isotretinoin and Bone-Diseases--Developmental

In the last decade, 13-cis-retinoic acid (13-cis-RA) has been added to the treatment of patients with high-risk neuroblastoma. In survivors of neuroblastoma, short stature is consistently observed. Causes include growth hormone deficiency and poor growth of irradiated long bones. Within the survivorship program at CHOP, we have observed that a number of these patients also have advanced bone ages. Children treated with 13-cis-RA are at risk for advanced bone age that may dramatically impact their linear growth. Ongoing evaluation is necessary to examine the effect of 13-cis-RA on final adult height and to inform clinical practice in this cohort.

Topics: Age Determination by Skeleton; Body Height; Bone Density; Bone Diseases, Developmental; Bone Marrow Transplantation; Child, Preschool; Cohort Studies; Combined Modality Therapy; Dermatologic Agents; Female; Growth; Growth Disorders; Humans; Infant; Isotretinoin; Male; Neuroblastoma; Prevalence; Radiation Dosage; Retrospective Studies; Survivors; Treatment Outcome

Prolonged therapy with retinoid drugs (chemically similar to vitamin A) often results in skeletal hyperostoses, similar to those seen in idiopathic skeletal hyperostosis. Eight patients, aged 5-26 years, with dermatologic disorders were treated with 13-cis-retinoic acid. Skeletal surveys were obtained before and during treatment. In 1 year, six of the eight patients had developed such skeletal hyperostoses in both axial and appendicular regions. The cervical spine was the most common site of involvement. None of the children demonstrated accelerated skeletal maturation. Two of the patients had mild musculoskeletal discomfort during this period. The findings indicate that high-dose 13-cis-retinoic acid therapy may cause skeletal hyperostoses, requiring radiographic monitoring during prolonged periods of treatment. An implication of these observations, relating to the etiology of idiopathic skeletal hyperostosis, is discussed.

Topics: Adolescent; Adult; Bone Diseases, Developmental; Child; Child, Preschool; Female; Humans; Isotretinoin; Keratosis; Male; Prospective Studies; Radiography; Spine; Time Factors; Tretinoin