Epiphyseal Research Articles

Effect of birth type and sex on growth performance, wither height, humerus-radius bone dimensions, humerus-ulna growth plate width and selected hormone profile in growing Gurcu goat kids.

In this study, the effects of sex and birth type on growth performance, withers height (WH), radiographic measurements and selected hormone profiles in Gurcu goat kids were investigated. Twenty kids (single female=5, single male=5, twin female=5, twin male=5) were included in the study. Body weight (BW), WH, radiographic measurements (humerus length [HL], radius length [RL], proximal humerus epiphyseal plate width [HEP] and distal ulna epiphyseal plate width [UEP]) and biochemical analysis (for serum calcitonin, free triiodothyronine [FT3], free thyroxine [FT4], growth hormone [GH] and insulin-like growth factor-I [IGF-I]) were performed at 1, 3, 5, 7, 9 and 12 months of age. BW was significantly higher in males starting from the seventh month compared to females (p<0.05). HL was higher in males at seventh (p=0.009) and ninth (p=0.033) months, whereas RL was lower in twins at the third month (p=0.021). UEP was wider in males at seventh (p=0.008) and ninth (p=0.036) months. Closure of HEP was observed in 65% of kids by the 12th month. Calcitonin was lower in twins at third (p=0.045) and fifth (p=0.006) months, with changes observed due to group and time effects (p<0.05), whereas other hormones only changed with time (p<0.05). Positive correlations were observed between BW, WH, HL, RL and IGF-I. There was a negative correlation between BW, WH, HL, RL, IGF-I and HEP, UEP, calcitonin, FT3, FT4, GH. Sex and birth type in Gurcu goat kids may have an impact on growth performance, radiographic measurements and certain hormonal profiles.

Autosomal recessive hypophosphatemic rickets type 2 due to ENPP1 deficiency (ARHR2)

Autosomal recessive hypophosphatemic rickets type 2 (ARHR2; MIM #613312) is a very rare disorder caused by biallelic loss-of-function mutations in the ENPP1 (ectonucleotide pyrophosphatase/phosphodiesterase 1) gene. ENPP1 deficiency encompasses a spectrum of phenotypes that includes, in addition to ARHR2, generalized arterial calcification of infancy (GACI), ossification of the posterior longitudinal ligament (OPLL), and pseudoxanthoma elasticum. ARHR2 can be found in GACI survivors, but it may also be the first manifestation of ENPP1 deficiency. Although the precise mechanisms are not fully elucidated, patients with GACI and ARHR2 have elevated serum FGF23 levels, leading to renal phosphate wasting and hypophosphatemia. As a result, the clinical and radiological phenotype of ARHR2 patients is very similar to that of patients affected with other forms of hypophosphatemic rickets, such as X-linked hypophosphatemia. Patients show signs of rickets (abnormal mineralization of growth plates in children) and osteomalacia (abnormal bone mineralization in children and adults) of varying severity. Clinical manifestations specific to ENPP1 loss-of-function mutations and common to GACI, such as ectopic calcifications (valvular, arterial, or periarticular), deafness, OPLL, and PXE, may also be found. Genetic confirmation of the disease is important so as to ensure that patients receive the appropriate treatment or have the opportunity to participate in clinical trials to evaluate the safety and efficacy of novel and promising recombinant enzyme therapies.

Functional analysis of a novel pathogenic variant in CREBBP associated with bone development.

CREBBP has been extensively studied in syndromic diseases associated with skeletal dysplasia. However, there is limited research on the molecular mechanisms through which CREBBP may impact bone development. We identified a novel pathogenic CREBBP variant (c.C3862T/p.R1288W, which is orthologous to mouse c.3789 C > T/p.R1289W) in a patient with non-syndromic polydactyly. We created a homozygous Crebbp p.R1289W mouse model and compared their skeletal phenotypes to wild-type (WT) animals. Bone marrow stem cells (BMSCs) were isolated and assessed for their proliferative capacity, proportion of apoptotic cells in culture, and differentiation to chondrocytes and osteocytes. We observed a significant decrease in body length in 8-week-old homozygous Crebbp p.R1289W mice. The relative length of cartilage of the digits of Crebbp p.R1289W mice was significantly increased compared to WT mice. BMSCs derived from Crebbp p.R1289W mice had significantly decreased cell proliferation and an elevated rate of apoptosis. Consistently, cell proliferative capacity was decreased and the proportion of apoptotic cells was increased in the distal femoral growth plate of Crebbp p.R1289W compared to WT mice. Chemical induction of BMSCs indicated that Crebbp p.R1289W may promote chondrocyte differentiation. The Crebbp p.R1289W variant plays a pathogenic role in skeletal development in mice. CREBBP has been extensively studied in syndromic diseases characterized by skeletal dysplasia. There is limited research regarding the molecular mechanism through which CREBBP may affect bone development. To our knowledge, we generated the first animal model of a novel Crebbp variant, which is predicted to be pathogenic for skeletal diseases. Certain pathogenic variants, such as Crebbp p.R1289W, can independently lead to variant-specific non-syndromic skeletal dysplasia.

MiR-322-5p is involved in regulating chondrocyte proliferation and differentiation in offspring’s growth plate of maternal gestational diabetes

Pregestational diabetes mellitus (PGDM) has an impact on fetal bone formation, but the underlying mechanism is still obscure. Although miRNAs have been extensively investigated throughout bone formation, their effects on fetal bone development caused by PGDM still need clarification. This study intends to examine the mechanism by which hyperglycemia impairs the bone formation of offspring via miR-322-5p (miR-322). In this study, miR-322 was selected by systemically screening utilizing bioinformatics and subsequent validation experiments. Using streptozotocin (STZ)-induced diabetic mice and ATDC5 cell lines, we found that miR-322 was abundantly expressed in the proliferative and hypertrophic zones of the growth plate, and its expression pattern was disturbed in the presence of hyperglycemia, suggesting that miR-322 is involved in the chondrocyte proliferation and differentiation in absence/presence of hyperglycemia. This observation was proved by manipulating miR-322 expression in ATDC5 cells by transfecting mimic and inhibitor of miR-322. Furthermore, Adamts5, Col12a1, and Cbx6 were identified as the potential target genes of miR-322, verified by the co-transfection of miR-322 inhibitor and the siRNAs, respectively. The evaluation criteria are the chondrocyte proliferation and differentiation and their relevant key gene expressions (proliferation: Sox9 and PthIh; differentiation: Runx2 and Col10a1) after manipulating the gene expressions in ATDC5 cells. This study revealed the regulative role miR-322 on chondrocyte proliferation and differentiation of growth plate by targeting Adamts5, Col12a1, and Cbx6 in hyperglycemia during pregnancy. This translational potential represents a promising avenue for advancing our understanding of bone-related complications in diabetic pregnancy and mitigating bone deficiencies in diabetic pregnant individuals, improving maternal and fetal outcomes.

The metalloproteinase PAPP-A is required for IGF-dependent chondrocyte differentiation and organization

Insulin-like growth factor (IGF) signaling is required for proper growth and skeletal development in vertebrates. Consequently, its dysregulation may lead to abnormalities of growth or skeletal structures. IGF is involved in the regulation of cell proliferation and differentiation of chondrocytes. However, the availability of bioactive IGF may be controlled by antagonizing IGF binding proteins (IGFBPs) in the circulation and tissues. As the metalloproteinase PAPP-A specifically cleaves members of the IGFBP family, we hypothesized that PAPP-A activity liberates bioactive IGF in cartilage. In PAPP-A knockout mice, the femur length was reduced and the mice showed a disorganized columnar organization of growth plate chondrocytes. Similarly, zebrafish lacking pappaa showed reduced length of Meckel’s cartilage and disorganized chondrocytes, reminiscent of the mouse knockout phenotype. Expression of chondrocyte differentiation markers (sox9a, ihha, and col10a1) was markedly affected in Meckel’s cartilage of pappaa knockout zebrafish, indicating that differentiation of chondrocytes was compromised. Additionally, the zebrafish pappaa knockout phenotype was mimicked by pharmacological inhibition of IGF signaling, and it could be rescued by treatment with exogenous recombinant IGF-I. In conclusion, our data suggests that IGF activity in the growing cartilage, and hence IGF signaling in chondrocytes, requires the presence of PAPP-A. The absence of PAPP-A causes aberrant chondrocyte organization and compromised growth in both mice and zebrafish.

Resveratrol alleviates thiram-induced tibial dyschondroplasia by regulating BMP-2, RUNX-2 and HIF-1α expressions in broiler chickens

Tetramethylthiuram disulfide (thiram) is a pesticide and fungicide, widely used in agriculture, and is a recognized cause of tibial dyschondroplasia (TD), a skeletal abnormality in fast-growing broiler chickens. This study aimed to investigate the effect of resveratrol (RSV) against TD induced by thiram in broilers. A total of 240 broilers were evenly divided into three groups (n = 80) i.e., Control, TD and RSV. All groups received feed and water ad libitum, whereas the TD and RSV groups received standard diet with an addition of thiram (50 mg/kg of feed) from 4–7 days to induce TD. After the cessation of thiram on day 8, the RSV group was administered RSV at 400 mg/kg body weight orally from 8–18 days. Histopathological changes in tibia were assessed using hematoxylin and eosin (H&E) staining. In addition, the mRNA and protein expressions of targeted genes were analyzed using RT-qPCR, immunohistochemistry, and western blotting. Thiram feeding resulted in an increased growth plate (GP) width, decreased vascularization, irregular shaped chondrocytes with pyknotic nuclei, lameness, poor production performance, reduced levels of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), total antioxidant capacity (T-AOC), alkaline phosphatase (ALP) and elevated levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and malondialdehyde (MDA). The mRNA and protein expressions of BMP-2 and RUNX-2 were downregulated, whereas HIF-1α was upregulated in TD affected broilers (p < 0.05). RSV administration resulted in a significant increase in mRNA and protein levels of BMP-2 and RUNX-2 (p < 0.05) and a decrease in the levels of HIF-1α. In addition, RSV improved vascularization, angiogenesis, alleviated lameness, and enhanced production efficiency. Furthermore, it restored the GP width, serum biochemical levels and liver antioxidant enzymes. In conclusion, this study indicated that resveratrol mitigated the adverse effects of thiram toxicity in broiler chickens.

Intraosseous contrast administration for coelomic computed tomography angiography in green iguanas (Iguana iguana): Preliminary findings show promise as an alternative to the intravenous route.

Computed tomography is commonly used to evaluate the reptile coelom. One challenge in the acquisition of contrast-enhanced CT studies in reptiles is the difficulty in placing intravenous catheters due to the poor conspicuity of peripheral vessels. To overcome these limitations, intraosseous catheterization of the long bones (humerus, femur, and tibia) can be used. The purpose of this prospective study was to assess the feasibility and diagnostic value of contrast-enhanced CT of the coelom using a femoral intraosseous route for contrast administration. Twelve healthy juvenile green iguanas were enrolled. In 9 of 12 iguanas, vascular phases were obtained, providing strong, homogeneous enhancement of the arterial and venous tree concurrently. In these nine cases, Phase #1, acquired 60s after beginning the injection of contrast medium, provided maximal contrast between the hepatic parenchyma and hepatic vasculature. In the remaining three cases, injection failure resulted from intracortical placement of the catheter tip. Histological examination of the liver, kidneys, and femur was performed to determine the pathomorphological correlates of the CT findings; in a third of patients, some degree of contrast-induced renal toxicity was documented, which in mammalians shows potential for reversibility. Four iguanas had iatrogenic structural damage to the femoral growth plates attributed to intraosseous catheter placement. A femoral intraosseous route can be used in green iguanas for iodinated contrast medium administration for CT angiography. For the greatest contrast between coelomic organs and vascular structures, at least one postcontrast acquisition 60s after initiation of contrast administration is recommended when using this technique.

Evaluation of the effect of osteosynthesis wires on the structural reorganization of metaepiphyseal cartilage (an experimental and morphological study)

Introduction Premature arrest of bone growth is the most common complication of bone fractures at the growth plate level.The purpose of the work was to evaluate the structural reorganization of metaepiphyseal cartilage following its direct injury with metal and biodegradable wires in an experiment.Materials and methods The metaepiphyseal cartilage of the distal femur of 18 lambs of both sexes was studied. The age of the animals at the beginning of the study was (43.92 ± 0.8) days, by 60 and 120 days (102.63 ± 0.82) and (161.1 ± 0.9) days, respectively. The animals underwent transphyseal insertion of wires/ pins: series 1 — Kirschner wires, series 2 — titanium wires, series 3 — poly-L-lactic acid pins. The duration of the experiment was 60 and 120 days. Clinical and radiographic studies were carried out. Histomorphometry was performed using an AxioScope.A1 microscope and Zenblue software (CarlZeissMicroImagingGmbH, Germany).Results Reactive changes in the growth plate at the interface with the wire were manifested by proliferation of chondrocytes in the zone of proliferating cartilage and in the reserve zone; the minimally expressed changes were noted in series 2, the most pronounced were in series 1. By the end of the experiment, at the interface with the wire in series 1, blood vessels penetrated into the metaepiphyseal cartilage; in series 3 the amount of the fibrous component was increased, which indicates further formation of “bone bridges” and “fibrous bridges,” respectively. In undamaged areas of the growth plate in all series, the zonal structure was preserved. By the end of the experiment, increased values of the thickness of the metaepiphyseal cartilage were noted (1.2 times higher than the control), differences between series were a tendency; in series 2 and 3 the ratio of metaepiphyseal cartilage zones was comparable to the control; in series 1 the proportion of the proliferating cartilage zone was increased by 4 %.Discussion The main problem with growth plate injuries is the formation of bone tissue or fibrosis, which affects the growing process. Currently, the question of choosing a treatment tactic for growth plate injury depending on the size of the “bone bridges” is debatable. Relevant are future comparative studies of the regeneration of metaepiphyseal cartilage defects after the use of fixators made from different materials.Conclusion Histomorphometric characteristics of the growth zone reliably showed that the insertion of wires, regardless of their material, was not accompanied by inhibition of the bone-forming function of the distal metaepiphyseal cartilage of the femur.

Reconstruction of the medial collateral ligament complex with aflat semitendinosus auto- or allograft

Replacement of superficial medial collateral ligament (sMCL) and posterior oblique ligament (POL) with an allograft. Chronic 3° isolated medial instability and combined anteromedial or posteromedial instability. Infection, open growth plates, restricted range of motion (less than E/F 0-0-90°). Longitudinal incision from medial epicondyle to superficial pes anserinus and exposure of the medial collateral ligament complex. Thawing of the allogeneic semitendinosus tendon graft at room temperature, reinforcement of the tendon ends with sutures and preparation of atwo-stranded graft. Placement of guidewires in the sMCL and POL insertions and control with image intensifier. Tunnel drilling. Pulling the graft loop into the femoral bone tunnel and fixation with aflip button. Pulling the two graft ends into the tibial tunnels. Tibial fixation by knotting the suture ends in a20° flexion on the lateral cortex. Suture the tendon bundles to the remaining remnants of the medial collateral ligament complex to adopt the flat structure of the natural medial collateral ligament complex. Six weeks partial weight-bearing, immediately postoperatively splint in the extended position, after 2weeks movable knee brace for another 4-6weeks. Mobility: 4weeks 0-0-60, 5th and 6th weeks 0-0-90. From 2015-2021, this surgical procedure was performed in 19patients (5women, 14men, age34years). Mean Lysholm score at follow-up after at least 2years was 89 (76-99) points. In 6patients, there was restricted range of motion 3months postoperatively, which resulted in further therapy (3 ×systemic cortisone therapy, 3 ×arthroscopically supported manipulations under anesthesia).

Skeletal and Non-skeletal Phenotypes in Children with Osteogenesis Imperfecta.

Although fractures are the defining characteristic of osteogenesis imperfecta (OI), the disorder affects many tissues. Here we discuss three facets of the OI phenotype, skeletal growth and development, skeletal muscle weakness and the dental and craniofacial characteristics. Short stature is almost universal in the more severe forms of OI and is probably caused by a combination of direct effects of the underlying genetic defect on growth plates and indirect effects of fractures, bone deformities and scoliosis. Recent studies have developed OI type-specific growth curves, which allow determining whether a given child with OI grows as expected for OI type. Impaired muscle function is an important OI-related phenotype in severe OI. Muscles may be directly affected in OI by collagen type I abnormalities in muscle connective tissue and in the muscle-tendon unit. Indirect effects like bone deformities and lack of physical activity may also contribute to low muscle mass and function. Dental and craniofacial abnormalities are also very common in severe OI and include abnormal tooth structure (dentinogenesis imperfecta), malocclusion, and deformities in the bones of the face and the skull. It is hoped that future treatment approaches will address these OI-related phenotypes.

Coactivator-independent vitamin D receptor signaling causes severe rickets in mice, that is not prevented by a diet high in calcium, phosphate, and lactose

The vitamin D receptor (VDR) plays a critical role in the regulation of mineral and bone homeostasis. Upon binding of 1α,25-dihydroxyvitamin D3 to the VDR, the activation function 2 (AF2) domain repositions and recruits coactivators for the assembly of the transcriptional machinery required for gene transcription. In contrast to coactivator-induced transcriptional activation, the functional effects of coactivator-independent VDR signaling remain unclear. In humans, mutations in the AF2 domain are associated with hereditary vitamin D-resistant rickets, a genetic disorder characterized by impaired bone mineralization and growth. In the present study, we used mice with a systemic or conditional deletion of the VDR-AF2 domain (VdrΔAF2) to study coactivator-independent VDR signaling. We confirm that ligand-induced transcriptional activation was disabled because the mutant VDRΔAF2 protein was unable to interact with coactivators. Systemic VdrΔAF2 mice developed short, undermineralized bones with dysmorphic growth plates, a bone phenotype that was more pronounced than that of systemic Vdr knockout (Vdr−/−) mice. Interestingly, a rescue diet that is high in calcium, phosphate, and lactose, normalized this phenotype in Vdr−/−, but not in VdrΔAF2 mice. However, osteoblast- and osteoclast-specific VdrΔAF2 mice did not recapitulate this bone phenotype indicating coactivator-independent VDR effects are more important in other organs. In addition, RNA-sequencing analysis of duodenum and kidney revealed a decreased expression of VDR target genes in systemic VdrΔAF2 mice, which was not observed in Vdr−/− mice. These genes could provide new insights in the compensatory (re)absorption of minerals that are crucial for bone homeostasis. In summary, coactivator-independent VDR effects contribute to mineral and bone homeostasis.

Effect of the Material Properties and Knee Position to the Bone Bruise Pattern in Skeletally Mature and Immature Subjects.

A bone bruise is generated by a bony collision that could occur when the ACL is injured, and its pattern supposedly depends on the injury mechanism and level of skeletal maturity. The objective of this study was to determine the effect of material properties and knee position on the bone bruise pattern in skeletally mature and immature subjects using finite element analysis. Finite element models were created from an MR image in the sagittal plane of a skeletally mature and immature male subject. The femur and tibia were collided at 2 m/s to simulate the impact and determine the maximum principal stress. The analysis was performed at 15, 30 and 45 degrees of knee flexion, and neutral, 10 mm anterior and posterior translated position at each flexion angle. Although high stress was distributed toward the metaphysis area in the mature model, the stress did not cross the growth plate in the immature model. The size of the stress area was larger in the mature model than those in the immature model. The location of the stress area was dependent on the joint position as well as Young's modulus of cartilage and trabecular bone. Thus, the bone bruise pattern was affected by the knee position and tissue quality. In conclusion, although the bone bruise distribution was generally called footprint of the injury, the combined evaluation of the quality of the structure and the bone bruise distribution is necessary for properly diagnosing tissue injury based on the MR imaging.

Fibronectin isoforms promote postnatal skeletal development

Fibronectin (FN) is a ubiquitous extracellular matrix glycoprotein essential for the development of various tissues. Mutations in FN cause a unique form of spondylometaphyseal dysplasia, emphasizing its importance in cartilage and bone development. However, the relevance and functional role of FN during skeletal development has remained elusive. To address these aspects, we have generated conditional knockout mouse models targeting the cellular FN isoform in cartilage (cFNKO), the plasma FN isoform in hepatocytes (pFNKO), and both isoforms together in a double knockout (FNdKO). We used these mice to determine the relevance of the two principal FN isoforms in skeletal development from postnatal day one to the adult stage at two months.We identified a distinct topological FN deposition pattern in the mouse limb during different gestational and postnatal skeletal development phases, with prominent levels at the resting and hypertrophic chondrocyte zones and in the trabecular bone. Cartilage-specific cFN emerged as the predominant isoform in the growth plate, whereas circulating pFN remained excluded from the growth plate and confined to the primary and secondary ossification centers. Deleting either isoform independently (cFNKO or pFNKO) yielded only relatively subtle changes in the analyzed skeletal parameters. However, the double knockout of cFN in the growth plate and pFN in the circulation of the FNdKO mice significantly reduced postnatal body weight, body length, and bone length. Micro-CT analysis of the adult bone microarchitecture in FNdKO mice exposed substantial reductions in trabecular bone parameters and bone mineral density. The mice also showed elevated bone marrow adiposity. Analysis of chondrogenesis in FNdKO mice demonstrated changes in the resting, proliferating and hypertrophic growth plate zones, consistent alterations in chondrogenic markers such as collagen type II and X, decreased apoptosis of hypertrophic chondrocytes, and downregulation of bone formation markers. Transforming growth factor-β1 and downstream phospho-AKT levels were significantly lower in the FNdKO than in the control mice, revealing a crucial FN-mediated regulatory pathway in chondrogenesis and bone formation.In conclusion, the data demonstrate that FN is essential for chondrogenesis and bone development. Even though cFN and pFN act in different regions of the bone, both FN isoforms are required for the regulation of chondrogenesis, cartilage maturation, trabecular bone formation, and overall skeletal growth.

Sustained release of MAPK14-targeting siRNA from polyelectrolyte complex hydrogels mitigates MSC osteogenesis in vitro with potential application in growth plate injury.

The growth plate is a cartilage structure at the end of long bones which mediates growth in children. When fractured, the formation of bony repair tissue known as a "bony bar" can occur and cause limb deformities. There are currently no effective clinical solutions for the prevention of the bony bar formation or regeneration of healthy growth plate cartilage after a fracture. This study employs previously developed alginate/chitosan polyelectrolyte complex (PEC) hydrogels as a sustained release vehicle for the delivery of short-interfering RNA (siRNA). Specifically, the siRNA targets the p38-MAPK pathway in mesenchymal stem cells (MSCs) to prevent their osteogenic differentiation. In vitro experimental findings show sustained release of siRNA from the hydrogels for 6 months. Flow cytometry and confocal imaging indicate that the hydrogels release siRNA to effectively knockdown GFP expression over a sustained period. MAPK-14 targeting siRNA was used to knockdown the expression of MAPK-14 and correspondingly decrease the expression of other osteogenic genes in MSCs in vitro over the span of 21 days. These hydrogels were used in a rat model of growth plate injury to determine whether siMAPK-14 released from the gels could inhibit bony bar formation. No significant reduction of bony bar formation was seen in vivo at the one concentration of siRNA examined. This PEC hydrogel represents a significant advancement for siRNA sustained delivery, and presents an interesting potential therapeutic delivery system for growth plate injuries and other regenerative medicine applications.

Electrochemical and aging model of li-ion batteries and estimation of total number of cycles during the lifecycle of the battery

Fast charging is a critical factor for the widespread adoption of electric vehicles (EVs), yet it poses challenges to the durability of lithium-ion batteries (LiBs). This study develops an aging model for a 10 Ah LiB cell using COMSOL Multiphysics, integrating a one-dimensional electrochemical model with a zero-dimensional thermal model. The model is constructed using cell design and electrochemical parameters derived from existing literature, tailored to the specific electrode and electrolyte materials utilized in this study. Key aging phenomena, such as the Solid Electrolyte Interface (SEI) growth and lithium plating, are embedded within the model to simulate the aging patterns and the interplay between these factors across various C-rates and temperatures. Simulation results suggest that while higher charging rates can reduce charging time, they also lead to increased degradation, with lithium plating becoming more severe at these elevated rates. The model also indicates that temperature management during cell operation can influence cycle life, with strategic temperature increases potentially mitigating some negative effects of fast charging. The study also explores the concept of total charging time as an alternative metric for battery wear, examining its relationship with the charging current profile and temperature. Results indicate that while fast charging offers convenience, it significantly impacts cycle life, underscoring the need for optimized charging strategies. The insights from this work enhance the understanding of Li-ion cell aging mechanisms, shedding light on the complex trade-offs between charging speed, temperature management, and lifespan. This contributes to the development of more sophisticated battery management systems and charging protocols that aim to extend the operational life of LiBs while accommodating the demands of fast charging.

Medial femoral condyleOCD (osteochondritis dissecans): correlation between imaging and arthroscopy.

Osteochondritis dissecans (OCD) describes a pathologic condition centered at the osteochondral junction that may result in an unstable subchondral fragment (progeny), disruption of the overlying cartilage, which may separate from the underlying parent bone. It is one of the causes of chronic knee pain in children and young adults. The current literature on OCD lesions focuses primarily on the medial femoral condyle (MFC), but inconsistent use of terminology, particularly in the distinction of OCD lesions between skeletally immature and mature patients has created uncertainty regarding imaging workup, treatment, and long-term prognosis. This article reviews the pathophysiology of MFC OCD lesions, highlighting the role of endochondral ossification at the secondary growth plate of the immature femoral condyles, the rationale behind the imaging work-up, and key imaging findings that can distinguish between stable lesions, unstable lesions, and physiologic variants. This overview also provides a case-based review to introduce imaging correlates with the ROCK (Research in Osteochondritis of the Knee) arthroscopic classification.

A conserved regulation of cell expansion underlies notochord mechanics, spine morphogenesis, and endochondral bone lengthening.

Cell size is a key contributor to tissue morphogenesis 1 . As a notable example, growth plate hypertrophic chondrocytes use cellular biogenesis and disproportionate fluid uptake to expand 10-20 times in size to drive lengthening of endochondral bone 2,3 . Similarly, notochordal cells expand to one of the largest cell types in the developing embryo to drive axial extension 4-6 . In zebrafish, the notochord vacuolated cells undergo vacuole fusion to form a single large, fluid-filled vacuole that fills the cytoplasmic space and contributes to vacuolated cell expansion 7 . When this process goes awry, the notochord lacks sufficient hydrostatic pressure to support vertebral bone deposition resulting in adult spines with misshapen vertebral bones and scoliosis 8 . However, it remains unclear whether endochondral bone and the notochord share common genetic and cellular mechanisms for regulating cell and tissue expansion. Here, we demonstrate that the 5'-inositol phosphatase gene, inppl1a , regulates notochord expansion, spine morphogenesis, and endochondral bone lengthening in zebrafish. Furthermore, we show that inppl1a regulates notochord expansion independent of vacuole fusion, thereby genetically decoupling these processes. We demonstrate that inppl1a -dependent notochord expansion is essential to establish normal mechanical properties of the notochord to facilitate the development of a straight spine. Finally, we find that inppl1a is also important for endochondral bone lengthening in fish, as has been shown in the human INPPL1 -related endochondral bone disorder, Opsismodysplasia 9 . Overall, this work reveals a conserved mechanism of cell size regulation that influences disparate tissues critical for skeletal development and short-stature disorders.

Posttraumatic growth disturbances of the distal radius in childhood

Fractures of the distal radius in childhood are frequent but rarely lead to relevant growth disturbances. The experiences of apediatric trauma center over 15years are exemplarily presented and discussed. Osteotomies of the distal radius were selected and the clinical and radiological findings were recorded and analyzed. Posttraumatic growth disturbances were corrected in 10 cases with amedian age of 13 ½ years. In six cases an iatrogenic cause was also possible. In two cases callus distraction with secondary palmar plate osteosynthesis was used for consolidation. In eight cases primary ad hoc corrections were carried out using palmar plate osteosynthesis (six with iliac crest and two with allogeneic grafts). In five cases the distal ulnar growth plate was also addressed. During follow-up breakage of one plate was registered. After an average of 31months postoperatively, 9 children had full range of motion (ROM) and in 1 case there was an extension deficit of 10o. It is important to evaluate the cause of the mostly partially inhibiting growth disturbances to draw preventive conclusions. From a clinical perspective the visible deformity is given priority and the pain and functional limitations are less relevant. The indications for corrective surgery must include the age of the patient, remaining growth potential, size and localization of the growth plate bridge, the deformity and the individual wishes of patients and parents. In most cases afull correction is possible with palmar plate osteosynthesis and an iliac crest graft. External fixation and callus distraction is an alternative in cases where the correction is more extensive. The distal ulnar growth plate should be controlled concerning further growth potential before hardware removal.

A Systematic Review of the Optimal Management of Pediatric Distal Radius Displacement Fractures: Open Reduction and Internal Fixation Versus Cast Placement.

Distal radius fracturesare among the most common pediatric injuries, affecting thousands of children each year. These fractures often require clinical intervention to reduce displacement and ensure the proper healing of the growth plate and wrist bone. The primary objective of this comprehensive analysis is to compare the effectiveness of open reduction and internal fixation (ORIF) versus cast placement in the treatment of pediatric distal radius fractures, with the aim of identifying the optimal treatment approach. Therefore, a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted on pediatric distal radius displacement fractures using extensive database searches from 2000 to 2024 for specific keywords, ensuring transparency and reproducibility. Our findings indicate that higher displacement necessitates ORIF to minimize long-term complications and ensure better functional outcomes for pediatric patients. Rare studies comparing ORIF and cast placement are analyzed, emphasizing the advantages and limitations of each approach. The document concludes that the choice between ORIF and casting depends on factors such as fracture severity, patient's age, and specific characteristics of the injury to ensure optimal outcomes in pediatric distal radius fracture management. In conclusion, our data suggests that ORIF and cast placement each have pros and cons for pediatric distal radius fractures, with the best treatment depending on fracture specifics and patient factors, but neither method is clearly superior for long-term outcomes.

Complex ontogeny of sexual size dimorphism in a female-larger gecko: Implications of determinate growth for lizard body size and life-history evolution.

Ectothermic vertebrates such as reptiles were assumed to be indeterminate growers, which means that there is no terminal point in time or size for growth in their lifetime. In recent years, evidence for the determinate nature of growth in lizards has accumulated, necessitating a re-examination of models of their ontogeny and evolution of sexual size dimorphism (SSD). In the female-larger gecko Paroedura vazimba, we monitored post-embryonic growth over a period of 15 months. After hatching, females grew faster than males but also reached their final body size, that is, closed growth of their vertebrae, earlier than males. The closure of bone growth in females correlates with the onset of reproductive maturation. We compared this pattern with the previously minutely studied, male-larger species Paroedura picta, where we documented determinate growth as well. We propose a model to explain the evolutionary switches in the direction of SSD in lizards based on bipotential effects of ovarian hormones on growth. In this model, male growth is assumed to require no male-specific growth modifier, such as sex-limited hormonal regulators, while growth is feminized by ovarian hormones in females. Low levels of ovarian hormones can promote bone growth, but high levels associated with maturation of the reproductive organs promote senescence of bone growth plates and thus cessation of bone growth. We suggest that models on growth, life-history and evolution of body size in many lizards should acknowledge their determinate nature of growth.