Current and future clinical applications of bone morphogenetic proteins in orthopaedic trauma surgery.
Ontology highlight
ABSTRACT:
SUBMITTER: Bishop GB
PROVIDER: S-EPMC2266667 | biostudies-other | 2007 Dec
REPOSITORIES: biostudies-other
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Project description:Bone morphogenetic proteins (BMPs) are members of the TGF? superfamily of secreted cysteine knot proteins that includes TGF?1, nodal, activins and inhibins. BMPs were first discovered by Urist in the 1960s when he showed that implantation of demineralized bone into intramuscular tissue of rabbits induced bone and cartilage formation. Since this seminal discovery, BMPs have also been shown to play key roles in several other biological processes, including limb, kidney, skin, hair and neuronal development, as well as maintaining vascular homeostasis. The multifunctional effects of BMPs make them attractive targets for the treatment of several pathologies, including bone disorders, kidney and lung fibrosis, and cancer. This review will summarize current knowledge on the BMP signalling pathway and critically evaluate the potential of recombinant BMPs as pharmacological agents for the treatment of bone repair and tissue fibrosis in patients.
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Project description:BackgroundMany articles on bone morphogenetic proteins (BMPs) have been published. Bibliometric analysis is helpful to determine the most influential studies in a specific field. This bibliometric analysis is aimed at identifying and analyzing the top 50 most-cited articles on the dental applications of BMPs.MethodsAn electronic search was conducted using the Web of Science (WoS) "All Databases" without any restriction of language, study design, or publication year. Of 1341 publications, the top 50 were included based on their citation count. After downloading the full texts, their bibliometric data including publication title, authorship, citation count, current citation index 2019, citation density, year of publication, country and institution of origin, journal of publication, type of BMP, study design, evidence level of publication, and keywords were extracted and analyzed.ResultsThe citation counts for the top 50 publications ranged from 81 to 557 (median 113.5). The most prolific year was 1997 (n = 7). Wikesjö UM (n = 12) and Wozney JM (n = 11) were the major contributors in this study. Most of the articles were generated primarily from the USA (n = 24), with Loma Linda University Medical Center, USA being the most prolific institution (n = 5). Majority of the articles were published in the Clinical Oral Implants Research and Journal of Periodontology, with nine publications each. Most of the publications were animal studies (n = 30) and focused on BMP-2 (n = 39). Most of the articles were within evidence level V (n = 36). The most frequently used keyword in the top articles was "bone regeneration" (n = 23).ConclusionThe present study presents insights into the past and recent trends in the applications of BMPs in dentistry. A statistically significant association was observed between citation count, citation density, and age of publication.
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Project description:The aim of this systematic literature review was to assess the clinical level of evidence of commercially available demineralised bone matrix (DBM) products for their use in trauma and orthopaedic related surgery.A total of 17 DBM products were used as search terms in two available databases: Embase and PubMed according to the Preferred Reporting Items for Systematic Reviews and Meta Analyses statement. All articles that reported the clinical use of a DBM-product in trauma and orthopaedic related surgery were included.The literature search resulted in 823 manuscripts of which 64 manuscripts met the final inclusion criteria. The included manuscripts consisted of four randomised controlled trials (level I), eight cohort studies (level III) and 49 case-series (level IV). No clinical studies were found for ten DBM products, and most DBM products were only used in combination with other grafting materials. DBM products were most extensively investigated in spinal surgery, showing limited level I evidence that supports the use Grafton DBM (Osteotech, Eatontown, New Jersey) as a bone graft extender in posterolateral lumbar fusion surgery. DBM products are not thoroughly investigated in trauma surgery, showing mainly level IV evidence that supports the use of Allomatrix (Wright Medical, London, United Kingdom), DBX (DePuy Synthes, Zuchwil, Switzerland), Grafton DBM, or OrthoBlast (Citagenix Laval, Canada) as bone graft extenders.The clinical level of evidence that supports the use of DBM in trauma and orthopaedic surgery is limited and consists mainly of poor quality and retrospective case-series. More prospective, randomised controlled trials are needed to understand the clinical effect and impact of DBM in trauma and orthopaedic surgery.Cite this article: J. van der Stok, K. A. Hartholt, D. A. L. Schoenmakers, J. J. C. Arts. The available evidence on demineralised bone matrix in trauma and orthopaedic surgery: A systemati c review. Bone Joint Res 2017;6:423-432. DOI: 10.1302/2046-3758.67.BJR-2017-0027.R1.
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Project description:AIM:To systematically review and quantify the efficacy of tranexamic acid (TXA) use in reducing the risk of receiving a blood transfusion in patients undergoing orthopaedic trauma surgery, in reducing blood loss, and risk of thromboembolic events. METHODS:A systematic literature search was performed using MEDLINE, Embase, ClinicalTrials.gov, and conference proceeding abstracts from 2014 to 2016. A minimum of 2 reviewers screened each study and graded quality. The primary outcome measure was the risk of receiving a blood transfusion in the TXA group versus control. A meta-analysis was performed to construct a combined odds ratio (OR) of receiving a blood transfusion, mean difference (MD) of blood loss, and OR of thromboembolic events. RESULTS:Twelve studies were included in the quantitative analysis (1,333 patients). The risk of blood transfusion was significantly less in patients who were administered TXA compared with controls [OR 0.407; 95% confidence interval (CI) 0.278-0.594, I = 34, Q = 17, P ? 0.001]. There was significantly less blood loss in the TXA group compared with controls, as the mean difference was 304 mL (95% CI, 142-467 mL) (I = 94, Q value = 103, P < 0.001). There was no significant difference in risk of symptomatic thromboembolic events (OR 0.968; 95% CI, 0.530-1.766, I = 0, Q value = 5, P = 0.684). CONCLUSIONS:In patients with orthopaedic trauma, TXA reduces the risk of blood transfusion, reduces perioperative blood loss, and has no significant effect on the risk of symptomatic thromboembolic events. More high-quality studies are needed to ensure the safety of the drug in these patients. LEVEL OF EVIDENCE:Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.
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Project description:BACKGROUND:The objective of this analysis is to evaluate the necessity of large clinical trials using FLOW trial data. METHODS:The FLOW pilot study and definitive trial were factorial trials evaluating the effect of different irrigation solutions and pressures on re-operation. To explore treatment effects over time, we analyzed data from the pilot and definitive trial in increments of 250 patients until the final sample size of 2447 patients was reached. At each increment we calculated the relative risk (RR) and associated 95% confidence interval (CI) for the treatment effect, and compared the results that would have been reported at the smaller enrolments with those seen in the final, adequately powered study. RESULTS:The pilot study analysis of 89 patients and initial incremental enrolments in the FLOW definitive trial favored low pressure compared to high pressure (RR: 1.50, 95% CI: 0.75-3.04; RR: 1.39, 95% CI: 0.60-3.23, respectively), which is in contradiction to the final enrolment, which found no difference between high and low pressure (RR: 1.04, 95% CI: 0.81-1.33). In the soap versus saline comparison, the FLOW pilot study suggested that re-operation rate was similar in both the soap and saline groups (RR: 0.98, 95% CI: 0.50-1.92), whereas the FLOW definitive trial found that the re-operation rate was higher in the soap treatment arm (RR: 1.28, 95% CI: 1.04-1.57). CONCLUSIONS:Our findings suggest that studies with smaller sample sizes would have led to erroneous conclusions in the management of open fracture wounds. TRIAL REGISTRATION:NCT01069315 (FLOW Pilot Study) Date of Registration: February 17, 2010, NCT00788398 (FLOW Definitive Trial) Date of Registration: November 10, 2008.
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Project description:Heterotopic Ossification (HO) is a potential long-term complication in orthopaedic surgery. It is commonly classified according to the Brooker classification, which is based on radiological findings. To our knowledge the correlation of histological features to the Brooker grade is unknown as is the association between HO and the indication for revision. The aim of this paper is to analyze the ossification grade of HO tissue in patients undergoing revision hip and knee arthroplasty and to propose a histologically based classification system for HO. We also assess the relationship between the grade of HO and the indication for revision (septic and aseptic revision). From January to May 2019 we collected 50 human HO samples from hip and knee revision arthroplasty cases. These tissue samples were double-blinded and sent for histopathological diagnostic. Based on these results, we developed a classification system for the progression of HO. The grade of ossification was based on three characteristics: Grade of heterotopic ossification (Grade 1-3), presence of necrosis (N0 or N1) and the presence of osteomyelitis (HOES-Score Type 1 to 5). Demographic data as well as surgical details and indication for surgery was prospectively collected from clinical records. Fifty tissue samples were harvested from 44 hips and 6 knee joints. Of these 33 exhibited Grade I ossifications (66%), followed by 11 Grade II (22%) and one Grade III (2%). Necrosis was noted in two tissue samples (4%) and 2 more had osteomyelitis findings according to HOES-Score. Six samples (12%) with radiologically suggestive of HO turned out to be wear-induced synovitis, SLIM Type 1. Of these cases 16 were septic (32%) and 34 aseptic (68%) revisions. Most of the HO tissue samples were classified as a low-grade. High-grade ossification-Score is rare. Higher grades of ossification seem to be associated with septic revision cases. Wear-induced synovitis potentially influences HO development. A histological scoring system for ossification grading can be derived from the data presented in this study.
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Project description:BackgroundBone morphogenetic protein (BMPs) as a substitute for iliac crest bone graft (ICBG) has been increasingly widely used in lumbar fusion. The purpose of this study is to systematically compare the effectiveness and safety of fusion with BMPs for the treatment of lumbar disease.MethodsCochrane review methods were used to analyze all relevant randomized controlled trials (RCTs) published up to nov 2013.Results19 RCTs (1,852 patients) met the inclusion criteria. BMPs group significantly increased fusion rate (RR: 1.13; 95% CI 1.05-1.23, P = 0.001), while there was no statistical difference in overall success of clinical outcomes (RR: 1.04; 95% CI 0.95-1.13, P = 0.38) and complications (RR: 0.96; 95% CI 0.85-1.09, p = 0.54). A significant reduction of the reoperation rate was found in BMPs group (RR: 0.57; 95% CI 0.42-0.77, p = 0.0002). Significant difference was found in the operating time (MD-0.32; 95% CI-0.55, -0.08; P = 0.009), but no significant difference was found in the blood loss, the hospital stay, patient satisfaction, and work status.ConclusionCompared with ICBG, BMPs in lumbar fusion can increase the fusion rate, while reduce the reoperation rate and operating time. However, it doesn't increase the complication rate, the amount of blood loss and hospital stay. No significant difference was found in the overall success of clinical outcome of the two groups.
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