isotretinoin and Myositis-Ossificans

Retinoids are a plausible family of therapeutic agents for fibrodysplasia ossificans progressiva due to their ability to inhibit differentiation of mesenchymal tissue into cartilage and bone. A prospective study was conducted to assess the efficacy of isotretinoin (13-cis-retinoic acid) in the prevention of heterotopic ossification in patients who had fibrodysplasia ossificans progressiva. Eleven anatomic regions were assessed in each of 21 patients by clinical examination, radiographs, and bone scans. An anatomic region was considered to be involved if there was clinical, radiographic, or radionuclide evidence of orthotopic or heterotopic ossification anywhere in the region. There were 143 involved anatomic regions and 88 uninvolved anatomic regions at the beginning of the study. Only one of the 88 anatomic regions that was completely uninvolved at the beginning of the study became involved during isotretinoin therapy. However, 16 of the 21 patients (76%) had major flare ups develop in 38 of 143 (27%) previously involved anatomic regions while administered isotretinoin therapy. Isotretinoin at steady state doses of 1 to 2 mg/kg per day decreased the incidence of heterotopic ossification at uninvolved anatomic regions compared with an external control group, as long as the medication was started before the appearance of any orthotopic or heterotopic ossification in that anatomic region. The data did not allow the determination of whether isotretinoin was effective or detrimental in preventing disease flareups in regions that had even minimal orthotopic or heterotopic ossification at the time the therapy began. Extreme caution should be exercised when using this medication in patients who have fibrodysplasia ossificans progressiva.

Topics: Adolescent; Adult; Child; Child, Preschool; Female; Humans; Isotretinoin; Male; Myositis Ossificans; Prospective Studies; Treatment Outcome

Fibrodysplasia ossificans progressiva is a rare genetic disorder in which the joints of patients become disabled by the formation of heterotopic bone. Data are available on the status of 11 joints of each of 21 patients before, during and after treatment with Accutane. These are compared with data obtained by questionnaire from 40 untreated patients to determine the efficacy of the treatment. Both left- and right-censoring are present in each group, which, together with the multivariate nature of the data and the time-dependent treatment covariate, makes analysis difficult. We consider two alternative parametric models for incorporating within-subject dependence: a marginal model and a frailty model. Both analyses suggest that Accutane treatment is effective. We discuss and illustrate the differences between the two approaches. We also discuss the extent to which the conclusions are compromised by the observational nature of the study.

Topics: Humans; Isotretinoin; Models, Statistical; Multivariate Analysis; Myositis Ossificans; Surveys and Questionnaires; Survival Analysis

The article reports the occurrence of osteochondroma in a fibrodysplasia ossificans progressiva patient. A 5-year-old boy presented with limited mouth opening and firm swelling of the right zygomatic complex area. The boy had bilateral hallux valgus of the great toes and heterotopic endochondral ossification of facial and neck regions. Associated osteochondroma of the coronoid process and aggressive heterotopic ossification of masticatory and neck muscles were found in response to traumatic injuries. Natural and clinical histories of fibrodysplasia ossificans progressiva were reviewed. An early diagnosis and avoidance of factors that aggravate ossification are key factors in reducing the expected degree of physical disabilities of patients. An early recognition of congenital skeletal deformities, early detection of abnormal ossification, and awareness of the disease by the involved physicians are important factors in the early diagnosis of the disease and in reducing any unnecessary trauma. Bone scintigrams and CT scans are effective noninvasive tools for an early detection of ossification and for monitoring the progression of the disease. Further investigation of its pathogenesis at a molecular level is important to understand better the nature of the disease and to develop an effective treatment protocol.

Topics: Child, Preschool; Combined Modality Therapy; Etidronic Acid; Humans; Isotretinoin; Male; Maxillary Neoplasms; Myositis Ossificans; Osteochondroma; Tomography, X-Ray Computed

Two patients with fibrodysplasia ossificans progressiva who presented with jaw immobilization due to formation of bone between the maxilla and mandible were treated with surgical resection of their ectopic bone in conjunction with experimental, adjunctive medical therapy using isotretinoin. Both patients had recurrence of their ectopic ossification within 2 months of surgery. Surgery to remove joint-bridging ossifications in FOP is not recommended.

Topics: Adolescent; Child, Preschool; Humans; Isotretinoin; Jaw Diseases; Male; Myositis Ossificans; Recurrence

A 9-year-old boy, treated with high-dose isotretinoin therapy for fibrodysplasia ossificans progressiva, developed dense metaphyseal bands and growth arrest. Discontinuance of isotretinoin therapy was followed by gradual decrease of metaphyseal bands and resumption of clinical growth. The dense metaphyseal bands may be related to the known action of retinoids as modulators of chondrocyte phenotype and gene expression.

Topics: Adolescent; Body Weight; Bone and Bones; Bone Development; Child; Growth; Humans; Isotretinoin; Male; Myositis Ossificans; Radiography; Torticollis; Tretinoin