Attributable Risk and Consequences of Bone Mineral Density Deficits in Childhood Cancer Survivors
Authors: Chelsea G. Goodenough, Jessica L. Baedke, Angela M. Delaney, Carmen L. Wilson, Tara M. Brinkman, Cindy Im, Megan E. Ware, Hiroto Inaba, Karen L. Clark, Gregory T. Armstrong, Daniel A. Mulrooney, Ching-Hon Pui, Daniel M. Green, Thomas E. Merchant, Deo Kumar Srivastava, Yutaka Yasui, Melissa M. Hudson, Leslie L. Robison, Sue C. Kaste, Kirsten K. Ness, Wassim Chemaitilly
Journal: JAMA Network Open (2025)

Importance Data characterizing the severity and changing prevalence of bone mineral density (BMD) deficits and associated nonfracture consequences among childhood cancer survivors decades after treatment are lacking. Objective To evaluate risk for moderate and severe BMD deficits in survivors and to identify long-term consequences of BMD deficits. Design, Setting, and Participants This cohort study used cross-sectional and longitudinal data from the St Jude Lifetime (SJLIFE) cohort, a retrospectively constructed cohort with prospective follow-up. Participants in SJLIFE are adult survivors of childhood cancer who were diagnosed between 1962 and 2012 and survived 5 years or more from diagnosis. Data were collected from November 2007 to June 2020 and analyzed from January 2021 to November 2023. Exposures Childhood cancer therapy exposures, clinically ascertained comorbid conditions, substance use, and sedentary lifestyle. Main Outcomes and Measures BMD was evaluated using lumbar quantitative computed tomography and classified by age- and sex-specific z scores with moderate (≤−1 SD) or severe (≤−2 SD) deficits. Multivariable logistic regression estimated odds ratios (ORs), attributable fractions (AFs), and associations between BMD deficits and long-term sequelae (social, functional, and quality of life [QOL]). Results Among 3919 five-year survivors (median [range] age, 31.7 [18.0-69.9] years; 2063 [52.6%] male; 105 [2.7%] Hispanic, 607 [15.5%] non-Hispanic Black, and 3153 [80.4%] non-Hispanic White), prevalence of moderate or severe BMD deficits were 21.7% (95% CI, 20.4%-23.0%) and 6.9% (95% CI, 6.1%-7.7%), respectively. Treatment exposures (including age at diagnosis), comorbid conditions, and smoking and sedentary behavior explained 18.5%, 10.2%, and 7.0% of moderate and 55.4%, 51.1%, and 9.9% of severe deficits. Severe deficits were associated with 30 Gy or greater cranial radiotherapy (CRT) (OR, 5.22; 95% CI, 3.74-7.30; AF, 33.0%), testicular or pelvic radiation (OR, 1.70, 95% CI, 1.19-2.44; AF, 11.5%), hypogonadism (OR, 3.27, 95% CI, 2.35-4.55; AF, 25.1%), growth hormone deficiency (OR, 5.28, 95% CI, 3.68-7.56; AF, 26.0%), smoking (OR, 1.71, 95% CI, 1.21-2.43; AF, 6.7%), and sedentary behavior (OR, 2.06, 95% CI, 1.15-3.69; AF, 6.2%). CRT exposure increased risk for declining BMD (OR, 2.94, 95% CI, 1.46-5.91; AF, 8.8%). Survivors with deficits were less likely to live alone and to be employed and more likely to require personal care assistance and to report depressive symptoms and poor QOL. Conclusions and Relevance While treatment exposures were associated with long-term BMD deficits, modifiable risk factors, including smoking, sedentary behavior, hypogonadism, and growth hormone deficiency, suggest feasible targets for intervention.