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Growth failure and bony changes induced by deferoxamine
N F Olivieri1, G Koren, J Harris
1Division of Haematology/Oncology, Hospital for Sick Children, University of Toronto, Ontario, Canada.
Insights
Deferoxamine therapy in children with beta thalassemia can cause growth failure and bone abnormalities, particularly when initiated before age two. This impacts linear growth and growth plate morphology.
Area of Science:
- Pediatric Endocrinology
- Hematology
- Bone Biology
Background:
- Beta-thalassemia requires iron chelation therapy to manage transfusional iron overload.
- Deferoxamine mesylate is a primary treatment for iron overload in thalassemia patients.
- Growth impairment is a known complication in children with beta-thalassemia.
Purpose of the Study:
- To investigate the impact of nightly subcutaneous deferoxamine therapy on linear growth and growth plate morphology in children with homozygous beta-thalassemia.
- To determine if deferoxamine therapy is a causative factor in growth failure and associated bony changes.
- To identify potential risk factors, such as age at initiation of therapy, associated with deferoxamine-induced growth impairment.
Main Methods:
- Retrospective review of children with homozygous beta-thalassemia receiving nightly subcutaneous deferoxamine.
- Analysis of monthly height percentiles before and for 36 months after therapy initiation.
- Assessment of growth plate morphology, specifically in distal ulnar, radial, and tibial metaphyses.
- Comparison of growth patterns between patients initiating deferoxamine before age 2 versus after age 5.
Main Results:
- 11 of 37 patients showed marked growth plate abnormalities and a significant decline in height percentile.
- These 11 patients received higher deferoxamine doses and had lower mean serum ferritin levels.
- Patients initiating deferoxamine before age 2 demonstrated a significant decline in height percentile by year three, implicating the therapy.
Conclusions:
- Deferoxamine therapy is directly related to both the decline in height percentile and observed bony changes in well-chelated patients.
- Early initiation of deferoxamine therapy (before age 2) is associated with a greater risk of growth failure.
- Growth plate abnormalities in the metaphyses are a key finding in patients experiencing deferoxamine-induced growth impairment.
Abstract:
We reviewed the linear growth and growth plate morphology in all children with homozygous beta 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 less than 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 less than 0.025) initial and average daily dose of deferoxamine, and had maintained a significantly lower (p less than 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 less than 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.(ABSTRACT TRUNCATED AT 250 WORDS)