fusion when sufficient recombinant human bone morphogenetic protein-2 (rhBMP-2) is used posterolaterally at L5-S1 in long spinal constructs for adult deformity via costs and radiographical and patient-reported outcome comparisons.. Many authors and investigators have suggested that an interbody fusion is mandatory at L5-S1 with long fusion to the sacrum with sacropelvic fixation. Past studies have shown competitive fusion rates using rhBMP-2 versus iliac crest bone graft for long fusions. There are various advocates for anterior lumbar interbody fusion versus posterior lumbar interbody fusion versus transforaminal lumbar interbody fusion (TLIF). The optimal strategy remains elusive.. Fifty-seven patients were studied at one institution. Thirty-one patients had no interbody fusion (NI group) with 20 mg of rhBMP-2 posterolaterally on 10 mL of carrier and 26 patients had TLIF at L5-S1 (TLIF group) with 6 mg of rhBMP-2 in the interbody space along with local bone graft and 6 mg of rhBMP-2 on carrier posterolaterally at L5-S1. Patients were followed for 24 to 87 months (mean follow-up, 3.92 yr). Demographics of the 2 groups were similar.. There were no detected nonunions at L5-S1 in either group. By our limited cost analysis, the expense of performing a TLIF at L5-S1 is higher than that of using extra rhBMP-2 posterolaterally at that segment. Improvement in outcomes scores, namely Scoliosis Research Society-22 and Oswestry Disability Index, were the same statistically in both groups. Blood loss was greater in the TLIF group than the NI group. There were no identified rhBMP-2 adverse events in either group.. Utilization of 20 mg of rhBMP-2 at L5-S1 has the potential to be less expensive than an interbody fusion in most patients having a primary long fusion for adult spinal deformity. The apparent fusion rates at L5-S1 were identical in both groups. Both strategies were successful in regard to improving patient outcomes and achieving apparent solid arthrodesis at the lumbosacral junction, which was the focus of this study.. 2.

Topics: Adult; Aged; Bone Morphogenetic Protein 2; Bone Transplantation; Combined Modality Therapy; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Lumbar Vertebrae; Lumbosacral Region; Male; Middle Aged; Pelvis; Radiography; Recombinant Proteins; Retrospective Studies; Sacrum; Scoliosis; Spinal Fusion; Transforming Growth Factor beta; Treatment Outcome

Matched cohort comparison.. To compare the use of bone morphogenetic protein (BMP) or iliac crest bone graft (ICBG) on the long-term outcomes in patients undergoing long fusions to the sacrum for adult spinal deformity.. No long-term studies beyond a 2-year follow-up have been performed comparing the use of BMP versus ICBG for fusion rates in long fusions to the sacrum in adult spinal deformity.. A total of 63 consecutive patients, from 1997-2006, comprised of 31 patients in the BMP group and 32 patients in the ICBG group, operated on at a single institution with a minimum 4-year follow-up (4-14 yr) were analyzed. Inclusion criteria were ambulators who were candidates for long fusions (thoracic as the upper level) to the sacrum. Exclusion criteria were revisions, neuromuscular scoliosis, ankylosing spondylitis, and patients who had both BMP and ICBG used for fusion. Oswestry Disability Index and 3 domains of the Scoliosis Research Society score were used to assess outcomes.. The 2 groups were similar with respect to age, sex, smoking history, comorbidities, BMI, number of fusion levels and Cobb angles. Eight patients in the BMP group underwent a posterior only, whereas 23 underwent combined anterior and posterior (A/P) surgery. All 32 patients in the ICBG had A/P fusion. The average BMP level was 11.1 mg (3-36 mg). The rate pseudarthrosis was 6.4% (2/31) in the BMP and 28.1% (9/32) in the ICBG group (P = 0.04) using Fisher exact test and odds ratio = 5.67. The fusion rates for BMP group were 93.5% and 71.9% for the ICBG group. Oswestry Disability Indexes were similar between groups. However, the BMP group demonstrated superior sum composite Scoliosis Research Society scores in pain, self-image and function domains (P = 0.02).. BMP is superior to ICBG in achieving fusion in long constructs in adult deformity surgery. The rate of pseudarthrosis was significantly higher in the ICBG group than BMP group. The concentration and dosage of recombinant human bone morphogenetic protein 2 (rhBMP-2) used seems to have an effect on the rate of fusion and pseudarthrosis rate because no patient receiving more than 5 mg per level had apparent or detected pseudarthroses (n = 20/20).. 3.

Topics: Adult; Bone Morphogenetic Protein 2; Bone Transplantation; Cohort Studies; Disability Evaluation; Follow-Up Studies; Humans; Ilium; Middle Aged; Pseudarthrosis; Radiography; Recombinant Proteins; Sacrum; Scoliosis; Spinal Fusion; Spine; Time Factors; Transforming Growth Factor beta; Treatment Outcome

Comparative study.. To compare the radiographic outcome of patients undergoing long spinal deformity surgery to the sacrum/ilium, using either rhBMP-2 without iliac crest bone graft (ICBG) or ICBG without rhBMP-2.. rhBMP-2 has been shown to be more effective in promoting successful bone union in patients undergoing single level lumbar spinal fusion than ICBG. However, to the best of our knowledge, there are no studies that compare the efficacy of rhBMP-2 versus ICBG in long spinal deformity surgery.. To obtain uniform background, we selected patients with adult spinal deformity who underwent primary spinal fusion from the thoracic spine to the sacrum/ilium and had a minimum 2-year follow-up. Fifty-five consecutive patients, consisting of 32 patients who underwent a fusion using ICBG without rhBMP-2 (ICBG group) and 23 patients who underwent a fusion using rhBMP-2 without ICBG (BMP group) were analyzed.. The 2 groups were similar with respect to age, gender, smoking history, comorbidity, and body mass index. The average number of vertebrae fused (11.3 in both groups) and the degree of preoperative deformity (major Cobb angle 58.3 degrees in ICBG group vs. 54.2 degrees in BMP group) were also similar in both groups. All but 2 patients had both anterior and posterior surgery. Both groups were similar in terms of final deformity correction. The average total amount of rhBMP-2 used in the BMP group was 119.2 mg (anterior 11.6 mg/level; posterior 10.0 mg/level). Of the 32 patients in the ICBG group, 9 patients (28.1%) developed a pseudarthrosis, while only 1 of 23 patients (4.3%) in the BMP group developed a pseudarthrosis with the caveat that the follow-up period was shorter in the BMP group (average follow-up of 4.9 vs. 2.7 years).. The pseudarthrosis rate in the BMP group compares favorably to pseudarthrosis rate in ICBG group, suggesting that the use of rhBMP-2 without iliac harvesting leads to a competitive fusion rate in long adult spinal deformity surgery, while avoiding ICBG harvest site morbidity.

Topics: Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Bone Transplantation; Female; Humans; Ilium; Male; Middle Aged; Postoperative Complications; Pseudarthrosis; Recombinant Proteins; Sacrum; Scoliosis; Spinal Fusion; Transforming Growth Factor beta

We carried out a prospective study to determine whether the addition of a recombinant human bone morphogenetic protein (rhBMP-2) to a machined allograft spacer would improve the rate of intervertebral body fusion in the spine. We studied 77 patients who were to undergo an interbody fusion with allograft and instrumentation. The first 36 patients received allograft with adjuvant rhBMP-2 (allograft/rhBMP-2 group), and the next 41, allograft and demineralised bone matrix (allograft/demineralised bone matrix group). Each patient was assessed clinically and radiologically both pre-operatively and at each follow-up visit using standard methods. Follow-up continued for two years. Every patient in the allograft/rhBMP-2 group had fused by six months. However, early graft lucency and significant (> 10%) subsidence were seen radiologically in 27 of 55 levels in this group. The mean graft height subsidence was 27% (13% to 42%) for anterior lumbar interbody fusion, 24% (13% to 40%) for transforaminal lumbar interbody fusion, and 53% (40% to 58%) for anterior cervical discectomy and fusion. Those who had undergone fusion using allograft and demineralised bone matrix lost only a mean of 4.6% (0% to 15%) of their graft height. Although a high rate of fusion (100%) was achieved with rhBMP-2, significant subsidence occurred in more than half of the levels (23 of 37) in the lumbar spine and 33% (6 of 18) in the cervical spine. A 98% fusion rate (62 of 63 levels) was achieved without rhBMP-2 and without the associated graft subsidence. Consequently, we no longer use rhBMP-2 with allograft in our practice if the allograft has to provide significant structural support.

Topics: Adolescent; Adult; Aged; Bone Matrix; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Bone Transplantation; Cervical Vertebrae; Female; Humans; Intervertebral Disc Displacement; Lumbar Vertebrae; Male; Middle Aged; Pain Measurement; Postoperative Complications; Prospective Studies; Radiography; Recombinant Proteins; Reoperation; Scoliosis; Spinal Cord Diseases; Spinal Fusion; Spondylolisthesis; Transforming Growth Factor beta; Treatment Outcome

To investigate the characteristics of the expression of transforming growth factor-beta(1) (TGF-beta(1)) and basic fibroblast growth factor (bFGF) in the apical articular process cartilages of adolescent idiopathic scoliosis (AIS) patients.. The specimens of articular processes of 22 AIS patients and 18 congenital scoliosis (CS) patients were collected during operation. The pathology of the processes was observed with H.E staining. Immunohistochemistry and in situ hybridization were adopted to detect the expression of TGF-beta(1) and bFGF. The differences in the pathological changes, and expression of TGF-beta(1) and bFGF between the apical processes and the end processes, the convex processes and the concave processes, and the AIS processes and CS processes. The images of immunohistochemistry and in situ hybridization were input into the image analysis system and were analyzed semi-quantitatively. The SAS (8.01) software was adopted and (128.1 +/- 50.6 vs 165.4 +/- 59.2, 126.5 +/- 47.0 vs 168.3 +/- 46.8; 76.6 +/- 29.9 vs 96.4 +/- 28.4, 73.7 +/- 31.6 vs 101.8 +/- 39.4; 77.1 +/- 52.2 vs 114.4 +/- 59.4, and 69.5 +/- 40.1 vs 109.8 +/- 51.0 (P < 0.05) was defined as the significant levels.. The expression of TGF-beta(1) and the expression of bFGF were not significantly different between the AIS patients and the CS patients. The TGF-beta(1) expression in the concave side of the apical vertebrae of the AIS group was 165.4 +/- 59.2, significantly higher than that in the convex sides (128.1 +/- 50.6, P = 0.03), and the TGF-beta(1) expression in the concave side of the apical vertebrae of the CS group was 168.3 +/- 46.8, significantly higher than that of the convex side (126.5 +/- 47.0, P = 0.02). However, there was no statistically significant differences in the TGF-beta(1) expression between the concave and convex sides of the upper and lower end vertebrae and between the upper and lower end vertebrae. The bFGF expression in the concave side of the apical vertebrae of the AIS group, and the bFGF expression in the concave side of the apical vertebrae of the CS group was 101.8 +/- 39.4, significantly higher than that of the convex side (73.7 +/- 31, P = 0.02). However, there were no statistically significant differences in the bFGF expression between the concave and convex sides of the upper and lower end vertebrae and between the upper and lower end vertebrae.. The cartilages of the apical processes show some signs of regression and hypoplasia in AIS patients, especially at the concave side in comparison with the convex side. Increase of TGF-beta(1) and bFGF in the concave sides of apical processes in AIS may be the results of reconstruction of extracellular matrix and the compensation reactions which are caused by abnormal biomechanical forces, especially compressive stresses.

Topics: Adolescent; Animals; Cartilage, Articular; Child; Fibroblast Growth Factor 2; Humans; Rabbits; Scoliosis; Transforming Growth Factor beta; Zygapophyseal Joint

Topics: Activin Receptors, Type I; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Bone Transplantation; Cervical Vertebrae; Humans; Lumbar Vertebrae; Orthopedics; Prostheses and Implants; Proteins; Recombinant Proteins; Scoliosis; Spinal Cord Injuries; Spinal Diseases; Spinal Fusion; Transforming Growth Factor beta

To compare the expression of cytokines and core protein of proteoglycan in the scoliotic concave and convex cartilaginous endplate using immunohistochemical staining.. To define the possible role of transforming growth factor beta 1 (TGFbeta1), basic fibroblast growth factor (bFGF), and core protein of proteoglycan in the development of adolescent idiopathic scoliosis.. Changes in the endplate composition have been implicated as possible etiologic factors in the pathogenesis of adolescent idiopathic scoliosis. Cytokines have exclusive effects on cartilage. Thus comparing the expression of the cytokines and matrix on the convex and concave sides of scoliotic endplate tissues may help to understand the role of endplate tissues in the induction and/or progression of idiopathic scoliosis.. The convex and concave half of cartilage endplate was collected at the apex and end vertebrae from 12 patients. The expression of TGFbeta1, bFGF, and core protein on both sides was examined with the immunohistochemistry method, and results were analyzed with the image analysis system.. TGFbeta1, bFGF, and core protein of proteoglycan were all expressed in the cytoplasm of chondrocytes in the cartilaginous endplate. The area density and quantity density of TGFbeta1 and bFGF on the concave side are expressed in an even significantly higher level than that on the convex side (P > or = 0.05). The expression of the core protein of proteoglycan on the convex side is higher than that on the concave side, the difference is not significant (P > 0.05).. There was a significantly higher expression of TGFbeta1 and bFGF, although a lower expression of the core protein on the concave side, which suggests a possible etiological factor or a secondary change in the development of adolescent idiopathic scoliosis.

Topics: Adolescent; Adult; Aggrecans; Cartilage, Articular; Child; Chondrocytes; Chondroitin Sulfate Proteoglycans; Cytoplasm; Extracellular Matrix Proteins; Female; Fibroblast Growth Factor 2; Humans; Immunohistochemistry; Lectins, C-Type; Male; Proteoglycans; Scoliosis; Spine; Staining and Labeling; Tissue Distribution; Transforming Growth Factor beta; Transforming Growth Factor beta1