Chin Youb Chung

Mobilization of endothelial progenitor cells in fracture healing and distraction osteogenesis

INTRODUCTION Fracture healing and distraction osteogenesis (DO) are unique postnatal bone formation processes, and neovascularization is critically required for successful bone regeneration. We investigated endothelial progenitor cell (EPC) mobilization during bone regeneration, and the possible contribution of EPCs to increased vascularization and new bone formation, especially in DO. METHODS Mouse tibia fracture and rat tibia DO models were used in this study. The proportion of EPCs among the peripheral and splenic mononuclear cells (MNCs) was determined by examining the endothelial lineage staining characteristics and EPC cell surface markers. Messenger RNA expression of molecules related to EPC mobilization and homing at the fracture site were analyzed by ribonuclease protection assay and reverse-transcription polymerase chain reaction. In the rat tibia DO model, we measured blood flow during DO, and determined the distribution of ex vivo-expanded and intravenously-infused EPCs. RESULTS The proportion of EPCs among the peripheral and splenic MNCs increased after fracture, peaked on post-fracture day 3, and returned to basal levels during the healing period. Messenger RNA expression of EPC mobilizing cytokines such as vascular endothelial growth factor (VEGF), stem cell factor, monocyte chemoattractant protein-1, and stromal cell-derived factor-1, were upregulated at the fracture callus. The plasma VEGF levels peaked prior to the increase in the EPC proportion. Adhesion molecules involved in EPC homing were expressed at the fracture callus. In the DO model, the temporal pattern of the increase in the EPC proportion was similar to that in the fracture healing model, but the EPC proportion increased again during the distraction and consolidation phases. The distraction gap was relatively ischemic during the distraction phase and blood flow increased profusely later in the consolidation phase. The number of EPCs homing to the bone regeneration site in the DO model correlated with the number of transplanted EPCs in a dose-dependent manner. CONCLUSIONS These findings suggest that signals from the bone regeneration site mobilize EPCs from the bone marrow into the peripheral circulation. Increased EPC mobilization and homing may contribute to neovascularization and thus to new bone formation in fracture healing and DO.

Statistical Consideration for Bilateral Cases in Orthopaedic Research

BACKGROUND Statistical independence means that one observation is not affected by another; however, the principle of statistical independence is violated if left and right-side measures within a subject are considered to be independent, because they are usually correlated and can affect each other. The purpose of the present study was to analyze the violation of statistical independence in recent orthopaedic research papers and to demonstrate the effect of statistical analysis that considered the data dependency within a subject. METHODS First, all original articles that had been published in The Journal of Bone and Joint Surgery (American Volume) over a two-year period were evaluated. The analysis was designed to identify articles that included bilateral cases and possible violations of statistical independence. Second, a demonstrative logistic regression without consideration of statistical independence was performed and was compared with a statistical analysis that considered data dependency within a subject. Radiographs of 1200 hips in 600 patients were used to examine the differences in terms of odds ratios (with 95% confidence intervals) of the risk factors for hip osteoarthritis. RESULTS Four hundred and eighty-six original articles were reviewed, and 151 articles (including forty-one articles involving the hip, thirty-four involving the knee, twenty-one involving the foot or ankle, nineteen involving the shoulder, ten involving the hand or wrist, nine involving the elbow, and seventeen involving other structures) were considered to include bilateral cases. Of the 486 articles that were reviewed, 120 articles (25%) (including thirty-six articles involving the hip, twenty-six involving the knee, fifteen involving the foot or ankle, fourteen involving the shoulder, seven involving the elbow, six involving the hand or wrist, and sixteen involving other structures) were found to have possibly violated statistical independence. Demonstrative statistical analysis showed that logistic regression was not robust to the violation of statistical independence. The 95% confidence intervals of the odds ratios for the risk factors showed narrower ranges (1.13 to 2.68 times) when data dependency within a subject was not considered. CONCLUSIONS Researchers need to consider statistical independence when performing statistical analysis, particularly in studies involving bilateral cases. If data dependency within a subject is not considered, studies involving bilateral cases can bias results, depending on the context of those studies.

Effect of tibial lengthening on the gastrocnemius muscle: A histopathologic and morphometric study in rabbits

We observed the changes of the gastrocnemius muscle in relation to the percentage of lengthening of the rabbits tibia by callotasis. 75 rabbits were separated into 3 lengthening groups, 10, 20, and 30 percent lengthening, respectively. Histopathologic observations, based on the fiber size variation, internalization of the nuclei, degeneration, regeneration, and endomysial fibrosis of muscle fibers, revealed that substantial changes occurred in the latter groups. Histomorphometrically, the decrease in the mean size of Types I and II muscle fibers was observed in all lengthening groups, but there was no significant change in the proportion of the muscle fiber types in any of the lengthening groups.

Pitfalls and Important Issues in Testing Reliability Using Intraclass Correlation Coefficients in Orthopaedic Research

Background Intra-class correlation coefficients (ICCs) provide a statistical means of testing the reliability. However, their interpretation is not well documented in the orthopedic field. The purpose of this study was to investigate the use of ICCs in the orthopedic literature and to demonstrate pitfalls regarding their use. Methods First, orthopedic articles that used ICCs were retrieved from the Pubmed database, and journal demography, ICC models and concurrent statistics used were evaluated. Second, reliability test was performed on three common physical examinations in cerebral palsy, namely, the Thomas test, the Staheli test, and popliteal angle measurement. Thirty patients were assessed by three orthopedic surgeons to explore the statistical methods testing reliability. Third, the factors affecting the ICC values were examined by simulating the data sets based on the physical examination data where the ranges, slopes, and interobserver variability were modified. Results Of the 92 orthopedic articles identified, 58 articles (63%) did not clarify the ICC model used, and only 5 articles (5%) described all models, types, and measures. In reliability testing, although the popliteal angle showed a larger mean absolute difference than the Thomas test and the Staheli test, the ICC of popliteal angle was higher, which was believed to be contrary to the context of measurement. In addition, the ICC values were affected by the model, type, and measures used. In simulated data sets, the ICC showed higher values when the range of data sets were larger, the slopes of the data sets were parallel, and the interobserver variability was smaller. Conclusions Care should be taken when interpreting the absolute ICC values, i.e., a higher ICC does not necessarily mean less variability because the ICC values can also be affected by various factors. The authors recommend that researchers clarify ICC models used and ICC values are interpreted in the context of measurement.

Validity and Reliability of Measuring Femoral Anteversion and Neck-Shaft Angle in Patients with Cerebral Palsy

BACKGROUND Increased femoral anteversion and coxa valga are common in patients with cerebral palsy. The purpose of the present study was to determine the validity and reliability of the methods that are commonly used to measure the proximal femoral geometry in patients with cerebral palsy. METHODS Thirty-six consecutive patients (mean age, eleven years; range, five to twenty years) with cerebral palsy were enrolled in the present study. The validity and the interobserver reliability of the physical examinations performed by three examiners were determined by comparing the results of a trochanteric prominence angle test, hip internal rotation measurements, and hip external rotation measurements (all with the patient in the prone position) with the amount of femoral anteversion on two-dimensional computed tomography. Validity and intraobserver and interobserver reliability were assessed by comparing the neck-shaft angle on the anteroposterior internal rotation radiograph of the hips with that on the multiplanar reformatted computed tomographic image. RESULTS The trochanteric prominence angle test showed excellent concurrent validity (R = 0.862, p < 0.001) and reliability (intraclass correlation coefficient, 0.809). Hip internal rotation also showed good concurrent validity (R = 0.787, p < 0.001) and excellent reliability (intraclass correlation coefficient, 0.889), whereas hip external rotation appeared to be unsuitable for predicting femoral anteversion. The neck-shaft angle on the anteroposterior internal rotation radiograph of the hips showed excellent concurrent validity (R = 0.892, p < 0.001) and reliability (intraclass correlation coefficient, 0.912). CONCLUSIONS A physical examination for determining femoral anteversion and the neck-shaft angle as measured on the internal rotation radiograph of the hips appear to be clinically relevant methods for evaluating the proximal femoral geometry and version in patients with cerebral palsy. Computed tomographic examination can probably be replaced by physical examination and an anteroposterior internal rotation radiograph of the hips for patients with stable hips who are able to walk.

Reliability and Validity of Radiographic Measurements in Hindfoot Varus and Valgus

BACKGROUND Clinical decision-making in the treatment of foot deformities is based primarily on the results of the physical examination and the radiographic findings. The purpose of this study was to determine the validity and reliability of commonly used radiographic measurements of hindfoot valgus and varus deformities. METHODS Seventy-two patients with hindfoot deformity (thirty-six hindfoot valgus, mean age 15.5 years; thirty-six hindfoot varus, mean age 30.2 years) were evaluated. Nine representative indices on weight-bearing radiographs were assessed. Three examiners measured the radiographic indices at two sessions, and intraobserver and interobserver reliability was determined. Discriminant validity of the radiographic measurements between hindfoot valgus and varus was evaluated. The correlation with pedobarographic findings in evaluating the distribution of foot pressure during gait was assessed for convergent validity. RESULTS Naviculocuboid overlap, anteroposterior talonavicular coverage angle, anteroposterior talus-first metatarsal angle, calcaneal pitch angle, and lateral talus-first metatarsal angle showed excellent reliability. Naviculocuboid overlap, anteroposterior talonavicular coverage angle, and anteroposterior talus-first metatarsal angle showed excellent discriminant validity (in terms of effect-size r) and convergent validity (in terms of correlation coefficients with pedobarography). CONCLUSIONS Naviculocuboid overlap, anteroposterior talonavicular coverage angle, and anteroposterior talus-first metatarsal angle are reliable and valid measures for the evaluation of hindfoot valgus and varus deformities.

Metatarsal lengthening in congenital brachymetatarsia: one-stage lengthening versus lengthening by callotasis.

We retrospectively reviewed and compared the outcomes of 15 one-stage metatarsal lengthenings with intercalary bone graftings in 10 patients with those of nine metatarsal lengthenings by callotasis in five patients younger than 15 years. In the one-stage lengthening group, the diaphyseal osteotomy site was gradually distracted intraoperatively for 20-30 min to relax the surrounding soft tissues. In the callotasis group, lengthening was achieved with mini-Orthofix M-100. There was little difference in the outcomes between the two groups in terms of length gain, percentage increase, and complications. However, the period to achieve bony consolidation was longer in the callotasis group (2.7 months/cm) than in the one-stage lengthening group (1.5 months/cm). No case of neurovascular impairment was found in both groups.

Calcaneal lengthening for the planovalgus foot deformity in children with cerebral palsy.

The authors studied the outcomes of calcaneal lengthening for the treatment of planovalgus foot deformity in ambulatory children with cerebral palsy (92 feet in 56 children, mean age 9.2 years), attempting to define the surgical indication in terms of the severity of the foot deformity. Sixty-nine cases (75%) showed satisfactory clinical outcomes at an average follow-up of 5.2 years (range 4.0-17.2 years). Gait parameters such as foot progression angle, ankle motion in sagittal plane, and its power generation improved after operation. Preoperative talocalcaneal angle, talo-first metatarsal angle, and calcaneal pitch on weight-bearing lateral radiographs were predictive of the satisfactory results of the index operation. The authors conclude that calcaneal lengthening is an effective procedure for moderate to severe planovalgus foot deformities in children with cerebral palsy, but there is a limit under which the index operation can be performed safely: less than 35 degrees of talocalcaneal angle, less than 25 degrees of talo-first metatarsal angle, and more than 5 degrees of calcaneal pitch on weight-bearing lateral radiographs.

Interlocking telescopic rod for patients with osteogenesis imperfecta.

BACKGROUND Intramedullary fixation with use of a telescopic rod with a T-piece is one of the standard methods for long-bone stabilization in growing children with osteogenesis imperfecta. However, installation and removal of this device can cause substantial damage to the distal joint, which limits its use, especially in the tibia. We devised a modification of the telescopic rod system--the interlocking telescopic rod--in which the obturator is a simple rod with a hole, instead of a T-piece, at its distal end. METHODS The clinical and radiographic outcomes were evaluated more than two years following treatment of thirty-two limb segments (twenty-three tibiae and nine femora) with this new rod system in fifteen patients with osteogenesis imperfecta. RESULTS All rods were inserted without an arthrotomy of the distal joint, and all telescoped successfully. The interlocking pin used in the first five limb segments backed out between five and thirty-three months postoperatively. A revised fixation technique was used in the remaining twenty-seven limb segments, and the interlocking pin had not backed out at an average 3.1 years postoperatively. Proximal migration of the obturator was observed in four tibiae after 2.5 years. The cumulative survival rate of the rod at four years postoperatively was 88.7%. CONCLUSIONS Both insertion and removal of an interlocking telescopic rod are much less invasive than insertion and removal of a conventional telescopic rod with a T-piece anchor. The interlocking pin at the distal epiphysis provides effective anchorage for telescoping. Our interim results showed survival of the device to be comparable with, or better than, that of the conventional telescopic rod.

Hip osteoarthritis and risk factors in elderly Korean population.

OBJECTIVE To investigate the prevalence of hip osteoarthritis (OA) in a community-based elderly Korean population and to identify its risk factors. DESIGN Radiographs of hip and knee were evaluated in 288 men and 386 women (age>or=65 years) that participated in the Korean Longitudinal Study on Health and Aging (KLoSHA). Minimum joint space widths (JSW), center-edge angles (CEA), and neck-shaft angles were measured on hip radiographs, and tibio-femoral angles on knee radiographs. Hip OA was defined as minimum JSW of <or=2mm or <or=2.5mm. The following potential risk factors of OA were examined; demographic data, acetabular dysplasia, large CEA (>or=40 degrees) and deformities of femoral neck and knee joint. Multivariate analysis with generalized estimating equation (GEE) model was performed to exclude confounding factors. RESULTS When hip OA was defined as JSW<or=2mm, the overall prevalence of the disease was 2.1% (95% confidence interval [CI], 1.0-3.2%), and only older age (>or=70 years) was identified as a significant risk factors with an odds ratio (OR) of 10.0. However, when hip OA was defined as a JSW of <or=2.5mm, the overall prevalence of the disease was 13.1% (95% CI, 10.5-15.6%), and older age (>or=70 years), female, large CEA (>or=40 degrees), and acetabular dysplasia (CEA<20 degrees) were identified as significant risk factors with ORs of 2.1, 2.1, 2.3, and 10.2, respectively. CONCLUSIONS The prevalence of hip OA in elderly Korean was 2.1% (JSW<or=2mm) in community-based population. Older age (>or=70 years), female, large CEA (>or=40 degrees), and acetabular dysplasia (CEA<20 degrees) appeared to be significant risk factors of hip OA.