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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 -
The Journal of Bone and Joint Surgery.... Jul 2015➤ Heterotopic ossification occurs most commonly after joint arthroplasty, spinal cord injury, traumatic brain injury, blast trauma, elbow and acetabular fractures, and... (Review)
Review
➤ Heterotopic ossification occurs most commonly after joint arthroplasty, spinal cord injury, traumatic brain injury, blast trauma, elbow and acetabular fractures, and thermal injury.➤ The conversion of progenitor cells to osteogenic precursor cells as a result of cell-mediated interactions with the local tissue environment is affected by oxygen tension, pH, availability of micronutrients, and mechanical stimuli, and leads to heterotopic ossification.➤ Radiation and certain nonsteroidal anti-inflammatory medications are important methods of prophylaxis against heterotopic ossification.➤ Well-planned surgical excision can improve patient outcomes regardless of the joint involved or the initial cause of injury.➤ Future therapeutic strategies are focused on targeted inhibition of local factors and signaling pathways that catalyze ectopic bone formation.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Arthroplasty; Bone Density Conservation Agents; Humans; Ossification, Heterotopic; Risk Factors; Wounds and Injuries
PubMed: 26135077
DOI: 10.2106/JBJS.N.01056 -
Seminars in Musculoskeletal Radiology Oct 2019Formation of the skeletal elements of the foot involves different stages of development. Failure in segmentation of the cartilaginous plate is supposed to be the... (Review)
Review
Formation of the skeletal elements of the foot involves different stages of development. Failure in segmentation of the cartilaginous plate is supposed to be the underlying mechanism leading to tarsal coalition. Variants or disorders in ossification might result in harmless osseous anomalies or symptomatic disease. When the ossification is almost completed, several secondary ossification centers start to ossify. They are usually incidental findings. In symptomatic patients they have to be differentiated from fractures or can be the source of complaints by themselves.
Topics: Diagnostic Imaging; Foot; Foot Diseases; Humans; Magnetic Resonance Imaging; Ossification, Heterotopic; Radiography; Tomography, X-Ray Computed
PubMed: 31556085
DOI: 10.1055/s-0039-1695721 -
BioMed Research International 2019This review is intended to summarize the risk factors, classification, diagnosis, and treatment of heterotopic ossification (HO) of previously published studies. (Review)
Review
BACKGROUND
This review is intended to summarize the risk factors, classification, diagnosis, and treatment of heterotopic ossification (HO) of previously published studies.
RESULTS
Heterotopic ossification is a common complication of total hip arthroplasty. Its prevalence is not the same in all of the patient groups. Frequency of HO varies from 15 to 90%. Hip ankylosis, male gender, and previous history of HO are said to be risk factors with a significant level. Diagnosis is based on a single AP radiograph: the Brooker classification that divides HO into four grades is the most commonly used. The confirmation test that can be used is a bone scan. A great amount of bone metabolic turnover markers have been tested, but none of them seems to be relevant in case of prevention or diagnosis of HO. The most effective prophylactic treatment is radiotherapy or administration of nonsteroidal anti-inflammatory drugs. Over the years a lot of different RT protocols have been tested. Nowadays the most often used regimen is 7 Gy given postoperatively in a single dose. The most commonly prescribed drug in prophylaxis of HO is indomethacin. Also, the efficacy of ibuprofen and diclofenac was proven. Recently researchers focused on selective COX-2 inhibitors. They appear to be as effective as nonselective NSAIDs having less side effects. The one and only treatment of HO is a revision arthroplasty.
Topics: Arthroplasty, Replacement, Hip; Female; Humans; Male; Ossification, Heterotopic; Postoperative Complications; Postoperative Period; Radiography; Risk Factors; Sex Characteristics; Treatment Outcome
PubMed: 31119167
DOI: 10.1155/2019/3860142 -
Journal of Cellular and Molecular... May 2020Much of the similarities of the tissue characteristics, pathologies and mechanisms of heterotopic ossification (HO) formation are shared between HO of tendon and... (Review)
Review
Much of the similarities of the tissue characteristics, pathologies and mechanisms of heterotopic ossification (HO) formation are shared between HO of tendon and ligament (HOTL). Unmet need and no effective treatment has been developed for HOTL, primarily attributable to poor understanding of cellular and molecular mechanisms. HOTL forms via endochondral ossification, a common process of most kinds of HO. HOTL is a dynamic pathologic process that includes trauma/injury, inflammation, mesenchymal stromal cell (MSC) recruitment, chondrogenic differentiation and, finally, ossification. A variety of signal pathways involve HOTL with multiple roles in different stages of HO formation, and here in this review, we summarize the progress and provide an up-to-date understanding of HOTL.
Topics: Biomarkers; Disease Susceptibility; Ligaments; Mesenchymal Stem Cells; Ossification, Heterotopic; Signal Transduction; Tendons
PubMed: 32293797
DOI: 10.1111/jcmm.15240 -
Journal of Pediatric Orthopedics 1998According to Ranvier (1889), cells in the ossification groove originate in cartilage and differentiate to osteoblasts. He was supported by others until some authors... (Review)
Review
According to Ranvier (1889), cells in the ossification groove originate in cartilage and differentiate to osteoblasts. He was supported by others until some authors stated after 1950 that the growth plate grows in width by apposition of cells from the groove. The apposition theory is still accepted in several textbooks. Our experiments with roentgen ray injury showed (1950) migration of cells toward the ossification groove in the germinal layer of the growth plate, a phenomenon not described by others. It was verified in normal bones with 35S (1967) and with vital staining (1993). In situ hybridization of bones in rabbits showed (1993) that cells in the groove and adjacent periosteum contain type II collagen messenger RNA (mRNA) characteristic of cartilage, a finding in accordance with Ranvier's views. The behavior of cells in the ossification groove plays a decisive role in the pathogenesis of several diseases of the growing skeleton.
Topics: Animals; Bone Development; Growth Plate; Humans; Ossification, Heterotopic; Osteogenesis; Rabbits; Radiography; Reference Values
PubMed: 9531398
DOI: No ID Found -
The Journal of the American Academy of... 2004Heterotopic ossification, the formation of bone in soft tissue, requires inductive signaling pathways, inducible osteoprogenitor cells, and a heterotopic environment... (Review)
Review
Heterotopic ossification, the formation of bone in soft tissue, requires inductive signaling pathways, inducible osteoprogenitor cells, and a heterotopic environment conducive to osteogenesis. Little is known about the molecular pathogenesis of this condition. Research into two rare heritable and developmental forms, fibrodysplasia ossificans progressiva and progressive osseous heteroplasia, has provided clinical, pathologic, and genetic insights. In fibrodysplasia ossificans progressiva, overexpression of bone morphogenetic protein 4 and underexpression of multiple antagonists of this protein highlight the potential role of a potent morphogenetic gradient. Research on fibrodysplasia ossificans progressiva also has led to the identification of the genetic cause of progressive osseous heteroplasia: inactivating mutations in the alpha subunit of the gene coding for the stimulatory G protein of adenylyl cyclase. Better understanding of the complex developmental and molecular pathology of these disorders may lead to more effective strategies to prevent and treat other, more common forms of heterotopic ossification.
Topics: Adolescent; Adult; Age Distribution; Bone Morphogenetic Proteins; Child; Child, Preschool; Disease Progression; Female; Follow-Up Studies; Gene Expression; Genetic Predisposition to Disease; Humans; Incidence; Male; Myositis Ossificans; Ossification, Heterotopic; Risk Assessment; Severity of Illness Index; Sex Distribution
PubMed: 15089085
DOI: 10.5435/00124635-200403000-00007 -
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 -
Korean Journal of Radiology Jun 2022
Topics: Diagnosis, Differential; Diagnostic Imaging; Hamartoma; Humans; Lung Neoplasms; Ossification, Heterotopic
PubMed: 35617995
DOI: 10.3348/kjr.2022.0156 -
Stem Cells Translational Medicine Nov 2022Heterotopic ossification (HO) is a dynamic, complex pathologic process that often occurs after severe polytrauma trauma, resulting in an abnormal mesenchymal stem cell...
Heterotopic ossification (HO) is a dynamic, complex pathologic process that often occurs after severe polytrauma trauma, resulting in an abnormal mesenchymal stem cell differentiation leading to ectopic bone growth in soft-tissues including tendons, ligaments, and muscles. The abnormal bone structure and location induce pain and loss of mobility. Recently, we observed that NGF (Nerve growth factor)-responsive TrkA (Tropomyosin receptor kinase A)-expressing nerves invade sites of soft-tissue trauma, and this is a necessary feature for heterotopic bone formation at sites of injury. Here, we assayed the effects of the partial TrkA agonist Gambogic amide (GA) in peritendinous heterotopic bone after extremity trauma. Mice underwent HO induction using the burn/tenotomy model with or without systemic treatment with GA, followed by an examination of the injury site via radiographic imaging, histology, and immunohistochemistry. Single-cell RNA Sequencing confirmed an increase in neurotrophin signaling activity after HO-inducing extremity trauma. Next, TrkA agonism led to injury site hyper-innervation, more brisk expression of cartilage antigens within the injured tendon, and a shift from FGF to TGFβ signaling activity among injury site cells. Nine weeks after injury, this culminated in higher overall levels of heterotopic bone among GA-treated animals. In summary, these studies further link injury site hyper-innervation with increased vascular ingrowth and ultimately heterotopic bone after trauma. In the future, modulation of TrkA signaling may represent a potent means to prevent the trauma-induced heterotopic bone formation and improve tissue regeneration.
Topics: Mice; Animals; Disease Models, Animal; Ossification, Heterotopic; Tenotomy; Burns; Neurons; Osteogenesis
PubMed: 36222619
DOI: 10.1093/stcltm/szac073