Department of Orthopaedic Surgery Works

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Improved Tissue Repair in Articular Cartilage Defects in Vivo by rAAV-Mediated Overexpression of Human Fibroblast Growth Factor 2
(Elsevier, 2005-08-01) Cucchiarini, Magali; Madry, Henning; Ma, Chunyan; Thurn, Tanja; Zurakowski, David; Menger, Michael D.; Kohn, Dieter; Trippel, Stephen B.; Terwilliger, Ernest F.; Orthopaedic Surgery, School of Medicine
Therapeutic gene transfer into articular cartilage is a potential means to stimulate reparative activities in tissue lesions. We previously demonstrated that direct application of recombinant adeno-associated virus (rAAV) vectors to articular chondrocytes in their native matrix in situ as well as sites of tissue damage allowed for efficient and sustained reporter gene expression. Here we test the hypothesis that rAAV-mediated overexpression of fibroblast growth factor 2 (FGF-2), one candidate for enhancing the repair of cartilage lesions, would lead to the production of a biologically active factor that would facilitate the healing of articular cartilage defects. In vitro, FGF-2 production from an rAAV-delivered transgene was sufficient to stimulate chondrocyte proliferation over a prolonged period of time. In vivo, application of the therapeutic vector significantly improved the overall repair, filling, architecture, and cell morphology of osteochondral defects in rabbit knee joints. Differences in matrix synthesis were also observed, although not to the point of statistical significance. This process may further benefit from cosupplementation with other factors. These results provide a basis for rAAV application to sites of articular cartilage damage to deliver agents that promote tissue repair.
Lumbar extraforaminal decompression: A technical note and retrospective study looking at potential complications as an outpatient procedure
(Elsevier, 2011) Miller, Justin W.; Sasso, Rick C.; Department of Orthopaedic Surgery, IU School of Medicine
BACKGROUND: Lumbar disc herniation and stenosis that results in compression of a nerve root lateral to the foramen is defined as extraforaminal. In recent years the recognition of such pathology has increased with technology and greater awareness. Various approaches and techniques have been developed for extraforaminal decompression in the lumbar region. The purpose of this study was two fold: 1) Determine the safety of treating patients operatively via a paramedian muscle splitting approach on an outpatient basis, and 2) Highlight the technical aspects of the approach to the extraforaminal region. METHODS: One hundred consecutive extraforaminal decompressions were performed from 1992 to 2007 by a single surgeon. A retrospective review was performed consisting of chart reviews. Summary statistics and the Pierson Chi-square test were used to analyze the data. The primary outcome measure was the need for hospital admission or readmission following surgical decompression. RESULTS: Seven of 100 patients (7%) were required to remain in the hospital for twenty-three hour observation due to Medicare requirements. Five (5%) of the patients originally scheduled for an outpatient procedure were converted to inpatient status due to postoperative pain. All were released within 2 days (average 1.25 days). Only one (1%) patient was readmitted for urinary retention that resolved without incident. There was no significant difference (P = 0.137) in complication rate between our control and those that underwent extraforaminal decompression. CONCLUSIONS: Extraforaminal lumbar decompression as an outpatient procedure can be done safely without the need for hospital admission.
A comparison of the shock-absorbing properties of cervical disc prosthesis bearing materials
(Elsevier, 2011) Dahl, Michael C.; Jacobsen, Stephen; Metcalf, Newton; Sasso, Rick; Ching, Randal P.; Department of Orthopaedic Surgery, IU School of Medicine
BACKGROUND DATA: Cervical arthroplasty offers theoretical advantages over traditional spinal fusion, including elimination of adjacent segment disease and elimination of the risk of pseudoarthrosis formation. Initial studies of cervical arthroplasty have shown promising results, however, the ideal design characteristics for disc replacement constructs have not been determined. The current study seeks to quantify the differences in the shock absorption characteristics of three commonly used materials in cervical disc arthroplasty. METHODS: Three different nucleus materials, polyurethane (PU), polyethylene (PE) and a titanium-alloy (Ti) were tested in a humidity- and temperature-controlled chamber. Ten of each nucleus type underwent three separate mechanical testing protocols to measure 1) dynamic stiffness, 2) quasi-static stiffness, 3) energy absorption, and 4) energy dissipation. The results were compared using analysis of variance. RESULTS: PU had the lowest mean dynamic stiffness (435 ± 13 N/mm, P < .0001) and highest energy absorption (19.4 ± 0.1 N/mm, P < .0001) of all three nucleus materials tested. PU was found to have significantly higher energy dissipation (viscous damping ratio 0.017 ± 0,001, P < .0001) than the PE or TI nuclei. PU had the lowest quasi-static stiffness (598 ± 23 N/mm, P < .0001) of the nucleus materials tested. A biphasic response curve was observed for all of the PU nuclei tests. CONCLUSIONS: Polyurethane absorbs and dissipates more energy and is less stiff than either polyethylene or titanium. LEVEL OF EVIDENCE: Basic Science/Biomechanical Study. CLINICAL RELEVANCE: This study characterizes important differences in biomechanical properties of materials that are currently being used for different cervical disc prostheses.
The Epidemiology and Demographics of Legg-Calvé-Perthes' Disease
(Wiley, 2011-09-05) Loder, Randall T.; Skopelja, Elaine N.; Orthopaedic Surgery, School of Medicine
The etiology of Legg-Calvé-Perthes' disease (LCPD) is unknown. There are many insights however from epidemiologic/demographic information. A systematic medical literature review regarding LCPD was performed. The incidence ranges from 0.4/100,000 to 29.0/100,000 children <15 years of age. There is significant variability in incidence within racial groups and is frequently higher in lower socioeconomic classes. The typical age at presentation ranges from 4 to 8 years (average 6.5 years), except for children from the Indian subcontinent (average 9.5 years). There is a mild familial component. The children demonstrate impaired growth in height, skeletal age, and birth weight. This impaired growth coincides with an age appropriate reduced somatomedin A activity and decreased levels of IGF. LCPD can be associated with abnormalities in the coagulation cascade, including an increase in factor V Leiden mutation, low levels of protein C and/or S, and decreased antithrombin activity. There is decreased turnover in type I collagen and synthesis of type III collagen, as well as reduced levels of urinary glycosaminoglycans in the active phases of the disorder. Subtle abnormalities in the opposite hip and other minor/major congenital defects are reported. Children with LCPD are active and score abnormally in certain standardized psychological tests.
The Epidemiology and Demographics of Slipped Capital Femoral Epiphysis
(Wiley, 2011-09-21) Loder, Randall T.; Skopelja, Elaine N.; Orthopaedic Surgery, School of Medicine
The etiology of slipped capital femoral epiphysis (SCFE) is unknown with many insights coming from epidemiologic/demographic information. A systematic medical literature review regarding SCFE was performed. The incidence is 0.33/100,000 to 24.58/100,000 children 8 to 15 years of age. The relative racial frequency, relative to Caucasians at 1.0, is 5.6 for Polynesians, 3.9 for Blacks, and 2.5 for Hispanics. The average age is 12.0 years for boys and 11.2 years for girls. The physiologic age when SCFE occurs is less variable than the chronologic age. The average symptom duration is 4 to 5 months. Most children are obese: >50% are >95th percentile weight for age with average BMI is 25-30 kg/m(2). The onset of SCFE is in the summer when north of 40°N. Bilaterality ranges from 18 to 50%. In children with bilateral involvement, 50-60% present with simultaneous SCFEs and those who present with a unilateral SCFE and subsequently develop a contralateral SCFE do so within 18 months. The age at presentation is younger for those who present with a unilateral SCFE and later develop a contralateral SCFE. The age-weight, age-height, and height test are useful to differentiate between an idiopathic and atypical SCFE.
The Epidemiology and Demographics of Hip Dysplasia
(Wiley, 2011-10-10) Loder, Randall T.; Skopelja, Elaine N.; Orthopaedic Surgery, School of Medicine
The etiology of developmental dysplasia of the hip (DDH) is unknown. There are many insights, however, from epidemiologic/demographic information. A systematic medical literature review regarding DDH was performed. There is a predominance of left-sided (64.0%) and unilateral disease (63.4%). The incidence per 1000 live births ranges from 0.06 in Africans in Africa to 76.1 in Native Americans. There is significant variability in incidence within each racial group by geographic location. The incidence of clinical neonatal hip instability at birth ranges from 0.4 in Africans to 61.7 in Polish Caucasians. Predictors of DDH are breech presentation, positive family history, and gender (female). Children born premature, with low birth weights, or to multifetal pregnancies are somewhat protected from DDH. Certain HLA A, B, and D types demonstrate an increase in DDH. Chromosome 17q21 is strongly associated with DDH. Ligamentous laxity and abnormalities in collagen metabolism, estrogen metabolism, and pregnancy-associated pelvic instability are well-described associations with DDH. Many studies demonstrate an increase of DDH in the winter, both in the northern and southern hemispheres. Swaddling is strongly associated with DDH. Amniocentesis, premature labor, and massive radiation exposure may increase the risk of DDH. Associated conditions are congenital muscular torticollis and congenital foot deformities. The opposite hip is frequently abnormal when using rigorous radiographic assessments. The role of acetabular dysplasia and adult hip osteoarthritis is complex. Archeological studies demonstrate that the epidemiology of DDH may be changing.
Evaluation of Joint Space Width and Narrowing After Isolated Partial Medial Meniscectomy for Degenerative Medial Meniscus Tears
(SAGE Publications, 2013-10) Shelbourne, K. Donald; Barnes, Adam F.; Urch, Scott E.; Gray, Tinker; Department of Orthopaedic Surgery, IU School of Medicine
BACKGROUND: Few studies have evaluated the effect of existing articular cartilage damage and sex on joint space measurements after isolated degenerative medial meniscus tears. PURPOSE: To determine what factors affected joint space width and narrowing in patients after removal of isolated degenerative medial meniscus tears. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: A total of 62 patients (15 women and 47 men) with all ligaments intact, no previous surgery to either knee, and an isolated degenerative medial meniscus tear removed in 1 knee were examined. The mean age at examination was 58.2 years at a mean follow-up of 9.4 years (range, 4-20 years). Subjective results were obtained with the International Knee Documentation Committee (IKDC) knee survey. Radiographs were taken using 45° weightbearing posteroanterior views. Midpoint and perceived minimum joint space width of the medial and lateral compartments of both knees were measured to the nearest 0.1 mm by 2 observers at different times, and they were blinded as to the previous measurements (Pearson intra- and interclass correlations, >0.93). Joint space narrowing was found by calculating the difference in joint space width between knees. Percentage of normal joint space loss was calculated by dividing joint space narrowing by the joint space width in the contralateral knee. Other factors considered were patient sex and Outerbridge grading of articular cartilage. RESULTS: Women had a mean 1.5 mm less normal joint space width than men in the involved and noninvolved knees (P < .01). Mean joint space narrowing was 0.7 mm for both measurements. The mean ± standard deviation narrowing was 0.4 ± 1.2 mm for patients with grade 0-2 damage and 1.1 ± 1.3 for patients with grade 3-4 damage (P = .04). Five women (33%) and 3 men (6%) had narrowing of >50% of the normal joint space as measured in the noninjured knee (P = .016). The mean IKDC total score was 66.1 points for women, which was statistically significantly lower than the mean of 82.7 points for men (P < .01). CONCLUSION: Patients undergoing partial medial meniscectomy have greater joint space narrowing and lower subjective scores after surgery if they also have existing Outerbridge grade 3-4 damage. Women have less normal joint space than men, and more women than men experience >50% joint space narrowing after surgery.
Endogenous versus Exogenous Growth Factor Regulation of Articular Chondrocytes
(Wiley, 2014) Shi, Shuiliang; Chan, Albert G.; Mercer, Scott; Eckert, George J.; Trippel, Stephen B.; Orthopaedic Surgery, School of Medicine
Seasonal variation in children with developmental dysplasia of the hip
(Sage, 2014) Loder, Randall T.; Shafer, Cody; Orthopaedic Surgery, School of Medicine
Background: It has been postulated that developmental dysplasia of the hip (DDH) is more frequent in infants born in the winter months. It was the purpose of this study to ascertain if there was any seasonal variation in DDH at the author's institution and compare/contrast our results with those in the literature using rigorous mathematical fitting. Methods: All children with DDH treated at the author's institution from 1993 to 2012 were identified. The month of birth was recorded and temporal variation was analyzed using cosinor analysis. Similar data from the literature was analyzed. Results: There were 424 children (363 girls, 61 boys). An additional 22,936 children were added from the literature for a total of 23,360. Pearson's Chi-square test demonstrated a non-uniform distribution in the month of birth for both our 424 children as well as the combined literature series in both the Northern and Southern hemispheres. Cosinor analysis of the 424 children demonstrated double peaks in mid-March and mid-October. For the entire 23,360 children, no seasonal variation was observed in 2,205 (9.4 %), a single winter peak in 16,425 (70.3 %), a single summer peak in 1,280 (5.5 %), and double peaks in the spring and autumn in 3,450 (14.8 %). Conclusions: This study partly supports the hypothesis of tight clothing/cold temperature as one factor in the etiology of DDH with the tighter clothing/swaddling increasing the risk of DDH. However ~20 % of the DDH births demonstrated a non-winter peak. The single summer and double spring/autumn peaks, as well as in those series where no seasonal variation was noted, refutes the cold winter clothing hypothesis. Perhaps these different patterns in seasonal variation represent the heterogeneity of the genetic factors in DDH interacting with external factors (temperature and clothing) and internal factors (metabolic). Further study will be required to understand these different patterns in DDH seasonal variation.
Generation of the first Autosomal Dominant Osteopetrosis Type II (ADO2) disease models
(Elsevier B.V., 2014-02) Alam, Imranul; Gray, Amie K.; Chu, Kang; Ichikawa, Shoji; Mohammad, Khalid S.; Capannolo, Marta; Capulli, Mattia; Maurizi, Antonio; Muraca, Maurizio; Teti, Anna; Econs, Michael J.; Del Fattore, Andrea; Department of Orthopaedic Surgery, IU School of Medicine
Autosomal Dominant Osteopetrosis Type II (ADO2) is a heritable osteosclerotic disorder dependent on osteoclast impairment. In most patients it results from heterozygous missense mutations in the chloride channel 7 (CLCN7) gene, encoding for a 2Cl−/1H+ antiporter. By a knock-in strategy inserting a missense mutation in the Clcn7 gene, our two research groups independently generated mouse models of ADO2 on different genetic backgrounds carrying the homolog of the most frequent heterozygous mutation (p.G213R) in the Clcn7 gene found in humans. Our results demonstrate that the heterozygous model holds true presenting with higher bone mass, increased numbers of poorly resorbing osteoclasts and a lethal phenotype in the homozygous state. Considerable variability is observed in the heterozygous mice according with the mouse background, suggesting that modifier genes could influence the penetrance of the disease gene.

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