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.

FIG 1.

Flow diagram of study participants. DXA, dual-energy x-ray absorptiometry; LS, lumbar spine; SJLIFE, St Jude Lifetime Cohort; TB, total body.

FIG 2.

Receiver operating characteristic curves of the prediction models for (A) low bone mineral density (BMD) and (B) very low BMD in the St Jude Lifetime Cohort (SJLIFE) development cohort and Dutch validation cohort.

FIG A1.

Distribution of (A) lumbar spine bone mineral density (BMD) z scores and (B) total-body BMD z scores in the St Jude Lifetime (SJLIFE) development cohort and Dutch validation cohort.