Back pain, male sex predict vertebral deformity among childhood leukaemia survivors

Vertebral deformity is prevalent among survivors of childhood acute lymphoblastic leukaemia (ALL), according to the PETALE Study. Male sex, back pain, and cumulative glucocorticoid dose are all associated with prevalent vertebral deformity.

“We report a significant prevalence of vertebral deformity in a moderately sized, well-characterized PETALE cohort of childhood ALL survivors, none of whom experienced relapse or received hematopoietic stem cell transplantation (HSCT),” the researchers said. “Persistent vertebral deformity may contribute to additional skeletal morbidity and/or hasten age-related skeletal complications.”

A total of 245 long-term childhood ALL survivors (median age at recruitment, 21.7 years; 49 percent male) from the Preventing Late Adverse Effects of Leukemia Cohort (French-Canadian ALL survivors treated between 1987 and 2010 with the Dana Farber Cancer Institute clinical trials protocols, who did not experience disease relapse and/or receive HSCT) were recruited.

Median time since diagnosis was 15.1 years (range, 5.4–28.2). All participants underwent spine radiograph and dual-energy X-ray absorptiometry scans.

Vertebral deformity had a prevalence of 23 percent in this cohort, with 88 precent classified as grade 1 according to the Genant method. Majority of these deformities were clinically silent. [J Clin Endocrinol Metab 2021;106:512-525]

“The lower occurrence of severe deformities in our cohort might be related to the exclusion of those who relapsed and/or received HSCT in our cohort but were included in the STOPP study,” the researchers said.

“The high proportion of mild deformity likely represents incompletely reshaped, older fractures. The cross-sectional nature of the study prevents us from differentiating between late occurring fractures and incompletely reshaped previous fractures,” they added.

In regression analysis, the following predictors of prevalent vertebral deformity were identified: male sex (risk ratio [RR], 1.94, 95 percent confidence interval [CI], 1.16–3.24; p=0.011), higher glucocorticoid cumulative dose (RR, 1.05, 95 percent CI, 1.00–1.10; p=0.032), and back pain (RR, 2.44, 95 percent CI, 1.56–3.84; p<0.001). Sex differences in these predictors were observed.

“Back pain emerging as a strong predictor of vertebral deformity underscores the importance of ongoing bone health surveillance in survivors with persistent vertebral deformities treated with these earlier protocols,” the researchers said.

Therapeutic protocols for ALL include potentially osteotoxic treatments such as cranial radiation therapy (CRT) and methotrexate (MTX). When controlling for other variables, exposure to CRT modeled as a binary variable and cumulative MTX dose did not correlate with vertebral deformity in this cohort.

“Although other studies have associated high doses of CRT with endocrinopathy and secondary repercussion on bone, the participants in our cohort received relatively low CRT doses (<20 Gy),” the researchers said. “This could in part explain why CRT did not emerge as a predictor of vertebral deformity.”

This study highlights the importance of continued follow-up of bone health in long-term survivors of childhood ALL with vertebral deformity, according to the researchers, adding that survivors with symptomatic vertebral deformity must be given conservative/medical or surgical treatment as appropriate.