Longitudinal changes in bone mineral density, bone turnover markers, and body composition in children and adolescents treated for acute lymphoblastic leukemia

Abstract

Impaired bone mineral density (BMD) is a common finding in young patients with acute lymphoblastic leukemia (ALL). Nevertheless, longitudinal trendlines of BMD and the impact of body composition (BC) on bone health still need to be explored among pediatric survivors. The objective of the study is to report longitudinal changes in BMD and BC in pediatric patients. This prospective, longitudinal study, collecting BMD and BC (assessed by dual-energy X-ray absorptiometry [DXA]) and circulating bone turnover markers every 6 months for 3 years, from diagnosis of ALL (T 0 ) until 1 year after the end of antiblastic treatment (T 6 ). Forty-nine patients were enrolled. At T 0 , lumbar spine (LS-)BMD Z-score was ≤−2.0 in 71.7% of patients [median: −2.8 (−3.5, −1.9)], possibly reflecting trabecular bone infiltration by lymphoblasts. Conversely, total body less than head (TBLH)-BMD Z-score was >−2.0 in 97.8% of patients at T 0 but abruptly declined after 6 months ( p < 0.001). Despite a recovery trend after the end of treatment, LS or TBLH-BMD Z-scores were still <−2.0 in 67.7% of the 31 patients still enrolled at T 6 . Bone turnover was increased between T 1 and T 4 . Lean mass decreased over time, while fat mass progressively increased. Multivariable analysis showed a statistically significant association between appendicular lean mass longitudinal recovery over time and T 1 –T 6 TBLH-BMD trendlines ( p = 0.008). In pediatric patients, LS-BMD is remarkably affected at diagnosis of ALL. TBLH-BMD, normal at diagnosis, promptly declines during treatment and baseline values are not retrieved after 36 months. Lean mass is positively associated with longitudinal improvements of subtotal BMD over time.