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At least 19 recordsLinked to original sources
PubMed1998

Animal models of heterotopic ossification.

Heterotopic ossification is often a severe clinical complication of joint arthroplasty, neurologic trauma, and muscle injury. In rare genetic disorders, such as fibrodysplasia ossificans progressiva, heterotopic ossification can be crippling and often leads to premature death. Reliable animal models of heterotopic ossifications that mimic pathologies seen in man would be invaluable for the development of new treatments to combat heterotopic ossification. Various methods used to induce heterotopic ossification in animals including the use of bone morphogenetic proteins, urinary tract epithelia, and transformed cell lines are described. Genetic animal models of heterotopic ossification and various miscellaneous examples of heterotopic ossification in animals are described. Finally, the use of transgenic mice to manipulate bone morphogenetic protein expression is discussed as a possible future animal model of heterotopic ossification.

Animals↗
PubMed1994

Immunohistochemical characterization of the small proteoglycans decorin and proteoglycan-100 in heterotopic ossification.

Heterotopic ossification is a metabolically active process which shares several properties of orthotopic bone formation and, therefore, represents an excellent model for studying bone matrix components. Immunohistochemical methods were used to investigate the distribution pattern of the small proteoglycans decorin and proteoglycan-100 during different stages of heterotopic ossification of pressure sores of paraplegic patients. Decorin and proteoglycan-100 exhibited a substantially divergent distribution pattern. Decorin was detectable in the perivascular matrix of granulation tissue as well as in the stroma of heterotopic ossification. The ossification zone was stained most strongly. In contrast, proteoglycan-100 was predominantly detectable in fibroblasts and preosteoblasts in early areas of osteogenesis. In more mature forms of heterotopic ossification immunostaining was markedly reduced in osteoblasts and osteocytes and even absent in so-called bone-lining cells. However, at least some osteoclasts were strongly positive. These results suggest indicate that decorin and proteoglycan-100 are important components during the formal pathogenesis of heterotopic ossification. The expression of the small proteoglycans, especially of proteoglycan-100, correlates with different phases during heterotopic ossification, showing a maximum for proteoglycan-100 in matrix-forming cells in early phases of bone formation, but in osteoclasts in mature bone.

Bone and Bones↗
PubMed1996

Heterotopic ossification.

Heterotopic ossification is a well-recognized condition frequently encountered by the orthopedic surgeon. Although typically asymptomatic, heterotopic ossification can be a complication of extreme severity. This article is a review of literature and attempts to clarify the definition, and delineates the etiology, incidence, risk factors, and current modes of prophylaxis and treatment of various types of heterotopic ossification.

Aged↗
PubMed2001

Disulfide bridge conformers of mature BMP are inhibitors for heterotopic ossification.

Heterotopic ossification is a frequent complication in patients who have suffered head and neck traumas or undergone total hip replacement. Heterotopic ossification occurs when osteogenic precursor cells present at the ectopic site receive the necessary signal(s) to differentiate into osteoblasts. At the protein level, the key factors in differentiation of cells to the osteogenic lineage are BMPs. Stable BMP variants derived from the identical amino acid sequence but with different disulfide bridge configurations have been investigated and found to be capable of inhibiting ossification in vitro and in vivo in rodents. These findings provide a concept for the straightforward development of a novel class of BMP antagonists that could lead to new treatments for traumatically and genetically induced heterotopic ossification and also, possibly, for disorders in which other members of the TGF-beta superfamily are involved.

Animals↗
PubMed1990

Heterotopic ossification.

Heterotopic ossification is becoming increasingly recognized as a phenomenon that can complicate trauma to the head and spinal cord. It can be a disabling accompaniment of thermal injury, and it may seriously compromise results in hip arthroplasty and the treatment of acetabular fractures. Etiologic factors, which are imprecise and incompletely understood, vary with the clinical situation. The five cases reported here illustrate the radiologic appearances, complications, and diagnostic problems, including the difficulty in determining the timing of surgical resection. Reported for the first time are cases of neurogenic heterotopic ossification associated with bilateral shoulder involvement and bilateral ulnar nerve entrapment at the elbow. Heterotopic ossification may mimic acute arthritis.

Adult↗
PubMed1994

[Collagens and growth factors in heterotopic ossification].

Heterotopic Ossification (HO) occurs as a consequence of several diseases and of various forms of trauma. HO is particularly frequent in paraplegic patients with spinal cord lesions. It is obvious that extraskeletal cells are able to differentiate into an osteogenic direction. However, the mechanisms of the induction process of HO and the stimulating agents are not precisely known. A novel tool for studying the ossification process at the level of transcription is the technique of non-radioactive in situ hybridisation. Using digoxigenin labeled cDNA probes we investigated the distribution patterns of types I, II and III collagen mRNAs and the mRNA of Transforming Growth Factor beta 1 (TGF-beta 1) in heterotopic ossification of pressure sores of paraplegic patients. The three collagen mRNAs as well as the TGF-beta 1 mRNA exhibited substantially divergent distribution patterns. Type I (alpha 1) collagen mRNA was predominantly detectable in preosteoblasts, chondroblasts and chondrocytes of the ossification zone. Type II (alpha 1) collagen mRNA was nearly exclusively found in cells of the chondrogenic lineage. Type III (alpha 1) collagen mRNA was detectable at low levels in soft tissue, but was strongly expressed by chondroblasts and chondrocytes of heterotopic cartilage. In contrast expression of TGF-beta 1 mRNA was found in a spatial different distribution pattern in areas of proliferation of mesenchymal tissue and in different stages of ectopic bone formation. As in the case of collagen Type I (alpha 1) and III (alpha 1) mRNAs the maximum of localization of TGF-beta 1 was detected in chondroblastic areas of heterotopic ossification. Taken together our in situ hybridization experiments provide evidence that chondrogenic cells play a central role in the process of HO with a phenotypic alteration in collagen type expression and a strong expression of TGF-beta 1 mRNA. These findings support individual in vivo function for TGF-beta 1 in local cellular regulation of ectopic bone formation.

Cartilage↗
PubMed2004

Gene expression in human osteoblastic cells from normal and heterotopic ossification.

Heterotopic ossification (HO), a possible complication of head injury, develops in sites where it is not normally present like at the vicinity of joints. It may cause pain, decrease motion and in severe cases complete joint ankylosis requiring surgical intervention. To our knowledge, no study has been made to analyze HO at the molecular level on human biopsies, whereas its etiology remains to be determined. We defined a procedure of cell fractionation from bone resections and developed quantitative RT-PCR to compare genetic expression patterns between human normal osteoblasts and heterotopic ossification forming cells. This quantitative study demonstrated a specific and strong overexpression of osteocalcin mRNA in HO-isolated cells associated with a significant upregulation of type 1 collagen and osteonectin mRNA while histological analysis showed only small cellular variations. Our results give a first molecular characterization of heterotopic ossification and we conclude that such overexpressions in HO-isolated cells could be associated with the high activity of this pathological bone.

Adult↗
PubMedDate not supplied

Heterotopic ossification.

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.

Adolescent↗
PubMed1996

[Value of ultrasound in diagnosis of post-traumatic heterotopic ossifications].

Heterotopic ossification is a non-neoplastic deposit of bone within soft tissue (myositis ossificans). The most common localized form is post-traumatic myositis ossificans. The ultrasonographic appearance of heterotopic ossification is characterized by highly echogenic areas with attenuation or complete disappearance of the acoustic signal distal to these areas. The size and extent of para-articular ossifications can also be evaluated, and the choice of the surgical approach is facilitated and damage to soft tissue minimized by the ultrasonographic examination.

Achilles Tendon↗
PubMed1997

A case of bilateral ulnar nerve palsy in a patient with traumatic brain injury and heterotopic ossification.

Heterotopic ossification after head injury may occur in the elbow joint. Rarely does this lead to entrapment of the ulnar nerve. We describe the case of a 20-year-old patient who developed heterotopic ossification 6 weeks after a traumatic brain injury. She subsequently developed bilateral ulnar nerve palsy which was confirmed by electrodiagnostic studies and treated by transposition of the ulnar nerve.

Adult↗
PubMed1999

Radiation therapy for heterotopic ossification.

Heterotopic ossification is a common complication after bone and joint surgery. If the disease progresses, it may cause pain and disability, eventually defeating the purpose of surgery in the first place. Today, prophylactic treatment is indicated after surgery. Both nonsteroidal antiinflammatory drugs and radiation therapy are effective. Radiation therapy is associated with fewer side effects and is preferred. Single-dose postoperative irradiation has been found to be as effective as fractionated radiation therapy.

Humans↗
PubMed2002

Heterotopic ossification.

Heterotopic ossification (HO) is the presence of bone in soft tissue where bone normally does not exist. The acquired form of HO most frequently is seen with either musculoskeletal trauma, spinal cord injury, or central nervous system injury. For example, patients who have recently undergone total hip arthroplasty or have paraplegia after spinal cord injury are at risk for HO. The fever, swelling, erythema, and occasional joint tenderness seen in early HO can be difficult to distinguish from cellulitis, osteomyelitis, or thrombophlebitis. Bone scanning and other imaging tests frequently are used to distinguish between these diagnostic possibilities. As treatment or prophylaxis for HO, either a nonsteroidal antiinflammatory drug (such as indomethacin), a diphosphonate (such as ethane-1-hydroxy-1,1-diphosphate), or local radiation therapy is recommended. Before therapy begins, bone scanning may be requested to confirm the diagnosis of HO. In addition, surgical resection of HO is used to preserve joint mobility; however, HO is likely to recur and possibly progress if resection is undertaken before the lesion has become mature. With a view toward avoiding recurrent HO and other operative complications, serial quantitative bone scans are used as an aid to time surgical intervention.

Bone and Bones↗
PubMed1975

Heterotopic ossification.

Heterotopic ossification occurs in 20 to 25 per cent of all traumatic spinal cord injured patients; it is sufficiently extensive in about 1/3 of the affected group to limit the range of motion of paralyzed joints. When necessary, resection of heterotopic deposits may be successfully accomplished in those patients in which the deposits consist of mature bone. A minimum of 14 months is required for maturity. The surgical procedure depends upon the anatomical location of the heterotopic bone.

Humans↗
PubMed1991

Heterotopic ossification.

Heterotopic ossification is a frequently encountered orthopaedic condition with multiple etiologies. Although not commonly problematic, it can be a devastating complication. Prophylactic measures, early recognition, and appropriate treatment are paramount in the management of this disorder. This article presents a review of the literature, delineates predisposing factors and identification of high-risk patients, and discusses current modes of prophylaxis and treatment of neurogenic and postoperative heterotopic bone formation.

Adult↗
PubMedDate not supplied

Heterotopic ossification.

Heterotopic ossification is well recognized following trauma to the head and spinal cord, total hip arthroplasty and internal fixation of acetabular fractures. Fortunately, effective prophylactic measures exist to minimize this occasionally devastating complication. This article reviews the pathophysiological events involved in heterotopic bone formation and outlines its clinical presentation and management.

Alkaline Phosphatase↗
PubMed1998

Pseudomalignant heterotopic ossification.

Pseudomalignant heterotopic ossification is a rare, self limited connective tissue disorder of unknown origin that may occur atypically during childhood and can simulate either soft tissue sarcoma or fibrodysplasia ossificans progressiva. A complex constellation of diagnostic features usually enable the differentiation of pseudomalignant heterotopic ossification from extraosseous osteosarcoma and fibrodysplasia ossificans progressiva during a time span of approximately 8 to 12 weeks. Orthopaedic surgeons who treat children with connective tissue tumors should be familiar with pseudomalignant heterotopic ossification and its differential diagnosis. The occasional mild and variable expression of fibrodysplasia ossificans progressiva rarely may make it more difficult to distinguish from pseudomalignant heterotopic ossification. It is possible that pseudomalignant heterotopic ossification is a form fruste of fibrodysplasia ossificans progressiva.

Child↗
PubMed2003

Deletion mutants of BMP folding variants act as BMP antagonists and are efficient inhibitors for heterotopic ossification.

UNLABELLED: Heterotopic ossification is a frequent complication in patients who have suffered head and neck traumas or have undergone total hip replacement. In this report, stable folding variants of the natural occurring osteoinductive BMPs were shown to act as inhibitors for heterotopic ossification. The most effective BMP folding variant construct performed even better than the natural occurring BMP antagonist Noggin because it also inhibited calcium deposition of pre-osteoblastic cells. INTRODUCTION: Signal transduction through receptor and ligand binding depends on the proper folding of all partners, especially when it involves the formation of a heterotetramer. In the case, the receptor binding of the ligand can be uncoupled from signal transduction, and folding variants of a ligand can be developed into antagonists of the natural bioactivity of the ligand. Here we present a deletion mutant of a bone morphogenetic protein (BMP) folding variant capable of inhibiting the bone-inducing action of natural occurring BMPs. MATERIALS AND METHODS: Deletion mutants and site-directed mutants of BMP folding variants were generated and tested for their ability to reduce alkaline phosphatase activity and mineralization in a pre-osteoblastic cell line. In vivo activity of the optimized folding variant was determined in a heterotopic ossification model in rodents and in two Xenopus laevis model systems. Biosensor interaction analysis was used to determine the affinity of the optimized BMP folding variant to the extracellular domain of BMP receptors. RESULTS: In vitro and in vivo tests in rodents revealed that the structural elements of the wrist epitope combined with finger 2 and a positive charge proximal to the tip of this finger are sufficient to induce osteoinhibition with deletion mutants and folding variants of mature BMP-4. The inhibitor designed to suppress heterotopic ossification showed BMP antagonist activity in embryos and animal caps of X. laevis. Binding studies of the inhibitor to ectodomains of type I and type II BMP receptors revealed a concentration-dependent binding, especially to the high-affinity BMP receptor. CONCLUSIONS: Deletion mutants of BMP folding variants are a new form of BMP antagonists and act through competition with osteoinductive BMP for BMP receptor binding. The excellent in vivo performance of the optimized folding variant is because of its ability to block signaling of endogenous BMPs deposited in the extracellular matrix even more effectively than the natural occurring BMP antagonist Noggin.

3T3 Cells↗
PubMed1987

Neurogenic heterotopic ossification.

Neurogenic heterotopic ossification is a potential sequela of neurological disorders, especially spinal cord injury and head injury. The etiology is unknown. Clinical, radiologic, and bone scan findings are typical. Complications may threaten function. The differential diagnosis is crucial in its early stages. Treatment options include diphosphonates, non-steroidal anti-inflammatory drugs, and surgery. This article has reviewed the literature on neurogenic heterotopic ossification (HO), soft tissue ossification of neurologic disease, including pathogenesis, histology, presentation, diagnosis, natural history, complications, and current treatments.

Animals↗