Impaired Bone Health and its Predictors in LongTerm Survivors of Childhood Acute Lymphoblastic Leukemia: Results from a Single Center in Bulgaria
Author: Belcheva, Milena I. 1, Popova, Ralitsa D.2, Usheva, Natalya V.3, Bocheva, Yana D.4, Pancheva, Ruzha Z.5, Balev, Boyan D.2, Hristozova, Hristina Y.1, Kaleva, Valeriya I.1, Iotova, Violeta M.6
2. Department of Imaging and Radiotherapy
3. Department of Social Medicine and Health Care Organization
4. Department of General Medicine and Clinical Laboratory
5. Department of Hygiene and Epidemiology
6. First Pediatric Clinic with DOIL, Varna Medical University
Abstract:
Aim: The aim of this study is to evaluate the bone health and to determine the factors affecting bone mineral density (BMD) in long-term survivors of childhood acute lymphoblastic leukemia (ALL).
Methods: We compared 46 long-term survivors, aged 9-32 years (mean age 20,6±6,2 y), to 35 age- and sexmatched controls and assessed anthropometric features and biochemical and hormonal parameters. BMD, BMD Z-score, bone mineral content (BMC), fat mass (FM), lean mass (LM) and appendicular muscle mass (AMM) were measured by whole body Dual-energy X-ray absorptiometry (DEXA). Participants’ physical activity (PA) was assessed by questionnaires and interview.
Results: Compared to controls, ALL survivors and especially those older than 18y had significantly lower BMD Z-scores (-0,017±0,88 vs 0,54±1,16, р=0,016 and -0,18±0,85 vs 0,69±1,18, р=0,003, respectively). Survivors younger than 18 y had BMD, BMD Z-score and BMC similar to those of their healthy peers, but lower serum levels of vitamin D, calcium and phosphorus, as well as reduced PA. Female survivors had significantly lower BMD (р=0,02), BMD Z-score (р=0,04) and BMD T-score (р=0,03) compared to female controls. No participants had SDS BMD lower than -2. The frequency rate of BMD Z-score below –1 was 13% among survivors and 5,7% among controls (р=0,26) and such S-scores were significantly more frequent among female survivors. ALL patients with BMD Z-score below –1 had lower weight and BMI, FМ and АММ, and experienced reduced PA. They were treated with more intensive therapy. Multivariate analysis indicates that cumulative glucocorticoid dose, weight and PA parameters are all independent predictors of low BMD in survivors.
Conclusion: Long-term childhood ALL survivors have lower BMD and BMD Z-scores at an age close to their individual bone mass peak compared to controls. Females treated with intensive therapy are at a higher risk of low BMD and this risk is increased by their low PA. Increasing PA is a safe and effective means to preventing and delaying the late morbidity.
Key words: bone mineral density, acute lymphoblastic leukemia, long-term survivors
