Bone Morphogenetic Protein for the Healing of Tibial Fracture: A Meta-Analysis of Randomized Controlled Trials.
ABSTRACT: To review the evidence from RCTs on clinical outcomes and benefit of acute tibial fracture and nonunion treated with and without BMPs.We searched multiple databases (MEDLINE, EMABSE, BIOSIS and Cochrane central) as well as reference lists of articles and contacted authors. Evaluated outcomes included union rate, revision rate, hardware failure and infection. The weighted and standard mean difference (WMD and SMD) or the relative risk (RR) was calculated for continuous or dichotomous data respectively. The quality of the trial was assessed, and meta-analyses were performed with the Cochrane Collaboration's REVMAN 5.0 software.Eight RCTs involving 1113 patients were included. For acute tibial fracture, BMP group was associated with a higher rate of union (RR, 1.16; 95% CI, 1.04 to 1.30) and a lower rate of revision (RR, 0.68; 95% CI, 0.54 to 0.85) compared with control group. No significant differences were found in rate of hardware failure and infection. The pooled RR for achieving union for tibial fracture nonunion was 0.98 (95% CI, 0.86 to 1.13). There was no significant difference between the two groups in the rate of revision (RR, 0.48; 95% CI, 0.13 to 1.85) and infection (RR, 0.61; 95% CI, 0.37 to 1.02).Study on acute tibial fractures suggests that BMP is more effective that controls, for bone union and for decreasing the rate of surgical revision to achieve union. For the treatment of tibial fracture nonunion, BMP leads to similar results to as autogenous bone grafting. Finally, well-designed RCTs of BMP for tibial fracture treatment are also needed.
Project description:<h4>Background</h4>Low-intensity pulsed ultrasonography (LIPUS) is a form of mechanical stimulation that is delivered via a special device to the fracture site for the acceleration of fracture healing. We conducted a meta-analysis to assess the effect of LIPUS for fresh fractures in adults.<h4>Methods</h4>MEDLINE, EMBASE and the Cochrane Library searched between Jan 1980 and Nov 2016. Studies should be quasi-randomized and randomized controlled trials (RCTs) comparing treatment with LIPUS to placebo or no treatment in adults with fresh fractures, reporting outcomes such as function; time to union; delayed union or non-union. Summary standard mean difference (SMD) and the risk ratio (RR) with their 95% confidence interval (CI) calculated with a random effects model. I statistic was used to assess the heterogeneity. Risk of bias was assessed by the Cochrane risk-of-bias tool. The GRADE system was used to evaluate the evidence quality.<h4>Results</h4>A total of 12 trials with 1099 patients were included. The pooled results showed that LIPUS significantly reduced the time to fracture union (SMD: 0.65, 95% CI: 1.13 to 0.17), improved the quality of life (SMD: 0.20, 95% CI: 0.03-0.37) without affecting the time to full weight bearing (SMD: 0.76, 95% CI: 1.92 to 0.4), the time to return to work (SMD: 0.06, 95% CI: 0.14 to 0.27), or the incidence rate of delayed union and nonunion (RR: 1.02, 95% CI: 0.60-1.74).<h4>Conclusions</h4>Moderate-to-high quality evidence shows that LIPUS treatment reduces the time to fracture union and improves the quality of life without affecting functional recovery and incident rate of delayed union and nonunion, suggesting that LIPUS treatment may be a good treatment modality for adults with fresh fractures. However, there are some methodological limitations in the eligible trials, further studies are needed to determine the clinical circumstances under which LIPUS is truly valid and to examine the optimal approach for the use of this adjunctive therapy.
Project description:<h4>Backgrounds</h4>There is no consensus concerning whether surgery or non-surgical treatment is preferred for displaced midshaft clavicle fracture. We performed a meta-analysis of randomized controlled trials (RCTs) to compare healing effects and cosmetic results between surgery and non-surgery.<h4>Methods</h4>We retrieved RCTs regarding open reduction and plate fixation (ORPF) and non-surgical method for the treatment of displaced midshaft clavicle fracture published before June 2018 from PubMed, EMBASE and Cochrane Library. The difference between the two treatments was comparatively discussed in aspects of nonunion, malunion, functional outcome, cosmetic results, and complications.<h4>Results</h4>Nine RCTs were included. The results showed that ORPF is advantageous over the non-surgical treatment in terms of nonunion rate (RR, 0.11[95%CI, 0.06-0.23]), malunion rate (RR, 0.16[95%CI, 0.08-0.35]), appearance dissatisfaction rate (RR, 0.35[95%CI 0.23-0.55]), and shoulder appearance defect rate (RR, 0.06[95%CI, 0.02-0.17]). The non-surgical treatment showed lower rate of complication (RR, 1.60[95%CI, 1.02-2.53]) and no significant differences were found between the 2 treatment groups with respect to functional outcome (disabilities of the arm, shoulder and hand (DASH) questionnaire score) (MD, -4.17[95%CI, -9.35 to 1.01]).<h4>Conclusions</h4>This meta-analysis updated previous results. The current findings suggested that ORPF yielded better efficacy than conservation treatment for displaced midshaft clavicle fracture from perspectives of fracture healing and appearance.
Project description:Surgical or nonsurgical treatment for scaphoid waist fracture with slight or no displacement is still controversial. This study compared the efficacy of the 2 methods through meta-analysis to provide a reference for the choice of clinical treatment options. Two individuals independently searched for relevant RCTs and cohort studies from PubMed (1946-February 2018), Embase (1946-February 2018), and Cochrane library (1997-February 2018). After quality assessment and data extraction, Stata 14 software was used for combining the effect size, testing heterogeneity, and studying bias. GRADEpro was used to rate the level of evidence. Ten RCTs and 4 cohort studies with 765 patients were included. No statistical difference in satisfaction, pain, and Disability of the Arm, Shoulder, and Hand score was found after surgical and nonsurgical treatments. Compared with nonsurgical treatment, surgical treatment shortened the time to union (SMD?=?-5.01, 95% CI: -7.47 to -2.58, P?=?.000), decreased the convalescence (SMD?=?-2.09, 95% CI: -3.08 to -1.11, P?=?.000), and reduced the incidence of nonunion (RR?=?0.47, 95% CI: 0.24-0.90), P?=?.023). Subgroup analyses showed that the percutaneous fixation treatment can shorten the time to union [SMD?=?-1.82, 95%CI (-2.22 to -1.42), P?=?=?.000] and the convalescence (SMD?=?-4.26, 95%CI: -6.16 to -2.35, P?=?=?.054), and open reduction fixation treatment can reduce the incidence of nonunion (RR?=?0.20, 95%CI: 0.06-0.69, P?=?=?.01). For scaphoid waist fractures with slight or no displacement, there was no statistical difference in patient satisfaction, pain, and The Disability of the Arm, Shoulder, and Hand scores between surgical treatment and nonsurgical treatment. Closed surgical treatment can shorten the time to union and convalescence, and open reduction can reduce the incidence of nonunion. On the basis of this conclusion, chief physicians can consider which treatment to use according to the patient's clinical situation and their subjective intention.
Project description:While the gold standard of treatment of nonunion is open autologous bone grafting, studies have shown that injecting bone marrow aspirate concentrates (BMAC) is effective in treating tibial nonunions with fracture gaps less than 5 mm.We aim to demonstrate that combining BMAC with osteoinductive agents can effectively treat delayed or nonunion regardless of fracture gap size, nonunion site, or osteoinductive agent used.In this non-randomized retrospective-prospective cohort study, 49 patients with tibial nonunion met the inclusion criteria and underwent BMAC injection with demineralized bone matrix (DBM) and/or recombinant human bone morphogenic protein-2 (rhBMP-2). Radiologic healing of the fracture was the primary outcome. Patients were followed until radiographic union was achieved or another procedure was performed. Radiographic healing was defined as bridging of three out of four cortices on anteroposterior and lateral films.There was no difference in the healing rate (p?=?0.81) between patients with fracture gaps less than and greater than 5 mm. On multivariate analysis, the use of rhBMP-2 was associated with a lower healing rate compared to DBM (p?=?0.036). Patients who underwent early intervention (within 6 months of fixation) had higher union rates (p?=?0.04).This study shows that percutaneous BMAC injection combined with either DBM and/or rhBMP-2 is a safe and effective treatment for delayed or nonunion regardless of the fracture gap size or fracture site. DBM may be superior to rhBMP-2 in this procedure.
Project description:BACKGROUND:To best inform evidence-based patient care, it is often desirable to compare competing therapies. We performed a network meta-analysis to indirectly compare low intensity pulsed ultrasonography (LIPUS) with electrical stimulation (ESTIM) for fracture healing. METHODS:We searched the reference lists of recent reviews evaluating LIPUS and ESTIM that included studies published up to 2011 from 4 electronic databases. We updated the searches of all electronic databases up to April 2012. Eligible trials were those that included patients with a fresh fracture or an existing delayed union or nonunion who were randomized to LIPUS or ESTIM as well as a control group. Two pairs of reviewers, independently and in duplicate, screened titles and abstracts, reviewed the full text of potentially eligible articles, extracted data and assessed study quality. We used standard and network meta-analytic techniques to synthesize the data. RESULTS:Of the 27 eligible trials, 15 provided data for our analyses. In patients with a fresh fracture, there was a suggested benefit of LIPUS at 6 months (risk ratio [RR] 1.17, 95% confidence interval [CI] 0.97-1.41). In patients with an existing nonunion or delayed union, ESTIM had a suggested benefit over standard care on union rates at 3 months (RR 2.05, 95% CI 0.99-4.24). We found very low-quality evidence suggesting a potential benefit of LIPUS versus ESTIM in improving union rates at 6 months (RR 0.76, 95% CI 0.58-1.01) in fresh fracture populations. CONCLUSION:To support our findings direct comparative trials with safeguards against bias assessing outcomes important to patients, such as functional recovery, are required.
Project description:Background ?Vascularized bone grafting (VBG) has the potential to yield reliable results in scaphoid nonunion; however, results across studies have been highly variable. This study critically evaluates surgical techniques, fracture location, and patient selection in relation to radiographic, clinical, and patient-centered outcomes after VBG for scaphoid nonunion. Methods ?We conducted a systematic review of the literature for the use of VBG in scaphoid nonunion. Physical examination, radiographic, and patient-centered outcomes were assessed. Four substratifications were performed: the location of scaphoid nonunion, pedicled versus free technique, Kirschner wire (K-wire) versus screw fixation, and VBG done as a primary versus revision procedure. Results ?A total of 41 publications were included in final analysis. VBG had an 84.7% union rate at 13 weeks after surgery. On an average, 89% of patients returned to preinjury activity levels by 18 weeks after surgery and 91% of patients reported satisfaction with the procedure. Proximal pole nonunions demonstrated similar union rates but lower functionality scores compared with nonunions across all regions of the scaphoid. Pedicled techniques demonstrated slightly improved range of motion compared with free technique. K-wire versus screw fixation demonstrated significantly higher union rates and faster union times. There were no differences in outcomes for VBG done as a primary versus revision procedure. Conclusion ?VBG serves as a viable option for the treatment of scaphoid nonunion, with consistent union rates in addition to significantly improved postoperative patient functionality. The fixation of these vascularized bone grafts with K-wires versus screw fixation may result in superior radiologic outcomes. Level of Evidence ?Therapeutic, Level III, systematic review.
Project description:BACKGROUND:There is no consensus regarding the surgical treatment of humeral shaft fracture. The present meta-analysis was performed to compare the efficacy and safety between antegrade intramedullary nailing (IMN) and plating for humeral shaft fracture. METHODS:PubMed, MEDLINE, Cochrane Library, EMBASE, Clinical Trails, Ovid, ISI Web of Science, and Chinese databases including WanFang Data, China National Knowledge Infrastructure were searched through March 10, 2019. The Review Manager software was adapted to perform statistical analysis and relative risk (RR) were used for the binary variables, and weighted mean difference and standardized mean difference (SMD) were used to measure the continuous variables. Each variable included its 95% confidence interval (CI). RESULTS:A total of 15 trials with 839 patients were included in the analysis. There was significant difference between IMN group and plate group in blood loss (SMD?=?3.49, 95% CI: 1.19, 5.79, P?=?.003) and postoperative infections (RR?=?3.04, 95% CI: 1.49, 6.24, P?=?.002). Additionally, significant difference was observed between minimally invasive plate osteosynthesis (MIPO) group and IMN group in nonunion rate (RR?=?3.20, 95% CI: 0.12, 0.84, P?=?.02). Statistical significance was also observed between the open reduction plate fixation group and IMN group in restriction of shoulder and elbow joints results (RR?=?0.49, 95% CI: 0.26, 0.96, P?<?.05). No significant difference was observed for the operation time, American Shoulder and Elbow Surgeons score, nerve injury, delayed union, reoperation in either group. CONCLUSION:IMN may be superior to plate in reducing blood loss and postoperative infections for the treatment of humeral shaft fracture. However, MIPO was superior to IMN group in nonunion and equal to IMN in other parameters. Further research is required and future studies should include analysis of assessments at different stages and follow-up after removal of the implants.
Project description:Most bone fractures typically heal, although a significant proportion (5%-10%) of fractures fail to heal, resulting in delayed union or persistent nonunion. Some preclinical evidence shows the therapeutic potential of peripheral blood CD34(+) cells, a hematopoietic/endothelial progenitor cell-enriched population, for bone fracture healing; however, clinical outcome following transplantation of CD34(+) cells in patients with fracture has never been reported. We report a phase I/IIa clinical trial regarding transplantation of autologous, granulocyte colony stimulating factor-mobilized CD34(+) cells with atelocollagen scaffold for patients with femoral or tibial fracture nonunion (n = 7). The primary endpoint of this study is radiological fracture healing (union) by evaluating anteroposterior and lateral views at week 12 following cell therapy. For the safety evaluation, incidence, severity, and outcome of all adverse events were recorded. Radiological fracture healing at week 12 was achieved in five of seven cases (71.4%), which was greater than the threshold (18.1%) predefined by the historical outcome of the standard of care. The interval between cell transplantation and union, the secondary endpoint, was 12.6 ± 5.4 weeks (range, 8-24 weeks) for clinical healing and 16.1 ± 10.2 weeks (range, 8-36 weeks) for radiological healing. Neither deaths nor life-threatening adverse events were observed during the 1-year follow-up after the cell therapy. These results suggest feasibility, safety, and potential effectiveness of CD34(+) cell therapy in patients with nonunion.
Project description:Fracture of the scaphoid bone is the most common fracture of the carpus, and frequently, diagnosis is delayed. The unique anatomy and blood supply of the scaphoid itself predisposes to delayed union or nonunion. The Synthes scaphoid screw is a cannulated headed screw, which provides superior compression compared with some other devices used to internally fix scaphoid nonunions. Our aim was to conduct a retrospective study looking at the union rate, time to union, and complications and correlating the outcome of treatment against the delay between injury and surgery and location of the fracture within the bone. This study is a review of a cohort of 30 patients treated with a cannulated Synthes scaphoid screw and corticocancellous bone grafting for scaphoid waist delayed union and nonunion at our center. We achieved 86% overall union rate. The patients with delayed union achieved a 100% union rate. Three out of four patients with persistent nonunion after surgery reported no pain and improved function. The failure rate was 75% in patients who had sustained their fracture more than 5 years previously. Our study demonstrates that delayed union of scaphoid waist fractures and scaphoid waist nonunions present for less than 5 years can be successfully treated by fracture compression and bone grafting.
Project description:The Radiographic Union Score for Hip (RUSH) is a previously validated outcome instrument designed to improve intra- and interobserver reliability when describing the radiographic healing of femoral neck fractures. The ability to identify fractures that have not healed is important for defining nonunion in clinical trials and predicting patients who will likely require additional surgery to promote fracture healing. We sought to investigate the utility of the RUSH score to define femoral neck fracture nonunion.(1) What RUSH score threshold yields at least 98% specificity to diagnose nonunion at 6 months postinjury? (2) Using the threshold identified, are patients below this threshold at greater risk of reoperation for nonunion and for other indications?A representative sample of 250 out of a cohort of 725 patients with adequate 6-month hip radiographs was analyzed from a multinational elderly hip fracture trial (FAITH). All patients had a femoral neck fracture and were treated with either multiple cancellous screws or a sliding hip screw. Two reviewers independently determined the RUSH score based on the 6-month postinjury radiographs and interrater reliability was assessed with the interclass correlation coefficient (ICC). There was substantial reliability between the reviewers assigning the RUSH scores (ICC, 0.81; 95% confidence interval [CI], 0.76-0.85). The RUSH score is a checklist-based system that quantifies four measures of healing: cortical bridging, cortical fracture disappearance, trabecular consolidation, and trabecular fracture disappearance.. Fracture healing was determined by two independent methods: (1) concurrently by the treating surgeon using both clinical and radiographic assessments as per routine clinical care; and (2) retrospectively by a Central Adjudication Committee using complete obliteration of the fracture line on radiographs alone. Receiver operating characteristic tables were used to define a RUSH threshold score that was > 98% specific for fracture nonunion.A threshold score of < 18 was associated with a 100% specificity (95% CI, 97%-100%) and a positive predictive value of 100% (95% CI, 73%-100%) for radiographic nonunion. In contrast, using the fracture healing assessments of the treating surgeons failed to identify a useful discriminatory nonunion threshold and the highest positive predictive value was 43%. With respect to complications, patients with RUSH scores below 18 had greater risk of undergoing reoperation for nonunion (reoperation when < 18: six of 13 [46%]; reoperation when ? 18: 11 of 237 [54%]; relative risk [RR], 9.9 [95% CI, 4.4-22.7]; p < 0.001) and for all indications (reoperation when < 18: eight of 13 [62%]; reoperation when ? 18: 54 of 237 [38%]; RR, 2.7 [95% CI, 1.7-4.4]; p = 0.004).The 6-month RUSH score is a reliable method for assessing radiographic healing. Our results highlight the discordance between radiographic determinations and clinician assessments of fracture healing and stress the need for clinical data to be incorporated in research studies evaluating fracture healing.Level III, diagnostic study.