Use Of Bone Morphogenic Protein Research Articles

Improvements in Quality, Safety and Costs Associated with Use of Implant Registries Within a Health System

Clinical quality registries (CQRs) are intended to enhance quality, safety, and cost reduction using real-world data for a self-improving health system. Starting in 2001, Kaiser Permanente established several medical device CQRs as a quality improvement initiative. This report examines the contributions of these CQRs on improvement in health outcomes, changes in clinical practice, and cost-effectiveness over the past 20 years. Eight implant registries were instituted with standardized collection from the electronic health record and other institutional data sources of patient characteristics, medical comorbidities, implant attributes, procedure details, surgical techniques, and outcomes (including complications, revisions, reoperations, hospital readmissions, and other utilization measures). A rigorous quality control system is in place to improve and maintain the quality of data. Data from the Implant Registries form the basis for multiple quality improvement and patient safety initiatives to minimize variation in care, promote clinical best practices, facilitate recalls, perform benchmarking, identify patients at risk, and construct reports about individual surgeons. Following the inception of the Implant Registries, there was an observed (1) reduction in opioid utilization following orthopedic procedures, (2) reduction in use of bone morphogenic protein during lumbar fusion allowing for cost savings, (3) reduction in allograft for anterior cruciate ligament reconstruction and subsequent decrease in organizationwide revision rates, (4) cost savings through expansion of same-day discharge programs for joint arthroplasty, (5) increase in the use of cement fixation in the hemiarthroplasty treatment of hip fracture, and (6) organizationwide discontinuation of an endograft device associated with a higher risk for adverse outcomes following endovascular aortic aneurysm repair. The use of Implant Registries within our health system, along with clinical leadership and organizational commitment to a learning health system, was associated with improved quality and safety outcomes and reduced costs. The exact mechanisms by which such registries affect health outcomes and costs require further study.

Bone Morphogenic Protein and Mesenchymal Stem Cells to Regenerate Bone in Calvarial Defects: A Systematic Review.

The use of bone morphogenic protein and mesenchymal stem cells has shown promise in promoting bone regeneration in calvarial defects. However, a systematic review of the available literature is needed to evaluate the efficacy of this approach. We comprehensively searched electronic databases using MeSH terms related to skull defects, bone marrow mesenchymal stem cells, and bone morphogenic proteins. Eligible studies included animal studies that used BMP therapy and mesenchymal stem cells to promote bone regeneration in calvarial defects. Reviews, conference articles, book chapters, and non-English language studies were excluded. Two independent investigators conducted the search and data extraction. Twenty-three studies published between 2010 and 2022 met our inclusion criteria after a full-text review of the forty-five records found in the search. Eight of the 23 studies used mice as models, while 15 used rats. The most common mesenchymal stem cell was bone marrow-derived, followed by adipose-derived. BMP-2 was the most popular. Stem cells were embedded in Scaffold (13), Transduction (7), and Transfection (3), and they were delivered BMP to cells. Each treatment used 2 × 104-1 × 107 mesenchymal stem cells, averaging 2.26 × 106. Most BMP-transduced MSC studies used lentivirus. This systematic review examined BMP and MSC synergy in biomaterial scaffolds or alone. BMP therapy and mesenchymal stem cells in calvarial defects, alone, or with a scaffold regenerated bone. This method treats skull defects in clinical trials. The best scaffold material, therapeutic dosage, administration method, and long-term side effects need further study.

Trends, payments, and costs associated with BMP use in Medicare beneficiaries undergoing spinal fusion

Bone morphogenic protein (BMP) promotes bony fusion but increases costs. Recent trends in BMP use among Medicare patients have not been well-characterized. To assess utilization trends, complication, payments, and costs associated with BMP use in spinal fusion in a Medicare-insured population. Retrospective cohort study. Total of 316,070 patients who underwent spinal fusion in a 20% sample of Medicare-insured patients, 2006 to 2015. Utilization trends across time and geography, complications, payments, and costs. Patients were stratified by fusion type and diagnosis. Multivariable logistic and linear regression were used to adjust for the effect of baseline characteristics on complications and total payments or cost, respectively. BMP was used in 60,249 cases (19.1%). BMP utilization rates decreased from 23.1% in 2006 to 12.0% in 2015, most significantly in anterior cervical (7.5%-3.1%), posterior cervical (17.0%-8.3%), and posterior lumbar fusions (31.5%-15.8%). There are significant state- and region-level geographic differences in BMP utilization. Across all years, states with the highest BMP use were Indiana (28.5%), Colorado (26.6%), and Nevada (25.7%). States with the lowest BMP use were Maine (2.3%), Vermont (8.2%), and Mississippi (10.4%). After multivariate risk adjustment, BMP use was associated with decreased overall complications in thoracic (odds ratios [OR] [95% confidence intervals [CI]): 0.89 [0.81-0.99]) and anterior lumbar fusions (OR [95% CI]: 0.89 [0.84-0.95]), as well as increased reoperation rates in anterior cervical (OR [95% CI]: 1.11 [1.04-1.19]), posterior cervical (OR (95% CI): 1.14 (1.04-1.25)), thoracic (OR (95% CI): 1.32 (1.23-1.41)), and posterior lumbar fusions (OR (95% CI): 1.11 (1.06-1.16)). BMP use was also associated with greater total costs, independent of fusion type, after multivariate risk adjustment (p<.0001). Payments, however, were comparable between groups in anterior and posterior cervical fusion with or without BMP. BMP use was associated with greater total payments in thoracic, anterior lumbar, and posterior lumbar fusions. Notably, the difference in payments was smaller than the associated cost increase in all fusion types. BMP use has declined across all fusion types over the last decade, after a peak in 2007. While BMP is associated with greater costs, reimbursement does not increase proportionally with BMP cost.

Factors Which Predict Adverse Outcomes in Anterior Cervical Discectomy and Fusion Procedures in the Nonelderly Adult Population.

Retrospective cohort. The largest published cohort of anterior cervical discectomy and fusion (ACDF) patients was queried to better characterize demographic and operative factors that predict 90-day complication and 2-year reoperation risk. The MarketScan Database was queried from 2007 to 2016 to identify adult patients until 65 years, who underwent an ACDF procedure using International Classification of Diseases 9th Version (ICD-9) and Current Procedural Terminology (CPT) codes. MarketScan is a national insurance claims database that contains millions of patient records across all 50 states. Multivariate logistic regression was used to identify factors associated with complications until 90 days and reoperations until 2 years. Of 138,839 ACDF procedures, 8500 patients (6.1%) experienced a complication within 90 days of the ACDF, and 7433 (5.4%) underwent surgical revision by 2 years. While the use of anterior cervical plating did not predict 2-year reoperation, it was associated with dramatically reduced 90-day complication risk (adjusted odds ratio [aOR]: 0.32; 95% confidence interval [CI]: 0.30-0.34; P <0.001). Upon multivariate analysis, female sex (aOR: 0.83; 95% CI: 0.79-0.87; P <0.001) was associated with decreased risk of 2-year reoperation, while depression predicted a 50% increase in reoperation risk (aOR: 1.51; 95% CI: 1.43-1.59; P <0.001). The single largest factor associated with reoperation risk, however, was the presence of a 90-day postoperative complication (aOR: 1.79; 95% CI: 1.66-1.94; P <0.001). Increased patient comorbidities and the use of bone morphogenic protein were found to increase the risk for postoperative complications, while cervical plating was associated with a strong decline in this risk. In addition, poor patient mental health outweighed the adverse of impact of other comorbidities on 2-year revision risk. The presence of a postoperative complication was the key modifiable risk factor associated with reoperation risk. Conclusions from this study may help surgeons better identify high-risk ACDF patients for more careful patient selection, counseling, informed consent, and management.

Risk Assessment of Anterior Lumbar Interbody Fusion Access in Degenerative Spinal Conditions.

This was a retrospective cohort study. Develop an evidence-based preoperative risk assessment scoring system for patients undergoing anterior lumbar interbody fusion (ALIF). ALIF may hold advantages over other fusion techniques in sagittal restoration and fusion rates, though it introduces unique risks to vascular and abdominal structures and thus possibly increased risk of operative morbidity. Primary, 1 or 2-level ALIFs were identified in a surgical registry. Baseline characteristics were recorded. Axial magnetic resonance imagings at L4-L5 and L5-S1 were reviewed for vascular confluence/bifurcation or anomalous structures, and measured for operative window size/slope. To assess favorable outcomes, a clinical grade was calculated: (clinical grade=blood loss×operative duration), higher value indicating poorer outcome. To establish a risk scoring system, a base risk score algorithm was established and stratified into 5 categories: high, high to intermediate, intermediate, intermediate to low, and low. Modifiers to base risk score included age, body mass index, operative level, history of bone morphogenic protein use, calcified vasculature, spondylolisthesis grade, working window size and slope, and abnormal vasculature. Modifiers were weighted for contribution to surgical risk. A total risk score was calculated and evaluated for strength of association with clinical outcome grades by Pearson correlation coefficient. A total of 65 patients were included. Mean clinical outcome grade was 5.6, mean total risk score 21.3±21.5. Multilevel procedures (L4-S1) mean total risk score was 57.3±7.8. L4-L5 mean total risk score was 23.6±5.2; L5-S1 mean total risk score 8.3±6.6. Correlation analysis demonstrated a significant and strong relationship (| r |=0.753; P <0.001) between total risk scores and clinical outcome grades. Calculated ALIF risk scores significantly correlated with operative duration and blood loss. This scoring system represents a potential framework to facilitate clinical decision-making and risk assessment for potential ALIF candidates with degenerative spinal pathologies.

Factors which predict adverse events following surgery in adults with cervical spinal deformity.

The aim of this study was to identify the risk factors for adverse events following the surgical correction of cervical spinal deformities in adults. We identified adult patients who underwent corrective cervical spinal surgery between 1 January 2007 and 31 December 2015 from the MarketScan database. The baseline comorbidities and characteristics of the operation were recorded. Adverse events were defined as the development of a complication, an unanticipated deleterious postoperative event, or further surgery. Patients aged < 18 years and those with a previous history of tumour or trauma were excluded from the study. A total of 13,549 adults in the database underwent primary corrective surgery for a cervical spinal deformity during the study period. A total of 3,785 (27.9%) had a complication within 90 days of the procedure, and 3,893 (28.7%) required further surgery within two years. In multivariate analysis, male sex (odds ratio (OR) 0.90 (95% confidence interval (CI) 0.8 to 0.9); p = 0.019) and a posterior approach (compared with a combined surgical approach, OR 0.66 (95% CI 0.5 to 0.8); p < 0.001) significantly decreased the risk of complications. Osteoporosis (OR 1.41 (95% CI 1.3 to 1.6); p < 0.001), dyspnoea (OR 1.48 (95% CI 1.3 to 1.6); p < 0.001), cerebrovascular accident (OR 1.81 (95% CI 1.6 to 2.0); p < 0.001), a posterior approach (compared with an anterior approach, OR 1.23 (95% CI 1.1 to 1.4); p < 0.001), and the use of bone morphogenic protein (BMP) (OR 1.22 (95% CI 1.1 to 1.4); p = 0.003) significantly increased the risks of 90-day complications. In multivariate regression analysis, preoperative dyspnoea (OR 1.50 (95% CI 1.3 to 1.7); p < 0.001), a posterior approach (compared with an anterior approach, OR 2.80 (95% CI 2.4 to 3.2; p < 0.001), and postoperative dysphagia (OR 2.50 (95% CI 1.8 to 3.4); p < 0.001) were associated with a significantly increased risk of further surgery two years postoperatively. A posterior approach (compared with a combined approach, OR 0.32 (95% CI 0.3 to 0.4); p < 0.001), the use of BMP (OR 0.48 (95% CI 0.4 to 0.5); p < 0.001) were associated with a significantly decreased risk of further surgery at this time. The surgical approach and intraoperative use of BMP strongly influence the risk of further surgery, whereas the comorbidity burden and the characteristics of the operation influence the rates of early complications in adult patients undergoing corrective cervical spinal surgery. These data may aid surgeons in patient selection and surgical planning. Cite this article: Bone Joint J2021;103-B(4):734-738.

Do PEEK Rods for Posterior Instrumented Fusion in the Lumbar Spine Reduce the Risk of Adjacent Segment Disease?

Polyetheretherketone (PEEK) rods were clinically introduced in the mid-2000s as an alternative to titanium (Ti) rods for posterior instrumented lumbar spine fusion, theorized to reduce the risk of adjacent segment disease (ASD). However, few studies have follow-up beyond 2 years. Consequently, we conducted a matched cohort study using data from Kaiser Permanente's spine registry to compare the 2 rod systems and risk for outcomes. Patients aged ≥18 undergoing first posterior lumbar fusion for a degenerative diagnosis from 2009 to 2018 using either a PEEK or a Ti rod were identified. Fusions using Ti rods were 2:1 propensity score matched to PEEK rods on the following factors: patient age, body mass index, smoking, American Society of Anesthesiologists classification, diagnosis, interbody use, bone morphogenic protein use, number of levels fused, fusion levels, and operative year. The matched sample included 154 PEEK and 308 Ti fusions. We used Cox regression to evaluate ASD and nonunion, and logistic regression to evaluate 90-day emergency department (ED) visit, readmission, and complication. We did not observe a difference in risk for ASD (hazard ratio = 1.02, 95% confidence interval [CI] = 0.66-1.59) or ED visit (odds ratio [OR] = 0.88, 95% CI = 0.48-1.59). A lower likelihood of readmission (OR = 0.34, 95% CI = 0.13-0.94) was observed following PEEK fusion compared with Ti. No nonunions or 90-day complications were observed for the PEEK group; 5 (2-year cumulative incidence = 0.7%) nonunions and 4 (1.3%) complications were observed for the Ti group. Our multicenter study did not support the hypothesis that PEEK rods are associated with a lower ASD risk. Reasons for readmission need to be identified to better understand the differences observed here. Further study of patients with TLIF using Ti and PEEK rods and posterolateral fusion with Ti and PEEK rods is needed. The present study adds to the literature supporting their midterm effectiveness of PEEK rods compared with Ti rods for both their safety and their effectiveness at the 5-7-year follow-up. 3.

Oro-Nasal Communication.

Breach in the palatal vault leading to an abnormal communication between oral and nasal cavity is known as oro-nasal communication. It is an uncommon presentation in day-to-day clinical practice except in some patients of cleft lip and palate.Etiology may be congenital or acquired. Alveolar and palatal cleft defects are the most common etiological factor. The acquired causes may be trauma, periapical pathology, infections, neoplasms, postsurgical complications, and radio and chemo necrosis.Clinical features like nasal regurgitation of food, defective speech, fetid odor, bad taste, and upper respiratory tract and ear infection are associated with oro-nasal communication.Management depends upon the size and site of defect, age of patient, and associated comorbidity. The definitive management is always surgical. Two layered closure provides greater support and stability and reduces the risk of failure. Palatal rotational flaps are suitable for smaller defects. The other local flaps are buccal mucosal flap, tongue flap, and facial artery myomucosal flap. Temporoparietal galeal flap, turbinate flap, free radial forearm flap, and scapular flap have also been successfully used for closure of oronasal communication. Newer procedures like the use of bone morphogenic protein, acellular dermal matrices, human amniotic membrane, and distraction osteogenesis have been tried successfully. The rate of recurrence is high.Unsuccessful surgical attempts and larger defects associated with compromised medical conditions are better managed nonsurgically with obturator incorporating the missing teeth.

The use of bone morphogenic protein in cervical spine fusions: A literature review

Bone morphogenic proteins (BMPs) are signaling proteins which promote osteogenesis and facilitate fusion of bone in lumbar spinal procedures. Research is targeted towards the benefits of use in lumbar fusions and the use of BMPs in anterior lumbar interbody fusions (ALIFs) is FDA approved. However, fewer studies have detailed adverse effects and use in cervical fusion procedures, which is currently considered “off-label”. BMP use in cervical fusion procedures may improve radiographic outcomes and functionality of patients in the long term, though overall rates of serious medical complications from use are increased in the early postoperative period. Complications of BMP use include: ectopic bone formation, inflammation, swelling and seroma. These adverse outcomes can be much more fatal in the cervical spine as compared to their occurrence in the lumbar spine. Because of the adverse effects, low doses of BMPs have been recommended, reducing risks of complications while still aiding in the fusion process. Additionally, BMPs have not been approved for use in pediatric populations, though off-label use in fusion patients with paucity of autologous bone may prove advantageous. Patients who are considered high risk for pseudoarthrosis may also be candidates for the use of BMPs in cervical procedures. Physicians and patients should be aware of the potential adverse outcomes of using BMPs in cervical fusion procedures and weigh the risks and benefits before deciding on use.

The use of bone morphogenic protein in spinal deformity surgery

The use of BMP in spinal deformity surgery is becoming common. Deformity spine surgeries have a high non-union rate due to the need to fuse many levels combined with a limited amount of autograft iliac crest bone and often the need for fusion at the lumbosacral junction. This situation has created a strong desire for a bone graft substitute/enhancer such as BMPs. However, there are no set guidelines with regards to dosage or method of utilization. This article will review the limited number of relevant studies, and make recommendations regarding BMP use in spinal deformity surgery.Bone morphogenic protein (BMP) as an adjunct to standard grafting techniques has become more and more common in spinal deformity surgery. There are several issues specific to deformity surgery that make these cases suitable for the use of BMP: the relatively high non-union rate due to the multiple fusion levels, the limited amount of iliac crest available for harvest, and the need for 360° fusions at the lumbosacral junction. However, there are concerns about using BMP for these surgeries, particularly as there are no set guidelines with regards to dosage as well as the method of utilization. In addition, the use of BMP posteriorly is technically off-label with regards to FDA approval, leaving compensation for its use in this scenario somewhat up in the air.

Primary vs. Revision Ankle Arthrodesis

Category: Ankle Arthritis Introduction/Purpose: The current standard treatment for failed ankle arthrodesis is a revision ankle arthrodesis. However, there is limited literature addressing postoperative outcomes in patients with revision tibiotalar arthrodesis. The objectives of the retrospective study were to compare (1) demographics, (2) surgical technique, (3) postoperative fusion rates, and (4) postoperative complication rates in patients with primary vs. revision tibiotalar arthrodesis. Methods: Between March 2002 and November 2014, 455 ankle arthrodeses were performed in our institution. There were 234 male and 221 female patients with a mean age of 55.6 ± 15.1 years (18.0-88.8). The mean weight, height, and body mass index (BMI) were 90.3 ± 21.3 kg (46-218), 172.8 ± 13.6 cm (147-208), and 30.2 ± 6.3 kg/m2 (18.9-61.7), respectively. Both patient groups were compared with regard to demographics including gender, weight, height, BMI, ASA classification, smoking, alcohol use, and comorbidities. The surgical technique has been analyzed in both groups including surgical approach, main fixation type, allograft/autograft use, and use of bone morphogenic protein. Finally, fusion rate and time to complete osseous fusion were analyzed. Complication rates including wound complications, deep vein thrombosis/pulmonary embolism, and any secondary procedures were described in both groups. The mean time to final follow-up was 38.3 ± 27.4 months (12.0-150.4). Results: There were 385 and 70 patients with primary and revision arthrodesis, respectively. Demographics and comorbidities were comparable in both groups. All revision surgeries were open procedures, while 63 of 385 primary ankle arthrodeses were performed arthroscopically. The most common main fixation type in patients with primary ankle arthrodesis was a screw construct, while plates were most common for revisions (P &lt; 0.001). The use of autograft was comparable in both groups (P = 0.886), however allograft was used more frequently in the revision arthrodesis group (P &lt; 0.001). The rate of osseous union was comparable in both groups with 90.4% and 91.4% in patients with primary and revision arthrodesis, respectively (P = 0.735). The complication rate was comparable in both groups. Conclusion: The osseous union rates and complication rates were comparable in both patient groups, with primary and revision ankle arthrodesis.

Fracture non-union epidemiology and treatment

Fracture non-union remains a clinical problem despite advances in the understanding of basic science and technology. Each fracture has a unique personality as does the patient suffering the injury. Thus, each case must be treated on an individual basis. This article defines the problem of fracture non-union and reports recent epidemiological studies. We discuss relevant risk factors and methods for assessing patients who have a tendency toward fracture non-union. There are many treatment options for patients with non-union, where a number of these modalities are still under review. We discuss current evidence with the use of bone morphogenic protein, platelet-rich plasma and low-intensity pulsed ultrasound to augment the treatment of fracture non-union.

Lumbar spine neuroarthropathy (Charcot joint) caused by a myxopapillary ependymoma

A 57-year old highly functional paraplegic man status post T10–S1 laminectomy and tumor resection followed by cobalt irradiation of a myxopapillary ependymoma 47 years previously, presented with increasing lumbar pain when upright and when transitioning from his wheelchair. Pain improved when supine. Lower extremity pain and spasms/spasticity were treated 30 years previously with a L3 and L4 rhizotomy/nerve transection. Continence required bladder selfcatheterization and maintenance of a colostomy. Examination was notable for flaccid paraplegia (longstanding and unchanged), a T10 segmental sensory level (also longstanding) and lumbar kyphosis. Current MRI (Fig. 1) revealed a pseudoarthrosis at the L2–3 disc interspace (1). Charcot joints may be seen in patients with loss of sensation (deafferentation) affecting a limb or trunk and are most often a complication of diabetes, syringomyelia or spinal cord trauma (2). Charcot arthropathies are however rare in spine. Spinal neuroarthropathies are induced by abnormal motion between vertebral bodies that lead to articular fracture and joint disruption together with disc degeneration and endplate fragmentation. These processes eventually lead to joint widening and subluxation that may be very deforming. The predominant changes may be atrophic, as in this case, with endplate and vertebral body resorption or, more commonly, there may be hypertrophic changes characterized by osteophyte formation, bony sclerosis and formation of a paraspinal mass of mixed bone formation and fragmentation [1]. The radiographic differential diagnosis includes pathologic vertebral fracture from primary or metastatic tumor or from osteomyelitis. These entities may be distinguishable most reliably on MRI with identification of an enhancing tumor mass or abnormal inflammatory infiltration of the disc space and paravertebral tissues with high T2 signal along with enhancement of the inflammatory tissue with or without abscess formation. In comparison, Charcot spine shows endplate and facet disruption, subluxation, bone fragmentation, intradiscal vacuum phenomena or intradiscal fluid collection [2]. Limited long-term outcome data on the surgical treatment of spinal Charcot joints is available. Nonetheless, the principles of surgical intervention focus on the immobilization of the unstable pseudoarthrosis. Strategies include circumferential debridement and stabilization across the pseudoarthrosis, use of a 4-rod construct to provide greater rigidity and improved biomechanical stress distribution, extension of constructs to the pelvis, and adjunctive use of bone-morphogenic protein [3]. M. C. Chamberlain (&) Department of Neurology, Seattle Cancer Care Alliance, Fred Hutchison Cancer Research Center, University of Washington, 825 Eastlake Ave East, MS G4940, Box 19023, Seattle, WA 98109, USA e-mail: chambemc@u.washington.edu; chambemc@uw.edu

Current Approaches of Bone Morphogenetic Proteins in Dentistry

Bone morphogenic proteins (BMPs) are a group of osteoinductive proteins obtained from nonmineralized bone matrix; they are capable of stimulating the differentiation of pluripotent mesenchymal cells to osteoprogenitor cells. They have become a likely treatment option, given their action on regeneration and remodeling of bone lesions and increasing the bone response around alloplastic materials. It may be feasible in the near future for BMPs to replace autologous and allogenic bone grafts. The application of specific growth factors for osteoinduction without using a bone graft constitutes a real impact on bone regeneration. The use of BMP is not only focused on osteogenic regeneration: There are a variety of studies investigating other properties, such as periodontal or dental regeneration from the conservative viewpoint. In this review, we will highlight the role of the BMP in bone, periodontal and dental regeneration.

Complications of Anterior and Posterior Lumbar Fusion with Use of Bone Morphogenic Proteins

The use of bone morphogenetic proteins (BMP) as an adjunct to spinal fusion has increased since FDA approval in 2002. The incidence of postoperative complications with the use of BMP, though, reported in case series and larger IDE trials, is not well characterized after lumbar fusions.

Fibroblast growth factor 2 inhibits bone morphogenetic protein 9-induced osteogenic differentiation of mesenchymal stem cells by repressing Smads signaling and subsequently reducing Smads dependent up-regulation of ALK1 and ALK2

Understanding the interactions between growth factors and bone morphogenic proteins (BMPs) signaling remains a crucial issue to optimize the use of mesenchymal stem cells (MSCs) and BMPs in bone tissue engineering. BMP9 is highly capable of promoting osteogenic differentiation of MSCs. Fibroblast growth factor 2 (FGF2) is abundantly secreted during the healing process of fractures or in surgery bone sites. Herein, we explore the detail effect of FGF2 on BMP9-induced osteogenic differentiation of MSCs. It was found that FGF2 inhibited BMP9-induced osteogenic differentiation by blocking BMP9-induced Smads signaling and subsequently reducing Smads dependent up-regulation of ALK1 and ALK2 in MSCs. This effect was rescued by exogenous expression of ALK1 and ALK2, which are proved to be receptors for BMP9. Our results discovered a clue to explain the mechanism involved in the inhibitory effect of FGF2 on BMP9-induced osteogenic differentiation of MSCs. This crosstalk between FGF2 and BMP9 should be emphasized in the future use of BMP9 in therapeutic purpose of fracture repair.

Complications from minimally invasive lumbar interbody fusion: Experience from 100 patients

Minimally invasive lumbar fusion is well described and is reported to offer significant advantages to patients in terms of blood loss, a reduction in post-operative pain and a quicker recovery. However, this technique may expose patients to a greater risk of complications when compared to open lumbar instrumented fusion that may negate these advantages. Between January 2007 and March 2001, we conducted a prospective observational study of 100 consecutive patients (48 males and 52 females, mean age of 54years) to investigate complications occurring from minimally invasive lumbar interbody fusion surgery using an image-guided technique. All patients underwent post-operative CT scans to assess implant placement. Scanning was repeated at 6months to assess bony fusion. We observed the following complications: 2.5% (11/435) pedicle screw misplacement, 1.7% (2/120) interbody cage misplacement; 0.8% (1/120) interbody cage migration; 0.8% (1/120) patients requiring a post-operative blood transfusion; 2% (2/100) venous thrombo-embolism and 3% (3/100) patients with complications thought to be related to the use of bone morphogenic protein. There were no occurrences of infection and no cerebrospinal fluid leaks. We concluded that the rate of complications from minimally invasive lumbar interbody fusion is low, and compares favourably with the rates of complication from open procedures. Moreover, computerised navigation systems can be used in place of real-time fluoroscopy to guide implant placement, without an increase in the rate of complications.

Growth factors in oral and maxillofacial surgery: potentials and challenges.

A growth factor (GF) is a naturally occurring substance capable of stimulating cellular growth, proliferation, and cellular differentiation, one of the key factors for tissue regeneration. Usually, it is a protein or a steroid hormone, with unique functions according to the need of the body. For example, bone morphogenic proteins (BMPs) stimulate bone cell differentiation, whereas fibroblast GFs and vascular endothelial GFs trigger blood vessel differentiation (angiogenesis)1. Various GFs have been tested in the field of oral and maxillofacial surgery to regenerate defective tissues and to enhance the therapeutic effect of conventional treatment. Among GFs, BMP-2, and BMP-7 have been predominantly studied for clinical applications and used in combination with collagen/collagen composite scaffolds2-5. To date, it has been possible to reconstruct mandibular defect measuring 4 to 8 cm, maxillary sinus augmentation, and cleft alveolus using BMP-2 or BMP-7 combined with collagen sponge as carrier2-5. Based on previous controlled studies, in the United States, BMP-2, BMP-7 are now commercially available for clinical use; the use of BMPs is approved by the Food and Drug Administration (FDA) for sinus augmentation and alveolar ridge augmentation associated with extraction sockets5. Nowadays, beyond these approved applications, the use of BMPs to treat several refractory diseases--including bisphosphonate-related osteonecrosis of the jaw (BRONJ)--is being attempted in the field of oral and maxillofacial surgery6. As another popular GF in our field, platelet-derived growth factor (PDGF) is known as a 'starter' of wound healing process when a tissue needs regeneration. Therefore, it is known to be effective for both soft and hard tissues. So far, periodontal defect and alveolar bone defect have been successfully regenerated using PDGF, which is also commercially available. Transforming growth factor (TGF)-β and insulin-like growth factor (IGF) may be the next candidates of commercially available products following BMPs and PDGF. TGF-β and IGF play an important role in cartilage regeneration in the temporomandibular joint, although those are somehow effective for a variety of cells2.

Takotsubo Cardiomyopathy following a L2–L5 Laminectomy and Fusion In Situ with Bone Morphogenic Protein

Takotsubo cardiomyopathy (TC) is a rare, transient cardiomyopathy, with symptoms mimicking myocardial infarction. It has been reported to typically occur in postmenopausal women and is often triggered by an intense physical or emotional event with stimulation of the sympathetic response; the exact etiology, however, is uncertain. Bone morphogenic protein (BMP) is widely used in spinal fusions and has been associated with numerous perioperative complications. BMP is known to stimulate sympathetic pathways. In this paper, we present the case of a patient with a 7-hour episode of TC after a spinal fusion with bone morphogenic protein. The patient's symptoms resolved and long-term followup has been uneventful. This is the first paper to describe TC in the setting of spine or other major orthopaedic surgery and it suggests another possible area for further investigation in peri-operative events potentially associated with the use of bone morphogenic protein.

Fibroblast growth factor 2 inhibits up-regulation of bone morphogenic proteins and their receptors during osteoblastic differentiation of human mesenchymal stem cells

Understanding the interactions between growth factors and bone morphogenic proteins (BMPs) signaling remains a crucial issue to optimize the use of human mesenchymal stem cells (HMSCs) and BMPs in therapeutic perspectives and bone tissue engineering. BMPs are potent inducers of osteoblastic differentiation. They exert their actions via BMP receptors (BMPR), including BMPR1A, BMPR1B and BMPR2. Fibroblast growth factor 2 (FGF2) is expressed by cells of the osteoblastic lineage, increases their proliferation and is secreted during the healing process of fractures or in surgery bone sites. We hypothesized that FGF2 might influence HMSC osteoblastic differentiation by modulating expressions of BMPs and their receptors. BMP2, BMP4, BMPR1A and mainly BMPR1B expressions were up-regulated during this differentiation. FGF2 inhibited HMSCs osteoblastic differentiation and the up-regulation of BMPs and BMPR. This effect was prevented by inhibiting the ERK or JNK mitogen-activated protein kinases which are known to be activated by FGF2. These data provide a mechanism explaining the inhibitory effect of FGF2 on osteoblastic differentiation of HMSCs. These crosstalks between growth and osteogenic factors should be considered in the use of recombinant BMPs in therapeutic purpose of fracture repair or skeletal bioengineering.