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Ear, Nose, & Throat Journal Dec 2022Significance StatementUnilateral Eagle Syndrome is relatively rare and highlights important concepts in anatomy and pathophysiology. Bilateral Eagle Syndrome is...
Significance StatementUnilateral Eagle Syndrome is relatively rare and highlights important concepts in anatomy and pathophysiology. Bilateral Eagle Syndrome is exponentially more rare and has only been mentioned several times in the literature. Understanding the impact this can have on the human body and the severity of symptoms and sequelae is valuable for several types of specialists that treat this disorder.
Topics: Humans; Temporal Bone; Ossification, Heterotopic
PubMed: 33258676
DOI: 10.1177/0145561320973551 -
Journal of Bone and Mineral Research :... Oct 2022Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare genetic disorder characterized by progressive heterotopic ossification (HO), often heralded by flare-ups,... (Randomized Controlled Trial)
Randomized Controlled Trial
Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare genetic disorder characterized by progressive heterotopic ossification (HO), often heralded by flare-ups, leading to reduced movement and life expectancy. This placebo-controlled, double-blind trial (NCT02190747) evaluated palovarotene, an orally bioavailable selective retinoic acid receptor gamma agonist, for prevention of HO in patients with FOP. Patients experiencing a flare-up were enrolled in two cohorts: (1) patients ≥15 years were randomized 3:1 to palovarotene 10/5 mg (weeks 1-2/3-6) or placebo; (2) patients ≥6 years were randomized 3:3:2 to palovarotene 10/5 mg, palovarotene 5/2.5 mg (weeks 1-2/3-6), or placebo. Cohort data were pooled. The primary endpoint was the proportion of responders (no/minimal new HO at flare-up body region by plain radiograph) at week 6. Change from baseline in HO volume and new HO incidence were assessed by computed tomography (CT) at week 12. Tissue edema was assessed by magnetic resonance imaging (MRI) or ultrasound. Forty patients (aged 7-53 years) were enrolled (placebo: n = 10; palovarotene 5/2.5 mg: n = 9; palovarotene 10/5 mg: n = 21). Disease history was similar between groups. In the per-protocol population, the proportion of responders at week 6 by plain radiograph was 100% with palovarotene 10/5 mg; 88.9% with palovarotene 5/2.5 mg; 88.9% with placebo (Cochran-Armitage trend test: p = 0.17). At week 12, the proportions were 95.0% with palovarotene 10/5 mg; 88.9% with palovarotene 5/2.5 mg; 77.8% with placebo (Cochran-Armitage trend test: p = 0.15). Week 12 least-squares mean (LSmean) new HO volume, assessed by CT, was 3.8 × 10 mm with palovarotene 10/5 mg; 1.3 × 10 mm with palovarotene 5/2.5 mg; 18.0 × 10 mm with placebo (pairwise tests versus placebo: p ≤ 0.12). Palovarotene was well-tolerated. No patients discontinued treatment or required dose reduction; one patient had dose interruption due to elevated lipase. Although these findings were not statistically significant, they support further evaluation of palovarotene for prevention of HO in FOP in larger studies. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Topics: Humans; Myositis Ossificans; Ossification, Heterotopic; Pyrazoles; Stilbenes
PubMed: 35854638
DOI: 10.1002/jbmr.4655 -
Clinics in Plastic Surgery Oct 2017Burns and trauma cause superficial and deep soft tissue wounds that cannot heal to the preinjury state. Healing requires cell proliferation and differentiation into the... (Review)
Review
Burns and trauma cause superficial and deep soft tissue wounds that cannot heal to the preinjury state. Healing requires cell proliferation and differentiation into the injured tissue type, laying down extracellular matrix, often as collagens. Heterotopic ossification causes severe pain, nonhealing wounds, and restricted range of motion. Treatment includes radiation therapy, nonsteroidal anti-inflammatory drugs, bisphosphonates, and possibly surgical excision and prophylactic measures. Hypertrophic scars, nonosseous lesions caused by excessive collagen deposition, are often painful, functionally limiting, and aesthetically displeasing. Treatment includes CO2 laser application, steroid injections, and excision with skin grafting. This article reviews the management of these pathologic wounds.
Topics: Burns; Cicatrix, Hypertrophic; Humans; Ossification, Heterotopic; Radiotherapy; Skin Transplantation; Wound Healing
PubMed: 28888300
DOI: 10.1016/j.cps.2017.05.006 -
Bone Apr 2018GNAS is a complex imprinted gene encoding the alpha-subunit of the stimulatory heterotrimeric G protein (Gsα). GNAS gives rise to additional gene products that exhibit... (Review)
Review
GNAS is a complex imprinted gene encoding the alpha-subunit of the stimulatory heterotrimeric G protein (Gsα). GNAS gives rise to additional gene products that exhibit exclusively maternal or paternal expression, such as XLαs, a large variant of Gsα that shows exclusively paternal expression and is partly identical to the latter. Gsα itself is expressed biallelically in most tissues, although the expression occurs predominantly from the maternal allele in a small set of tissues, such as renal proximal tubules. Inactivating mutations in Gsα-coding GNAS exons are responsible for Albright's hereditary osteodystrophy (AHO), which refers to a constellation of physical and developmental disorders including obesity, short stature, brachydactyly, cognitive impairment, and heterotopic ossification. Patients with Gsα mutations can present with AHO in the presence or absence of end-organ resistance to multiple hormones including parathyroid hormone. Maternal Gsα mutations lead to AHO with hormone resistance (i.e. pseudohypoparathyroidism type-Ia), whereas paternal mutations cause AHO alone (i.e. pseudo-pseudohypoparathyroidism). Heterotopic ossification associated with AHO develops through intramembranous bone formation and is limited to dermis and subcutis. In rare cases carrying Gsα mutations, however, ossifications progress into deep connective tissue and skeletal muscle, a disorder termed progressive osseous heteroplasia (POH). Here I briefly review the genetic, clinical, and molecular aspects of these disorders caused by inactivating GNAS mutations, with particular emphasis on heterotopic ossification.
Topics: Animals; Chromogranins; Cyclic AMP; GTP-Binding Protein alpha Subunits, Gs; Humans; Mutation; Ossification, Heterotopic
PubMed: 28889026
DOI: 10.1016/j.bone.2017.09.002 -
Bone Apr 2018Tissue regeneration following acute or persistent inflammation can manifest a spectrum of phenotypes ranging from the adaptive to the pathologic. Heterotopic... (Review)
Review
Tissue regeneration following acute or persistent inflammation can manifest a spectrum of phenotypes ranging from the adaptive to the pathologic. Heterotopic Ossification (HO), the endochondral formation of bone within soft-tissue structures following severe injury serves as a prominent example of pathologic differentiation; and remains a persistent clinical issue incurring significant patient morbidity and expense to adequately diagnose and treat. The pathogenesis of HO provides an intriguing opportunity to better characterize the cellular and cell-signaling contributors to aberrant differentiation. Indeed, recent work has continued to resolve the unique cellular lineages, and causative pathways responsible for ectopic bone development yielding promising avenues for the development of novel therapeutic strategies shown to be successful in analogous animal models of HO development. This review details advances in the understanding of HO in the context of inciting inflammation, and explains how these advances inform the current standards of diagnosis and treatment.
Topics: Animals; Cell Differentiation; Disease Models, Animal; Humans; Inflammation; Models, Biological; Ossification, Heterotopic; Wounds and Injuries
PubMed: 28987285
DOI: 10.1016/j.bone.2017.09.019 -
Head and Neck Pathology Dec 2015Eagle's Syndrome (ES) refers to a symptomatic anomaly due to elongation of the styloid process or mineralization of the styloid complex. If not diagnosed timely and...
Eagle's Syndrome (ES) refers to a symptomatic anomaly due to elongation of the styloid process or mineralization of the styloid complex. If not diagnosed timely and treated properly, elongation of the styloid process or the hyper-mineralization of the stylohyoid ligament may eventually lead to complete ossification of the stylohyoid complex. Non-specific head and neck symptoms of the ES may pose diagnostic challenges to the clinician. Therefore it is crucial to include ES among differential diagnosis when evaluating patients with similar head and neck symptoms. Once the diagnosis is confirmed, treatment plan should be tailored in accordance with the individual requirements of the case and performed without delay. Both pharmacological and surgical methods have been described for the treatment of the patients with ES. However for those who suffer from persistent symptoms, surgical removal of the elongated styloid process is the treatment of choice and can be done with an intraoral or an extraoral approach. The aim of this work is to present unusual clinical symptoms and radiologic findings of ES due to complete ossification of the stylohyoid complex. The importance of a correct diagnosis and appropriate treatment are highlighted.
Topics: Female; Humans; Middle Aged; Ossification, Heterotopic; Temporal Bone
PubMed: 25537830
DOI: 10.1007/s12105-014-0599-4 -
Radiology and Oncology Sep 2019Background Heterotopic Ossification (HO) is a common condition referring to ectopic bone formation in soft tissues. It has two major etiologies, acquired (more common)... (Review)
Review
Background Heterotopic Ossification (HO) is a common condition referring to ectopic bone formation in soft tissues. It has two major etiologies, acquired (more common) and genetic. The acquired form is closely related to tissue trauma. The exact pathogenesis of this disease remains unclear; however, there is ongoing research in prophylactic and therapeutic treatments that is promising. Conclusions Due to HO potential to cause disability, it is so important to differentiate it from other causes in order to establish the best possible management.
Topics: Calcinosis; Chondrocalcinosis; Diagnosis, Differential; Fractures, Avulsion; Gout; Humans; Magnetic Resonance Imaging; Myositis Ossificans; Ossification, Heterotopic; Osteosarcoma; Radiography; Tendinopathy; Wounds and Injuries
PubMed: 31553710
DOI: 10.2478/raon-2019-0039 -
Biomolecules Apr 2024The formation of bone outside the normal skeleton, or heterotopic ossification (HO), occurs through genetic and acquired mechanisms. Fibrodysplasia ossificans... (Review)
Review
The formation of bone outside the normal skeleton, or heterotopic ossification (HO), occurs through genetic and acquired mechanisms. Fibrodysplasia ossificans progressiva (FOP), the most devastating genetic condition of HO, is due to mutations in the gene and is relentlessly progressive. Acquired HO is mostly precipitated by injury or orthopedic surgical procedures but can also be associated with certain conditions related to aging. Cellular senescence is a hallmark of aging and thought to be a tumor-suppressive mechanism with characteristic features such as irreversible growth arrest, apoptosis resistance, and an inflammatory senescence-associated secretory phenotype (SASP). Here, we review possible roles for cellular senescence in HO and how targeting senescent cells may provide new therapeutic approaches to both FOP and acquired forms of HO.
Topics: Humans; Ossification, Heterotopic; Cellular Senescence; Myositis Ossificans; Animals; Activin Receptors, Type I
PubMed: 38672501
DOI: 10.3390/biom14040485 -
Zhongguo Xiu Fu Chong Jian Wai Ke Za... Mar 2022To review and evaluate the research progress of traumatic heterotopic ossification (HO). (Review)
Review
OBJECTIVE
To review and evaluate the research progress of traumatic heterotopic ossification (HO).
METHODS
The domestic and foreign related research literature on traumatic HO was widely consulted, and its etiology, pathogenesis, pathological progress, diagnosis, prevention, and treatment were summarized.
RESULTS
Traumatic HO is often caused by severe trauma such as joint operation, explosion injury, nerve injury, and burn. At present, it is widely believed that the occurrence of traumatic HO is closely related to inflammation and hypoxia. Oral non-steroidal anti-inflammatory drugs and surgery are the main methods to prevent and treat traumatic HO.
CONCLUSION
Nowadays, the pathogenesis of traumatic HO is still unclear, the efficiency of relevant prevention and treatment measures is low, and there is a lack of specific treatment method. In the future, it is necessary to further study the pathogenesis of traumatic HO and find specific prevention and treatment targets.
Topics: Burns; Humans; Hypoxia; Inflammation; Ossification, Heterotopic
PubMed: 35293183
DOI: 10.7507/1002-1892.202110078 -
American Journal of Medical Genetics.... May 2017Craniosynostosis, the premature ossification of one or more skull sutures, is a clinically and genetically heterogeneous congenital anomaly affecting approximately one... (Review)
Review
Craniosynostosis, the premature ossification of one or more skull sutures, is a clinically and genetically heterogeneous congenital anomaly affecting approximately one in 2,500 live births. In most cases, it occurs as an isolated congenital anomaly, that is, nonsyndromic craniosynostosis (NCS), the genetic, and environmental causes of which remain largely unknown. Recent data suggest that, at least some of the midline NCS cases may be explained by two loci inheritance. In approximately 25-30% of patients, craniosynostosis presents as a feature of a genetic syndrome due to chromosomal defects or mutations in genes within interconnected signaling pathways. The aim of this review is to provide a detailed and comprehensive update on the genetic and environmental factors associated with NCS, integrating the scientific findings achieved during the last decade. Focus on the neurodevelopmental, imaging, and treatment aspects of NCS is also provided.
Topics: Congenital Abnormalities; Cranial Sutures; Craniosynostoses; Humans; Ossification, Heterotopic; Phenotype
PubMed: 28160402
DOI: 10.1002/ajmg.a.38159