Vitamin D status and bone biomarkers in childhood cancer

Early detection of abnormalities in bone turnover may be facilitated by assessing biomarkers of bone metabolism including vitamin D status. In many children with cancer, biomarkers of bone formation (osteocalcin, bone specific alkaline phosphatase and carboxy-(or N terminal) propeptide of type 1 procollagen) were observed to be suppressed, while bone resorption was elevated as measured by serum cross-linked (or C-terminal) telopeptide of type 1 collagen. Insulin-like growth factor 1, which stimulates bone formation, may be suppressed indirectly indicating a growth hormone insufficiency. Leptin may also play a role in bone remodeling as hyperleptinemia has been observed in association with acute lymphoblastic leukemia. Evaluation of bone status using such biomarkers is complicated by the lack of universally accepted reference values and the variation by age, gender, or pubertal status. Etiologic factors contributing to the observed skeletal morbidities include disease process, chemotherapy (drugs such as glucocorticoids and methotrexate) and radiotherapy. Other factors common to children with cancer, such as chronic inflammation, dietary changes and physical inactivity, must also be taken into account. The current evidence for abnormalities in biomarkers of vitamin D status and bone turnover will be the focus of this review of published studies.