Incidence of skeletal complications during treatment of childhood acute lymphoblastic leukemia: comparison of fracture risk with the General Practice Research Database.
BACKGROUND
Skeletal complications during or after treatment of acute lymphoblastic leukemia (ALL) have been frequently reported and can cause substantial morbidity, yet their incidence is not well established. The present study assessed the incidence of fractures, osteonecrosis (ON), and bone pain during ALL treatment and compared the fracture incidence with age- and sex-specific reference data from the UK General Practice Research Database (GPRD).


METHODS
Medical records of 122 ALL patients diagnosed at our institution from 1992 to 2004 were reviewed for information on fractures, ON, bone pain, and their anatomical location, risk group, phase of antileukemic therapy, and time since diagnosis. Evaluation of skeletal complications was followed up until July 2005 or the patient's death. Thirteen children were excluded as they were transferred to other institutions shortly after diagnosis.


RESULTS
Skeletal complications occurred at a 5-year incidence of 32.7%. The 5-year incidence of fractures, ON, and isolated bone pain was 13.5%, 12.1%, and 12.3%, respectively. The relative rate of fractures adjusted for age and sex was 2.03 (95% confidence interval 1.15-3.57) compared to the GPRD, with greatest rates in children <5 years. Thirty ON occurred in 10 patients with a 15 times greater incidence in children >10 years than in those <5 years. Nearly all skeletal complications occurred during maintenance therapy at a median of 14.92 months (range 0.0-53.8) after diagnosis and in weight-bearing bones.


CONCLUSIONS
The doubled fracture rate and the high incidence of skeletal complications during the first years after diagnosis suggest the developing skeleton is very vulnerable in this period. Adolescents develop more ON whereas younger children may be more prone to fractures. Serious "immediate effects" of chemotherapy on bone appear of great concern and should entail preventative studies in this group of patients.
Högler
Wolfgang
W
Department of Pediatrics and Adolescent Medicine, Medical University Innsbruck, Innsbruck, Austria. wolfgang.hoegler@uibk.ac.at
Wehl
Götz
G
van Staa
Tjeerd
T
Meister
Bernhard
B
Klein-Franke
Andreas
A
Kropshofer
Gabriele
G
D000293:Adolescent; D000367:Age Factors; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D050723:Fractures, Bone / Q000139:chemically induced* / Q000401:mortality* / Q000517:prevention & control; D006801:Humans; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D010865:Pilot Projects; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications* / Q000188:drug therapy / Q000401:mortality*; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors