ICCBH2013 Oral Communications Chronic diseases (6 abstracts)
Bone mineral density at diagnosis determines fracture rate in children-treated according to the DCOG-ALL9 protocol
Mariël Lizet te Winkel 1,* , Rob Pieters 1, , Wim C J Hop 3 , Jan C Roos 4 , Inge M van der Sluis 1 , Jos P M Bökkerink 2, , Jan A Leeuw 2, , Marrie C A Bruin 2, , Wouter J W Kollen 2, , Anjo J P Veerman 2, , Hester A de Groot-Kruseman 2 & Marry M van den Heuvel-Eibrink 1,
1Department of Pediatric Oncology/ Hematology, Erasmus MC-Sophia Children’s Hospital, Rotterdam, The Netherlands; 2The Dutch Childhood Oncology Group, The Hague, The Netherlands; 3Department of Biostatistics, Erasmus MC - University Medical Center, Rotterdam, The Netherlands; 4Department of Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands; 5Department of Pediatric Oncology, Hematology, University Medical Center St Radboud, Nijmegen, The Netherlands; 6Department of Pediatric Oncology, Beatrix Children’s Hospital, University of Groningen, The Netherlands; 7Department of Pediatric Oncology, University Medical Center Utrecht, The Netherlands; 8Department of Pediatrics, Leiden University Medical Center, The Netherlands; 9Department of Pediatric Oncology, Hematology, VU University Medical Center, Amsterdam, The Netherlands. *Winner of New Investigator Award
Objectives: To elucidate the incidence and risk factors of skeletal toxicity in children with ALL treated with the dexamethasone-based DCOG-ALL9 protocol.
Methods: Prospectively, the cumulative incidence of fractures was assessed in 672 patients and compared between different subgroups using the log-rank test. Serial measurements of bone mineral density of the lumbar spine (BMDLS) were performed in 399 ALL patients using dual energy X-ray absorptiometry (DXA). We evaluated risk factors for a low BMD using multivariate regression. Osteoporosis was defined as having a BMDLS ≤−2 SDS combined with clinical significant fractures.
Results: The cumulative incidence of fractures at 3 years was 17.8%. At diagnosis, mean BMDLS of ALL patients was lower than that of healthy peers (mean BMDLS=−1.10 SDS, P<0.001), and this remained significant lower during and after treatment (8 months: BMDLS=−1.10 SDS, P<0.001; 24 months: BMDLS=−1.27 SDS, P<0.001; 36 months: BMDLS=−0.95 SDS, P<0.001). Multivariate linear regression analysis showed that age at diagnosis, weight and B-cell-immunophenotype were associated with a lower BMDLS at diagnosis. After correction for weight, height, gender and immunophenotype, stratification to the HR protocol arm and older age had a significant independent larger decline of BMDLS during treatment (HR group: β=−0.52, P<0.01 and age: β=−0.16, P<0.001) Cumulative incidences of fractures between ALL risk groups and age groups were not significantly different. Patients who developed fractures had a lower BMDLS during treatment than those without fractures. Treatment-related bone loss was similar in patients with and without fractures (respectively: ΔBMDLS=−0.36 SDS and ΔBMDLS=−0.12 SDS; interaction group time, P=0.295). Twenty of the 399 patients (5%) met the criteria of osteoporosis.
Conclusion: This large prospective study shows that a low absolute value of BMDLS both at diagnosis and during treatment, rather than the treatment-related decline of BMDLS, determines the markedly increased fracture risk of 17.8% in children with ALL.
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