Bioactive glass granules versus standard autologous and allogeneic bone grafts: a randomized trial of 49 adult bone tumor patients with a 10-year follow-up.

BACKGROUND AND PURPOSE: As a synthetic bone void filler, bioactive glasses (BGs) may enhance angiogenesis and osteogenesis. In this randomized trial, we compared the clinical efficacy of BG granules and standard bone grafts in patients undergoing surgery for benign bone tumors. PATIENTS AND METHODS: 49 recruited patients were randomized to receive BG granules or undergo conventional bone grafting to fill defects following tumor removal. As the standard of care, small-sized defects were filled with autologous graft, and large-sized defects were filled with allogeneic graft. The primary endpoint was treatment success at 1 year, defined by no reoperation, no tumor recurrence, and no device-related adverse events. Secondary endpoints included patient-reported outcomes (Rand-36 and pain scores) and quantitative assessment of blood flow and metabolic activity by means of 18F-fluoride PET/CT imaging. As an off-trial group, 15 children and adolescents (age < 18 years) underwent tumor removal and BG-filling, without randomization. RESULTS: At 1-year, 21 of 25 BG-treated patients (risk estimate 0.84, 95% confidence interval [CI] 0.70-0.98) and 20 of 24 patients in the standard of care group (0.83, CI 0.68-0.98) met the criteria for treatment success. The groups had similar Rand-36 scores. In patients with small defects, BG filling was associated with shorter operative time and less postoperative pain at 1 month. In patients with large defects, blood flow was similar, but BG-filled defects showed higher metabolic activity than allograft-filled defects at 1-year. The survey of the postoperative period ≥10 years revealed no BG-related adverse events. INTERPRETATION: BG granules had similar overall rates of treatment success compared with autografts and allografts, but large-scale trials are needed for the confirmation of clinical equivalence. The extended metabolic activity confirms the expected cellular responses of osseointegrated BG granules.

Evaluation of a New Skeletal Troponin I Assay in Patients with Idiopathic Inflammatory Myopathies.

BACKGROUND: The current biomarkers for diagnosis and monitoring of injured and diseased skeletal muscles, such as creatine kinase (CK), have limited tissue specificity and incapability to differentiate between pathological and physiological changes. Thus, new biomarkers with improved diagnostic accuracy are needed. Our aim was to develop and validate a novel assay for skeletal troponin I (skTnI), and to assess its clinical performance in patients with idiopathic inflammatory myopathies (IIM). METHODS: A two-step fluoroimmunoassay was used to analyze samples from healthy reference individuals (n = 140), patients with trauma (n = 151), and patients with IIM (n = 61). RESULTS: The limit of detection was 1.2 ng/mL, and the upper reference limit (90th percentile) was 5.2 ng/mL. The median skTnI concentrations were

Radiostereometric analysis of the initial stability of internally fixed femoral neck fractures under differential loading.

We examined the feasibility of radiostereometric analysis (RSA) in the assessment of the initial stability of internally fixed femoral neck fractures. The study included 16 patients (mean age 73 years). During surgery, multiple RSA-beads were inserted on both sides of the fracture. Radiographs for RSA were taken in the supine position within the first 3 days and 6, 12, 24, and 52 weeks after surgery. To detect any inducible motion at the fracture-site, radiographs for RSA were taken with the patient resting or applying a load through the fracture. Fracture loading was achieved by the patient pressing the ipsilateral foot as much as tolerated on a force plate while providing a counterforce through both hands. Micromotion exceeding the precision values of RSA (≥0.3 mm for the translation vector and/or ≥1.2 degrees for the rotation vector) was considered significant. Permanent three-dimensional fracture-site displacement was also recorded. Voluntary loading induced fracture-site micromotion, which exhibited a dichotomous distribution. In patients with uncomplicated fracture union, inducible micromotion was detectable only at baseline-if at all. Conversely, fractures that developed a nonunion were characterized by the continuation of inducible micromotion beyond baseline. Permanent fracture-site displacement was, on average, nearly an order of magnitude greater than the inducible micromotion. Fracture unions were characterized by the cessation of permanent fracture-site displacement by 12 weeks. Nonunions presented as outliers in permanent fracture-site displacement. Large-scale studies are warranted to evaluate whether the detection of inducible micromotion beyond baseline could serve as an indicator of insufficient fixation stability. © 2018 The Authors. Journal of Orthopaedic Research® Published by Wiley Periodicals, Inc. on behalf of the Orthopaedic Research Society.

Predicting the outcome of hip fracture patients by using N-terminal fragment of pro-B-type natriuretic peptide.

OBJECTIVE: To examine the prognostic value of perioperative N-terminal fragment of pro-brain natriuretic peptide (NT-proBNP) in hip fracture patients. DESIGN: Blinded prospective cohort study. SETTING: Single centre trial at Turku University Hospital in Finland. PARTICIPANTS: Inclusion criterion was admittance to the study hospital due to hip fracture during the trial period of October 2009--May 2010. Exclusion criteria were the patient's refusal and inadequate laboratory tests. The final study population consisted of 182 patients. PRIMARY AND SECONDARY OUTCOME MEASURES: NT-proBNP was assessed once during the perioperative period and later if clinically indicated, and troponin T (TnT) and ECG recordings were evaluated repeatedly. The short-term (30-day) and long-term (1000 days) mortalities were studied. RESULTS: Median (IQR) follow-up time was 3.1 (0.3) years. The median (IQR) NT-proBNP level was 1260 (2298) ng/L in preoperative and 1600 (3971) ng/L in postoperative samples (p=0.001). TnT was elevated in 66 (36%) patients, and was significantly more common in patients with higher NT-proBNP. Patients with high (>2370 ng/L) and intermediate (806-2370 ng/L) NT-proBNP level had significantly higher short-term mortality compared with patients having a low (<806 ng/L) NT-proBNP level (15 vs 11 vs 2%, p=0.04), and the long-term mortality remained higher in these patients (69% vs 49% vs 27%, p<0.001). Intermediate or high NT-proBNP level (HR 7.8, 95% CI 1.03 to 59.14, p<0.05) was the only independent predictor of short-term mortality, while intermediate or high NT-proBNP level (HR 2.27, 95% CI 1.30 to 3.96, p=0.004), the presence of dementia (HR 1.74, 95% CI 1.13 to 2.66, p=0.01) and higher preoperative American Society of Anesthesiologists' (ASA) classification (HR 1.59, 95% CI 1.06 to 2.38, p=0.02) were independent predictors of long-term mortality. CONCLUSION: An elevated perioperative NT-proBNP level is common in hip fracture patients, and it is an independent predictor of short-term and long-term mortality superior to the commonly used clinical risk scores. TRIAL REGISTRATION NUMBER: NCT01015105; Results.

Osteointegration of PLGA implants with nanostructured or microsized ß-TCP particles in a minipig model.

Bioresorbable suture anchors and interference screws have certain benefits over equivalent titanium-alloy implants. However, there is a need for compositional improvement of currently used bioresorbable implants. We hypothesized that implants made of poly(l-lactide-co-glycolide) (PLGA) compounded with nanostructured particles of beta-tricalcium phosphate (ß-TCP) would induce stronger osteointegration than implants made of PLGA compounded with microsized ß-TCP particles. The experimental nanostructured self-reinforced PLGA (85L:15G)/ß-TCP composite was made by high-energy ball-milling. Self-reinforced microsized PLGA (95L:5G)/ß-TCP composite was prepared by melt-compounding. The composites were characterized by gas chromatography, Ubbelohde viscometry, scanning electron microscopy, laser diffractometry, and standard mechanical tests. Four groups of implants were prepared for the controlled laboratory study employing a minipig animal model. Implants in the first two groups were prepared from nanostructured and microsized PLGA/ß-TCP composites respectively. Microroughened titanium-alloy (Ti6Al4V) implants served as positive intra-animal control, and pure PLGA implants as negative control. Cone-shaped implants were inserted in a random order unilaterally in the anterior cortex of the femoral shaft. Eight weeks after surgery, the mechanical strength of osteointegration of the implants was measured by a push-out test. The quality of new bone surrounding the implant was assessed by microcomputed tomography and histology. Implants made of nanostructured PLGA/ß-TCP composite did not show improved mechanical osteointegration compared with the implants made of microsized PLGA/ß-TCP composite. In the intra-animal comparison, the push-out force of two PLGA/ß-TCP composites was 35-60% of that obtained with Ti6Al4V implants. The implant materials did not result in distinct differences in quality of new bone surrounding the implant.

Usefulness of troponin T to predict short-term and long-term mortality in patients after hip fracture.

The purpose was to evaluate the short-term (30-day) and long-term (1,000-day) prognostic values of perioperative troponin T (TnT) and electrocardiographic (ECG) findings in hip fracture patients. A consecutive cohort of 200 patients (68 men) was enrolled. Blinded TnT levels and ECG were assessed on admission, before operation, and on first and second postoperative days. Median (interquartile range) follow-up time was 3.1 (0.3) years. TnT elevation was observed in 71 patients (35.5%): already before the operation in 36 patients (51%) and only after surgery in 35 patients (49%). New ischemic ECG changes were detected in 101 of 194 patients (52%), including 7 ST elevations. Patients with TnT elevation had higher short-term (17% vs 4.7%, respectively, p=0.008) and long-term (61% vs 40%, respectively, p=0.005) mortality, the short-term mortality being higher in patients with major (TnT≥0.15 µg/L) compared with minor TnT elevation (24% vs 13%, respectively, p=0.005). TnT elevation was the only independent predictor of short-term mortality (hazard ratio [HR] 3.87, 95% confidence interval [CI] 1.45 to 10.3, p=0.007), whereas TnT elevation (HR 1.73, 95% CI 1.14 to 2.64, p=0.01), increasing age (HR 1.03, 95% CI 1.01 to 1.06, p=0.01), dementia (HR 1.84, 95% CI 1.22 to 2.78, p=0.004), and atrial fibrillation (HR 1.86, 95% CI 1.18 to 2.93, p=0.007) remained independent predictors of long-term mortality. ECG findings other than ST elevation did not affect mortality. In conclusion, elevated perioperative TnT level is a strong predictor of short-term and long-term mortality. Routine TnT measurements and earlier diagnosis together with appropriate treatment may improve survival of this fragile patient group.

Perioperative myocardial infarctions are common and often unrecognized in patients undergoing hip fracture surgery.

BACKGROUND: The aim of this prospective cohort study was to assess the incidence and characteristics of acute myocardial infarction in patients undergoing surgery for acute hip fracture. METHODS: A consecutive cohort of patients (n = 200, 68 men) referred to acute surgical correction of hip fracture was studied. Troponin T (TnT) measurements and electrocardiographic (ECG) recordings were performed at admission, before operation, and on the first and 2nd postoperative days, which were used for diagnosis. RESULTS: The age of the patients ranged from 32 to 98 years (mean, 80.8 years), and 65 patients had a history of coronary artery disease. A significant rise in TnT as a sign of myocardial infarction was observed in 71 patients (35.5%), and 25 of them had a TnT elevation exceeding five times the upper normal limit. TnT elevation was observed in 36 patients (51%) already before surgery. Seven patients (10%) had ST elevation myocardial infarction, 23 patients (32%) had new ST depressions, and 21 patients (30%) had no new ST segment changes in the serial electrocardiographic recordings. In 40 patients (56%), the perioperative myocardial infarction was the first manifestation of coronary artery disease. Multivariate logistic regression revealed that old age (odds ratio [OR], 1.06; 95% confidence interval [CI], 1.02-1.10; p = 0.002), earlier revascularization (OR, 3.29; 95% CI 1.12-9.73; p = 0.03), and heart failure (OR, 2.42; 95% CI 1.04-5.61; p = 0.04) were independent predictors of TnT elevation. Majority of myocardial infarctions were asymptomatic or unrecognized. Evidence-based medications of myocardial infarction were seldom started and cardiologist was consulted in 12 patients (16.9%). CONCLUSION: Patients with hip fracture often develop asymptomatic and clinically unrecognized perioperative myocardial infarctions. Earlier diagnosis and appropriate treatment of cardiac infarction may improve survival of hip fracture patients. LEVEL OF EVIDENCE: Epidemiologic study, level III.

Conservative treatment, plate fixation, or prosthesis for proximal humeral fracture. A prospective randomized study.

BACKGROUND: Proximal humerus fracture is the third most common fracture type after hip and distal radius fracture in elderly patients. A comprehensive study by Palvanen et al. demonstrated an increase in the annual fracture rate of 13.7% per year over the past 33 years. Should this trend continue, the fracture rate would triple over the next three decades. The increasing incidence of low-energy fractures raises questions about the optimal treatment in terms of functional outcome, pain, and rehabilitation time, as well as the economical impact. Despite the high incidence and costs of proximal humerus fractures, there is currently no valid scientific evidence for the best treatment method. Several publications, including a Cochrane review outline the need for high-quality, well-designed randomized controlled trials. METHODS/DESIGN: The study is a prospective, randomized, national multi-center trial. The hypothesis of the trial is that surgical treatment of displaced proximal humerus fractures achieves better functional outcome, pain relief, and patient satisfaction compared to conservative treatment. The trial is designed to compare conservative and surgical treatment of proximal humerus fractures in patients 60 years and older. The trial includes two strata. Stratum I compares surgical treatment with locking plates to conservative treatment for two-part fractures. Stratum II compares multi-fragmented fractures, including three- and four-part fractures. The aim of Stratum II is to compare conservative treatment, surgical treatment with the Philos locking plate, and hemiarthroplasty with an Epoca prosthesis. The primary outcome measure will be the Disabilities of the Arm, Shoulder and Hand (DASH) score and the secondary outcome measures will be the EuroQol-5D (EQ-5D) value, OSS, Constant-Murley Score, VAS, and 15D.Recruiting time will be 3 years. The results will be analyzed after the 2-year follow-up period. DISCUSSION: This publication presents a prospective, randomized, national multi-center trial. It gives details of patient flow, randomization, aftercare and also ways of analysis of the material and ways to present and publish the results. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01246167.

Radiostereometric analysis in measurements of migration and inducible micromotion in intra-articular distal radius fractures treated with a volar plate.

OBJECTIVES: This study examined the use of radiostereometric analysis (RSA) in the assessment of fixation stability and healing characteristics in intra-articular fractures of the distal radius treated with a volar locking plate. DESIGN: Prospective cohort study. SETTING: University hospital. PATIENTS: Fifteen patients between 39 and 67 years of age with OTA type C distal radius fractures. INTERVENTION: All fractures were treated with a locked volar plate, and tantalum markers were inserted into fracture fragments. RSA was performed at 2, 6, 12, 18, and 52 weeks postoperatively. RSA measurements were also performed using maximal voluntary grip to create inducible micromotion at the fracture site at 6, 12, 18, and 52 weeks. MAIN OUTCOME MEASUREMENTS: Interfragmentary migration and inducible micromotion in terms of translation and rotation in 3 orthogonal axes were determined. The total translation and rotation were also calculated. RESULTS: Precision of measurements along individual axes was between 0.08 and 0.17 mm and 0.70-0.94 degrees for migration and between 0.04 and 0.07 mm and 0.29 and 0.86 degrees for inducible micromotion. Fractures underwent significant translational and rotational migration (P = 0.004 for both) during the first 2 weeks after surgery. This permanent migration was not detectable on conventional radiographs. Inducible fracture micromotion, measured during maximal grip, was detectable up to 18 weeks, even after achievement of radiographic union. CONCLUSIONS: RSA seems to have the potential to be a unique tool in redefining the biologic progress of fracture union. In plated fractures of the distal radius, the method is technically challenging due to difficulties in achieving a good scatter and visibility of tantalum RSA markers. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Repair of bone segment defects with surface porous fiber-reinforced polymethyl methacrylate (PMMA) composite prosthesis: histomorphometric incorporation model and characterization by SEM.

BACKGROUND AND PURPOSE: Polymer technology has provided solutions for filling of bone defects in situations where there may be technical or biological complications with autografts, allografts, and metal prostheses. We present an experimental study on segmental bone defect reconstruction using a polymethylmethacrylate-(PMMA-) based bulk polymer implant prosthesis. We concentrated on osteoconductivity and surface characteristics. MATERIAL AND METHODS: A critical size segment defect of the rabbit tibia in 19 animals aged 18-24 weeks was reconstructed with a surface porous glass fiber-reinforced (SPF) prosthesis made of polymethylmethacrylate (PMMA). The biomechanical properties of SPF implant material were previously adjusted technically to mimic the properties of normal cortical bone. A plain PMMA implant with no porosity or fiber reinforcement was used as a control. Radiology, histomorphometry, and scanning electron microscopy (SEM) were used for analysis of bone growth into the prosthesis during incorporation. RESULTS: The radiographic and histological incorporation model showed good host bone contact, and strong formation of new bone as double cortex. Histomorphometric evaluation showed that the bone contact index (BCI) at the posterior surface interface was higher with the SPF implant than for the control. The total appositional bone growth over the posterior surface (area %) was also stronger for the SPF implant than for controls. Both bone growth into the porous surface and the BCI results were related to the quality, coverage, and regularity of the microstructure of the porous surface. INTERPRETATION: Porous surface structure enhanced appositional bone growth onto the SPF implant. Under load-bearing conditions the implant appears to function like an osteoconductive prosthesis, which enables direct mobilization and rapid return to full weight bearing.

Bedside femoral block performed on the first postoperative day after unilateral total knee arthroplasty: a randomized study of 49 patients.

This randomized study compared the effectiveness of a femoral nerve block with other methods of pain control on the first postoperative day after total knee arthroplasty. The femoral block consisted of a single injection administered at patients' bedside during the surgeon's hospital rounds. Compared with control group patients, femoral block patients reported less pain on a visual analog scale and required one half the amount of oxycodone (P = .021). Additional femoral block or continued epidural analgesia was required more frequently by control group patients. Thus, pain management with femoral blocks resulted in less work for nursing staff (P = .004). Performing a femoral nerve block as needed during the surgeon's hospital rounds is quick and requires minimal additional time without any special equipment. Bedside femoral block is a useful adjunct to other pain control methods following primary total knee arthroplasty.

Injectable bioactive glass/biodegradable polymer composite for bone and cartilage reconstruction: concept and experimental outcome with thermoplastic composites of poly(epsilon-caprolactone-co-D,L-lactide) and bioactive glass S53P4.

Injectable composites (Glepron) of particulate bioactive glass S53P4 (BAG) and Poly(epsilon-caprolactone-co-D,L-lactide) as thermoplastic carrier matrix were investigated as bone fillers in cancellous and cartilagineous subchondral bone defects in rabbits. Composites were injected as viscous liquid or mouldable paste. The glass granules of the composites resulted in good osteoconductivity and bone bonding that occurred initially at the interface between the glass and the host bone. The bone bioactivity index (BBI) indicating bone contacts between BAG and bone, as well as the bone coverage index (BCI) indicating bone ongrowth, correlated with the amount of glass in the composites. The indices were highest with 70 wt % of BAG, granule size 90-315 microm and did not improve by the addition of sucrose as in situ porosity creating agent in the composite or by using smaller (<45 microm) glass granules. The percentage of new bone ingrowth into the composite with 70 wt % of BAG was 6-8% at 23 weeks. At the articular surface cartilage regeneration with chondroblasts and mature chondrocytes was often evident. The composites were osteoconductive and easy to handle with short setting time. They were biocompatible with low foreign body cellular reaction. Results indicate a suitable working concept as a filler bone substitute for subchondral cancellous bone defects.