There is an increasing population of childhood cancer survivors (CCS) at risk for treatment-related toxicities, including skeletal morbidities. Bone mineral density (BMD) is a proxy for bone health and reductions are associated with osteoporosis and fractures. To investigate bone health in CCS by conducting a systematic review and meta-analysis of BMD after completed treatments. We searched Medline, Embase, Cochrane, and Web of Science in May 2019 and updated in May 2023. Studies reporting BMD Z-scores measured with dual-energy x-ray absorptiometry in CCS after treatment completion. We performed a pooled analysis of studies reporting BMD Z-scores and thereafter we analyzed studies comparing BMD in survivors and healthy controls. All analyses were performed based on the site of BMD measurement. Of 4243 studies, 84 were included (N = 8106). The mean time off-treatment across the studies ranged from 2 months to 24 years. The overall pooled mean Z-score was -0.57 (95% confidence interval [CI] -0.59 to -0.55) in the whole-body, -0.84 (95% CI -0.86 to -0.83) in the lumbar spine, -0.79 (95% CI -0.81 to -0.77) in the femoral neck and -0.14 (95% CI -0.18 to -0.11) in the total hip. When comparing survivors with controls, BMD was significantly lower in survivors at all sites. English publications, study-level meta-analysis. We showed a significant reduction of BMD Z-scores in CCS. Given the increased fracture risk already within -1 SD, these results emphasize the need for BMD surveillance and secondary prevention in CCS.
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