Severity of reduced bone mineral density and risk of fractures in long‐term survivors of childhood leukemia and lymphoma undergoing guideline‐recommended surveillance for bone health

Abstract

Background Survivors of childhood leukemia/lymphoma are at increased risk for reduced bone mineral density (BMD). The authors sought to determine the frequency of reduced BMD detected by off‐therapy surveillance, factors associated with reduced BMD, and the association of reduced BMD with fractures. Methods This cross‐sectional study included childhood leukemia/lymphoma survivors attending 2 survivorship clinics who received guideline‐recommended BMD surveillance ≥2 years post‐therapy with dual‐energy x‐ray absorptiometry (from January 1, 2004 to August 31, 2016). Lumbar spine BMD z‐scores were height‐for‐age–adjusted. Low and very low BMD were >1 SD and >2 SDs below norms, respectively. Treatment, chronic conditions, and fractures were abstracted from medical records. Logistic regression was used to examine the association of low BMD with patient/treatment factors and fractures. Results In total, 542 patients (51.5% female) with a mean age of 15.5 years (range, 4.4‐52.2 years) who were 6 years post‐therapy (range, 2.0‐35.1 years) were evaluated, including 116 who reported post‐therapy fractures. Lumbar spine low BMD was identified in 17.2% of survivors, and very low BMD was identified in 3.5% of survivors, but frequencies varied considerably between subgroups; 10.8% of survivors aged 15 to 19 years at diagnosis had very low BMD. In multivariable analyses, older age at diagnosis, white race, and being underweight were significantly associated with low BMD. Survivors with low BMD had greater odds of nondigit fractures (odds ratio, 2.2; 95% CI, 1.3‐3.7) and specifically long‐bone fractures (odds ratio, 2.7; 95% CI, 1.5‐4.7). Conclusions In this study of childhood leukemia/lymphoma survivors undergoing guideline‐recommended dual‐energy x‐ray absorptiometry surveillance, patients who were older at diagnosis, white, and underweight were at the highest risk for lumbar spine low BMD. Low BMD was associated with a greater risk of fractures, emphasizing the clinical importance of surveillance.

Prevalence and risk factors for vitamin D deficiency in long‐term childhood cancer survivors

“…3 Survivors with low bone mineral density (BMD) have a greater than twofold risk of developing fractures compared to those with normal BMD. 3 This risk is likely multifactorial in CCS, including treatment exposures and co-morbid late effects in addition to the established risk factors in the nononcology population. 4 In the general population, vitamin D replacement in individuals who have deficiency is associated with improved BMD, 5 which is associated with reduced risk of fractures.…”

“…In these survivors, the burden of chronic health conditions, including metabolic and musculoskeletal disease, is substantial. It is estimated that by 10 years after completion of cancer‐directed therapy, up to 20% of CCS will develop at least one pathologic fracture 3 . Survivors with low bone mineral density (BMD) have a greater than twofold risk of developing fractures compared to those with normal BMD 3 .…”

Low bone mineral density in children and adolescents with cancer

“…40) Also, 10.8% of survivors aged 15-19 years at diagnosis had very low BMD (z-score <-2), indicating that those of an older age were at high risk for low BMD. 40) A pharmacogenetic study evaluated the influence of single nucleotide polymorphisms in 4 genes (i.e., vitamin D receptor, collagen type I alpha 1, estrogen receptor 1, and glucocorticoid receptor) on body composition, BMD, and fracture risk. The vitamin D receptor gene (VDR) 5'-end (Cdx-2/GATA) haplotype 3 was a risk factor for lower lumbar spine BMD during treatment of pediatric ALL.…”

“…Chemotherapy for ALL includes corticosteroids and methotrexate, and a decrease in BMD occurs during chemotherapy. In a study of childhood leukemia and lymphoma survivors, lumbar spine BMD was low ( z -score <-1) in 17.2% of subjects [ 40 ]. Also, 10.8% of survivors aged 15–19 years at diagnosis had very low BMD ( z -score <-2), indicating that those of an older age were at high risk for low BMD [ 40 ].…”

“…In a study of childhood leukemia and lymphoma survivors, lumbar spine BMD was low ( z -score <-1) in 17.2% of subjects [ 40 ]. Also, 10.8% of survivors aged 15–19 years at diagnosis had very low BMD ( z -score <-2), indicating that those of an older age were at high risk for low BMD [ 40 ]. A pharmacogenetic study evaluated the influence of single nucleotide polymorphisms in 4 genes (i.e., vitamin D receptor, collagen type I alpha 1, estrogen receptor 1, and glucocorticoid receptor) on body composition, BMD, and fracture risk.…”