Isotretinoin therapy is associated with early skeletal radiographic changes

Eight patients with disorders of keratinization (six with ichthyosis, one with Darier's disease, and one with palmar-plantar keratoderma) were treated with isotretinoin for 9 months (1 patient) to 1 year (7 patients). The patients ranged from 5 to 26 years of age. The average isotretinoin dose was 2 mg/kg/day (range, 1.0-2.9 mg/kg/day). Radiographic skeletal surveys were performed prior to therapy, and after 6 months and 1 year of therapy. After 1 year of isotretinoin treatment, six of the eight patients had small but unequivocal skeletal hyperostoses. Five of the patients had multiple hyperostoses. While only two patients were judged to have hyperostoses after 6 months of isotretinoin therapy during prospective evaluation, retrospective comparison with the radiographs obtained after 1 year revealed skeletal hyperostoses after 6 months of treatment in an additional three patients. Between 6 months and 1 year of therapy, some of the hyperostoses remained unchanged while others had progressed. In three patients, hyperostoses were seen at 12 months that were not detectable at 6 months. Based on this prospective study of skeletal changes during isotretinoin therapy, we recommend that patients taking high doses of isotretinoin for long periods be monitored radiographically.