Growth failure and bony changes induced by deferoxamine

We reviewed the linear growth and growth plate morphology in all children with homozygous β thalassemia followed in Toronto, for whom monthly height percentiles were available before, and for a 36-month period after, the initiation of nightly subcutaneous deferoxamine therapy. All patients were <7 years of age when begun on deferoxamine, and had received nightly deferoxamine for a minimum of 36 months. Marked abnormalities of the metaphyseal growth plate were readily observed in the distal ulnar, radial, and tibial metaphyses in 11 of 37 patients in whom a significant decline in mean height percentile was also noted. (In 10 of these 11 patients, height was less than the 15th percentile after 36 months.) These 11 patients had received a significantly greater (p < 0.025) initial and average daily dose of deferoxamine, and had maintained a significantly lower (p < 0.025) mean serum ferritin concentration over the 36 months, than the remainder of the cohort. To determine whether deferoxamine played a causative role in growth failure, growth in patients who began deferoxamine before the age 2 years was compared to that of patients who began after age 5 years, for the period between 2 and 5 years of age. Only patients begun on deferoxamine prior to age 2 years demonstrated a significant (p < 0.01) decline in height percentile by the third year, implicating deferoxamine therapy as the cause of growth failure. We conclude that both the decline in height percentile and the bony changes observed in well-chelated patients are directly related to deferoxamine therapy. They can be observed even in older patients begun on deferoxamine as late as 5 years of age, with significant declines in serum ferritin over a short period of time, and are not confined to those begun in infancy on nightly deferoxamine. These changes may result from a direct toxic effect of deferoxamine. They may, alternatively or in addition, be due to chelation of other trace minerals required for normal growth, although serum levels of several trace elements tested were normal. Serial radiographs of the radii and femurs in thalassemic patients on deferoxamine may demonstrate early metaphyseal changes. Observation of these abnormalities should be followed by reduction of the nightly dose of deferoxamine to the lowest level that results in negative iron balance, and growth velocity should be observed carefully, in parallel with regular follow-up of bone abnormalities.