Prevalence of Osteopathologies in Children and Adolescents After Diagnosis of Acute Lymphoblastic Leukemia

Abstract

Background: Impaired bone health is a late effect of childhood malignancies which can be difficult to detect in juvenile survivors. It may, however, lead to compromised quality of life, or even permanent disability later in life due to osteoporosis, pain or fractures if left untreated. Acute lymphoblastic leukemia (ALL) is the most frequent childhood malignancy with an over 85% five-year survival. ALL and its treatment cause bone alterations in adults, but little information on the bone health status in juvenile survivors is available. Objective: To report data on skeletal late effects in juvenile survivors of childhood ALL based on a comprehensive assessment of bone health and to assess the influence of a vitamin D deficiency on bone health in this cohort. Methods: In a single center cross sectional study 128 pediatric patients (11.9 ± 4.76 years) with a mean follow up of 5.88 ± 3.75 years after diagnosis of ALL were recruited. The bone health status of the survivors was assessed based on clinical examination, review of medical records, biochemical and radiographic analyses, by clinical experts. A score which utilized 8 different parameters was formed and used to assess the effect of a vitamin D deficiency on bone health. Results: In this cohort, 18% of survivors displayed overt osteopathologies as defined by clinical expert assessment. Impaired bone health, defined by at least one pathological screening parameter, was detected in 77%. Despite recommendations for adequate vitamin D supplementation, 15% displayed a vitamin D deficiency associated with hyperparathyroidism. The applied score identified survivors with osteopathologies with high sensitivity and specificity. The median score did not differ between patients without and with severe vitamin D deficiency. Conclusion: Our findings suggest that impaired bone health and osteopathologies are common skeletal late effects following treatment of childhood ALL. Major contributing factors are BMT, irradiation and older age at diagnosis. Vitamin D deficiency likely Schündeln et al. Osteopathologies After Acute Lymphoblastic Leukemia accounts for hyperparathyroidism in some patients but does not seem to further affect bone health in this cohort. Survivors of ALL need thorough surveillance to investigate bone health, since bone morbidity is common and still poorly understood. Early detection and appropriate intervention may improve bone health.

Prevalence of osteopathologies in a single center cohort of survivors of childhood primary brain tumor

“…In some cases, information was missing and in many cases data was unconcise. This was comparable to our experience with the data in survivors of childhood ALL ( 15 ) and reflects the complexity and difficulty of the task to identify those survivors in need for attention for bone health issues in the routine clinic [as recently reviewed by Marcucci et al ( 14 )].…”

“…The frequency of aberrant biochemical and radiological findings based on normative values as described in Schündeln et al ( 15 ) are summarized in Table 3 . Overall in 65% of patients any kind of bone health impairment was detected.…”

“…The assessment process of defining the bone health status for the purpose of this study has been previously described in detail ( 15 ) The terms “osteopathology” and “impaired bone health” are being used in this manuscript to describe different levels of skeletal late effects. The term “osteopathology” refers to overt bone disease and the term “impaired bone health” refers to a condition with at least one pathological reading in selected parameters of bone health, as displayed in Table 3 .…”

“…Closely related to the endocrine late effects, bone health has been shown to be impaired in a significant number of children and adults surviving pediatric malignancies ( 14 , 15 ). Adolescent survivors of CPBTs are prone to osteoporosis as reported by Cohen et al ( 16 ) and Remes et al ( 17 ).…”

“…To date the onset of osteopathologies in survivors of childhood malignancies is not yet well characterized. Recent studies in ALL indicate that impaired bone health may be observed as early as at the time of manifestation of the malignancy ( 18 , 19 ) and is present in many survivors during follow-up ( 15 ).…”