Tibial Growth Research Articles

Laying hens under smallholder conditions: laying performance, growth and bone quality of tibia and femur including essential elements

The study aimed to assess laying performance, growth rate, and bone quality properties of tibia and femur bones of various genotypes of laying hens, including determining essential element composition at the end of the laying cycle in smallholder conditions. The study included three genotypes of laying hens; Czech golden spotted (CGS), White Leghorn (LE) and Dominant Partridge D300 (D300) hens. In total, 180 hens (60/genotype) were used in 3 replications (20 hens/replication). The eggs were collected to determine egg lay and hen-day egg production. Additionally, feed consumption was recorded to determine feed consumption per day or egg, resp. The mortality rate was recorded. Hens were individually weighed every 10 wk to analyze the growth performance and body weight changes during the laying cycle. The differences in performance characteristics were observed as significant in all studied parameters. The bone quality analysis consisted of the determination of bone weight, length, width, and fracture toughness. Furthermore, dry matter, ash, and selected elements, which included boron (B), calcium (Ca), cadmium (Cd), copper (Cu), iron (Fe), magnesium (Mg), manganese (Mn), sodium (Na), phosphorus (P), lead (Pb), and zinc (Zn) were assessed. Regarding the results of tibia and femur bones, the effect of genotype was determined as significant in all evaluated properties. In terms of element composition, all evaluated elements significantly differed among the genotypes in the tibia (with one exception of Cu) and in the femur (with one exception of Cd). In conclusion, our results showed that hens’ performance, production quality, mortality and bone properties significantly differed among genotypes under smallholder conditions. Thus, every genotype needs to be carefully considered, when the rearing conditions are set.

Transcriptome-based biomarker gene screening and evaluation of the extracellular fatty acid-binding protein (Ex-FABP) on immune and angiogenesis-related genes in chicken erythrocytes of tibial dyschondroplasia

BackgroundTibial dyschondroplasia (TD) is a bone disorder in which dead chondrocytes accumulate as a result of apoptosis and non-vascularization in the tibial bone of broiler chickens. The pathogenicity of TD is under extensive research but is yet not fully understood. Several studies have linked it to apoptosis and non-vascularization in the tibial growth plate (GP). We conceived the idea to find the differentially expressed genes (DEGs) in chicken erythrocytes which vary in expression over time using a likelihood-ratio test (LRT). Thiram was used to induce TD in chickens, and then injected Ex-FABP protein at 0, 20, and 50 μg.kg-1 to evaluate its therapeutic effect on 30 screened immunity and angiogenesis-related genes using quantitative PCR (qPCR). The histopathology was also performed in TD chickens to explore the shape, circularity, arrangements of chondrocytes and blood vessels.ResultsClinical lameness was observed in TD chickens, which decreased with the injection of Ex-FABP. Histopathological findings support Ex-FABP as a therapeutic agent for the morphology and vascularization of affected chondrocytes in TD chickens. qPCR results of 10 immunity (TLR2, TLR3, TLR4, TLR5, TLR7, TLR15, IL-7, MyD88, MHCII, and TRAF6) and 20 angiogenesis-related genes (ITGAV, ITGA2, ITGB2, ITGB3, ITGA5, IL1R1, TBXA2R, RPL17, F13A1, CLU, RAC2, RAP1B, GIT1, FYN, IQGAP2, PTCH1, NCOR2, VAV-like, PTPN11, MAML3) regulated when Ex-FABP is injected to TD chickens.ConclusionImmunity and angiogenesis-related genes can be responsible for apoptosis of chondrocytes and vascularization in tibial GP. Injection of Ex-FABP protein to thiram induced TD chickens decrease the chondrocytes damage and improves vascularization.

Lower limb deformities and limb length discrepancies in hereditary multiple exostoses.

There is a high rate of lower limb deformity and limb length discrepancy in patients with hereditary multiple exostoses (HME). The aim of this study was to evaluate the type and frequency of lower limbs axial deviation and limb length discrepancy and the type of exostoses being risk factors for theses deformities. We retrospectively reviewed standing full-length radiograph of 32 HME patients (64 limbs) followed in our institution between October 2009 and December 2020. Patient demographics were recorded. Radiographic analysis of the coronal limb alignment was performed, limb length discrepancy was measured and topography of the exostoses was recorded. We propose a classification of lower legs in 2 groups and 4 types according to the presence and the location of exostoses. In group I, there is an intertibio- fibular exostose with fibular origin at the level of the tibiofibular joints. In type IA, at the level of the distal tibiofibular joint with ascension of the distal fibula; in type IB at the level of the proximal tibiofibular joint with a bracketing effect on the proximal tibia and a lateral slope of the proximal tibial growth plate; the type IC is combining features of both IA and IB. In group II, there is no intertibio-fibular exostose coming from the fibula and no growth abnormality is obvious. A clinically notable lower limb discrepancy (LLD) of ≥2 cm was found in 19% of our patients. Approximately 33% of patients had a knee valgus deformity and 44% had an ankle valgus deformity. The knee valgus deformity was due to fibular growth anomalies and not to distal femur anomalies. The majority of lower legs had fibular growth anomalies (72%) which was a significant risk factor for knee valgus deformity and leg length discrepancy. On the contrary, we found no correlation between number, location and volume of distal femoral exostoses and genu valgum nor leg length discrepancy. Presence of intertibio-fibular exostoses is a risk factor for knee valgus deformity and leg length discrepancy. The presence of these exostoses should lead to a close follow-up of the patient.

The heterogeneous mechanical properties of adolescent growth plate cartilage: A study in rabbit

The growth plate is a cartilaginous tissue that functions to lengthen bones in children. When fractured, however, the growth plate can lose this critical function. Our understanding of growth plate fracture and mechanobiology is currently hindered by sparse information on the growth plate’s microscale spatial gradients in mechanical properties. In this study, we performed microindentation across the proximal tibia growth plate of 9-week-old New Zealand White rabbits (n = 15) to characterize spatial variations in mechanical properties using linear elastic and nonlinear poroelastic material models. Mean indentation results for Hertz reduced modulus ranged from 380 to 690 kPa, with a peak in the upper hypertrophic zone and significant differences (p < 0.05) between neighboring zones. Using a subset of these animals (n = 7), we characterized zonal structure and extracellular matrix content of the growth plate through confocal fluorescent microscopy and Raman spectroscopy mapping. Comparison between mechanical properties and matrix content across the growth plate showed that proteoglycan content correlated with compressive modulus. This study is the first to measure poroelastic mechanical properties from microindentation across growth plate cartilage and to discern differing mechanical properties between the upper and lower hypertrophic zones. This latter finding may explain the location of typical growth plate fractures. The spatial variation in our reported mechanical properties emphasize the heterogeneous structure of the growth plate which is important to inform future regenerative implant design and mechanobiological models.

Rebound predictors of varus-valgus deformities around the knee corrected by guided growth.

Coronal plane deformities around the knee are rather common condition in children. Guided growth by temporary hemiepiphysiodesis is considered to be the preferred primary treatment in many cases. Despite the popularity of hemiepiphysiodesis, the incidence of recurrence of deformity and predictors for rebound are not well defined. The objectives of this study were to determine the incidence of the recurrence of varus-valgus deformities around the knee treated by temporary hemiepiphysiodesis and possible predictors for the rebound. We retrospectively reviewed medical records and x-ray images of 130 patients with varus-valgus deformities around the knee treated by tension-band (eight-plate) hemiepiphysiodesis, between the years 2006 and 2016 in our institution. The incidence of rebound of varus-valgus deformities around the knee and possible predictors were analyzed. Rebound of the deformity was observed in 10% of patients. Risk factors found to be in correlation with recurrence include young age, deformity of proximal tibia, proximal tibial medial growth plate beaking, and comorbidities (like metabolic disorders, multiple hereditary exostoses and genetic syndromes). The results of this study show that there is a noteworthy incidence of rebound in patients treated by temporary hemiepiphysiodesis for coronal deformities around the knee. The risk factors are also outlined. These patients, especially the ones with risk factors, require close surveillance until maturity. Level III-Case control study.

Glycine receptor subunit-β-deficiency in a mouse model of spasticity results in attenuated physical performance, growth, and muscle strength.

Spasticity is the most common neurological disorder associated with increased muscle contraction causing impaired movement and gait. The aim of this study was to characterize the physical performance, skeletal muscle function, and phenotype of mice with a hereditary spastic mutation (B6.Cg-Glrbspa/J). Motor function, gait, and physical activity of juvenile and adult spastic mice and the morphological, histological, and mechanical characteristics of their soleus and gastrocnemius medialis muscles were compared with those of their wild-type (WT) littermates. Spastic mice showed attenuated growth, impaired motor function, and low physical activity. Gait of spastic mice was characterized by a typical hopping pattern. Spastic mice showed lower muscle forces, which were related to the smaller physiological cross-sectional area of spastic muscles. The muscle-tendon complex length-force relationship of adult gastrocnemius medialis was shifted toward shorter lengths, which was explained by attenuated longitudinal tibia growth. Spastic gastrocnemius medialis was more fatigue resistant than WT gastrocnemius medialis. This was largely explained by a higher mitochondrial content in muscle fibers and relatively higher percentage of slow-type muscle fibers. Muscles of juvenile spastic mice showed similar differences compared with WT juvenile mice, but these were less pronounced than between adult mice. This study shows that in spastic mice, disturbed motor function and gait is likely to be the result of hyperactivity of skeletal muscle and impaired skeletal muscle growth, which progress with age.

Напружено-деформований стан проксимального відділу великогомілкової кістки дитини при tibia vara в умовах однобічного блокування проксимальної росткової зони фіксаторами різних типів

Актуальність. Сучасним стандартом хірургічного лікування фронтальних епіметафізарних деформацій колінного суглоба у дітей є метод керованого росту. Для тимчасового блокування росткової зони використовуються різні фіксатори: скоби Блаунта, пластини з гвинтами. Проте дослідження, присвячені вивченню напружено-деформованого стану при використанні зазначених фіксаторів, відсутні.Мета: дослідження напружено-деформованого стану моделі проксимального відділу великогомілкової кістки дитини при однобічному блокуванні росткової зони фіксаторами різних типів в умовах навантажень, характерних для tibia vara.Матеріали і методи. За допомогою програми Solid Works створена і проаналізована методом кінцевих елементів 3D-модель проксимального відділу великогомілкової кістки дитини з латеральним блокуванням одним із 3 фіксаторів: скоба Блаунта, блокована пластина, стандартна пластина в умовах навантаження, характерних для tibia vara.Результати. В умовах навантаження, характерних для tibia vara, відзначено збільшення напружень у медіальній частині росткової зони. При однобічному блокуванні фіксаторами виявлено нові зони підвищених навантажень у кістковій тканині метаепіфіза нижче від росткової зони. Найбільше напруження у фіксаторах відзначено в зоні контакту проксимального гвинта з пластиною, а також у верхній частині скоби.Висновок. Варусна деформація проксимального відділу великогомілкової кістки веде до підвищення навантажень у медіальній частині проксимальної росткової зони. Використання різних фіксаторів для однобічного блокування проксимальної росткової зони великогомілкової кістки призводить до появи відмінних напружень у проксимальному її епіметафізі. До мінімального підвищення напружень у кістковій тканині метафіза приводять варіанти фіксації із застосуванням пластин, а використання скоб Блаунта значно підвищує напруження в кістковій тканині в ділянці розташування скоб.

Guided Growth for Tibial Recurvatum.

Aim and objectiveSagittal guided growth of the distal anterior femur has been shown to be effective for the correction of fixed knee flexion deformity that is encountered in clinical practice. The opposite deformity, namely genu recurvatum, is comparatively uncommon in children. The most common aetiology is post-traumatic. Acute correction by means of osteotomy has significant associated risks. Our objective was to determine whether a posterior 8-plate would suffice in correcting tibial recurvatum and obviate the need for an osteotomy.Materials and methodsWe included a total of five deformities, three boys (one bilateral) and one girl, managed by means of tethering of the posterior proximal tibial physis with a tension band plate. Standard radiographs obtained preoperatively and at follow-up included a standing anteroposterior (AP) of the legs noting limb lengths and the mechanical axis. We also obtained standing lateral views of each knee in maximal extension to measure and compare the posterior proximal tibial angle (PPTA).ResultsThe same-day surgery was well tolerated and there were no surgical or post-operative complications. The preoperative PPTA ranged from 106° to 117° and averaged 84° at follow-up. Correction occurred in an average of 20 months (range of 18–24 months). The patient with bilateral recurvatum due to Hurler's syndrome developed unilateral recurrent recurvatum culminating in percutaneous reinsertion of the metaphyseal screw. For each patient, knee hyperextension and associated pseudo-laxity resolved and limb lengths remained equal at follow-up.ConclusionChildren with progressive genu recurvatum typically present with an insidious onset of symptoms. Guided growth of the posterior proximal tibia is a safe and effective means of correcting the deformity; osteotomy was avoided in this series.Level of evidenceIII – retrospective case series – no controls.How to cite this articleStevens P, Stephens A, Rothberg D. Guided Growth for Tibial Recurvatum. Strategies Trauma Limb Reconstr 2021;16(3):172–175.

Evaluation of Intra-Articular Injection of Bevacizumab on the Prevention of Physeal Bar Formation in Type 4 Salter Harris Model in Rats: A Pilot Study

Background: This study was designed to achieve a new method as a preventive treatment for complications of growth plate fractures. In this study, we investigate the effect of intra-articular injection of anti-vascular endothelial growth factor (anti-VEGF) antibody bevacizumab on the repair process of articular cartilage in a type 4 Salter Harris injury model.&#x0D; Methods: A Salter Harris injury was created on the proximal tibial growth plate of 14 rats by a 1.8 mm drill. The rats were randomly classified into two groups: group LD, administration of high-dose intra-articular injection of bevacizumab (250 μg), and group HD, administration of low-dose intra-articular injection of bevacizumab (50 μg) after injury. The rats were killed 2 months postoperatively and their tibia underwent micro-computed tomography (CT) analysis, histological assessment, and measurement of tibial bone length.&#x0D; Results: Bony bar formation was observed in 71% of the samples in the high-dose group and in 100% of the low-dose group. Relative increase in physeal cartilage thickness (P = 0.007) and decrease in bony bar formation (P = 0.029) were observed significantly in the high dose group. There was no significant difference in tibia length between the two groups (P = 0.150).&#x0D; Conclusion: Intra-articular administration of bevacizumab demonstrated positive restorative effects. We suggest this method of treatment due to its potential of improving cartilage repair and capability to be used as a main or adjacent treatment in osteochondral defects.

Varus knee deformity in adolescent soccer players

The lower limb axis develops dynamically throughout the first and second decades of life. In recent years, with respect to youth athletes, we have been facing a progressive increase in the intensity of exercise during training and competition (involving increased time, frequency, and power), and, as a result, there hasbeen an increase in the number of acute and chronic overuse injuries. There are some sports with a higher incidence of injuries, one of which is soccer. A review of literature for the past 15 years with a focus on varus knee deformities in adolescent soccer players showed that varus axial deformities of the lower limbsoccur more frequently in soccer players than in the general population and in athletes from other sport, probably due to the specific loading pattern in soccer training. Varus deformities alter knee biomechanics, which results in medial joint space overloading, and consequently an early onset of degenerative joint disease. In addition, bowlegs predisposes athletes to patellofemoral pain syndrome and meniscal lesions. The etiology of genu varum in soccer is thought to be multifactorial, ranging from the natural selection of players to mechanical overload of the proximal medial tibial growth plate. A growing number of clinical reports and animal studies have indicated that intensive sport training may precipitate pathologic changes of the knee joint growth plate, and even produce a growth disturbance.

The relationship between bipedalism and growth: A metric assessment in a documented modern skeletal collection (Certosa Collection, Bologna, Italy).

ObjectivesLong bone variations during growth are susceptible to the combined action of nutritional, hormonal, and genetic factors that may modulate the mechanical forces acting upon growing individuals as they progressively acquire a mature gait. In this work, we explore diaphyseal length and breadth variations of tibia and fibula during ontogeny (a) to test the presence of changes in relation to early toddling, and (b) to further our understanding of developmental patterns in relation to sex.Materials and MethodsLengths, breadths, and indices were analyzed on right and left leg bones of 68 subadult individuals (Human Identified Skeletal Collection of the University of Bologna, Italy). Analyses included intersex and age classes (1, 0–1 year; 2, 1.1–3 years; 3, 3.1–6 years) comparisons, linear regressions with age and assessment of correlation among tibial and fibular measurements, as well as principal component analysis.ResultsA significant difference emerged among age class 1 and the others. Age class 1 and 3 differ between them, while age class 2 overlaps with the others. No sex dimorphism was detected. All measurements were strongly correlated with age. Tibial and fibular measurements correlated with each other.ConclusionsOur results relate the progressive emergence of toddling attempts in growing individuals at the end of the first year of age. No significant sex differences were found, suggesting that tibial and fibula growth might diverge between sexes in later childhood. We provide quantitative data regarding tibial and fibular linear growth and its timing in a modern documented osteological sample from Italy.

EXTH-70. ESTABLISHMENT OF INTRAVENTRICULAR SHH INHIBITION AS A THERAPEUTIC OPTION IN YOUNG PATIENTS WITH MEDULLOBLASTOMA

Abstract Medulloblastoma is the most common malignant brain tumor in children. The embryonal tumor arises in the posterior fossa and disseminates via the cerebrospinal fluid. Medulloblastoma divides in four molecular subgroups, one of which is characterized by mutations in the sonic-hedgehog (SHH) -pathway. SHH inhibition provides an elegant way of targeted therapy. The small molecule Vismodegib allosterically inhibits Smoothened (SMO), an upstream activator of SHH. Unfortunately, Vismodegib has shown to cause irreversible premature epiphyseal growth plate fusions in preclinical studies and clinical trials, preventing its systemic application in children (Kimura et al. 2008; Robinson et al. 2017). We established an intraventricular therapy with Vismodegib, combining the benefits of targeted drug delivery and minimizing systemic side effects. In a mouse model for SHH medulloblastoma, we compare intraventricular, oral and placebo treatment regarding effects on survival, tumor biology, and bone morphology. Math1-cre::Ptch1 Fl/Fl mice show a homozygous loss of PTCH1 in Math1-positive cells, resulting in SHH-pathway overactivation and development of SHH medulloblastomas. At postnatal day 11-13, Math1-cre::Ptch1 Fl/Fl mice were randomized in four treatment arms: group A (n= 9) received placebo intrathecally, B (n= 9) received Vismodegib 200 mg/kd/d orally, C (n= 19) received Vismodegib 0.2 mg/kg/d intrathecally, and D (n= 8) received Vismodegib 1.6 mg/kg/d intrathecally. Kaplan-Meier survival analysis showed a significant survival benefit for 1.6 mg/kg/d intraventricular Vismodegib compared to placebo (p= 0.012). Bone histology and X-ray analysis of intraventricular treated mice showed intact femoral and tibial growth plates, in contrast to orally treated mice that developed skeletal malformations. Further analyses such as DNA sequencing, gene expression analysis, and histological evaluation are ongoing and will add to the picture of the anti-tumor effects of intraventricular SHH-inhibition. Based on the preliminary experimental results, we conclude that intrathecal application of a SMO-inhibitor might evolve as a promising new way of targeted treatment of SHH medulloblastomas.

Blount Disease: A Case Report and Review of the Literature

Introduction: Blount disease is an asymmetrical disorder of proximal tibial growth that produces a three-dimensional deformity. Tibia vara is the main component of the deformity. There is general agreement that two clinical forms should be distinguished based on age, infantile and adolescent, with 10 years as the cut-off. Case: We present a case of 11 year old girl admitted to our radiology department with chronic bilateral gonalgia and genu varum evoluting for a year. The clinical examination reveals bilateral varus deformity of the proximal tibia, a palpable prominence or “beaking” of the proximal medial tibial epiphysis and metaphysic. The diagnosis of blount disease has been confirmed on standard radiography. Conclusion: Blount's disease remains a rare disease whose etiology is still unknown, seems to involve hereditary and environmental factors explaining its very particular distribution. Radiological investigations are helpful to the diagnosis by showing medial varus malalignment of the tibial metaphysis. Many angles have been described. A mongthem, the mostuseful are the mechanical tibio-femoral angle, metaphyseal-diaphyseal angle (MDA) of Levine and Drennan, and bony tibial slope.

Characterisation of Growth Plate Dynamics in Murine Models of Osteoarthritis.

The purpose of this study was to investigate growth plate dynamics in surgical and loading murine models of osteoarthritis, to understand whether abnormalities in these dynamics are associated with osteoarthritis development. 8-week-old C57BL/6 male mice underwent destabilisation of medial meniscus (DMM) (n = 8) surgery in right knee joints. Contralateral left knee joints had no intervention (controls). In 16-week-old C57BL/6 male mice (n = 6), osteoarthritis was induced using non-invasive mechanical loading of right knee joints with peak force of 11N. Non-loaded left knee joints were internal controls. Chondrocyte transiency in tibial articular cartilage and growth plate was confirmed by histology and immunohistochemistry. Tibial subchondral bone parameters were measured using microCT and correlated to 3-dimensional (3D) growth plate bridging analysis. Higher expression of chondrocyte hypertrophy markers; Col10a1 and MMP13 were observed in tibial articular cartilage chondrocytes of DMM and loaded mice. In tibial growth plate, Col10a1 and MMP13 expressions were widely expressed in a significantly enlarged zone of proliferative and hypertrophic chondrocytes in DMM (p=0.002 and p<0.0001, respectively) and loaded (both p<0.0001) tibiae of mice compared to their controls. 3D quantification revealed enriched growth plate bridging and higher bridge densities in medial compared to lateral tibiae of DMM and loaded knee joints of the mice. Growth plate dynamics were associated with increased subchondral bone volume fraction (BV/TV; %) in medial tibiae of DMM and loaded knee joints and epiphyseal trabecular bone volume fraction in medial tibiae of loaded knee joints. The results confirm articular cartilage chondrocyte transiency in a surgical and loaded murine models of osteoarthritis. Herein, we reveal spatial variation of growth plate bridging in surgical and loaded osteoarthritis models and how these may contribute to anatomical variation in vulnerability of osteoarthritis development.

Enhanced Extracellular Matrix Degradation in Growth Plate Contributes to Manganese Deficiency-Induced Tibial Dyschondroplasia in Broiler Chicks.

Manganese (Mn) is a crucial trace element for poultry nutrition, and its deficiency compromises tibial cartilage development, leading to perosis and a higher incidence of slipped tendon. Tibial dyschondroplasia (TD) is a metabolic cartilage disease characterized by disruption of endochondral bone formation, which is closely related to extracellular matrix (ECM) degradation, in which Mn deficiency plays an important role. Previous studies have confirmed the role of matrix metalloproteinases (MMPs) in the pathogenesis of TD, but whether dysregulated ECM degradation and MMP expression profiles in growth plate are involved in Mn deficiency-induced avian TD has not been fully elucidated yet. Thus, this study was conducted to clarify these issues. Firstly, we successfully established TD model induced by Mn deficiency in broiler chicks. Mn deficiency decreased the number of chondrocytes, contents of proteoglycan, and type II collagen in tibial growth plate, demonstrating the tibial growth plate damage with enhanced ECM degradation. Also, Mn deficiency inhibited the Nrf2 signaling pathway and enhanced the protein levels of NLRP3, active caspase-1, and active IL-1β in tibial growth plate, indicating the oxidative stress and inflammatory response in Mn deficiency-induced TD. Additionally, upregulated expression levels of MMPs (MMP1, 9, and 13) were observed in tibial growth plate of Mn deficiency group. In summary, these findings suggest that Mn deficiency-enhanced ECM degradation is involved in avian TD, which may be correlated with oxidative stress, inflammatory response, and upregulation of MMPs.

Manganese deficiency induces avian tibial dyschondroplasia by inhibiting chondrocyte proliferation and differentiation

Manganese (Mn) is an essential trace element for bone growth, and its deficiency has been shown to increase the incidence of leg abnormalities in fast-growing broilers, such as tibial dyschondroplasia (TD). Proliferation and differentiation of growth plate chondrocyte are critical for tibia development, but their roles in Mn deficiency-induced TD remains to be elucidated. Thirty 1-day-old Arbor Acres chicks were randomly divided into two groups and fed with control diet (60 mg Mn/kg diet) and Mn-deficiency diet (22 mg Mn/kg diet) for 42 days, respectively. Mn deficiency-induced TD model was successfully established and samples from proximal tibia metaphysis and growth plate were collected for assays. Pathological observation showed that Mn deficiency induced morphological abnormality and irregular arrangement of chondrocytes in proliferative and hypertrophic zone of tibial growth plate. Also, Mn deficiency decreased mRNA and protein expression levels of type II collagen and type X collagen in tibial growth plate, indicating the impairment of proliferating and hypertrophic chondrocytes. Moreover, down-regulated gene expression levels of Sox9, Tgf-β, Ihh, Runx2, Mef2c and Bmp-2 were shown in tibial growth plate of Mn-deficiency group, demonstrating that Mn deficiency inhibited the transcription levels of key regulators to disrupt chondrocyte proliferation and differentiation. Collectively, these findings confirmed that Mn deficiency affected the proliferation and differentiation of chondrocytes in tibial growth plate via inhibiting related regulatory factors, leading to TD in broilers.

Application of the \u201ctelescopic rod\u201d in a combined surgical technique for the treatment of congenital pseudarthrosis of the tibia in children

BackgroundThe current surgical treatment of choice is the combination surgical technique, involving tibial intramedullary fixation to maintain the mechanical axis and mechanical stability of tibial pseudarthrosis. In traditional combined surgery, the Williams rod is often used. Long-term intramedullary fixation of the foot and ankle will affect the ankle joint function of children. The intramedullary rod is relatively shorter due to the growth of the distal tibia. In addition, there are some complications such as epiphyseal bone bridge and high-arched foot. The use of a telescopic intramedullary rod may avoid these complications.PurposesTo investigate the initial effect of the “telescopic rod” in a combined surgical technique for the treatment of congenital pseudarthrosis of the tibia in children.MethodsA retrospective study including 15 patients with Crawford type IV CPT who were treated using a combined surgical technique and the telescopic rod from January 2017 to May 2018. The average age at the time of surgery was 43.3 months (16–126 months). Of the 15 patients, 7 had proximal tibia dysplasia and 12 exhibited neurofibromatosis type 1. The combined surgical technique using the telescopic rod included the excision of pseudarthrosis, intramedullary rod insertion, installation of Ilizarov’s fixator, tibia-fibular cross union, and wrapping autogenic iliac bone graft. The incidence of refracture, ankle valgus, tibial valgus, and limb length discrepancy (LLD) in patients were investigated.ResultsAll patients achieved primary union with an average follow-up time of 37.3 months (26–42 months). The mean primary union time was 4.5 months (4.0–5.6 months). Nine cases showed LLD (60%), with an average limb length of 1.1 cm (0.5–2.0 cm). Ankle valgus, proximal tibial valgus, telescopic rod displacement, and epiphyseal plate tethering occurred in 1 case (6.6%) (18°), 3 cases (20%) (10°, 5°, and 6°, respectively), 6 cases (40%), and 2 cases (13%), respectively. There were no refractures during the follow-up periods.ConclusionAlthough there are complications such as intramedullary rod displacement while using the telescopic rod in a combined surgery, the primary healing rate of congenital pseudarthrosis of the tibia in children is high.

G-Protein-Coupled Estrogen Receptor-1 Positively Regulates the Growth Plate Chondrocyte Proliferation in Female Pubertal Mice.

Estrogen enhances long bone longitudinal growth during early puberty. Growth plate chondrocytes are the main cells that contribute to long bone elongation. The role of G-protein-coupled estrogen receptor-1 (GPER-1) in regulating growth plate chondrocyte function remains unclear. In the present study, we generated chondrocyte-specific GPER-1 knockout (CKO) mice to investigate the effect of GPER-1 in growth plate chondrocytes. In control mice, GPER-1 was highly expressed in the growth plates of 4- and 8-week-old mice, with a gradual decline through 12 to 16 weeks. In CKO mice, the GPER-1 expression in growth plate chondrocytes was significantly lower than that in the control mice (80% decrease). The CKO mice also showed a decrease in body length (crown–rump length), body weight, and the length of tibias and femurs at 8 weeks. More importantly, the cell number and thickness of the proliferative zone of the growth plate, as well as the thickness of primary spongiosa and length of metaphysis plus diaphysis in tibias of CKO mice, were significantly decreased compared with those of the control mice. Furthermore, there was also a considerable reduction in the number of proliferating cell nuclear antigens and Ki67-stained proliferating chondrocytes in the tibia growth plate in the CKO mice. The chondrocyte proliferation mediated by GPER-1 was further demonstrated via treatment with a GPER-1 antagonist in cultured epiphyseal cartilage. This study demonstrates that GPER-1 positively regulates chondrocyte proliferation at the growth plate during early puberty and contributes to the longitudinal growth of long bones.

Staged Bilateral Total Knee Arthroplasty for Neglected Blount Disease Using a Gap Balancing Technique.

Blount disease is an acquired, asymmetrical disorder of proximal tibial growth that results in a complex three-dimensional proximal tibial deformity, with tibial varus being the dominating feature. Although the exact pathophysiology is unknown, Blount disease is separated into 2 clinical variants, infantile and adolescent, based on the onset of symptoms occurring before or after the age of 10 years. If recognized and treated early, affected patients generally have a favorable prognosis; however, if neglected, it can lead to progressive malalignment and premature osteoarthritis. We present a patient with bilateral neglected Blount disease who underwent successful bilateral total knee arthroplasty performed in a staged fashion using a gap balancing technique with constrained condylar knee implants.

Outcomes of Fixed-Hinged Knee Prosthesis for Distal Femoral Osteosarcoma in Skeletally Immature Patients: First Results.

The best surgical choice for distal femur osteosarcoma in skeletally immature patients remains controversial. A fixed hinged knee prosthesis has been designed to preserve the growth plates in the adjacent tibia, expecting tibial growth to be continued. This study aims to report the (1) clinical outcomes after prosthetic replacement, (2) postoperative complications, and (3) length of discrepancy of the operative tibia with the unaffected tibia. Thirty-four skeletally immature patients (averaged 9 years at surgery; range, 5-12 years) with distal femoral osteosarcoma underwent placement of this hinged knee prosthesis between January 2015 and August 2018. Postoperative function and complications were assessed. Length discrepancy was measured using a series of full-length standing anteroposterior radiographs of the bilateral lower extremity. The average follow-up duration was 34 months (2.8 years). In the last follow-up, four patients expired because of pulmonary metastasis. Two patients presented with local recurrence of the soft tissue. Postoperatively, the flexion range of the knee joint range was between 100 and 130 degrees, with an average of 115.2 degrees. The mean functional score of living patients evaluated using the Musculoskeletal Tumor Society scoring system was 89.2% (range, 76.7-100%). Types 1 (three patients), 2 (one patient), 3 (two patients), and 5 (two patients) complications exist. Among them, three patients received revision surgery. The proximal tibial physis still grew after surgery, with an average of 74.3% (range, 30-100%) growth potential compared with the unaffected proximal tibial physis. Moreover, 27 children exhibited tibial length discrepancy compared with the contralateral tibia, and the mean discrepancy in tibial length was 1.1 cm (range, 0.2-3.1 cm). This hinged knee prosthesis can keep the growth potential in the adjacent tibia, provides satisfying functional outcomes, and has a lower postoperative complication rate. Thus, it could serve as an alternative intervention for distal femoral osteosarcoma in skeletally immature patients.