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Heterotopic ossification within the small-bowel mesentery.

Heterotopic bone formation has been previously noted in abdominal laparotomy scars, but the presence of ectopic bone within the peritoneum is extremely rare. Our patient had recurrent formation of heterotopic bone involving the abdominal wall, peritoneum, and small-bowel mesentery. The features of various types of ectopic calcification are discussed, and several theories concerning the pathogenesis and treatment of heterotopic ossification are examined.

Abdominal Muscles↗

Diaphragmatic defects, limb deficiencies, and ossification defects of the skull: a distinctive malformation syndrome.

We report on prenatal and postnatal findings in 4 consecutive fetuses with a pattern of severe congenital anomalies who were born to a healthy nonconsanguineous couple. The spectrum of malformations includes diaphragmatic defects, hypoplastic lungs, omphalocele, limb deficiencies, syndactyly of toes, and ossification defects of the skull. This specific spectrum of anomalies is not fully compatible with that of any established syndrome. No prenatal exposure to any possible teratogen was found. Family history is suggestive for autosomal recessive inheritance, even though germ-line mosaicism in one of the parents cannot completely be excluded.

Abnormalities, Multiple↗

Osteosarcoma arising in heterotopic ossification of dermatomyositis: case report and review of the literature.

A patient with dermatomyositis developed malignant transformation of the benign interfascial heterotopic bone. This patient had classic childhood dermatomyositis at the age of 3 years, and the disease was arrested after a one-year course of corticosteroid therapy. Extensive subcutaneous calcinosis cutis and deep interfascial calcinosis were the residua of the disease. Twenty-eight years later, the patient developed a high-grade osteosarcoma within the benign intermuscular heterotopic calcification and ossification that had been previously documented at the age of 8 years by a roentgenogram and at the age of 16 years by biopsy. This case represents the first report of the association of osteosarcoma and dermatomyositis, and possibly the first well-documented case of malignant transformation of benign heterotopic bone.

Adult↗

Pharmacological interventions for treating acute heterotopic ossification.

BACKGROUND: Heterotopic ossification (HO) is the formation of mature lamellar bone in soft tissue sites outside the skeleton. HO frequently complicates burns, arthroplasty, fractures, and spinal cord and brain injuries. It can impair joint function. OBJECTIVES: To determine the efficacy of medications to treat acute HO on radiological, symptomatic, functional impairment, and disability outcomes. SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Injuries Group specialised register, the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 2, 2004), MEDLINE (1966 to August 2004), EMBASE (1980 to August 2004), CINAHL (1982 to August 2004), other databases, reference lists of articles, and contacted trialists and drug companies. No language restrictions were applied. SELECTION CRITERIA: All randomised or quasi-randomised controlled trials that assessed the efficacy of any medication for treating acute HO (confirmed by bone scintigraphy, radiography, ultrasonography, or biopsy) and which used radiography to grade post-treatment HO severity. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed the study quality and extracted data. We analysed two dichotomous outcomes: no progression in HO grade (versus progression) and improvement in HO grade (versus no improvement). MAIN RESULTS: Two randomised trials comparing disodium etidronate versus placebo were included (Ono 1988; Stover 1976), from which ninety-two participants with spinal cord injury had radiographically-proven HO at baseline. At the completion of the 12 week intervention, the Ono study but not the Stover study, suggested that disodium etidronate was associated with a significantly greater likelihood of successfully preventing the progression of radiographic HO grade, (relative risk (RR) 1.50; 95% confidence interval (CI) I 1.16 to 1.93; and RR 1.48; 95% CI 0.78 to 2.84 respectively) and a significantly greater likelihood of improvement in HO grade (RR 2.78; 95% CI 1.66 to 4.66; and RR 0.71; 95% CI 0.20 to 2.53 respectively). There was evidence of statistical heterogeneity for the latter outcome. Longer term radiographic, clinical or side effect outcomes were unavailable. Data was not pooled due to this heterogeneity and the inadequate duration of follow up. REVIEWERS' CONCLUSIONS: Given the absence of long term radiographic outcomes in the included studies, there is insufficient evidence to recommend the use of disodium etidronate or other pharmacological agents for the treatment of acute HO. It has been previously suggested that disodium etidronate acts by delaying, rather than preventing, the mineralization of HO, and that mineralization may occur after treatment cessation in many cases, thereby negating the benefit of disodium etidronate on eventual HO grade. Further studies are required to assess all pharmacological treatments for acute HO with sufficient follow-up duration.

Etidronic Acid↗

Prenatal growth deficiency with narrowness of the cervical spine, subglottic stenosis, hip dislocation, and severe delayed bone ossification: a new skeletal dysplasia.

A boy with a severe prenatal onset dysplasia, prominent occiput, hypertelorism, epicanthus inversus, low-set ears, flat nasal bridge, small nares, cleft palate, subglottic stenosis, narrow cervical canal, undermodeled bones, cortical thinning of the diaphyses, hip dislocation, severely delayed bone ossification, and apparently normal intellectual development is described. Osseous histopathological studies were unremarkable. The boy's parents are first cousins, suggesting recessive inheritance. To the best of our knowledge, this association has not been reported before, and may be considered a novel syndrome.

Abnormalities, Multiple↗

Vertebral sarcoidosis with paravertebral ossification.

A young black male with sarcoidosis developed quadriplegia after a fall. Roentgenograms of the spine revealed extensive lytic and scierotic changes with paravertebral bony bridges simulating ankylosing spondylitis. He recovered on corticosteroid therapy after laminectomy and cervical fusion. Review of the literature suggests that this case of vertebral sarcoidosis is the most severe yet reported and the first with paravertebral ossification.

Adult↗

Sudden quadriplegia complicating ossification of the posterior longitudinal ligament and diffuse idiopathic skeletal hyperostosis.

The association of ossification of the posterior longitudinal ligament (OPLL) and diffuse idiopathic skeletal hyperostosis (DISH) has been recently described. It may result in devastating compressive myelopathy. We report a case of quadriplegia complicating OPLL in a patient with DISH. In addition, we present a brief review of the literature on OPLL. This report illustrates the importance of appropriate neurologic and radiologic evaluation of persons with DISH, to help prevent severe neurologic complications.

Accidental Falls↗

Heterotopic ossification in the setting of neuromuscular blockade.

OBJECTIVE: Heterotopic ossification (HO) is a disorder characterized by the formation of new bone in tissue that does not ossify under normal conditions. We report a series of 6 cases in which HO occurred in the setting of adult respiratory distress syndrome (ARDS). We wished to show that HO can occur after neuromuscular blockade and that these cases might provide additional evidence that HO is influenced by neural mechanisms. METHODS: Cases of HO were selected from the consultation services at the Massachusetts General Hospital and the Brigham and Women's Hospital. Affected patients all had ARDS and had been treated with a neuromuscular blocking agent. Patients with a history of stroke, burn, head trauma, spinal cord injury, or joint replacement were excluded from this study. RESULTS: Heterotopic bone appeared around large joints in a pattern identical to that seen in patients with paralysis, traumatic brain injury, severe burns, or trauma. New bone formation was self-limited over a period of 1-2 years. Alkaline phosphatase and technetium bone scan were sensitive ways of detecting early disease and monitoring disease activity. Medical therapies had limited benefit. Surgical excision of mature new bone appeared to be the only definitive therapy. CONCLUSION: Neuromuscular blockade in the setting of ARDS appears to be an important risk factor for the development of HO. The similarity of these cases of HO occurring in patients with brain or spinal cord injury raises the possibility that neural mechanisms may be important in the pathogenesis of this disease. Whether the type of neuromuscular blocking agent and the duration of use are important determinants of disease severity remains to be determined.

Adult↗

Styloid chain ossification: report of a case with articulations.

A bilateral ossified stylohyoid ligament was observed in a cadaver specimen. On the left side, the stylohyoid chain was markedly enlarged. The stylohyoid ligament was completely ossified into two segments separated by a diarthrodial-like joint. An articulation was also observed between the enlarged styloid process and the ossified ligament. On the right side, the styloid process had a normal appearance. The middle part of the stylohyoid ligament was ossified and it was attached to the styloid process and to the hyoid bone by a fibrous band. Proposed theories to account for the ossification of this ligament are discussed. Since the presence of an enlarged and ossified stylohyoid chain can cause much discomfort and pain, a greater understanding of the causative factors responsible for this anomaly is needed to provide for more effective diagnosis and treatment.

Humans↗

Heterotopic ossification: a review of symptoms and treatment.

Heterotopic ossification (HO) is the abnormal development of bone tissue within soft tissue. Its etiology and pathology are uncertain. This condition is often seen near one or more joints in people who have sustained traumatic injuries of varying types. Symptoms include localized swelling, pain, increase in temperature, and loss of the joint's range of motion at the affected site. Further testing generally reveals an increase in serum alkaline phosphatase, a positive three-phase bone scan, and the identification of bone formation on radiographs. A review of the literature reveals that common treatment options include range-of-motion exercises to maintain joint function, pharmacologic intervention, possible irradiation of the site, and surgical removal of ankylosing bone. The rehabilitation nurse must be aware of this medical complication to participate in its identification and treatment, as well as to be effective in counseling and educating patients and their families.

Humans↗

Heterotopic ossification in rectal cancer: Rare finding with a novel proposed mechanism.

The rare finding of heterotopic ossification in a case of primary rectal adenocarcinoma is described along with a review of the literature. Immunohistochemistry for a bone morphogenic protein (BMP-2) and fibroblast growth factor (FGF-2), both of which induce and stimulate bone formation, was performed and revealed overexpression of BMP-2 by the tumor cells, elucidating a possible mechanism which up to now had been based merely on speculation.

Adenocarcinoma↗

Hypertrophy and laminar calcification of cartilage in loose bodies as probable evidence of an ossification abnormality.

Of 83 loose bodies containing hyaline cartilage, 54 were composed of cartilage alone, and 29 of cartilage and bone. In both groups, hypertrophy of the cartilage was common but 53 per cent of the chondral bodies contained in laminar calcification close to the tidemark. The evidence suggested that this feature ante-dated separation of the loose body, and may have indicated a metabolic insufficiency because of the increased thickness of the cartilage. The most likely explanation for the hypertrophy was that it was secondary to a local retardation of ossification in the periphery of the epiphysis.

Adolescent↗

Effect of gestational sex steroid exposure on limb development and endochondral ossification in the pregnant C57Bl/6J mouse: I. Medroxyprogesterone acetate.

Although data supporting the teratogenic potential of intrauterine progestin exposure is lacking, concern persists among some individuals within the scientific community that these drugs have the potential for nongenital teratogenesis, especially with regard to limb reduction defects. Our laboratory has been interested in the ontogeny of steroid receptors in the developing embryo and in the role of steroid-receptor interactions in limb development, particularly the process of endochondral ossification. Since limb reduction defects can be produced from abnormal processes that are operative during organogenesis or during midgestation (vascular disruption) we have designed an animal study whereby embryos were exposed to sex steroids throughout organogenesis and fetal development. The present study assesses the effects of medroxyprogesterone acetate (MPA) on intrauterine endochrondral bone development specifically, as well as overall embryo-fetal development. Primagravid C57Bl/6J mice were treated via subdermal pellets which deliver MPA at dosages of 5.0, 50.0, and 500.0 mg/kg/day on gestational days 7 through 19. These doses were 25-, 250-, and 2,500-fold higher on a mg/kg basis than the human dose equivalent (HDE). No increases in nongenital malformations were noted at any evaluated MPA dosage level. At 25 X the HDE, MPA did not influence endochondral bone development as evidenced by a lack of significant effects on assessed bone growth parameters. In the 250- and 2,500-fold HDE dosage groups, MPA was shown to exert an embryotoxic effect inducing 48 and 100% resorptions respectively. Mean embryo weights/litter were significantly reduced by MPA exposure at 250 X the HDE. Intrauterine exposure to 250 X the MPA HDE induced reductions in humeral and femoral diaphyseal length in proportion to a reduction in overall growth. The data demonstrate that MPA, administered at dosages of up to several orders of magnitude in excess of the HDE and which permitted embryo survival, did not induce increases in the frequency of nongenital teratogenesis at any dose or gestational stage. Importantly, limb reduction defects were not noted even in instances where the dosage of MPA induced an inhibition of endochondral bone growth.

Animals↗

Intermittent claudication of the spinal cord due to ossification of the ligamentum flavum. A report of two cases.

Two patients are described who developed intermittent claudication of the spinal cord which caused spastic paraparesis during walking. The cause in both was multi-level ossification of the ligamentum flavum. Epidural spinal cord evoked potentials showed disappearance of the third negative component in one case, and positive-going waves in the most compressed area. Both patients had excellent neurological improvement after resection of the ossified ligament.

Adult↗