Background: Isotretinoin is part of standard therapy of HR-NBL given for 6 courses at 160mg/m2/day. Partial or complete growth arrest, physeal narrowing, short stature, and osteopenia have been reported with isotretinoin use. However this has primarily been reported in the dermatology literature where dosing is lower but given on a protracted schedule.
Methods: Clinical data on all patients between 5/2006 – 1/2016 with HR-NBL treated at Children’s Hospital Los Angeles who had orthopedic consults not related to fractures were retrospectively reviewed. Data abstracted were: disease/therapy history, orthopedic presentation history, type of bony defect and surgical intervention.
Results: 111 patients with HR-NBL (69 male) were identified. The median age at diagnosis was 3 years (5 m – 15 y). 3 (2 male)/111 were noted to have distal femoral physeal growth arrest, all with isotretinoin exposure at 7 years of age (two stage 3, one stage 4). All presented with a valgus deformity of the knee on exam 1-4 years from initiation of isotretinoin therapy. These patients developed a physeal bridge of the distal femur, involving the central and lateral physis, confirmed by radiographs and MRI. All had surgical correction with one who developed a significant leg-length discrepancy, requiring further surgical intervention.
Conclusions:
Growth arrest leading to angular deformity was noted in 3% of our patient population who were treated with isotretinoin. The same age of exposure to istotretinoin, the pattern of presentation (valgus deformity) as well as physeal arrest of the central and lateral aspect of distal femur suggest a common mechanism of action. Careful consideration to bony abnormalities, particularly for this age group may be warranted.