Prediction of Low and Very Low Bone Mineral Density Among Adult Survivors of Childhood Cancer

Abstract

PURPOSE To develop and validate prediction models for low and very low bone mineral density (BMD) on the basis of clinical and treatment characteristics that identify adult survivors of childhood cancer who require screening by dual-energy x-ray absorptiometry. PATIENTS AND METHODS White survivors of childhood cancer (n = 2,032; median attained age, 29.3 years [range, 18.1 to 40.9 years]) enrolled in the St Jude Lifetime Cohort (SJLIFE; development) and survivors treated at the Erasmus Medical Center (validation) in the Netherlands (n = 403; median age, 24.2 years [range, 18.0 to 40.9 years]) were evaluated with dual-energy x-ray absorptiometry to determine lumbar spine BMD and total-body BMD. Low and very low BMD were defined as lumbar spine BMD and/or total-body BMD z scores of −1 or lower or −2 or lower, respectively. Multivariable logistic regression was used to build prediction models; performance was assessed using receiver operating characteristic curves. Diagnostic values were calculated at different probabilities. RESULTS Low BMD was present in 51% and 45% of SJLIFE and Dutch participants, respectively, and very low BMD was present in 20% and 10%, respectively. The model for low BMD included male sex (odds ratio [OR], 3.07), height (OR, 0.95), weight (OR, 0.98), attained age (OR, 0.97), current smoking status (OR, 1.48), and cranial irradiation (OR, 2.11). Areas under the curve were 0.72 (95% CI, 0.70 to 0.75) in the SJLIFE cohort and 0.69 (95% CI, 0.64 to 0.75) in the Dutch cohort. The sum of the sensitivity (69.0%) and specificity (64.0%) was maximal at the predicted probability of 50%. The model for very low BMD included male sex (OR, 3.28), height (OR, 0.95), weight (OR, 0.97), attained age (OR, 0.98), cranial irradiation (OR, 2.07), and abdominal irradiation (OR, 1.61), yielding areas under the curve of 0.76 (95% CI, 0.73 to 0.78; SJLIFE cohort) and 0.75 (95% CI, 0.67 to 0.83; Dutch cohort). CONCLUSION Validated prediction models for low and very low BMD, using easily measured patient and treatment characteristics, correctly identified BMD status in most white adult survivors through age 40 years.

Low bone mineral density in children and adolescents with cancer

“…The prevalence of low BMD among CCS ranges from 9%-51%. [2][3][4] Multiple factors contribute to development of low BMD in patients with cancer, as described above. In a collaborative cohort study of St. Jude and Dutch CCS, shorter height, lower weight, younger attained age, use of alkylating agent, and prior exposure to cranial and abdominal irradiation were closely related with low BMD (z-score≤-1).…”

“…In a collaborative cohort study of St. Jude and Dutch CCS, shorter height, lower weight, younger attained age, use of alkylating agent, and prior exposure to cranial and abdominal irradiation were closely related with low BMD (z-score≤-1). 4) In children with cancer, treatments affect bone health during the first year, causing a significant decrease in BMD. BMD decreased during the first 6 months in patients with leukemia or lymphoma and during the latter 6 months of therapy for those with solid tumors.…”

“…The prevalence of low BMD among CCS ranges from 9%–51% [ 2 - 4 ]. Multiple factors contribute to development of low BMD in patients with cancer, as described above.…”

“…Previous studies have included small numbers of cases, various age groups, heterogeneous treatments, different sites of BMD measurement, and different definitions of low BMD. [2][3][4] The terminology and definitions of low BMD in CCS are diverse. The World Health Organization's (WHO) definitions of osteopenia and osteoporosis are based on T-scores, which are used to compare patient BMD with the maximum BMD of young adults, applying only to postmenopausal women.…”

“…CCS have increased risk of low bone mineral density (BMD) because cancer treatments interfere with gains in BMD. Previous studies have included small numbers of cases, various age groups, heterogeneous treatments, different sites of BMD measurement, and different definitions of low BMD [ 2 - 4 ]. The terminology and definitions of low BMD in CCS are diverse.…”