Childhood cancer survival rates exceed 85%, but survivors face an enhanced risk of developing early-onset chronic health conditions, involving the skeletal system. Bone mineral density (BMD) is a key indicator for assessing bone strength and health including structural integrity and reflects the cumulative effects of habits and lifetime exposures on bones. Generally, higher BMD is typically observed during childhood and adolescence. However, altered BMD was reported in children with cancer undergoing intensive therapies that lead to changes in hormone production and bone metabolism. Within 5 years of diagnosis, approximately 30% of survivors are diagnosed with low levels of BMD.
Survivors with low BMD or poor bone health at diagnosis or shortly after cancer-intensive treatment may experience further bone loss due to various lifestyle factors such as alcohol consumption, smoking, physical activity, and diet. Survivors often exhibit insufficient nutrient intake and physical activity compared to their peers, which can result in an accelerated decline in BMD over time. Moreover, an association of chronic health conditions with survivorship may further worsen skeletal health problems.
Kirsten K. Ness et al. conducted the St. Jude Lifetime (SJLIFE) cohort study to determine the BMD deficit as a distinct health outcome during long-term survivorship. The purpose of this clinical study was to evaluate the prevalence, severity, and longitudinal trajectory of BMD deficits; examine the impact of demographic variables, treatment, and lifestyle factors in BMD deficits; and explore the relationship between BMD deficits, functional independence, and quality of life (QOL) in childhood cancer survivors. This study was published in JAMA Network Open on January 10, 2025.
In this SJLIFE cohort (NCT00760656), participants were recruited from St Jude Children’s Research Hospital which is a retrospective study group with prospective health outcome follow-up for pediatric cancer survivors. Data were collected between November 2007 and June 2020. A total of 3919 (median age = 31.7 years, 52.6% male, 2.7% Hispanic, 15.5% non-Hispanic black, and 80.4% non-Hispanic white) of childhood cancer at least ≥5 years from diagnosis and aged ≥18 years. BMD was calculated by lumbar quantitative computed tomography (CT) whereas health outcomes were by brief symptom inventory 18 (BSI-18) and medical outcomes survey 36-item short form.
In this cross-sectional analysis, 27.1% and 6.9% of participants had moderate and severe BMD deficits at a median survival of 23.0 years (Interquartile range [IQR]: 16.4-31.4). Moderate (27.1% vs 15.6%) and severe (8.8% vs 4.8%) BMD deficits were higher in males compared to females (P < 0.001). Survivors with severe BMD deficits, compared to normal BMD, were more likely to have been diagnosed between the ages of 5 and 9 years, and to have received 30 Gy or greater cranial radiotherapy (CRT) (Odds ratio [OR], 5.22; 95% confidence interval [CI], 3.74-7.30; attributable fraction [AF], 33.0%) and testicular or pelvic radiation (OR, 1.70, 95% CI, 1.19-2.44; AF, 11.5%).
Additional risk factors such as being underweight (OR, 3.95; 95% CI, 2.28-6.85; AF, 7.0%), leading a sedentary lifestyle (OR, 2.06, 95% CI, 1.15-3.69; AF, 6.2%), and current smoking (OR, 1.71, 95% CI, 1.21-2.43; AF, 6.7%). Collectively these factors accounted for an AF of 72.3% among the 271 survivors with severe BMD deficits.
Survivors with severe deficits were more likely to have hypogonadism (58% female and 53.1% male) and growth hormone deficiency (95.1%) compared to normal BMD survivors. However, treatment exposures and demographic characteristics associated with developing BMD deficits were 30 Gy or greater cranial radiotherapy (OR, 2.94, 95% CI, 1.46-5.91; AF, 8.8%) in survivors with normal BMD. Additionally, survivors with severe deficits were likely to need personal care due to depressive symptoms and poor QOL in physical and social functioning as well as mental health, as measured by the SF-36 scale. Similarly, survivors with moderate deficits were likely to report poor QOL.
“Our findings highlight that moderate and severe BMD deficits are more prevalent among survivors of childhood cancer. Testicular or pelvic radiation, CRT, growth hormone deficiency (GHD), sedentary behavior, smoking, were linked to a higher risk of severe BMD deficits,” says Kirsten K. Ness, PhD, Department of Epidemiology and Cancer Control, St Jude Children’s Research Hospital, Hyderabad, Telangana, India.
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
