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Journal of Orthopaedic Research :... Nov 2022As cancer survivorship increases, so does the number of patients that suffer from the late effects of radiation therapy. This includes arthrofibrosis, the development of...
As cancer survivorship increases, so does the number of patients that suffer from the late effects of radiation therapy. This includes arthrofibrosis, the development of stiff joints near the field of radiation. Previous reports have concentrated on skin fibrosis around the joint but largely ignored the deeper tissues of the joint. We hypothesized that fat, muscle, and the joint tissues themselves would play a more significant role in joint contracture after radiation than the skin surrounding the joint. To address this hypothesis, we irradiated the right hind flanks of mice with fractionated and unfractionated dose schedules, then monitored the mice for 3 months postradiotherapy. Mice were euthanized and physiological indications of arthrofibrosis including limb contracture and joint resting position were assessed. Stifle (knee) joints demonstrated significant arthrofibrosis, but none was observed in the hock (ankle) joints. During these studies, we were surprised to find that male and female mice showed a significantly different response to radiation injury. Female mice developed more injuries, had significantly worse contracture, and showed a greater difference in the expression of all markers studied. These results suggest that women undergoing radiation therapy might be at significantly greater risk for developing arthrofibrosis and may require specific adjustments to their care.
Topics: Animals; Ankle Joint; Contracture; Female; Fibrosis; Joint Diseases; Knee Joint; Male; Mice
PubMed: 35148568
DOI: 10.1002/jor.25297 -
Human Mutation Jul 2022Different pathogenic variants in the fibrillin-1 gene (FBN1) cause Marfan syndrome and acromelic dysplasias. Whereas the musculoskeletal features of Marfan syndrome... (Review)
Review
Different pathogenic variants in the fibrillin-1 gene (FBN1) cause Marfan syndrome and acromelic dysplasias. Whereas the musculoskeletal features of Marfan syndrome involve tall stature, arachnodactyly, joint hypermobility, and muscle hypoplasia, acromelic dysplasia patients present with short stature, brachydactyly, stiff joints, and hypermuscularity. Similarly, pathogenic variants in the fibrillin-2 gene (FBN2) cause either a Marfanoid congenital contractural arachnodactyly or a FBN2-related acromelic dysplasia that most prominently presents with brachydactyly. The phenotypic and molecular resemblances between both the FBN1 and FBN2-related disorders suggest that reciprocal pathomechanistic lessons can be learned. In this review, we provide an updated overview and comparison of the phenotypic and mutational spectra of both the "tall" and "short" fibrillinopathies. The future parallel functional study of both FBN1/2-related disorders will reveal new insights into how pathogenic fibrillin variants differently affect the fibrillin microfibril network and/or growth factor homeostasis in clinically opposite syndromes. This knowledge may eventually be translated into new therapeutic approaches by targeting or modulating the fibrillin microfibril network and/or the signaling pathways under its control.
Topics: Brachydactyly; Fibrillin-1; Fibrillin-2; Humans; Marfan Syndrome; Musculoskeletal Abnormalities; Phenotype
PubMed: 35419902
DOI: 10.1002/humu.24383 -
African Journal of Paediatric Surgery :... 2021Infantile systemic hyalinosis (ISH) is an autosomal recessively inherited disorder. The classical natural history of the disease is characterised by hypotonia, multiple...
BACKGROUND
Infantile systemic hyalinosis (ISH) is an autosomal recessively inherited disorder. The classical natural history of the disease is characterised by hypotonia, multiple contractures, skin lesions, osteopenia, joint pain, bone fractures, persistent diarrhoea and growth deficiency.
MATERIALS AND METHODS
Two children manifested the severe type of ISH underwent genotypic confirmation. In order to identify which other family members have inherited the disease. We included siblings and cousins in this study. The baseline tool to study other family subjects was based on the phenotypic characterisations of each child.
RESULTS
. Two children with the severe type of ISH showed craniosynostosis (brachycephaly and scaphocephaly) associated with multiple contractures, progressive joint osteolysis ending up with multiple joint dislocations. The full exome sequencing was carried out, revealing a previously reported heterozygous nonsense mutation с.1294С>Т and a novel heterozygous non-synonymous substitution c. 58T>A in ANTRX2 gene. Three children (sibling and cousins) manifested variable clinical manifestations relevant to ISH. Specifically, asymptoamtic skin and skeletal abnormalities of hypoplastic clavicles and 'shepherd's crook' deformity and coxa vara.
CONCLUSION
It is mandatory to perform extensive family pedigree search to detect asymptomatic clinical features in siblings and cousins in families with first degree related marriages. Interestingly, in the mild and the moderate types of ISH, we observed undescribed combination of asymptomatic skin and skeletal abnormalities. This is a comparative study between the severe and the mild/moderate types in a group of children from consanguineous families. Our current study extends the phenotypic characterisations of ISH.
Topics: Child; Humans; Hyaline Fibromatosis Syndrome; Receptors, Peptide
PubMed: 34341308
DOI: 10.4103/ajps.AJPS_162_20 -
Muscle & Nerve Jun 2020Limb contractures are debilitating complications associated with various muscle and nervous system disorders. This report summarizes presentations at a conference at the... (Review)
Review
Limb contractures are debilitating complications associated with various muscle and nervous system disorders. This report summarizes presentations at a conference at the Shirley Ryan AbilityLab in Chicago, Illinois, on April 19-20, 2018, involving researchers and physicians from diverse disciplines who convened to discuss current clinical and preclinical understanding of contractures in Duchenne muscular dystrophy, stroke, cerebral palsy, and other conditions. Presenters described changes in muscle architecture, activation, extracellular matrix, satellite cells, and muscle fiber sarcomeric structure that accompany or predispose muscles to contracture. Participants identified ongoing and future research directions that may lead to understanding of the intersecting factors that trigger contractures. These include additional studies of changes in muscle, tendon, joint, and neuronal tissues during contracture development with imaging, molecular, and physiologic approaches. Participants identified the requirement for improved biomarkers and outcome measures to identify patients likely to develop contractures and to accurately measure efficacy of treatments currently available and under development.
Topics: Cerebral Palsy; Chicago; Contracture; Education; Humans; Muscular Dystrophy, Duchenne; Musculoskeletal Diseases; Nervous System Diseases; Research Report
PubMed: 32108365
DOI: 10.1002/mus.26845 -
Biomedicines Sep 2023Adhesive capsulitis, characterized by progressive fibrosis, causes a gradual, painful loss of both active and passive articular motion, leading to the final contracture... (Review)
Review
Adhesive capsulitis, characterized by progressive fibrosis, causes a gradual, painful loss of both active and passive articular motion, leading to the final contracture of the joint capsule. The condition commonly referred to as "frozen ankle" (FA), which Goldman was the first to use, relates to the ankle joint and is challenging to both diagnose and treat. Data acquired from people who suffer from this type of damage in other joints such as the shoulder, hip, and wrist also exists. Despite the fact that a well-defined model for the medical management of FA does not exist, a wide spectrum of local treatments, both surgical and non-surgical, exist. This review gives an overview of the current scientific position of the frozen ankle in terms of evolutionary factors, etiology, the different mechanisms of action involved, current treatment options, and other possible interventions based on recent discoveries of pathophysiological mechanisms. The application of extracorporeal shockwave therapy, stretching exercises, and corticosteroid injections combined with physical therapy modalities that enhance pain management, range of motion, and functional capacity is highly advisable for the treatment of adhesive capsulitis, commonly known as "frozen joints". Furthermore, the addition of interventions both impacting and analyzing chronic hypoxia, low-grade inflammation, and sedentary life is proposed.
PubMed: 37760901
DOI: 10.3390/biomedicines11092461 -
Journal of Orthopaedic Research :... Dec 2022Stiff joints formed after trauma, surgery or immobilization are frustrating for surgeons, therapists and patients alike. Unfortunately, the study of contracture is...
Stiff joints formed after trauma, surgery or immobilization are frustrating for surgeons, therapists and patients alike. Unfortunately, the study of contracture is limited by available animal model systems, which focus on the utilization of larger mammals and joint trauma. Here we describe a novel mouse-based model system for the generation of joint contracture using 3D-printed clamshell casts. With this model system we are able to generate both reversible and irreversible contractures of the knee and ankle. Four- or 8-month-old female mice were casted for either 2 or 3 weeks before liberation. All groups formed measurable contractures of the knee and ankle. Younger mice immobilized for less time formed reversible contractures of the knee and ankle. We were able to generate irreversible contracture with either longer immobilization time or the utilization of older mice. The contracture formation translated into differences in gait, which were detectable using the DigiGait® analysis system. This novel model system provides a higher throughput, lower cost and more powerful tool in studying the molecular and cellular mechanisms considering the large existing pool of transgenic/knockout murine strains.
Topics: Female; Mice; Animals; Contracture; Ankle Joint; Gait; Knee Joint; Hindlimb; Joint Diseases; Disease Models, Animal; Joint Dislocations; Printing, Three-Dimensional; Range of Motion, Articular; Mammals
PubMed: 35266583
DOI: 10.1002/jor.25313 -
Journal of Orthopaedic Surgery (Hong... 2020We intend to assess the efficacies and limitations of collagenase clostridium histolyticum (CCH) and fasciectomy in treating Dupuytren's contracture, and the associated... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
We intend to assess the efficacies and limitations of collagenase clostridium histolyticum (CCH) and fasciectomy in treating Dupuytren's contracture, and the associated complications and rate of recurrences aiming to present a treatment algorithm.
METHODS
A literature search within the PubMed, Web of Sciences, Cochrane Library, and EMBASE databases was performed using the combined key words 'Dupuytren, palmar aponeurosis contracture, collagenase clostridium histolyticum and fasciectomy', including all possible studies with a set of predefined inclusion and exclusion criteria.
RESULTS
Thirty studies were assessed for eligibility from 215 identified records. Seventeen publications satisfied the inclusion criteria including 2142 joints in 1784 patients. The mean follow-up time was 18.0 months (3-60).
CONCLUSION
Acceptable contractures release was obtained in both techniques. Severe complications associated with fasciectomy outrank those of CCH, whereas the low rate of recurrence favors the fasciectomy technique.
Topics: Clostridium; Dupuytren Contracture; Fasciotomy; Humans; Microbial Collagenase; Treatment Outcome
PubMed: 32484064
DOI: 10.1177/2309499020921747 -
Journal of Brachial Plexus and... Jan 2019Contractures of the shoulder joint and glenohumeral joint dysplasia are well known complications to obstetrical brachial plexus palsy. Despite extensive description of... (Review)
Review
Contractures of the shoulder joint and glenohumeral joint dysplasia are well known complications to obstetrical brachial plexus palsy. Despite extensive description of these sequelae, the exact pathogenesis remains unknown. The prevailing theory to explain the contractures and glenohumeral joint dysplasia states that upper trunk injury leads to nonuniform muscle recovery and thus imbalance between internal and external rotators of the shoulder. More recently, another explanation has been proposed, hypothesizing that denervation leads to reduced growth of developing muscles and that reinnervation might suppress contracture formation. An understanding of the pathogenesis is desirable for development of effective prophylactic treatment. This article aims to describe the current state of knowledge regarding these important complications.
PubMed: 31308856
DOI: 10.1055/s-0039-1692420 -
Trends in Pharmacological Sciences May 2021Fibrosis is the dysregulated biosynthesis of connective tissue that results from persistent infection, high serum cholesterol, surgery, trauma, or prolonged joint... (Review)
Review
Fibrosis is the dysregulated biosynthesis of connective tissue that results from persistent infection, high serum cholesterol, surgery, trauma, or prolonged joint immobilization. As a disease that impacts connective tissue, it is prevalent across the body and disrupts normal extracellular and tissue organization. Ultimately, fibrosis impairs the tissue structural, mechanical, or biochemical function. This review describes the clinical landscape of joint fibrosis, that is, arthrofibrosis, including the risk factors and causes, as well as current clinical treatments and their shortcomings. Because treating arthrofibrosis remains an unmet clinical challenge, we present several animal models used for exploration of the physiopathology of arthrofibrosis and summarize their use for testing novel treatments. We then discuss therapeutics for the prevention or treatment of arthrofibrosis that are in preclinical development and in ongoing clinical trials. We conclude with recent findings from molecular biological studies of arthrofibroses that shed insight on future areas of research for improved treatments.
Topics: Animals; Fibrosis; Joint Diseases; Knee Joint; Prevalence; Prognosis
PubMed: 33795150
DOI: 10.1016/j.tips.2021.02.007 -
Acta Stomatologica Croatica Mar 2020Hyaline fibromatosis syndrome (HFS) is a rare autosomal recessive genetic disorder characterized by accumulation of hyalinized fibrous tissue with cutaneous, mucosal,... (Review)
Review
Hyaline fibromatosis syndrome (HFS) is a rare autosomal recessive genetic disorder characterized by accumulation of hyalinized fibrous tissue with cutaneous, mucosal, osteoarticular, and systemic involvement. The condition is caused by a mutation of ANTXR2 gene that results in a faulty synthesis of a transmembrane protein which leads up to excessive deposition of hyaline material in extracellular space. The first signs may be present at birth or appear during infancy, and joint stiffness is the first, most common, symptom. Other manifestations include joint contractures, hyperpigmented macules over bony prominences of the joints, and gingival hypertrophy. The symptom that raises suspicion of HFS is present later, along with subcutaneous growths. The progression of the disease includes enteropathy with extensive protein loss, chronic diarrhea and frequent infections. We present a case of a five-year-old girl with severe gingival hypertrophy that caused difficulties in eating and speaking. To the best of our knowledge, this is also the first patient in Croatia with a confirmed ANTXR2 gene mutation described in the literature.
PubMed: 32523159
DOI: 10.15644/asc54/1/8