Over 28% of childhood cancer survivors experience moderate to severe bone mineral density deficits decades after treatment, with cranial radiotherapy and endocrine dysfunction among the leading contributors, according to a recent study.

Researchers addressed the prevalence, risk factors, and long-term consequences of bone mineral density (BMD) deficits in survivors of childhood cancer. Utilizing data from the St Jude Lifetime cohort, this study, published in JAMA Network Open, analyzed cross-sectional and longitudinal BMD data from 3,919 survivors diagnosed between 1962 and 2012, who were at least five years post-diagnosis. Quantitative computed tomography was used to assess BMD, classifying results as normal (>−1 standard deviation [SD]), moderate (≤−1 SD to >−2 SD), or severe deficits (≤−2 SD).

The cohort had a median age of 31.7 years (range 18.0–69.9 years) at their most recent evaluation, with 52.6% male participants. Moderate and severe BMD deficits were prevalent in 21.7% (95% confidence interval [CI], 20.4%-23.0%) and 6.9% (95% CI, 6.1%-7.7%) of participants, respectively. Multivariable analyses identified key risk factors for severe deficits, including cranial radiotherapy (cranial radiotherapy [CRT] ≥30 Gy; odds ratio [OR], 5.22; 95% CI, 3.74-7.30; attributable fraction [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%), and growth hormone deficiency (OR, 5.28; 95% CI, 3.68-7.56; AF, 26.0%). Behavioral factors, including 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%), also significantly contributed to risk.

The researchers observed that survivors with BMD deficits experienced social and functional impairments, including reduced employment rates, reliance on personal care assistance, and diminished quality of life. Survivors with normal BMD at baseline were at risk for developing deficits within 3 to 5 years if exposed to CRT (OR, 2.94; 95% CI, 1.46-5.91; AF, 8.8%), underscoring the importance of longitudinal monitoring.

While the study identifies modifiable risk factors, including smoking and sedentary behavior, for targeted interventions, it also notes that these measures may not fully mitigate deficits directly attributable to cancer therapies. The findings support the Children’s Oncology Group recommendation for conducting initial and follow-up BMD screenings in childhood cancer survivors identified as high-risk when entering long-term care.

The study identifies modifiable risk factors, including smoking and sedentary behavior, and suggests targeted interventions, such as smoking cessation, hormone replacement therapy, and exercise programs. Researchers also recommend regular BMD monitoring and multidisciplinary care to address the long-term skeletal and functional health challenges faced by childhood cancer survivors.

Full disclosures can be found in the published study.