Bone mineral density in childhood acute lymphoblastic leukemia (ALL) during and after treatment

To the Editor: With interest, we have read the study of Swiatkiewicz et al. [1]. Indeed, during the last decades the survival rate after childhood acute lymphoblastic leukemia (ALL) has improved substantially, consequently sideeffects of ALL and its treatment gained importance of which osteoporosis is an important issue. Interestingly, they studied a group of 27 patients using bone mineral density (BMD) datameasured in the proximal forearm.As previous studies showed marked differences in cortical and trabecular bone mass at different time points during treatment, it would be interesting to know where the localization of the BMD measurement was performed, as the ultradistal part predominantly contains trabecular bone, whereas the proximal forearm at one third mainly represents cortical bone. Moreover, BMD measured with dual energy X-ray absorptiometry (DXA) is highly correlatedwith height and bone size. Therefore, correction for height or bone size is important, especially in longitudinal studies in children with impaired growth. A method to correct for bone size is to calculate bonemineral apparent density [2]. We do not agree with the statement that only Halton et al. [3] reported that most children with ALL have pathological changes in bone metabolism and bone mass at diagnosis. Several other studies confirmed these findings, and also additionally an increased fracture risk has been reported in children treated for ALL. We studied children with ALL during and 1 year after cessation of treatment according to the ALL9 protocol of the Dutch Childhood Leukemia Study Group (DCLSG) [4]. BMD of lumbar spine (trabecular bone) was decreased at diagnosis and remained low during treatment, while BMD of total body (mainly cortical bone) was normal at diagnosis and decreased during treatment especially in the first 32 weeks. One year after cessation of treatment BMD tended to increase. The fracture risk was six times higher compared to healthy controls. This higher fracture risk was not correlated with BMD standard deviation score (SDS), but the decrease in BMD during the first 6 months of treatment was significantly larger than the change in the non-fracture group, suggesting the change in BMDplays a role rather than the absolute value of the SDS. In addition, changes in bone elasticity or micro-architecture which cannot be assessed by DXA might also play a role. In another study, we measured children approximately 8 years after cessation of the DCLSG-ALL6 protocol which is a similar dexamethasone-based treatment protocol without cranial irradiation as the ALL9 protocol. BMD was normal in these patients, but again retrospectively, fracture risk was increased particularly during and in the year after cessation of therapy [5]. Swiatkiewicz et al. also measured parameters of bone turnover. As reported in previous studies, ALP and b-CTX increased significantly during treatment but no information is given whether the values are increased or normal at baseline. In concordance with other studies [3,6], we found reducedmarkers of bone formation at diagnosis, but normal levels of bone resorption markers. In conclusion, bone formation appears to be more impaired than bone resorption at diagnosis. Formation and resorption markers increased during therapy reflecting a higher bone remodeling state resulting in a decrease of BMD. Todate, the negative effects ofALL and its treatment on bone mass and fracture risk is well established. However, no clear correlation between low BMD or biochemical bone markers and increased fracture risk has been found. Next studies should aim at identifying the patients at risk and at developing preventive strategies.