scholarly journals Evaluation of impaired growth plate development of long bones in skeletally immature mice by antirheumatic agents

Author(s):  
Marjolein M. J. Caron ◽  
Bert Rietbergen ◽  
Tessy M. R. Castermans ◽  
Mirella J. J. Haartmans ◽  
Lodewijk W. Rhijn ◽  
...  
Cartilage ◽  
2019 ◽  
pp. 194760351983314
Author(s):  
Marjolein M. J. Caron ◽  
Tessy M. R. Castermans ◽  
Bert van Rietbergen ◽  
Mirella J. J. Haartmans ◽  
Lodewijk W. van Rhijn ◽  
...  

2019 ◽  
Author(s):  
Holly Dupuis ◽  
Michael Andrew Pest ◽  
Ermina Hadzic ◽  
Thin Xuan Vo ◽  
Daniel B. Hardy ◽  
...  

AbstractLongitudinal bone growth occurs through endochondral ossification (EO), controlled by various signaling molecules. Retinoid X Receptor (RXR) is a nuclear receptor with important roles in cell death, development, and metabolism. However, little is known about its role in EO. In this study, the agonist SR11237 was used to evaluate RXR activation on EO.Rats given SR11237 from post-natal day 5 to 15 were harvested for micro-computed tomography scanning and histology. In parallel, newborn CD1 mouse tibiae were cultured with increasing concentrations of SR11237 for histological and whole mount evaluation.RXR agonist-treated rats were smaller than controls, and developed dysmorphia of the growth plate. Cells invading the calcified and dysmorphic growth plate appeared pre-hypertrophic in size and shape corresponding with P57 immunostaining. Additionally, SOX9 positive cells were found surrounding the calcified tissue. The epiphysis of SR11237 treated bones showed increased TRAP staining, and additional TUNEL staining at the osteo-chondral junction. MicroCT revealed morphological disorganization in the long bones of treated animals. Isolated mouse long bones treated with SR11237 grew significantly less than their DMSO controls.This study demonstrates that stimulation of the RXR receptor causes irregular ossification, premature closure of the growth plate, and disrupted long bone growth in rodent models.


2020 ◽  
Vol 8 (7_suppl6) ◽  
pp. 2325967120S0047
Author(s):  
Simone Gruber ◽  
Rhiannon Miller ◽  
Beth Shubin Stein ◽  
Joseph Nguyen

Objectives: Medial patellofemoral ligament (MPFL) reconstruction is the standard of care surgical treatment for recurrent patellar instability. Recurrent patellar instability is common after a first-time dislocation in the skeletally immature population. Adult-type reconstruction techniques are often avoided in skeletally immature patients due to the proximity of the femoral insertion of the MFPL to the distal femoral physis. It is currently unclear how outcomes of MPFL reconstruction in skeletally immature patients compare to those for skeletally mature patients. The objective of this study is to present the outcomes of isolated MPFL reconstruction in skeletally immature patients and compare their findings to a skeletally mature population. Methods: Patients were identified from an institutional patellofemoral registry who underwent isolated MPFL reconstruction from March 2014 to July 2018. Demographic, radiographic, and knee-specific patient-reported outcome measures (PROMs) were collected prior to surgery. Follow-up data collection included knee surveys collected at 1 and 2-years following MPFL reconstruction. Additionally, return to sport rates and episodes of re-dislocations were also collected. Comparisons of demographic and clinical data were made between skeletally immature and mature patients. Sub-analysis was performed on outcomes in skeletally immature patients who underwent MPFL reconstruction where the graft was placed distal to the physis to avoid the growth plate versus those who had standard placement of the graft. Baseline factors were analyzed using independent samples t-tests or chi-square analysis. Longitudinal analysis of knee PROMs was conducted using generalized estimating equation (GEE) modeling. Statistical significance was defined as p-values of 0.05 or less. Results: The study cohort included 107 patients (25 skeletally immature, 82 skeletally mature). Mean age of the study groups was 13.8 years in the immature group (range 11-15) and 21.3 in the mature group (range 14-34). No differences in sex (72% female in both groups) or obesity (0% vs. 8%) was observed between immature and mature patients. Radiographic measures of Caton-Deschamps Index (1.18 in both groups), TT-TG (14.9 vs. 14.8), and Dejour classification (P=0.328) also saw no differences between groups. Longitudinal outcomes in KOOS QoL, IKDC, KOOS PS, and Kujala surveys found no differences between immature versus mature patients over time. However, higher PediFABS was observed in the immature group versus mature at baseline (21.6 vs. 11.9, P<0.001), 1-year (18.1 vs. 11.5, P=0.006), and 2-years (22.4 vs. 11.5, P=0.003). Low incidence of post-operative dislocation and a high return to sport rate was observed in both skeletally immature and mature patients. No statistical differences were observed in all outcomes between immature patients who had standard graft placement and those where the graft was placed distal to the physis. Conclusion: Controversy exists in how best to treat the skeletally immature patient with recurrent lateral patellar instability. Due to the risk of injury to the growth plate, many believe it is best to wait to stabilize these patients until they have stopped growing. However, given the high risk of cartilage injury with each dislocation and the long term sequelae of such injuries in these young knees, the risk of waiting may be high. This study demonstrates similar outcomes and recurrence rates in skeletally immature patients with those seen in the mature population without disturbance or injury to the growth plates. [Figure: see text][Figure: see text]


1992 ◽  
Vol 21 (1) ◽  
Author(s):  
Carlo Orzincolo ◽  
PierNuccio Scutellari ◽  
Giuseppe Castaldi

2021 ◽  
Vol 27 (4) ◽  
pp. 406-412
Author(s):  
A. Andreacchio ◽  
◽  
F. Alberghina ◽  
F. Canavese ◽  
◽  
...  

Introduction Management of pediatric long bones fractures is a complex and rapidly evolving field. Traditionally, casting and conservative techniques played a key-role in the management of fractures in skeletally immature patients. However, the surgical approach has evolved steadily over the past four decades or so and increasing evidence has been published supporting the advantages of fixation techniques over conservative methods. The purpose of this narrative review is to outline how innovations in orthopedic surgery have changed the rationale of treating long bones fractures in children and adolescents with focus on surgical techniques, particularly elastic stable intramedullary nailing (ESIN). Material and methods We aimed to describe the main trends in pediatric long bones fractures management and to identify its specificities and difficulties as well as the best standard of care. Results The introduction of ESIN has profoundly influenced the management of pediatric upper and lower extremity fractures. Overall, in comparison to conservative techniques, advantages of ESIN include minimally invasiveness, short hospital stay, primary bone union, early mobilization and progressive weight bearing, and good outcome with low complication rate. Moreover, the flexible nail can be used as a closed reduction tool itself. Conclusions Irrespective of the technique performed, the key-concepts remain 1) the proper understanding of the injury to treat; 2) the identification the main characteristics of the patient; 3) the pros and cons of each technique; and 4) the potential complications.


2016 ◽  
Vol 16 (04) ◽  
pp. 1650054 ◽  
Author(s):  
JOHANA MARIA GUEVARA ◽  
HECTOR ALFONSO CASTRO-ABRIL ◽  
LUIS ALEJANDRO BARRERA ◽  
DIEGO ALEXANDER GARZÓN-ALVARADO

The growth plate is a cartilaginous structure located in the metaphysis of long bones, characterized histologically by its stratification and columnar arrangement. It is responsible for assuring longitudinal growth. Evaluation of growth plate histological characteristics has been traditionally performed using qualitative observation; however, some quantitative approaches have been reported using complex techniques. Here, we propose a simple quantitative images based analysis in order to evaluate objectively columnar arrangement within growth plate. For this, we defined six descriptors that were condensated in a geometric tensor. This tensor could be used as a single parameter to evaluate the growth plate organization. Validation of the tensor was performed with growth plate microphotographs of three healthy species (rat, pig and rabbit) and an abnormal one (Csf1tl/Csf1tl rat) found in specialized literature. According to our results, the descriptors and the tensor give a complete picture of the organization of the growth plate, reflecting the expected stratification and columnar arrangement of the cells within the tissue. This methodology could be a reliable tool for evaluation of growth plate structure for research and diagnostic purposes, taking into account that it can be easily implemented.


2017 ◽  
Vol 2017 ◽  
pp. 1-4 ◽  
Author(s):  
Heather A. Cole ◽  
Hernan Correa ◽  
Jonathan G. Schoenecker

Osteochondromas are common benign tumors of cartilage and bone. They are usually found as contiguous bone with a cartilage cap at the end of the growth plate of long bones. Similar to structure are extraskeletal osteochondromas. However, unlike typical osteochondromas, extraskeletal osteochondromas are noncontinuous with bone. To our knowledge, all reported extraskeletal osteochondromas have been contained within fascial compartments. Here we present the case of a 5-year-old female who had a slow growing mass of the anterior distal right thigh. Imaging studies revealed an ossified mass extending from dermal layer of the subcutaneous tissue with no connection to the underlying deep fascia. An excisional biopsy was performed and proved to be a subdermal extraskeletal osteochondroma.


2019 ◽  
Vol 20 (20) ◽  
pp. 5198
Author(s):  
Holly Dupuis ◽  
Michael Andrew Pest ◽  
Ermina Hadzic ◽  
Thin Xuan Vo ◽  
Daniel B. Hardy ◽  
...  

Longitudinal bone growth occurs through endochondral ossification (EO), controlled by various signaling molecules. Retinoid X Receptor (RXR) is a nuclear receptor with important roles in cell death, development, and metabolism. However, little is known about its role in EO. In this study, the agonist SR11237 was used to evaluate RXR activation in EO. Rats given SR11237 from post-natal day 5 to post-natal day 15 were harvested for micro-computed tomography (microCT) scanning and histology. In parallel, newborn CD1 mouse tibiae were cultured with increasing concentrations of SR11237 for histological and whole-mount evaluation. RXR agonist-treated rats had shorter long bones than the controls and developed dysmorphia of the growth plate. Cells invading the calcified and dysmorphic growth plate appeared pre-hypertrophic in size and shape, in correspondence with p57 immunostaining. Additionally, SOX9-positive cells were found surrounding the calcified tissue. The epiphysis of SR11237-treated bones showed increased TRAP staining and additional TUNEL staining at the osteo-chondral junction. MicroCT revealed morphological disorganization in the long bones of the treated animals. This study suggests that stimulation of RXR causes irregular ossification, premature closure of the growth plate, and disrupted long bone growth in rodent models


2021 ◽  
Vol 8 ◽  
Author(s):  
Marco Turati ◽  
Silvia Franchi ◽  
Giulio Leone ◽  
Massimiliano Piatti ◽  
Nicolò Zanchi ◽  
...  

The intra-articular synovial fluid environment in skeletally immature patients following an ACL tear is complex and remains undefined. Levels of inflammatory and anti-inflammatory cytokines change significantly in response to trauma and collectively define the inflammatory environment. Of these factors the resolvins, with their inherent anti-inflammatory, reparative, and analgesic properties, have become prominent. This study examined the levels of resolvins and other cytokines after ACL tears in skeletally immature and adult patients in order to determine if skeletal maturity affects the inflammatory pattern. Skeletally immature and adult patients with an anterior cruciate ligament injury and meniscal tears were prospectively enrolled over a 5-month period. Synovial fluid samples were obtained before surgery quantifying Resolvin E1, IL-1β, TNF-α, and IL-10 by ELISA. Comparisons between skeletally immature patients and adults, the influence of meniscal tear, growth plate maturity and time from trauma were analyzed. Skeletally immature patients had significantly greater levels of Resolvin E1 and IL-10 compared with adults with an isolated anterior cruciate ligament lesion. Among the injured skeletally immature patients Resolvin E1 levels were greater in the open growth plate group compared with those with closing growth plates. Moreover, levels of Resolvin E1 and IL-10 appeared to decrease with time. Our results suggest that skeletally immature patients have a stronger activation of the Resolvin pattern compared to adult patients and that synovial fluid Resolvins could play an antinflammatory role in the knee after anterior cruciate ligament lesion and that its activity may be synergistic with that of IL-10.


2020 ◽  
Author(s):  
Sarah Rubin ◽  
Ankit Agrawal ◽  
Johannes Stegmaier ◽  
Jonathan Svorai ◽  
Yoseph Addadi ◽  
...  

AbstractThe activity of the epiphyseal growth plates, which drive longitudinal growth of long bones, is dependent on the ability of chondrocytes to change their shape and size extensively as they differentiate. However, organ size, extracellular matrix density and cell number have hindered the study of chondrocyte morphology. Here, we describe a new pipeline called 3D Morphometric Analysis for Phenotypic significance (3D MAPs), which overcomes these obstacles. By using 3D MAPs, we have created an image database of hundreds of thousands of cells from orthologous long bones. Analysis of this database revealed the growth strategies that chondrocytes use during differentiation. We found that chondrocytes employed both allometric and isometric growth, and that allometric growth is achieved by changes either in volume or surface area along a specific cell axis in a zone-specific manner. Additionally, we discovered a new organization of chondrocytes within the growth plate, where cells are orientated such that their longest axis always aligns with the dorsal-ventral axis of the bone. To demonstrate the ability of 3D MAPs to explore mechanisms of growth plate regulation, we studied the abnormally short tibiae of Gdf5-null mice. 3D MAPs identified aberrant cellular growth behaviors which resulted in a 3-fold reduction in volumetric cell growth, as well as affected cell morphology and orientation, highlighting GDF5 as a new regulator of growth plate activity. Overall, our findings provide new insight into the morphological sequence that chondrocytes undergo during differentiation and highlight the ability of 3D MAPs to uncover molecular and cellular mechanisms regulating this process. More broadly, this work provides a new framework for studying growth plate biology.


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