Child Fractures: Are We Getting More Surgical? / Fraturas na criança: Estamos ficando mais cirúrgicos?

Abstract Historically, surgeries on the immature skeleton were reserved for open or articular fractures. In recent years, the improvement in the quality and safety of anesthesia, new imaging equipment, implants designed especially for pediatric fractures, associated with the possibility of shorter hospitalization time and rapid return to social life has demonstrated a new tendency to evaluate and treat fractures in children. The purpose of this update article is to answer the following questions: (1) Are we really turning more surgical in addressing fractures in children? (2) If this is true, is this surgical conduct based on scientific evidence? In fact, in recent decades, the medical literature demonstrates articles that support better evolution of fractures in children with surgical treatment. In the upper limbs, this is very evident in the systematization of the reduction and percutaneous fixation of supracondylar fractures of the humerus and fractures of the forearm bones. In the lower limbs, the same occurs with diaphyseal fractures of the femur and tibia. However, there are gaps in the literature. The available published studies show low scientific evidence. Thus, it can be inferred that, even though the surgical approach is more present, the treatment of pediatric fractures should always be individualized and conducted according to the knowledge and experience of the professional physician, taking into account the presence of technological resources available for the care of the small patient. All possibilities, non-surgical and/or surgical, should be included, always instituting actions based on science and in agreement with the family's wishes.

Resumo Historicamente, as cirurgias no esqueleto imaturo eram reservadas às fraturas expostas ou articulares. Nos últimos anos, a melhora na qualidade e segurança das anestesias, novos equipamentos de imagem, implantes desenhados especialmente para fraturas pediátricas, associados à possibilidade de menor tempo de hospitalização e rápido retorno ao convívio social vêm demonstrando uma nova tendência de avaliar e tratar fraturas na criança. O objetivo deste artigo de atualização é responder às seguintes questões: (1) estamos realmente ficando mais cirúrgicos na abordagem das fraturas em crianças? (2) Caso isto seja verdadeiro, esta conduta cirúrgica está baseada em evidências científicas? De fato, nas últimas décadas, a literatura médica demonstra artigos que suportam melhor evolução das fraturas na criança com o tratamento cirúrgico. Nos membros superiores, isto fica muito evidente na sistematização da redução e fixação percutânea das fraturas supracondilianas do úmero e das fraturas de ossos do antebraço. Nos membros inferiores, o mesmo ocorre com fraturas diafisárias do fêmur e tíbia. No entanto, há lacunas na literatura. Os estudos publicados são geralmente com baixa evidência científica. Assim, pode-se deduzir que, mesmo sendo a abordagem cirúrgica mais presente, o tratamento de fraturas pediátricas deve ser sempre individualizado e conduzido de acordo com o conhecimento e experiência do médico profissional, levando em conta a presença de recursos tecnológicos disponíveis para o atendimento do pequeno paciente. Deve-se incluir todas as possibilidades, não cirúrgicas e/ou cirúrgicas, sempre instituindo ações baseadas na ciência e em concordância com os anseios da família.

Crecimiento guiado en extremidades inferiores / Guided growth in lower extremities

El crecimiento guiado es una opción quirúrgica de uso creciente para la corrección de las deformidades angulares de extremidades inferiores en pacientes esqueléticamente inmaduros. Es posible de realizar en múltiples planos o segmentos, con excelentes resultados. Su uso más frecuente es en deformidades del plano coronal alrededor de la rodilla. La epifisiodesis permanente se puede realizar en pacientes dentro de los dos años previos al término del crecimiento longitudinal del segmento a tratar, considerando la epifisiodesis temporal para los pacientes con más de 2 años de crecimiento restante.En casos leves a moderados las tasas de éxito llegan incluso al 100% en algunas series, en tanto, pacientes con enfermedad de Blount, obesidad, edad esquelética avanzada o deformidades severas, tienen menos posibilidades de lograr una corrección completa.Independientemente de la técnica quirúrgica, es necesario una adecuada planificación preoperatoria, educación familiar y un seguimiento estricto para así minimizar las complicaciones y permitir una excelente corrección de la deformidad con una morbilidad mínima.

Guided Growth is a surgical option of increasing use for the correction of angular deformities of the lower extremities in skeletally immature patients. It is possible to perform in multiple planes or segments, with excellent results. Its most frequent use is in deformities of the coronal plane around the knee. Permanent epiphysiodesis can be performed in patients within 2 years before the end of longitudinal growth of the segment to be treated, considering temporary epiphysiodesis for patients with more than 2 years of remaining growth.In mild to moderate cases, the success rates reach even 100% in some series, while patients with Blount's disease, obesity, advanced skeletal age or severe deformities are less likely to achieve a complete correction.Regardless of the surgical technique, adequate preoperative planning, family education and strict follow-up are necessary to minimize complications and allow excellent correction of the deformity with minimal morbidity

Inestabilidad tibioperonea proximal atraumática en pacientes con fisis abiertas. Reporte de caso / Atraumatic proximal tibiofibular joint instability in patient with open physis. Case report

La inestabilidad de la articulación tibioperonea proximal puede presentarse con una luxación, con escasos síntomas laterales de la rodilla, dolor, malestar e incomodidad durante distintas actividades o síntomas relacionados con la irritación del nervio peroneo común. Un preciso diagnóstico prequirúrgico es imperativo, así como el tratamiento conservador con inmovilización y kinesiología por cuatro a seis semanas. En la población adolescente, el planeamiento prequirúrgico puede ser dificultoso por la presencia de los cartílagos abiertos, por lo tanto, se debe tomar precaución en la realización de los túneles y en la colocación de implantes en relación con la fisis abierta. El objetivo del siguiente trabajo es presentar el caso de un niño de once años con inestabilidad tibioperonea proximal recurrente, además mostrar detalles de la técnica quirúrgica, protocolo postoperatorio y sus excelentes resultados

Instability of the proximal tibiofibular joint (PTFJ) can present as dislocations, vague symptoms of lateral knee pain, discomfort during activity, or symptoms related to irritation of the common peroneal nerve. An accurate preoperative diagnosis is imperative and should include a trial of taping of the PTFJ for a 4- to 6-week time frame before surgical reconstruction is indicated. In the adolescent population, surgical planning can be complicated by the presence of open physes; therefore, caution must be taken to avoid drilling through or placing screw fixation across the physes. Potential complications include growth arrest and limb length discrepancy. Therefore, the purpose of this case report is to describe the surgical technique for addressing PTFJ instability in adolescent patients. The aim of this case report is to present a case of instability of the proximal tibiofibular joint (PTFJ) treated surgically in an eleven-year-old male soccer player, focused on technical tips, strict rehab protocol with excellent results

Upper Zone of Growth Plate and Cartilage Matrix (UCMA) Levels in Patients with Chronic Kidney Disease

Abstract Chronic kidney disease (CKD) is an important health problem across the world affecting the adult population with an enormous social and economic burden. Calcium regulation is also affected in patients with CKD, and related to several disorders including vascular calcifications, mineral bone disorders, and cardiovascular diseases (CVD). Upper zone of growth plate and cartilage matrix (UCMA) is vitamin K-dependent protein (VKDP) and acts as a calcification inhibitor in the cardiovascular system. The molecular mechanism of UCMA action remains unclear in CKD. In the current study, we aimed to investigate serum total UCMA levels and its association with calcium metabolism parameters in CKD patients including hemodialysis (HD) patients. Thirty-seven patients with CKD stage 3-5, 41 HD patients, and 34 healthy individuals were enrolled in this cross-sectional study. Serum UCMA and calcification related protein levels (Matrix Gla Protein (MGP), Osteocalcin (OC), and Fetuin-A) were analyzed with enzyme-linked immunosorbent assay (ELISA). Calcium mineral disorder parameters (Serum Ca, P, iPTH) were quantified with routine techniques. We, for the first time, report the potential biomarker role of UCMA in CKD including HD. Serum total UCMA levels were significantly higher in patients with CKD including HD patients than the healthy controls. Also, serum UCMA levels showed negative correlations with serum calcium, and eGFR, while showed positive relationships with P, iPTH, MGP, OC. Increased total UCMA levels may have a role in the Ca metabolism disorder and related to the pathogenesis of Vascular Calcification in patients with CKD.

Rabbit growth plate morphology in temporary bilateral blocking / Morfología de la placa de crecimiento de conejos durante bloqueo bilateral temporario

Blocking of the growth plate (GP) using plates with screws (tension band plating) is a modern method used to correct deformities and moderate leg length discrepancy in growing children. Determining the duration of temporary bilateral blocking without the occurrence of irreversible changes of GP is of paramount importance important. Methods: Two-month-old Californian breed male rabbits (n=30) were exposed to bilateral blocking of the distal GP of the right femur locking plates with screws for 3, 5, and 7 weeks. The fixators were removed after 5 and 7 weeks in 18 rabbits and 3 weeks after that, animals were sacri!ced. The contralateral limb was used as a control. Histological, histomorphometric, and X-ray analyses were performed. Results: During GP blocking, its height gradually decreased. This decreased was more pronounced after 7 weeks. Destructive changes progressed with an increase in the blocking duration. Three weeks after discontinuation of the bilateral blocking that lasted 5 weeks, the height of the GP signi!cantly increased 1.2 times on the lateral side and 1.9 times on the medial side (p<0.001) compared to the control. When blocking was discontinued after 7 weeks, the structure of the GP was partially restored after 3 weeks, the height of GP signi!cantly increased 1.2 times on the lateral side, and 1.07 times on the medial side (p<0.01) compared to the control. Conclusion: Restoration of the structuralfunctional features of the GP after the removal of the plates depends on the duration of temporary bilateral blocking, which must be taken into account in the clinical setting. (AU)

El bloqueo de la placa de crecimiento (PC) utilizando placas con tornillos (banda de tensión) es un método moderno utilizado para corregir deformidades y alteraciones moderadas en la longitud de las piernas en niños en crecimiento. Es de suma importancia determinar cuál debe ser la duración del bloqueo bilateral temporal sin que ocurran cambios irreversibles en la PC. Métodos: Conejos machos de raza californiana de dos meses de edad (n = 30) fueron expuestos al bloqueo bilateral de la PC distal colocando placas del fémur derecho con tornillos durante 3, 5 y 7 semanas. Los fijadores fueron retirados después de 5 y 7 semanas en 18 de los conejos, y 3 semanas después los animales fueron sacrificados. La extremidad contralateral se utilizó como control. Se realizaron análisis histológicos, histomorfométricos y de rayos X. Resultados: Durante el bloqueo de la PC, su altura disminuyó gradualmente. Esta disminución fue más pronunciada después de 7 semanas. Los cambios destructivos se incrementaron a medida aumentaba la duración del bloqueo. Tres semanas después de la interrupción del bloqueo bilateral que duró 5 semanas, la altura de la PC aumentó significativamente 1.2 veces en el lado lateral y 1.9 veces en el lado medial (p <0.001) en comparación con el control. Conclusión: La restauración de las características funcionales estructurales de la PC después de la extracción de las placas depende de la duración del bloqueo bilateral temporal, lo que debería tenerse en cuenta en el tratamiento clínico de estas alteraciones. (AU)

Genu Valgo: un reto inquientante para el ortopedista / Cómo se pronuncia Genu Valgo: a disturbing challenge for the orthopedist

Genu valgo es una deformidad común en la infancia. La mayoría mejora espontáneamente al ángulo femorotibial del adulto normal antes de los ocho años. Ocasionalmente, las deformidades se extienden más allá del límite fisiológico para producir síntomas que pueden ser de origen idiopático o estar relacionados con trastornos de la formación de la placa de crecimiento o hueso. Puede haber dolor y limitación de la actividad.

Genu valgum, known as "knock-knee", is a common deformity in childhood. Most improve spontaneously to the normal adult femoro-tibial angle before age eight. Occasionally, the deformities extend beyond the physiological limits to cause symptomatology. These cases may be of idiopathic origin or be related to disorders of growth plate or bone formation. Pain and limitation of activity may occur.

TGF-β Signalling is Suppressed under Pro-Hypertrophic Conditions in MSC Chondrogenesis Due to TGF-β Receptor Downregulation

BACKGROUND AND OBJECTIVES: Mesenchymal stem cells (MSCs) become hypertrophic in long term despite chondrogenic differentiation following the pathway of growth plate chondrocytes. This terminal differentiation leads to phenotypically unstable cartilage and was mirrored in vitro by addition of hypertrophy inducing medium. We investigated how intrinsic TGF-β signaling is altered in pro-hypertrophic conditions. METHODS AND RESULTS: Human bone marrow derived MSC were chondrogenically differentiated in 3D culture. At day 14 medium conditions were changed to 1. pro-hypertrophic by addition of T3 and withdrawal of TGF-β and dexamethasone 2. pro-hypertrophic by addition of BMP 4 and withdrawal of TGF-β and dexamethasone and 3. kept in prochondrogenic medium conditions. All groups were treated with and without TGFβ-type-1-receptor inhibitor SB431542 from day 14 on. Aggregates were harvested for histo- and immunohistological analysis at d14 and d28, for gene expression analysis (rt-PCR) on d1, d3, d7, d14, d17, d21 and d28 and for Western blot analysis on d21 and d28. Induction of hypertrophy was achieved in the pro-hypertrophic groups while expression of TGFβ-type-1- and 2-receptor and Sox 9 were significantly downregulated compared to pro-chondrogenic conditions. Western blotting showed reduced phosphorylation of Smad 2 and 3 in hypertrophic samples, reduced TGF-β-1 receptor proteins and reduced SOX 9. Addition of SB431542 did not initiate hypertrophy under pro-chondrogenic conditions, but was capable of enhancing hypertrophy when applied simultaneously with BMP-4. CONCLUSIONS: Our results suggest that the enhancement of hypertrophy in this model is a result of both activation of pro-hypertrophic BMP signaling and reduction of anti-hypertrophic TGFβ signaling.

Genetic regulation of linear growth

Linear growth occurs at the growth plate. Therefore, genetic defects that interfere with the normal function of the growth plate can cause linear growth disorders. Many genetic causes of growth disorders have already been identified in humans. However, recent genome-wide approaches have broadened our knowledge of the mechanisms of linear growth, not only providing novel monogenic causes of growth disorders but also revealing single nucleotide polymorphisms in genes that affect height in the general population. The genes identified as causative of linear growth disorders are heterogeneous, playing a role in various growth-regulating mechanisms including those involving the extracellular matrix, intracellular signaling, paracrine signaling, endocrine signaling, and epigenetic regulation. Understanding the underlying genetic defects in linear growth is important for clinicians and researchers in order to provide proper diagnoses, management, and genetic counseling, as well as to develop better treatment approaches for children with growth disorders.

Prolonged continuous infusion of teriparatide promotes bone metabolism in normal but not in castrated mice / 南方医科大学学报

OBJECTIVE@#To investigate the effects of continuous pumping of teriparatide (TPTD) on bone metabolism in ovariectomized and normal mice and provide experimental evidence for the selection of animal models for studying the effects of TPTD and its related peptides on osteoclasts.@*METHODS@#Twenty-four female C57BL mice (6-weeks old) were subjected to ovariectomy (OVX) or sham operation followed 7 days later by continuous pumping of TPTD or the solvent vehicle (VEH) a micropump (SHAM-VEH, SHAM-TPTD, OVX-VEH, and OVX-TPTD groups; =6). Two weeks later, the tibial and femoral bones were harvested for micro-CT scanning to measure the parameters of the tibia and the femoral cortical bone. Histopathological examinations of the tibial tissue were conducted using HE staining and TRAP staining and the number of osteoclasts and the growth plate thickness were determined. The serum Ca2 + levels of the mice were measured. The primary osteoblasts from the cranial bone were treated with estradiol (E2) and TPTD for 48 h, and the expressions of β-catenin and RANKL protein in the cells were analyzed.@*RESULTS@#The trabecular bone mass of OVX mice was significantly lower than that of sham-operated mice ( < 0.05). Continuous TPTD pumping significantly reduced tibial cancellous bone mass and femoral cortical bone area in the sham-operated mice, while in the castrated mice, TPTD pumping increased the cancellous bone mass without changing the cortical bone area. TRAP staining showed that cancellous osteoblasts in the tibia increased significantly in the castrated mice as compared with the sham-operated mice, and TPTD pumping significantly increased the number of cancellous osteoblasts in the sham-operated mice ( < 0.05). In the primary cultured osteoblasts, treatment with both E2 and TPTD obviously lowered the expression of β-catenin and increased the expression of RANKL as compared with TPTD treatment alone.@*CONCLUSIONS@#Continuous pumping of TPTD promotes bone resorption in normal mice but does not produce obvious bone resorption effect in the ovariectomized mice, suggesting that castrated mice are not suitable models for studying the effect of TPTD and the related peptides on the osteoclasts.

Undernutrition impairs the quality of growth plate and trabecular and cortical bones in growing rats

Abstract Purpose: To investigate the effects of dietary restriction on the growth plate and long bone tissue in growing rats. Methods: Sixty male Wistar rats were randomly assigned to two groups: Control (Con) and Diet-restricted (Res). After weaning, the Res rats were offered 50% of the chow ingested by the control (ad libitum food intake). The animals were subdivided into two subgroups with follow-ups up to 56 or 70 days. After euthanasia, the growth plate of tibias was analyzed by histomorphometry, micro-computed tomography, and mechanical test. The trabecular and compact bones were evaluated by histomorphometry, dual-energy X-ray absorptiometry, and micro-computed tomography (μCT). Real-time PCR was used to analyze gene expression. Results: Although dietary restriction did not alter gene expression, several phenotypic changes were seen in the growth plate; i.e., decrease in volume, reduction in total area and height, decrease in the area ossified zones, mechanical weakening, reduction in mass of trabecular and cortical bone, lower bone density, deterioration of the trabecular and cortical microarchitecture, and trabeculae with lower collagen deposition. Conclusion: Dietary restriction had severe detrimental effects on the growth plate and trabecular and cortical bone.

Zoledronic acid effect on bone of growing rats / Efecto del ácido zoledrónico en el hueso de ratas en crecimiento

Zoledronic acid (ZA) is an antiresorptive drug used in children with bone diseases like osteogenesis imperfecta, juvenil osteoporosis, fibrous dysplasia and primary bone tumors. The aim of the present study was to evaluate the effects of ZA dose accumulation on growing bone during different periods of treatment in normal rats. Methods: A 4x2 factorial design was used to study the effect of the dose of ZA (D: 0-2.5-12.5-25 µg Z/kg body weight/s.c. weekly) and the length of treatment (T: 15-30 days) in normal female Sprague Dawley rats. Bone morphometric, histomorphometric, densitometric and biomechanical studies were performed. Results: Femoral length and cross-sectional area were affected by both D and T. A significant interaction between D and T was observed in length with a lower value at higher dose and 30 days of treatment. Growth plate of the tibia showed a decrease in total thickness with D and T. Histomorphometric and connectivity parameters of trabecular bone were significantly increased with D and several parameters were also affected by T. Cortical bone strength was increased only with T. Biomechanical parameters of trabecular bone showed significant interaction with greater effect at higher D and T. Conclusion: Even though a mild negative effect of the highest dose of ZA on linear and appositional growth was observed, the other bone parameters evaluated were improved. A careful risk/benefit analysis would lead us to conclude that the mild deleterious effects of ZA during growth are outweighed by the benefit obtained with treatment. (AU)

El ácido zoledrónico (AZ) es un fármaco antirresortivo utilizado en niños con enfermedades óseas como osteogénesis imperfecta, osteoporosis juvenil, displasia fibrosa y tumores óseos primarios. El objetivo del presente estudio fue evaluar los efectos de las dosis acumuladas de AZ en el hueso en crecimiento de ratas hembras normales durante diferentes períodos de tratamiento. Métodos: se utilizó un diseño factorial de 4x2 para estudiar el efecto de la dosis de AZ (D: 0-2,5-12,5-25 µg Z / kg de peso corporal /sc semanalmente) y el período de tratamiento (T: 15-30 días) en ratas Sprague Dawley. Se realizaron estudios óseos morfométricos, histomorfométricos, densitométricos y biomecánicos. Resultados: la longitud y el área de sección transversal del fémur se vieron afectadas tanto por D como por T. Se observó una interacción significativa entre D y T en la longitud obteniéndose un valor más bajo a la dosis más alta y a 30 días de tratamiento. El cartílago de crecimiento de la tibia mostró una disminución en el espesor total con D y T. Los parámetros histomorfométricos y de conectividad del hueso trabecular aumentaron significativamente con D y varios parámetros también se vieron afectados por T. La fortaleza ósea cortical aumentó solo con T. Los parámetros biomecánicos del hueso trabecular mostraron una interacción significativa con un mayor efecto a mayor D y T. Conclusión: a pesar que se observó un leve efecto negativo de la dosis más alta de AZ sobre el crecimiento lineal y aposicional, el resto de los parámetros óseos evaluados mejoraron. Un análisis cuidadoso del riesgo /beneficio permite concluir que los efectos negativos leves del AZ durante el crecimiento son superados por el beneficio obtenido con el tratamiento. (AU)

Tibial dyschondroplasia is closely related to suppression of expression of hypoxia-inducible factors 1α, 2α, and 3α in chickens

Tibial dyschondroplasia (TD) cases has not been reported in Tibetan chickens (TBCs), but it is commonly seen in commercial broilers characterized by lameness. The underlying mechanism remains unclear. Hypoxia-inducible factors (HIFs) are important regulators of cellular adaptation to hypoxic conditions. In this study, we investigated the role of HIF-1α,

Effect of the Orally Active Growth Hormone Secretagogue MK-677 on Somatic Growth in Rats

PURPOSE: Growth hormone secretagogues (GHSs) possess the ability to release growth hormone (GH) in the body. This study aimed to investigate the effects of MK-677, an orally active GHS, on somatic growth in rats. MATERIALS AND METHODS: The serum levels of GH were measured after oral administration of MK-677 to confirm GH stimulatory effects. Body weight, body length, tibia length, epiphyseal plate width, and serum levels of insulin-like growth factor (IGF)-I were measured after oral administration of 4 mg/kg of MK-677 for 6 weeks to investigate growth-promoting effects. RESULTS: Oral administration of MK-677 at 4 mg/kg increased peak GH concentrations by 1.8-fold, compared to baseline. However, oral administration of MK-677 for 6 weeks did not increase body growth or serum levels of IGF-I. At 6 weeks after treatment, the GH response to MK-677 was abolished. Pituitary GH mRNA and hypothalamic GH-releasing hormone mRNA, and GH secretagogue receptor (GHSR) mRNA expression in the pituitary and hypothalamus did not differ between the control and treatment group. Somatostatin (SST) mRNA expression in the hypothalamus was markedly increased in the treatment group, whereas SST receptor (SSTR)-2 mRNA expression in the pituitary gland was decreased. Protein expression of hypothalamic GHSR, SST, and pituitary SSTR-2 showed patterns similar to those for mRNA expression. CONCLUSION: Our results suggest that prolonged administration of MK-677 in rats does not promote growth despite the GH stimulatory effect of MK-677, which may be related to increased expression of SST in the hypothalamus. Further studies are needed to overcome the observed desensitization to GHS.

Changes of the growth plate in children: 3-dimensional magnetic resonance imaging analysis / 소아과

PURPOSE: This pilot study assessed changes in the growth plate and growth rates in children during a 6-month period. METHODS: The study included 31 healthy children (17 boys, 14 girls) under evaluation for growth retardation. Height, weight, bone age, insulin like growth factor-1 (IGF-1), and insulin like growth factor binding protein 3 (IGF-BP3) were measured at baseline and after 6 months. In addition, the diameter, thickness, and volume of the femoral and tibial growth plates were measured using magnetic resonance imaging. RESULTS: The mean bone age in boys and girls was 11.7 and 10.7 years, respectively. In boys, height (z score) (−0.2 vs. 0.0), weight (z score) (0.8 vs. 1.1), body mass index (BMI) (z score) (1.27 vs. 1.5), IGF-1 (ng/mL) (343.6 vs. 501.8), and IGF-BP3 (ng/mL) (5,088.5 vs. 5,620.0) were significantly higher after 6 months. In girls, height (z score) (−1.0 vs. −0.7), weight (z score) (−0.5 vs. 0.1), BMI (z score) (−0.02 vs. 0.3), IGF-1 (ng/mL) (329.3 vs. 524.6), and IGF-BP3 (ng/mL) (4,644.4 vs. 5,593.6) were also significantly higher after 6 months. In both sexes, the mean diameter and volume of the femoral and tibial growth plates were significantly increased 6 months later. CONCLUSION: No significant correlation was found between changes in the growth plate and clinical parameters in children with growth retardation in this study, other than correlations of change in femoral diameter with weight and BMI. A larger, long-term study is needed to precisely evaluate the correlation between change in the growth plate and growth.

Identification of a novel heterozygous mutation of ACAN in a Korean family with proportionate short stature

Aggrecan is a proteoglycan in the extracellular matrix of growth plate and cartilaginous tissues. Aggrecanopathy has been reported as a genetic cause not only for severe skeletal dysplasia but also for autosomal dominant short stature with normal to advanced bone age. We report a novel heterozygous mutation of ACAN in a Korean family with proportionate short stature identified through targeted exome sequencing. We present a girl of 4 years and 9 months with a family history of short stature over three generations. The paternal grandmother is 143 cm tall (−3.8 as a Korean standard deviation score [SDS]), the father 155 cm (−3.4 SDS), and the index case 96.2 cm (−2.9 SDS). Evaluation for short stature showed normal growth hormone (GH) peaks in the GH provocation test and a mild delayed bone age for chronological age. This subject had clinical characteristics including a triangular face, flat nasal bridge, prognathia, blue sclerae, and brittle teeth. The targeted exome sequencing was applied to detect autosomal dominant growth palate disorder. The novel variant c.910G>A (p.Asp304Asn) in ACAN was identified and this variant was found in the subject's father using Sanger sequencing. This is the first case of Korean familial short stature due to ACAN mutation. ACAN should be considered for proportionate idiopathic short stature, especially in cases of familial short stature.

Effects of underwater lipus on the morphohistology of the CF-1 mice growth plate in late lactation stage / Efectos del ultrasonido subacuático sobre la morfohistología de la placa de crecimiento de ratones CF-1 en etapa de lactancia tardía

SUMMARY: Ultrasound is one of the most used tools in physiotherapy, its LIPUS modality allows to treat musculoskeletal injuries, but like the conventional ultrasound it is contraindicated its application in areas close to growth cartilage by a possible closure of this one. In the literature there is no conclusive evidence of this contraindication, so the objective of the present study is to evaluate the effects of doses equivalent to underwater LIPUS on the histomorphometry of the proximal tibial epiphysis growth plate in an animal model. LIPUS was applied in underwater mode in the right pelvic limb to 8 mice in p 15 for 4 days, 2 times a day. On completion of 8 sessions the histology of the stimulated limb growth plate was sacrificed and the histology. When evaluating the histomorphometry of the plaque, a significant increase in the thickness and area of the proliferative zone stimulated with LIPUS (p = 0.048) was observed. In the hypertrophic area were observed no significant differences in thickness or areas, but in the hypertrophic area there were significant changes in the histological organization, observing a significant increase of the entire columns in the stimulated plaque (p = 0.04). LIPUS in underwater modality modifies the histomorphometry of the proximal epiphyseal PC of the tibia of rodents in the late postnatal stage, promoting proliferation and columnar organization in the proliferative and hypertrophic zone, respectively.

RESUMEN: El ultrasonido es una de las herramientas más utilizadas en fisioterapia, su modalidad LIPUS permite tratar lesiones músculo-esqueléticas, pero al igual que el ultrasonido convencional está contraindicada su aplicación en zonas próximas a cartílago de crecimiento por un posible cierre de éste. En la literatura no existe evidencia contundente de esta contraindicación, por lo cual el objetivo del presente estudio fue evaluar los efectos de dosis equivalentes a LIPUS subacuático sobre la histomorfometría de la placa de crecimiento de la epífisis proximal de tibia en un modelo animal. Metodología. Se aplicó LIPUS en modalidad subacuática en el miembro pélvico derecho a 8 ratones en p 15 por 4 días, 2 veces al día. Al cumplir 8 sesiones se sacrificaron y se evaluó la histología de la placa de crecimiento del miembro estimulado. Al evaluar la histomorfometría de la placa se observó un aumento significativo en el espesor y el área de la zona proliferiva estimulada con LIPUS (p=0.048). En la zona hipertrófica no se observaron diferencias significativas en el espesor ni en las áreas, pero si existieron cambios significativos en la organización histológica de la zona, observando un aumento significativo de las columnas completas en la placa estimulada (p=0,04). El LIPUS en modalidad subacuática modifica la histomorfometría de la PC epifisiaria proximal de la tibia de roedores en el etapa postnatal tardía, promoviendo la proliferación y la organización columnar en la zona proliferativa e hipertrófica, respectivamente.

Excesso de tiroxina materna associado ao hipertireoidismo pós-natal reduz o crescimento ósseo e o perfil proliferativo e angiogênico das cartilagens de crescimento de ratos / Excess maternal thyroxine associated with postnatal hyperthyroidism reduces bone growth and proliferative and angiogenic profile of rats growth cartilage

Foram estudados os efeitos do excesso da tiroxina materna associado ao hipertireoidismo pós-natal sobre o crescimento ósseo e o perfil proliferativo e angiogênico das cartilagens. Dezesseis ratas Wistar adultas foram distribuídas nos grupos tratados com L-tiroxina e controle. A prole do grupo tratado recebeu L-tiroxina do desmame até 40 dias de idade. Ao desmame, foi realizada dosagem plasmática de T4 livre nas mães. Na prole, foram realizados: dosagem plasmática de T3 total e T4 livre, morfometria das tireoides, mensuração do comprimento e largura do fêmur. Nas cartilagens, foi avaliada a expressão imuno-histoquímica e gênica de CDC-47, VEGF, Flk-1, Ang1, Ang2 e Tie2. As médias entre grupos foram comparadas pelo teste T de Student. As concentrações de T4 livre das mães tratadas e de T3 total e T4 livre da prole foram significativamente mais elevadas. A largura do fêmur foi menor nos animais tratados. Houve também redução da imunoexpressão de CDC-47 e de VEGF e dos transcritos gênicos para VEGF e Ang1 nas cartilagens. Conclui-se que o excesso de tiroxina materna associado ao hipertireoidismo pós-natal reduz a largura da diáfise femoral, a proliferação celular e a expressão de VEGF e de Ang1 nas cartilagens de crescimento de ratos.(AU)

The effects of excess of maternal thyroxine associated with postnatal hyperthyroidism at bone growth and proliferative and angiogenic profile of cartilage were studied. Sixteen adult Wistar rats were divided into treated and control groups. The offspring of the treated group received L-thyroxine from weaning to 40 days-old. At weaning, plasma assay of free T4 was measurement on female rats. In the offspring, the following assessments were performed: measurement of total T3 and free T4, histomorphometry analysis of the thyroid, measurement of body weight and length and width of the femur. In femoral growth cartilage, immunostaining of CDC-47, gene or protein expression of VEGF, Flk-1, Ang1, Ang2 and Tie2 were evaluated. Data were analyzed using Student's t-test. Free T4 was significantly higher in treated rats and total T3 and free T4 were significantly higher in offspring. The width of the femur was significantly lower in treated animals. There was lower immunoreactivity of CDC-47, VEGF and lower expression of gene transcripts for VEGF and Ang1. We concluded that the excess maternal thyroxine associated with postnatal hyperthyroidism reduces the width of the femoral shaft, the cell proliferation and gene and protein expression of VEGF and gene expression of Ang1 on the growth cartilage in rats.(AU)

Spinal Tuberculosis in Children: Predictable Kyphotic Deformity after Cure of the Tuberculosis / 대한정형외과학회잡지

PURPOSE: To assess the chronological changes of disease-related kyphosis after chemotherapy alone. MATERIALS AND METHODS: A total of 101 children aged 2 to 15 years with spinal tuberculosis, accompanied by various stages of disease processes were enrolled for analysis. By utilizing the images in them, the growth plate condition and chronological changes of kyphosis after chemotherapy were analyzed at two points in time; the first assessment was at post-chemotherapy one-year and second at the final discharge. RESULTS: Complete disc destruction in the cervical, dorsal and lumbosacral spines was observed in 2 out of 40 children (5.0%), 8 out of 30 children (26.7%), and 6 out of 31 children (19.4%), respectively. In those cases, the residual kyphosis inevitably developed. In the remaining children, the discs were intact or partially damaged. Among the 101 children kyphotic deformity was maintained without change in 20 children (19.8%). Kyphosis decreased in 14 children (13.9%), while it increased in 67 children (66.3%) with non-recoverably damaged growth plate. CONCLUSION: Although it is tentatively possible to predict the deformity progress or non-progress and spontaneous correction at the time of the initial treatment, its predictive accuracy is low. Therefore, assessment of the chronological changes should be performed at the end of chemotherapy. In children with progressive curve change, assessment of deformity should be continued until maturity.

Novel genetic cause of idiopathic short stature

Traditionally, the growth hormone – insulin-like growth factor I (GH – IGF-I) axis is the most important signaling pathway in linear growth, and defects in this axis present as growth hormone deficiencies or IGF-I deficiencies. However, subtle changes in serum levels of GH or IGF-I, caused by gene mutations involved in the GH – IGF-I axis, can present as idiopathic short stature (ISS). This paper briefly discusses GHR and IGFALS. In addition, recent studies have shown that many factors, including paracrine signals, extracellular matrix, and intracellular mechanisms of chondrocytes, regulate the growth plate independent of the GH – IGF-I system. Rapid development of diagnostic technologies has enabled discovery of many genetic causes of ISS. This paper discusses 5 genes, SHOX, NPR2, NPPC, FGFR3, and ACAN, that may lead to better understanding of ISS.

Protective effect of Rhus verniciflua Stokes extract in an experimental model of post-menopausal osteoporosis / 대한해부학회지

Post-menopausal osteoporosis (PMO) is a major global human health concern. Owing to the need for therapeutic drugs without side effects, natural extracts containing various polyphenolic compounds that may exert estrogenic effects have been studied in depth. Rhus verniciflua Stokes (RVS), which has been used as a traditional herbal medicine for centuries in Korea, was recently revealed to exert estrogenic effects attributable to its bioactive ingredients sulfuretin and butein, which have strong estrogen receptor–binding affinities. In this study, the protective potential of RVS in PMO was evaluated by using an experimental animal model of PMO, which was established by ovariectomy (OVX) of female Sprague Dawley rats. The oral administration of RVS at 20 mg/kg or 100 mg/kg for 8 weeks markedly protected against OVX-induced atrophy of the uterine tube and reversed the elevation in the ratio of serum receptor activator of nuclear factor-κB ligand to osteoprotegerin, which is a marker of disease severity. In addition, RVS inhibited OVX-induced tibia bone loss, activated osteogenic activity, and suppressed osteoclastic activity in the tibial epiphyseal plate, a region of bone remodeling. Collectively, these factors indicated that the oral intake of RVS might be beneficial for the prevention of PMO.