ESPE2024 Poster Category 1 Bone, Growth Plate and Mineral Metabolism 3 (10 abstracts)
Prospective longitudinal assessment of bone mineral density, circulating markers of bone turnover and changes in body composition in children and adolescents treated for acute lymphoblastic leukemia
Silvia Molinari 1 , Maria Laura Nicolosi 1 , Giulia Capitoli 2 , Daniele Tondelli 2 , Sabrina Corbetta 3,4 , Silvia Vai 4 , Silvia Radaelli 5 , Andrea Biondi 1,6 , Balduzzi Adriana Cristina 1,6 , Alessandra Sala 1 & Alessandro Cattoni 1,6
1Department of Pediatrics, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy. 2Bicocca Bioinformatics, Biostatistics and Bioimaging B4 Centre, University of Milano-Bicocca, Monza, Italy. 3Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy. 4UOS Bone Metabolism and Diabetes, IRCCS Istituto Auxologico Italiano, Milan, Italy. 5Department of Pediatrics, Papa Giovanni XXIII Hospital, Bergamo, Italy. 6Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy
Background: Acute lymphoblastic leukemia (ALL) is the most frequently reported cancer in paediatrics. Reduced bone mineral density (BMD) and increased risk of fractures have been well-documented in this population, but long-term longitudinal trendlines of BMD and data about the impact of bone turnover markers are still scarce. Additionally, changes in body composition have to be furtherly analysed among childhood ALL survivors.
Study design: Prospective, monocentric study. Children diagnosed with ALL between 3 and 18 years and without additional risk factors for reduced BMD were included. Dual-energy X-ray absorptiometry (DXA), anthropometric and biochemical data were collected at diagnosis (T0), every 6-months during the 2-year treatment phase (T1-T4), and 6 (T5) and 12 months (T6) after the end of the antiblastic treatment.
Results: Forty-nine patients fulfilled the inclusion criteria. Lumbar spine bone mineral apparent density (LS-BMAD) Z-scores were ≤-2.0 in 33/46 children (71.7% - median-2.8 [-3.5, -1.9]) at T0 and were consistently low all through the treatment phase. Median height-adjusted total body less than head (TBLH) BMD was -0.72 [-1.23, 0.01] at T0, but showed an abrupt decline from T1 onwards (P <0.001). Both LS-BMAD and TBLH-BMD improved after the end of treatment, but at T6 BMD was still ≤-2 in 54.8% and 41.9% of patients, respectively. Bone resorption markers were low at T0 but showed a steep increase from T1 onwards. Neither bone formation nor reabsorption markers showed a significant impact on BMD at T0 and on deltaT6-T0 BMD. In terms of body composition, the percentage of lean mass showed a progressive decrease over time, with values at T1-T6 being statistically lower than at T0 (P <0.01). Conversely, fat mass showed a consistent and progressive increase from T1 onwards (P <0.01). The age adjusted-sarcopenic index at T0 positively affected TBLH-BMD at diagnosis (P <0.001), while its improvement over time resulted positively correlated with TBLH-BMD at T6 (p 0.020).
Conclusions: As a result of the detrimental effect of blasts infiltrating the trabecular bone, LS-BMD is dramatically reduced at diagnosis. Conversely, TBLH-BMD is normal at T0 but steeply decreases over time. After 3 years, more than 2/3 of patients show either LS or TBLH-BMD ≤-2. Bone turnover was increased. The sarcopenic index was directly correlated with TBLH-BMD. Children with ALL showed a trend to develop sarcopenic obesity, particularly in the first 12 months after diagnosis.
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