Bone mineral density among long‐term survivors of childhood acute lymphoblastic leukemia: Results from the St. Jude Lifetime Cohort Study

Abstract

Background The prevalence of low bone mineral density (BMD) in adult survivors of childhood acute lymphoblastic leukemia (ALL), and the degree of recovery or decline, are not well elucidated. Procedure Study subjects (age ≥ 18 years and ≥ 10 years post-diagnosis) participated in an institutional follow-up protocol and risk-based clinical evaluation based on Children’s Oncology Group guidelines. Trabecular volumetric BMD was ascertained using quantitative computed tomography, reported as age- and sex-specific Z-scores. Results At median age 31 years, 5.7% of 845 subjects had a BMD Z-score of ≤ - 2 and 23.8% had a Z-score of - 1 to -2. Cranial radiation dose of ≥ 24 Gray, but not cumulative methotrexate or prednisone equivalence doses, was associated with a 2-fold elevated risk of a BMD Z-score of ≤ -1. The cranial radiation effect was stronger in females than in males. In a subset of 400 subjects, 67% of those who previously had a BMD Z-score of ≤ -2 improved by one or more categories a median of 8.5 years later. Conclusions Very low BMD was relatively uncommon in this sample of adult survivors of childhood ALL, and BMD Z-scores tended to improve from adolescence to young adulthood. High dose cranial or craniospinal radiation exposure was the primary predictor of suboptimal BMD in our study. Given that cranial radiation treatment for childhood ALL is used far more sparingly now than in earlier treatment eras, concerns about persistently low BMD among most current childhood ALL patients may be unwarranted.

DIAGNOSIS OF ENDOCRINE DISEASE: Endocrine late-effects of childhood cancer and its treatments

“…Prolonged treatment with high-dose glucocorticoids in children with ALL may also result in acute complications such as vertebral body compression fractures and avascular necrosis of the bones (165,166). Skeletal recovery was noted to begin shortly after the completion of ALL treatments, but BMD may remain abnormally low for age over several years depending on a variety of factors such as the severity of the deficit at baseline, the presence of other chronic health issues and lifestyle variables (165,166,167 (179,180). Changes in bone remodeling and secondary hyperparathyroidism have been recently described in patients treated with TKI (8).…”

Are Survivors of Childhood Acute Lymphoblastic Leukemia at Increased Risk for Low Bone Mass?

“…As an increasing number of cancer survivors reaches adulthood, there may be consequences of the treatment, including adiposity, metabolic syndrome traits [2][3][4][5][6][7][8][9] and occasionally low bone mass [10][11][12][13][14][15][16][17][18], which is a condition not totally understood, so far.…”

“…Cancer survivors, particularly ALL patients, are part of one of these important groups and there are several important concerns regarding their bone heath [10][11][12][13][14][15][16][17][18][19]. Low bone mass has been observed in all phases of the disease: at diagnosis, during treatment, and throughout the post-treatment period for as long as 20 years [21].…”

“…Several pediatric conditions may have an increased risk for low bone mass, which is attributed to the disease itself, genetic characteristics, intensive therapy against the disease [10][11][12][13][14][15][16][17][18][19], as well as body composition modifications [20]. Cancer survivors, particularly ALL patients, are part of one of these important groups and there are several important concerns regarding their bone heath [10][11][12][13][14][15][16][17][18][19].…”

Atypical Presentation of Acute Lymphoblastic Leukemia in a 7 Year Old Child

“…In addition, various inflammatory cytokines like tumor necrosis factor alpha (TNF-a), interleukins are released and results in bone erosion [8]. Furthermore, the drugs used for treatment mainly steroids, methotrexate and radiotherapy cause osteoporosis in ALL [6,10]. The radiographic changes described in ALL include osteopenia, metaphyseal bands, periosteal new bone formation, geographic osteolysis, osteosclerosis, mixed osteolysis-sclerosis and permeative destruction [6,11].At diagnosis, vertebral fracture is seen 16 % of children with ALL.…”