Advanced vertebral fracture among newly diagnosed children with acute lymphoblastic leukemia: results of the Canadian Steroid-Associated Osteoporosis in the Pediatric Population (STOPP) research program

Abstract

Vertebral compression is a serious complication of childhood acute lymphoblastic leukemia (ALL). The prevalence and pattern of vertebral fractures, as well as their relationship to BMD and other clinical indices, have not been systematically studied. We evaluated spine health in 186 newly diagnosed children (median age, 5.3 yr; 108 boys) with ALL (precursor B cell: N = 167; T cell: N = 19) who were enrolled in a national bone health research program. Patients were assessed within 30 days of diagnosis by lateral thoraco-lumbar spine radiograph, bone age (also used for metacarpal morphometry), and BMD. Vertebral morphometry was carried out by the Genant semiquantitative method. Twenty-nine patients (16%) had a total of 75 grade 1 or higher prevalent vertebral compression fractures (53 thoracic, 71%; 22 lumbar). Grade 1 fractures as the worst grade were present in 14 children (48%), 9 patients (31%) had grade 2 fractures, and 6 children (21%) had grade 3 fractures. The distribution of spine fracture was bimodal, with most occurring in the midthoracic and thoraco-lumbar regions. Children with grade 1 or higher vertebral compression had reduced lumbar spine (LS) areal BMD Z-scores compared with those without (mean +/- SD, -2.1 +/- 1.5 versus -1.1 +/- 1.2; p < 0.001). LS BMD Z-score, second metacarpal percent cortical area Z-score, and back pain were associated with increased odds for fracture. For every 1 SD reduction in LS BMD Z-score, the odds for fracture increased by 80% (95% CI: 10-193%); the presence of back pain had an OR of 4.7 (95% CI: 1.5-14.5). These results show that vertebral compression is an under-recognized complication of newly diagnosed ALL. Whether the fractures will resolve through bone growth during or after leukemia chemotherapy remains to be determined.

Figure 1

(A–C) Examples of mild, moderate and severe fractures which were representative of the types of fractures assigned the three severity scores. (A) 5 year old girl with mild (Genant grade 1), anterior wedging at T10. (B) 8 year old boy with moderate (Grade 2) anterior wedging at T7. (C) 8 year old boy with severe (Grade 3) anterior wedging at T7. (D–F) Examples of typical radiological signs of fractures observed in this cohort. (D) 5 year old girl with loss of endplate parallelism on the T9 inferior endplate. (E) 5 year old boy with anterior cortical buckling at L2. (F) 8 year old boy with endplate interruption at L2.

Figure 2

(A) The frequency and location of vertebral fractures in children with ALL at diagnosis in relation to the number of fractures identified as mild (grade 1), moderate (grade 2) and severe (grade 3) at each vertebral level. (B) The morphology of vertebral fractures in relation to location and frequency among children with ALL at diagnosis

Figure 3

Median LS BMD Z-score for children with ALL at diagnosis in relation to fracture severity grade (25th and 75th percentiles). Patients with multiple compression fractures were classified according to the highest severity score. a. Significant difference in LS BMD Z-score between children with grade 3 vs. grade 0 compression (p=0.05); b. Significant difference in LS BMD Z-score between children with grade 2 vs. grade 0 compression (p= 0.001)