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Models correctly predict low bone mineral density among adult childhood cancer survivors
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Validated prediction models accurately identified low and very low bone mineral density among young, white adult survivors of childhood cancer, according to results of a study published in Journal of Clinical Oncology.
“Adult survivors of childhood cancer are at risk for low bone mineral density (BMD) as a result of disturbances in bone metabolism during childhood or adolescence, which may inhibit attainment of peak bone mass,” Jenneke E. van Atteveld, MD, pediatrician at Princess Maxima Center for Pediatric Oncology in the Netherlands, and colleagues wrote. “Although many studies have identified risk factors for low BMD among survivors of childhood cancer, no prediction model has been developed, and the optimal surveillance strategy for survivors at risk for low BMD has not been established.”
Van Atteveld and colleagues sought to develop and validate prediction models that could identify young adult survivors of childhood cancer at risk for low or very low BMD based on patient characteristics and previous cancer treatment.
The study included a development cohort of 2,032 white survivors of childhood cancer (median age, 29.3 years; range, 18.2-40.9) in the St. Jude Lifetime Cohort Study, which monitors childhood cancer survivors with periodic clinical assessments.
The validation cohort included 403 childhood cancer survivors (median age, 24.2 years; range, 18-40.9) treated at Erasmus Medical Center in the Netherlands.
Researchers evaluated all survivors using dual-energy X-ray absorptiometry to determine lumbar spine BMD and total body BMD.
They defined low BMD as lumbar spine and/or total body BMD z score of -1 or lower, and
very low BMD as lumbar spine and/or total body BMD z score of -2 or lower.
Results showed 51% of patients from the St. Jude development cohort and 45% of patients in the Dutch validation cohort had low BMD. Researchers observed very low BMD among 20% of the St. Jude cohort and 10% of the Dutch cohort.
Predictors for low BMD — identified through backward multivariable logistic regression analysis — included male sex (OR = 3.07; 95% CI, 2.35-4.02), shorter height (OR = 0.95; 95% CI, 0.93-0.96), lower weight (OR = 0.98; 95% CI, 0.97-0.98), younger attained age (OR = 0.97; 95% CI, 0.96-0.99), current smoking status (OR = 1.48; 95% CI, 1.19-1.85) and cranial irradiation (OR = 2.11; 95% CI, 1.69-2.63). Areas under the curve were 0.72 (95% CI, 0.7-0.75) in the St. Jude development cohort and 0.69 (95% CI, 0.64-0.75) in the Dutch validation cohort.
Predictors for very low BMD included male sex (OR = 3.28; 95% CI, 2.37-4.54), shorter height (OR = 0.95; 95% CI, 0.93-0.96), lower weight (OR = 0.97; 95% CI, 0.96-0.98), younger attained age (OR = 0.98; 95% CI, 0.96 to 1), cranial irradiation (OR = 2.07; 95% CI, 1.59-2.68) and abdominal irradiation (OR = 1.61; 95% CI, 1.23-2.11). Areas under the curve were 0.76 (95% CI, 0.73-0.78) in the St. Jude cohort and 0.75 (95% CI, 0.67-0.83) in the Dutch cohort.
Possible selection bias in the Dutch cohort and a lack of diversity served as study limitations. The results must be validated among childhood cancer survivors of other races and ethnicities, researchers noted.
“Because these models identify most survivors with low BMD correctly, we consider their use a reasonable tool for personalized diagnostics and surveillance,” van Atteveld and colleagues wrote. “For patients with confirmed deficits, targeted treatment directed at improving bone health and preventing fractures among this vulnerable population can be provided.”
Several questions need to be considered before the model can be recommended for general use, Roderick Skinner, MbChB, PhD, consultant in pediatric and adolescent oncology/bone marrow transplantation and honorary professor of childhood cancer at Great North Children’s Hospital and Northern Institute for Cancer Research at Newcastle University in the United Kingdom, wrote in an accompanying editorial.
These questions include whether the model could be improved by the inclusion of data from ethnically diverse patients and additional risk factors and whether the balance of sensitivity vs. specificity is appropriate.
“Perhaps the biggest question is as yet largely unanswered: How effective are lifestyle, pharmacologic and endocrine interventions at improving reduced BMD and reducing future fracture risk?” Skinner wrote. “In this respect, it is pertinent to remind ourselves that the seeds of osteoporosis in childhood cancer survivors are laid in childhood and that the most effective interventions, therefore, will be those implemented during puberty, when most bone mass is accrued, which highlights the important need for effective surveillance strategies to detect reduced BMD before adult age served by this model.” – by John DeRosier
Disclosures: Van Atteveld reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures. Skinner reports a consultant/advisory role with Clinigen.
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