Incident Vertebral Fractures in Children With Leukemia During the Four Years Following Diagnosis

Abstract

Objectives: The purpose of this article was to determine the incidence and predictors of vertebral fractures (VF) during the 4 years after diagnosis in pediatric acute lymphoblastic leukemia (ALL).

Patients and methods: Children were enrolled within 30 days of chemotherapy initiation, with incident VF assessed annually on lateral spine radiographs according to the Genant method. Extended Cox models were used to assess the association between incident VF and clinical predictors.

Results: A total of 186 children with ALL completed the baseline evaluation (median age, 5.3 years; interquartile range, 3.4-9.7 years; 58% boys). The VF incidence rate was 8.7 per 100 person-years, with a 4-year cumulative incidence of 26.4%. The highest annual incidence occurred at 12 months (16.1%; 95% confidence interval [CI], 11.2-22.7), falling to 2.9% at 4 years (95% CI, 1.1-7.3). Half of the children with incident VF had a moderate or severe VF, and 39% of those with incident VF were asymptomatic. Every 10 mg/m(2) increase in average daily glucocorticoid dose (prednisone equivalents) was associated with a 5.9-fold increased VF risk (95% CI, 3.0-11.8; P < .01). Other predictors of increased VF risk included VF at diagnosis, younger age, and lower spine bone mineral density Z-scores at baseline and each annual assessment.

Conclusions: One quarter of children with ALL developed incident VF in the 4 years after diagnosis; most of the VF burden was in the first year. Over one third of children with incident VF were asymptomatic. Discrete clinical predictors of a VF were evident early in the patient's clinical course, including a VF at diagnosis.

Figure 1. Disposition of patients from baseline to 48 months with reasons for lack of vertebral fracture data

Disposition of patients from baseline to 48 months based on completion of the vertebral fracture evaluation by lateral spine radiograph. Some patients (n=6) originally classified as missing the 12 months visit in the Alos J Clin Oncology 2012 publication were later confirmed to be lost to follow-up (n=5) or died (n=1), as shown in the far right box at the top. At 12 months, among the 17 children who had a poor-quality spine radiograph (n=2) or did not undergo the spine radiograph (n=15), 6 children returned for a spine radiograph at 24 months, 4 children returned at 36 months, 5 returned at 48 months, and *2 children returned subsequent to 48 months. At 24 months, among the 5 children who did not undergo the spine radiograph, 3 children returned for a spine radiograph at 36 months,1 child returned at 48 months, and *1 child returned subsequent to 48 months. At 36 months, among the 9 children who had a poor-quality spine radiograph (n=1) or did not undergo the spine radiograph (n=8), 7 children returned for a radiograph at 48 months, and *2 returned subsequent to 48 months. At 48 months, *9 children who had a poor-quality spine radiograph (n=3) or did not undergo the spine radiograph (n=6) at 48 months returned for a radiograph subsequent to 48 months. *For these children, their data beyond 48 months are not reported since this study focuses on the natural history in the first 4 years following diagnosis.

Figure 2

A, Severity, frequency and distribution of incident vertebral fractures in children with ALL. B, Distribution and frequency of incident VF morphology.

Figure 3

Changes in mean glucocorticoid exposure, lumbar spine bone mineral density Z-scores and body mass index Z-scores over 48 months in children with leukemia.