Risk factors and surveillance for reduced bone mineral density in pediatric cancer survivors

Abstract

Background: Pediatric cancer survivors are at increased risk of developing low bone mineral density (BMD) due to cancer treatment. This study assessed the yield of screening for low BMD in pediatric-aged cancer survivors as per the Children's Oncology Group Long-Term Follow-Up (COG-LTFU) Guidelines, which recommend screening survivors who received steroids, methotrexate, or hematopoietic cell transplant (HCT).

Methods: This is a retrospective cohort study of 475 pediatric blood cancer and noncentral nervous system solid tumor survivors screened for low BMD with dual-energy X-ray absorptiometry (DXA) as per the COG-LTFU Guidelines from 2003 to 2010. Risk factors for low BMD (DXA Z-score ≤-2) were evaluated by univariate and multivariate analysis.

Results: The mean DXA Z-score was -0.1 for both whole body and lumbar spine measurements. Among at-risk survivors, 8.2% (39/475) had low BMD. Multivariate analysis of survivors with low BMD showed significant association with male gender (odds ratio [OR] 3.4, 95% confidence interval [CI], 1.3-9.0), exposure to total body irradiation (TBI), cranial, or craniospinal radiation (OR 5.2, 95% CI, 1.8-14.9), and gonadal dysfunction (OR 4.3, 95% CI, 1.4-13.0). Methotrexate exposure was not significantly associated with low BMD. Survivors receiving HCT had a reduced risk of low BMD (OR 0.2, 95% CI, 0.1-0.9).

Conclusion: The highest risk factors for low BMD were male gender, exposure to TBI, cranial, or craniospinal radiation, and gonadal dysfunction. Survivors receiving methotrexate or HCT therapy have the lowest risk for low BMD among those screened. Future studies should investigate risk of low BMD for survivors receiving HCT without radiation exposure.

Keywords: bone mineral density; late effects; pediatric cancer survivors.