Vosoritide para acondroplasia con epífisis abierta / Vosoritide for achondroplasia with epiphysis open

INTRODUCCIÓN: La acondroplasia es la causa más común de baja estatura desproporcionada. Es causada por una mutación patogénica en el gen del receptor 3 del factor de crecimiento de fibroblastos (FGFR3, siglas del inglés Fibroblast Growth Factor Receptor 3), que codifica un receptor transmembrana importante en la regulación del crecimiento lineal de los huesos largos. Esto resulta en una alteración de la osificación endocondral, provocando un crecimiento desproporcionado, donde el crecimiento del tronco no se ve tan gravemente afectado como el de las extremidades y el cráneo. En el 80% de los casos es producida por una mutación genética de novo, siendo de herencia autosómica dominante. Cuando ambos padres tienen acondroplasia, la probabilidad de que cada uno de sus futuros hijos pueda tener una estatura promedio es del 25%, tener acondroplasia es del 50% y finalmente tener acondroplasia homocigota (que suele ser letal) es del 25%. La acondroplasia afecta el crecimiento de casi todos los huesos del cuerpo, incluidos el cráneo, la columna vertebral, los brazos y las piernas, lo que da como resultado una estatura muy baja con una apariencia característica: acortamiento predominantemente proximal (humero, fémur) de los huesos largos de las extremidades (rizomelia); de los dedos de las manos secundario a huesos metacarpianos cortos (braquidactilia), cifosis (deformidad convexa de la unión torácica-lumbar), compresión cervicomedular (debido al estrechamiento en la parte superior de la columna secundario al estrechamiento del foramen magnum); macrocefalia y rasgos faciales caracterizado por prominencia frontal y retrusión del tercio medio facial. Las personas afectadas pueden sufrir alguna de las complicaciones adicionales: hidrocefalia; estenosis del canal vertebral (pacientes después de su segunda o tercera década de vida); obstrucción de la vía aérea superior/apnea obstructiva del sueño (secundario a la reducción del espacio de las vías respiratorias por la retrusión de la parte media de la cara junto con el agrandamiento de adenoides y amígdalas); deformidades óseas (genu varum: desviación hacia afuera debido al arqueamiento); malformación de Arnold-Chiari; microftalmos, y disfunción del oído medio, obesidad, hipertensión arterial, problemas de movilidad, dolor crónico y baja actividad física. OBJETIVO: El objetivo del presente informe es evaluar la evidencia disponible acerca de la eficacia, seguridad, aspectos económicos, recomendaciones de sociedades científicas y las políticas de cobertura (PC) para el uso del vosoritide para personas con acondroplasia y epífisis abierta. DESCRIPCIÓN DE LA TECNOLOGÍA: El vosoritide (BMN 111) es un péptido natriurético humano tipo C recombinante modificado que es producido en células de Escherichia coli mediante tecnología de ADN recombinante. En los pacientes con acondroplasia, el gen FGFR3 que regula el crecimiento está "activado" permanentemente, impidiendo el crecimiento normal de los huesos por lo que terminan siendo más cortos de lo habitual.33 Vosoritide actúa uniéndose a un receptor denominado receptor del péptido natriurético tipo B, que reduce la actividad de FGFR3, y esto, promueve la proliferación y diferenciación de condrocitos y el crecimiento óseo endocondral. MÉTODOS: Las búsquedas se llevaron a cabo en las principales bases de datos bibliográficas: PUBMED, CRD (Centre for Reviews and Dissemination), Cochrane, TRIPdatabase (TRIP: Turning Research Into Practice), Epistemonikos, BRISA (Base Regional de Informes de Evaluación de Tecnologías en Salud de las Américas), LILACS (Literatura Latinoamericana y del Caribe en Ciencias de la Salud), INAHTA (International Network of Agencies for Health Technology Assessment), PROSPERO (International Prospective Register Of Systematic Reviews), en buscadores genéricos de internet y en sitios web de financiadores de salud. Se realizó una búsqueda sistemática de información publicada con fecha límite hasta el 29 de junio sobre el uso del vosoritide en pacientes con Acondroplasia y epífisis abierta. Se priorizó para la búsqueda inicial, la identificación de Revisiones Sistemáticas (RS) y Metaanálisis (MA), Evaluaciones de Tecnologías Sanitarias (ETS), Evaluaciones Económicas (EE), Guías de Práctica Clínica (GPC), políticas de cobertura (PC) de diferentes sistemas de salud y ensayos clínicos aleatorizados (ECA), se realizó una búsqueda con los filtros metodológicos correspondientes. RESULTADOS: Como resultado de la búsqueda bibliográfica, se recuperaron 12 estudios: ocho en curso, cuatro finalizados (estudio 111-101 [NCT01590446], estudio 111-202 [NCT02055157], Savarirayan y cols. 2020 [111-301, NCT03197766] y Savarirayan y cols. 2021 [111-302, NCT03424018]; tres Evaluaciones de Tecnologías Sanitarias (ETS); una revisión sistemática en curso; cinco Guías de Práctica Clínica (GPC) / Consensos / Recomendaciones. No se han hallado estudios primarios con comparación "cabeza-cabeza" entre el vosoritide versus cirugía de alargamiento u hormona de crecimiento. CONCLUSIONES: Al momento, no está autorizada su comercialización en Argentina, pero está en evaluación por el Registro de Especialidades Médicas. No se han encontrado estudios primarios con comparación "cabeza-cabeza" entre el vosoritide versus cirugía de alargamiento u hormona de crecimiento. No se recuperó evidencia relacionado con la tasa de complicaciones graves como: estrechez de la unión cérvico-medular; macrocefalia/hidrocefalia; estenosis del canal vertebral; obstrucción de la vía aérea superior; deformidades óseas; malformación de Arnold-Chiari; microftalmos. No hubo diferencias clínicamente significativas en la calidad de vida relacionada con la salud, ni tampoco en la independencia funcional para vosoritide frente a placebo en personas de 5 a 18 años de edad con acondroplasia y epífisis abierta (certeza alta ⨁⨁⨁⨁). Aumenta la velocidad de crecimiento anualizada (1,57 cm/año más alto), aunque se desconoce si se sostiene en el tiempo para vosoritide frente a placebo en personas de 5 a 18 años de edad con acondroplasia y epífisis abierta (certeza alta ⨁⨁⨁⨁). Aumenta la puntuación Z a 52 semanas de seguimiento (cambio medio de mínimos cuadrados 0.28 más alto), aunque se desconoce si se sostiene en el tiempo, para vosoritide frente a placebo en personas de 5 a 18 años de edad con acondroplasia y epífisis abierta (certeza alta ⨁⨁⨁⨁). No hay diferencias en la proporción de segmentos corporales superiores e inferiores entre el inicio y el final de seguimiento, para vosoritide frente a placebo en personas de 5 a 18 años de edad con acondroplasia y epífisis abierta (certeza alta ⨁⨁⨁⨁). Si bien probablemente no aumente el riesgo de eventos adversos serios, y aumenta el riesgo de cualquier evento adverso (certeza alta ⨁⨁⨁⨁). No se recuperaron Guías de Práctica Clínica que recomienden su utilización y la mayoría de las políticas de cobertura relevadas no la mencionan en la indicación evaluada. Si bien no existen evaluaciones económicas locales, se estima que podría ser NO costoefectiva en Argentina. Se estimó que el impacto en términos de costo de oportunidad requeriría sumar 32.870 gastos en salud per cápita por año, o limitaría el pago de 1.232 haberes jubilatorios mínimos anuales.

A new family with epiphyseal chondrodysplasia type Miura.

Epiphyseal chondrodysplasia, Miura type (ECDM) is a skeletal dysplasia with tall stature and distinctive skeletal features caused by heterozygous NPR2 pathogenic variants. Only four families have been reported. We present a family with five affected individuals (mother, three sons, and daughter). The mother's phenotype was relatively mild: borderline tall stature and elongated halluces operated during childhood. The children were remarkably more severely affected with tall stature, scoliosis, and elongated toes and fingers leading to suspicion of Marfan syndrome. Progressive valgus deformities (at the hips, knees, and ankles) were the main complaints and necessitated orthopedic investigations and surgery. Radiographs showed coxa valga, scoliosis, multiple pseudoepiphyses of the fingers and toes with uneven elongation of the digits and ankle valgus. The two older brothers underwent osteotomies and guided growth for axial deformities and arthrodesis for elongated halluces. Genetic testing confirmed the clinical diagnosis of ECDM: all affected individuals had a heterozygous c.2647G>A (p.Val883Met) NPR2 variant in a highly conserved region in the carboxyl-terminal guanylyl cyclase domain. This two-generation family elucidates the clinical and radiological variability of the disease. These rare cases are important to gain further understanding of the fundamental processes of growth regulation.

Novel progressive acrodysostosis-like skeletal dysplasia, cerebellar atrophy, and ichthyosis.

Acrodysostosis refers to a rare heterogeneous group of bone dysplasias that share skeletal features, hormone resistance, and intellectual disability. Two genes have been associated with acrodysostosis with or without hormone resistance (PRKAR1A and PDE4D). Severe intellectual disability has been reported with acrodysostosis but brain malformations and ichthyosis have not been reported in these syndromes. Here we describe a female patient with acrodysostosis, intellectual disability, cerebellar hypoplasia, and lamellar ichthyosis. The patient has an evolving distinctive facial phenotype and childhood onset ataxia. X-rays showed generalized osteopenia, shortening of middle and distal phalanges, and abnormal distal epiphysis of the ulna and radius. Brain magnetic resonance imaging showed cerebellar atrophy without other brainstem abnormalities. Genetic workup included nondiagnostic chromosomal microarray and skeletal dysplasia molecular panels. These clinical findings are different from any recognized form of acrodysostosis syndrome. Whole exome sequencing did not identify rare or predicted pathogenic variants in genes associated with known acrodysostosis, lamellar ichthyosis, and other overlapping disorders. A broader search for rare alleles absent in healthy population databases and controls identified two heterozygous truncating alleles in FBNL7 and PPM1M genes, and one missense allele in the NPEPPS gene. Identification of additional patients is required to delineate the mechanism of this unique disorder.

Trevor's disease of the distal radioulnar joint in two children with achondroplasia.

Two children with achondroplasia who developed an abnormal bony outgrowth at the distal radioulnar joint (DRUJ), indistinguishable from an osteochondroma on histology, but the radiographic appearance, location, and asymmetry suggested the rare diagnosis of dysplasia epiphysealis hemimelica (DEH or "Trevor's disease"). One child experienced symptomatic relief with surgical excision and one was observed clinically due to lack of significant symptoms. These are the first presented cases of DEH in achondroplasia, both affecting the DRUJ. Due to the infrequency of DEH, more research is needed to better understand the potential connection to achondroplasia. For management, we suggest shared surgical decision making based on symptoms.

Biallelic variants p.Arg1133Cys and p.Arg1379Cys in COL2A1: Further delineation of phenotypic spectrum of recessive Type 2 collagenopathies.

The phenotypic spectrum of Type 2 collagenopathies ranges from lethal achondrogenesis Type 2 to milder osteoarthritis with mild chondrodysplasia. All of them are monoallelic except for the two recent reports showing that biallelic variants in COL2A1 can cause spondyloepiphyseal dysplasia congenita in two children. Here we report two additional families with homozygous variants, c.4135C>T (p.Arg1379Cys) and c.3190C>T (p.Arg1133Cys) in COL2A1 resulting in two distinct skeletal dysplasia phenotypes of intermediate severity. Though all six patients from four families exhibit a spondylo-epimetaphyseal dysplasia, they demonstrate a wide variation in severity of short stature and involvement of epiphyses, metaphyses, and vertebrae. We hypothesize that the variants are likely to be hypomorphic, given the underlying mechanisms of disease causation for known heterozygous variants in COL2A1. With this report, we provide further evidence to the existence of autosomal recessive Type 2 collagenopathy.

Predicting growth plate orientation with altered hip loading: potential cause of cam morphology.

Proximal femoral deformities can result from altered hip joint loading patterns during growth. The growth plate hyaline cartilage has low resistance to shear stress. Therefore, we hypothesized that the growth plate orients in a direction which minimizes the shear stress on its surface. A finite element model of the proximal femur was generated with a simplified flat growth plate. Hip joint forces were estimated for standing upright and standing in hip flexion. We also parametrically studied the effects of posteriorly and laterally directed loads. An algorithm was developed to predict the shape of the femoral growth plate in a plane of minimum shear (along the principal stress vectors). To characterize and compare the growth plate shapes, we represented the distance from the growth plate to a reference plane as a two-dimensional contour plot, providing information of shape and orientation across the entire surface. We also assessed the clinical measures of growth plate shape to compare our predicted growth plates with previous clinical studies data. The shape of the growth plate predicted for an upright standing load correlated closely with morphological properties of the growth plane of a typically developing child. The shape of the growth plate predicted for femoral hip flexion force was similar to the growth plate in subjects with cam morphology, a hip shape that has documented growth plate changes. The model proposed here allows for investigation of the relation between joint forces and growth plate shape, which will help predict the development of bony deformities.

Is the Femoro-Epiphyseal Acetabular Roof (FEAR) index on MRI a relevant predictive factor of instability in a borderline dysplastic hip?

AIMS: A borderline dysplastic hip can behave as either stable or unstable and this makes surgical decision making challenging. While an unstable hip may be best treated by acetabular reorientation, stable hips can be treated arthroscopically. Several imaging parameters can help to identify the appropriate treatment, including the Femoro-Epiphyseal Acetabular Roof (FEAR) index, measured on plain radiographs. The aim of this study was to assess the reliability and the sensitivity of FEAR index on MRI compared with its radiological measurement. PATIENTS AND METHODS: The technique of measuring the FEAR index on MRI was defined and its reliability validated. A retrospective study assessed three groups of 20 patients: an unstable group of 'borderline dysplastic hips' with lateral centre edge angle (LCEA) less than 25° treated successfully by periacetabular osteotomy; a stable group of 'borderline dysplastic hips' with LCEA less than 25° treated successfully by impingement surgery; and an asymptomatic control group with LCEA between 25° and 35°. The following measurements were performed on both standardized radiographs and on MRI: LCEA, acetabular index, femoral anteversion, and FEAR index. RESULTS: The FEAR index showed excellent intraobserver and interobserver reliability on both MRI and radiographs. The FEAR index was more reliable on radiographs than on MRI. The FEAR index on MRI was lower in the stable borderline group (mean -4.2° (sd 9.1°)) compared with the unstable borderline group (mean 7.9° (sd 6.8°)). With a FEAR index cut-off value of 2°, 90% of patients were correctly identified as stable or unstable using the radiological FEAR index, compared with 82.5% using the FEAR index on MRI. The FEAR index was a better predictor of instability on plain radiographs than on MRI. CONCLUSION: The FEAR index measured on MRI is less reliable and less sensitive than the FEAR index measured on radiographs. The cut-off value of 2° for radiological FEAR index predicted hip stability with 90% probability. Cite this article: Bone Joint J 2019;101-B:1578-1584.

Finite element modelling of the developing infant femur using paired CT and MRI scans.

Bone finite element (FE) studies based on infant post-mortem computed tomography (CT) examinations are being developed to provide quantitative information to assist the differentiation between accidental and inflicted injury, and unsuspected underlying disease. As the growing skeleton contains non-ossified cartilaginous regions at the epiphyses, which are not well characterised on CT examinations, it is difficult to evaluate the mechanical behaviour of the developing whole bone. This study made use of paired paediatric post mortem femoral CT and magnetic resonance imaging (MRI) examinations at two different stages of development (4 and 7 months) to provide anatomical and constitutive information for both hard and soft tissues. The work aimed to evaluate the effect of epiphyseal ossification on the propensity to shaft fractures in infants. The outcomes suggest that the failure load of the femoral diaphysis in the models incorporating the non-ossified epiphysis is within the range of bone-only FE models. There may however be an effect on the metaphysis. Confirmation of these findings is required in a larger cohort of children.

Distraction-suppression effect on osteosarcoma.

Osteosarcoma is the most common primary malignant bone tumor. It occurs mainly in children and adolescents. In patients with open growth plate, epiphyseal distraction is used to separate the uninvolved epiphysis from adjacent tumor. This helps preserve the growth potential and restore joint and limb function to a great extent. Interestingly, epiphyseal distraction also appears to inhibit the proliferation of osteosarcoma tumor cells and to increase sensitivity to chemotherapy. Tumor interstitial pressure (TIP) is often elevated in the microenvironment of most solid tumors, including osteosarcoma. Elevated TIP can promote the proliferation, invasion, and migration ability of osteosarcoma cells and also decrease the uptake and distribution of chemotherapeutic agents. Studies have confirmed that the sustained volumetric strain produced in distracted tissue decreases TIP; it stretches extracellular matrix, decreases interstitial density, and increases vessel diameter. We hypothesize that lowering of TIP during the period of epiphyseal distraction inhibits the proliferation and invasion of osteosarcoma cell and, at the same time, increases blood perfusion in the tumor and thus enhances uptake and distribution of chemotherapy agents. If the hypothesis is proved to be true, distraction of tumor segment could be a novel supplementary treatment for osteosarcoma by manipulation of TIP.

Bone fragility after spinal cord injury: reductions in stiffness and bone mineral at the distal femur and proximal tibia as a function of time.

Computed tomography and finite element modeling were used to assess bone structure at the knee as a function of time after spinal cord injury. Analyzed regions experienced degradation in stiffness, mineral density, and content. Changes were well described as an exponential decay over time, reaching a steady state 3.5 years after injury. INTRODUCTION: Spinal cord injury (SCI) is associated with bone fragility and an increased risk of fracture around the knee. The purpose of this study was to investigate bone stiffness and mineral content at the distal femur and proximal tibia, using finite element (FE) and computed tomography (CT) measures. A cross-sectional design was used to compare differences between non-ambulatory individuals with SCI as a function of time after injury (0-50 years). METHODS: CT scans of the knee were obtained from 101 individuals who experienced an SCI 30 days to 50 years prior to participation. Subject-specific FE models were used to estimate stiffness under axial compression and torsional loading, and CT data was analyzed to assess volumetric bone mineral density (vBMD) and bone mineral content (BMC) for integral, cortical, and trabecular compartments of the epiphyseal, metaphyseal, and diaphyseal regions of the distal femur and proximal tibia. RESULTS: Bone degradation was well described as an exponential decay over time (R2 = 0.33-0.83), reaching steady-state levels within 3.6 years of SCI. Individuals at a steady state had 40 to 85% lower FE-derived bone stiffness and robust decreases in CT mineral measures, compared to individuals who were recently injured (t ≤ 47 days). Temporal and spatial patterns of bone loss were similar between the distal femur and proximal tibia. CONCLUSIONS: After SCI, individuals experienced rapid and profound reductions in bone stiffness and bone mineral at the knee. FE models predicted similar reductions to axial and torsional stiffness, suggesting that both failure modes may be clinically relevant. Importantly, CT-derived measures of bone mineral alone underpredicted the impacts of SCI, compared to FE-derived measures of stiffness. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01225055, NCT02325414).

The Role of the Basement Plate in Physeal Bar Formation.

BACKGROUND: Physeal fractures and resultant physeal bars can pose significant problems in skeletal development for the injured growing child. Although now well-recognized, only a small body of experimental literature covering this problem is available. The goal of this study was to help further develop an understanding of the different regions of the physis and the way in which each region responds to injury/fracture. METHODS: This Institutional Animal Care and Use Committee (IACUC)-approved study assessed bar formation using radiologic and histologic methods and measured leg lengths of skeletally immature rats. The right tibia was used as the control to measure leg length discrepancy (LLD), and the left tibia received either a fracture only (F), an epiphyseal scrape (ES), an epiphyseal drilling procedure (ED), or metaphyseal drilling (MD). Radiographs and LLD measurements were obtained at postoperative days 0, 21, and 56. RESULTS: A significant LLD was present at day 56 in the ED group (P=0.01). Radiographic identification of bars showed significant evidence of bar formation for the ES and ED groups at 21 days and the ED group at 56 days (P<0.05). Histologic examination showed a high incidence of histologic physeal bar formation in the ES, ED, and MD groups at 21 and 56 days. CONCLUSIONS: Findings showed that the physis was able to continue to grow following an injury to the physis' hypertrophic region. MD produced little effects with few physeal bars and little LLD. By postoperative day 56, ED animals showed greater LLD than ES animals. Penetration of the basement plate was more likely to lead to bar formation/growth retardation than was ablation of the epiphyseal region of the physis (including resting cells). CLINICAL RELEVANCE: Data presented here provides insight into the importance of different regions of the physis and its repair/continued growth after physeal fracture. We suggest that a better understanding of the physiological cause of physeal arrest after physeal fracture will be important for the development of treatments to prevent physeal arrest or to treat physeal arrest after it occurs.

The potential role of variations in juvenile hip geometry on the development of Legg-Calvé-Perthes disease: a biomechanical investigation.

Legg-Calvé-Perthes disease (LCP) is one of the most poorly understood diseases in paediatric orthopaedics. One common trait of LCP is the marked morphological difference between healthy and pathological hips, early deviations of which (i.e. prior to disease onset) have been suggested to lead to the overload and collapse of the epiphysis. Here, the impact of common variations in geometry is investigated with a finite element model of a juvenile femur under single leg standing and landing. Here, the impact of typical variations in geometry is investigated with a finite element model of a juvenile femur under single leg standing and landing. The variations appear to have only a limited effect on the stress distribution in the femoral epiphysis even during high impact activities. This suggests that, for this individual at least, they would be unlikely to cause epiphyseal overload and collapse, even in the presence of a skeletally immature epiphysis.

The effects of surgical treatment with chondroblastoma in children and adolescents in open epiphyseal plate of long bones.

BACKGROUND: Chondroblastoma is a rare benign cartilaginous tumor, which primarily occurs in children and adolescents. Chondroblastoma commonly originates in the epiphyseal plate of long bones. An aggressive curettage treatment is recommended to manage lesion, which may jeopardize an open epiphyseal plate and result in limb shortening and deformity as the limb grows and develops. The purpose is to observe surgical effects of chondroblastoma on open epiphyseal plate of long bones in children and adolescents and explore influences on limb growth and development. METHODS: We retrospectively reviewed 18 cases of long bone chondroblastoma with open epiphyseal growth plate during March 2004 to October 2010 in our center. Seven females and 11 males with mean age of 11.6 ± 2.0 years old (8-15 years) were included. Patients, who suffered from trauma and pathological fracture of the epiphyseal plate or congenital diseases such as poliomyelitis, congenital dementia, and cartilage malnutrition, were excluded. All patients were treated with meticulous intralesional curettage and inactivity with alcohol followed by bone grafts. All cases were followed up 8.2 ± 1.7 years (5-11.5 years). RESULTS: All had no local recurrence and distance metastasis. The length of the affected limb was short, 18.47 ± 7.22 mm (1.5-30 mm). There was no obvious relativity with tumor activity (P = 0.061). Meanwhile, there were obvious relativity with the greatest dimension of the lesion (TGD) (P = 0.003), the vertical dimension between edge of lesion and epiphyseal line (TVD) (P = 0.010), and area ratio of lesion to local epiphysis (lesion/growth plate) (P = 0.015). The MSTS93 (Revised Musculoskeletal Tumor Society Rating Scale 93) and SF-36 (Medical Outcomes Study 36-Item Short-Form Health Survey) had been significantly improved (P < 0.01). CONCLUSION: Managing of chondroblastoma located in open epiphyseal plate of a long bone with meticulous curettage, inactivity, and bone grafts can control tumor progression and recurrence effectively. Meanwhile, early detection and prompt surgical treatment intervention, which reduced significantly the tumor to influence limb growth and development, get encouraging limb function. TRIAL REGISTRATION: This is a retrospective study, which was not registered in any trial registry.

Restoration of Blood Flow to the Proximal Femoral Epiphysis in Unstable Slipped Capital Femoral Epiphysis by Modified Dunn Procedure: A Preliminary Angiographic and Intracranial Pressure Monitoring Study.

BACKGROUND: The major complication of unstable slipped capital femoral epiphysis (SCFE) is avascular necrosis (AVN) of the femoral head. The purpose of this study was to document by angiography the preoperative and postoperative perfusion to the proximal femoral epiphysis following an unstable SCFE. A specific aim was to determine whether blood flow could be restored. A secondary aim was to determine the efficacy of an intracranial pressure (ICP) monitor to assess blood flow within the femoral head intraoperatively. METHODS: Nine patients with an unstable SCFE underwent superselective angiogram of the medial circumflex femoral artery preoperatively, followed by operative fixation with an open reduction using a modified Dunn approach. Femoral head blood flow was evaluated with an ICP monitor. Angiography was repeated postoperatively. Patients were followed radiographically to assess for AVN. RESULTS: Follow-up averaged 22 months. Six patients did not have arterial flow to the femoral head on the preoperative angiogram. Flow was restored postoperatively on angiogram in 4 of the 6 patients. Two patients developed AVN. One had no flow to the femoral head preoperatively or postoperatively on angiogram and complete tearing of the periosteum was noted. In 1 patient, there was no ICP waveform after the initial reduction. After removing more callous and repeating reduction, the waveform returned. Of the 2 patients with AVN, 1 had an ICP waveform after reduction. CONCLUSIONS: This study documents that some patients with unstable SCFE present with reduced femoral head blood supply due to SCFE. It also demonstrates blood flow restoration in 4 patients by angiogram and 5 by ICP monitor after surgical treatment. No patient immediately lost blood flow due to surgery. ICP monitor is a safe intraoperative tool for real-time assessment of femoral head blood flow during open reduction of unstable SCFE. Presence of flow by ICP is not a guarantee that AVN will not develop, but absence of flow was predictive of AVN. LEVEL OF EVIDENCE: Therapeutic level I-prognostic. See Instructions for Authors for a complete description of levels of evidence.

Surgical Techniques for Displaced Radial Neck Fractures: Predictive Factors of Functional Results.

BACKGROUND: Fractures of the radial neck represent about 1% of all childhood fractures and 5% to 10% of childhood traumatic lesions involving the elbow. Management of these fractures in children is still controversial. Intramedullary percutaneous nail reduction (Métaizeau technique) is considered the most effective surgical technique because of its excellent results and easy learning curve. Complications may arise, however, especially in Böhler technique, in which a percutaneous pin is placed over the radial head. When this technique does not provide correct reduction, open reduction must be performed. Because open reduction is traditionally associated with a high risk of complications, however, its use is restricted to severely displaced fractures and only when the percutaneous techniques have failed or their application contraindicated because of associated injuries to the distal radius. METHODS: In this retrospective study, we evaluated 51 children between the ages of 6 and 15 years who presented to our institution from 1996 to 2012 with Métaizeau-modified Judet grades 3, 4a, and 4b radial head fractures. The surgical techniques used were closed reduction and casting under general anesthesia (n=7), closed reduction and intramedullary nailing using Métaizeau technique (n=27), and Métaizeau technique and open reduction with intramedullary nailing (n=17). Functional results of the 3 surgical techniques were evaluated using the Mayo Elbow Performance Score (MEPS) and compared by modified Judet classification using χ analysis. RESULTS: No statistic significant association was found between type of surgery and final MEPS was observed (P=0.110). However, a significant association was found between initial modified Judet grade and final MEPS. CONCLUSIONS: In the present study, final functional outcome seems to be not affected by open reduction but was significantly associated with initial modified Judet grade. LEVEL OF EVIDENCE: Level III-retrospective study comparing closed and open reduction techniques, performed at the same institution.

Meagre effects of disuse on the human fibula are not explained by bone size or geometry.

Fibula response to disuse is unknown; we assessed fibula bone in spinal cord injury (SCI) patients and able-bodied counterparts. Group differences were smaller than in the neighbouring tibia which could not be explained by bone geometry. Differential adaptation of the shank bones may indicate previously unknown mechanoadaptive behaviours of bone. INTRODUCTION: The fibula supports only a small and highly variable proportion of shank compressive load (-8 to +19 %), and little is known about other kinds of stresses. Hence, whilst effects of habitual loading on tibia are well-known, fibula response to disuse is difficult to predict. METHODS: Therefore, we assessed fibular bone strength using peripheral quantitative computed tomography (pQCT) at 5 % increments from 5 to 90 % distal-proximal tibia length in nine participants with long-term spinal cord injury (SCI; age 39.2 ± 6.2 years, time since injury 17.8 ± 7.4 years), representing a cross-sectional model of long-term disuse and in nine able-bodied counterparts of similar age (39.6 ± 7.8 years), height and mass. RESULTS: There was no group difference in diaphyseal fibula total bone mineral content (BMC) (P = 0.22, 95 % CIs -7.4 % to -13.4 % and +10.9 % to +19.2 %). Site by group interactions (P < 0.001) revealed 27 and 22 % lower BMC in SCI at 5 and 90 % (epiphyseal) sites only. Cortical bone geometry differed at mid and distal diaphysis, with lower endocortical circumference and greater cortical thickness in SCI than able-bodied participants in this region only (interactions both P < 0.01). Tibia bone strength was also assessed; bone by group interactions showed smaller group differences in fibula than tibia for all bone parameters, with opposing effects on distal diaphysis geometry in the two bones (all Ps < 0.001). CONCLUSIONS: These results suggest that the structure of the fibula diaphysis is not heavily influenced by compressive loading, and only mid and distal diaphysis are influenced by bending and/or torsional loads. The fibula is less influenced by disuse than the tibia, which cannot satisfactorily be explained by differences in bone geometry or relative changes in habitual loading in disuse. Biomechanical study of the shank loading environment may give new information pertaining to factors influencing bone mechanoadaptation.

A Structural and Mechanism-Based Perspective Toward Understanding Pediatric and Adult Sports Injuries.

OBJECTIVE: The purpose of this article is to compare the injury patterns in skeletally mature patients versus skeletally immature patients to better understand the factors that cause the specific injury appearance. The physis as the essential factor in the injury manifestation will be examined. CONCLUSION: The physis and immature chondroosseous junctions operate as the weak links in the immature skeleton and are the deciding factors in the pattern of injury, even though the injury mechanisms are identical to those in adults.

Internal Fixation With Absorbable Rods for the Treatment of Displaced Radial Neck Fractures in Children.

BACKGROUND: The treatment of radial neck fractures with complete displacement or severe displacement and an angle of >30 degrees is controversial. The currently used methods, including the Metaizeau technique, are associated with drawbacks such as imperfect reduction, epiphyseal damage, and delayed functional recovery. To overcome these drawbacks, we used absorbable rod fixation followed by early functional training for the treatment of displaced radial neck fractures in children. METHODS: In this study, 68 patients (age, 4 to 12 y; average, 8.4 y; average angle, 58 degrees; average displacement, 53%) with radial neck fractures with Salter-Harris grades II to IV underwent lateral elbow open reduction and absorbable rod fixation. At 3 weeks postoperatively, the patients' plaster casts were removed, and functional training was started. RESULTS: Anatomic reduction was achieved in all patients. We followed-up 68 patients for 6 months to 4 years (average, 41 mo). No cases of radial nerve injury, radial bone necrosis, myositis ossificans, and postoperative infection were observed. The functional recovery was "excellent" in 43 patients, "good" in 13 patients, "average" in 12 patients, and "bad" in 0 patients, according to the Morrey evaluation standard. CONCLUSION: Open reduction with absorbable rod fixation for the treatment of displaced radial neck fractures in children was feasible and was a choice in children. LEVEL OF EVIDENCE: Therapeutic II.

Subchondral and epiphyseal bone remodeling following surgical transection and noninvasive rupture of the anterior cruciate ligament as models of post-traumatic osteoarthritis.

OBJECTIVE: Animal models are frequently used to study post-traumatic osteoarthritis (PTOA). A common anterior cruciate ligament (ACL) injury model is surgical transection, which may introduce confounding factors from surgery. Noninvasive models could model human injury more closely. The purpose of this study was to compare subchondral and epiphyseal trabecular bone remodeling after surgical transection and noninvasive rupture of the ACL. METHODS: Thirty-six rats were randomized to an uninjured control, surgical transection (Transection), or noninvasive rupture (Rupture). Animals were randomized to 4 or 10 week time points (n = 6 per group). Micro computed tomography (µCT) imaging was performed with an isotropic voxel size of 12 µm. Subchondral and epiphyseal bone was segmented semi-automatically, and morphometric analysis was performed. RESULTS: Transection caused a greater decrease in subchondral bone volume fraction (BV/TV) than Rupture in the femur and tibia. Rupture had greater subchondral bone tissue mineral density (TMD) at 4 and 10 weeks in the femur and tibia. Subchondral bone thickness (SCB.Th) was decreased in the femur in Transection only. Epiphyseal BV/TV was decreased in Transection only, and Rupture exhibited increased femoral epiphyseal TMD compared to both Control and Transection. Rupture exhibited greater femoral epiphyseal trabecular thickness (Tb.Th.) compared to Control and Transection at 4 weeks, and both Rupture and Transection had increased femoral epiphyseal Tb.Th. at 10 weeks. Epiphyseal trabecular number (Tb.N) was decreased in both injury groups at both time points. Femoral and tibial epiphyseal structure model index (SMI) increased in both groups. CONCLUSIONS: The two injury models cause differences in post-injury bone morphometry, and surgical transection may be introducing confounding factors that affect downstream bony remodeling.

Pediatric Knee Dislocations and Physeal Fractures About the Knee.

Given the high incidence of vascular and neurologic injury associated with pediatric knee dislocations and displaced physeal injuries about the knee, a thorough understanding of the clinical and radiographic signs associated with these injuries, relevant anatomy, workup, reduction techniques, and surgical management is crucial. A higher incidence of these injuries in children is anticipated because of increased participation in high-energy activities that result in contact or collision during sports or recreation. Complications, such as vascular and nerve injuries and compartment syndrome, can be diagnosed early in the workup to prevent catastrophic outcomes. The clinical examination should include evaluation of the motor and sensory status of the limb, palpation of pulses, and measurement of ankle brachial indices. Radiographic examination should include plain radiography and supplemental advanced imaging, if indicated. Vascular imaging or expert consultation should be considered when the pulse or ankle brachial index is abnormal on clinical examination. Selection of nonsurgical or surgical treatment depends on the fracture pattern and stability.