Childhood Cancer Survivors with BMD Deficits Face Ongoing Social, Functional, and Quality of Life Challenges: Study Finds

"Severe BMD deficits were strongly associated with several factors, including cranial radiotherapy of 30 Gy or more (OR, 5.22), testicular or pelvic radiation (OR, 1.70), hypogonadism (OR, 3.27), growth hormone deficiency (OR, 5.28), smoking (OR, 1.71), and sedentary behavior (OR, 2.06)," the researchers reported in JAMA Network Open.

The researchers note that although 85% of childhood cancer survivors reach 5-year survival, many face early-onset chronic health conditions, including altered bone health. Bone mineral density (BMD) measures the impact of treatments and habits on the skeleton. Survivors often experience low BMD within 5 years of diagnosis, with poor nutrition, exercise, and other behaviors contributing to ongoing bone loss.

Data on the severity and changing prevalence of BMD deficits, as well as the associated nonfracture consequences, among childhood cancer survivors decades after treatment are lacking. Therefore, Chelsea G. Goodenough, Department of Epidemiology and Cancer Control, St Jude Children’s Research Hospital, Memphis, Tennessee, and colleagues aimed to evaluate the risk of moderate and severe BMD deficits in survivors and identify the long-term consequences of these deficits.

For this purpose, the researchers used cross-sectional and longitudinal data from the St Jude Lifetime (SJLIFE) cohort, which includes adult survivors of childhood cancer diagnosed between 1962 and 2012 and who survived at least 5 years. Data were collected from November 2007 to June 2020, with analysis conducted from 2021 to 2023.

The study examined childhood cancer therapy exposures, comorbid conditions, substance use, and sedentary lifestyle. Bone mineral density was assessed using lumbar quantitative computed tomography and categorized by z scores. Multivariable logistic regression analyzed BMD deficits and their long-term social, functional, and quality of life impacts.

The following were the key findings of the study:

• Among 3919 five-year survivors (median age 31.7 years), 21.7% had moderate and 6.9% had severe BMD deficits.
• Treatment exposures, comorbid conditions, smoking, and sedentary behavior explained 18.5%, 10.2%, and 7.0% of moderate deficits, and 55.4%, 51.1%, and 9.9% of severe deficits.
• Severe BMD deficits were linked to 30 Gy or greater cranial radiotherapy (CRT), testicular or pelvic radiation, hypogonadism, growth hormone deficiency, smoking, and sedentary behavior.
• CRT exposure was associated with an increased risk of declining BMD.
• Survivors with BMD deficits were less likely to live alone, employed, and more likely to need personal care, report depressive symptoms, and have poor quality of life.

This cohort study found that moderate or severe BMD deficits were common among childhood cancer survivors. Severe BMD deficits were associated with CRT, testicular or pelvic radiation, hypogonadism, GHD, smoking, and sedentary behavior.

"Future research should focus on modifiable risk factors, such as hypogonadism, GHD, smoking, and sedentary behavior, to explore potential targeted interventions," the researchers concluded.

Reference:

Goodenough CG, Baedke JL, Delaney AM, et al. Attributable Risk and Consequences of Bone Mineral Density Deficits in Childhood Cancer Survivors. JAMA Netw Open. 2025;8(1):e2454069. doi:10.1001/jamanetworkopen.2024.54069