The Predictive Value of Vitamin D Serum Concentration for Osteopenia and Fractures in Children with Hematological Malignancies

Background -Impaired bone mineral density (BMD) is a frequently reported side-effect of patients with childhood cancer. Vitamin D deficiency is suggested to be a risk factor for diminished BMD and fractures during and after cessation of treatment of childhood hematological malignancies.

Objective - The aim of our study was to assess the predictive value of a deficient vitamin D serum concentrations for osteopenia and fractures in children with hematological malignancies during and after cessation of treatment.

Methods - An extensive literature search was conducted in PubMed, Embase and Cochrane databases. Studies with a prospective study design and written in English, Dutch, French or German, addressing children with hematological malignancies were considered eligible if vitamin D and bone mineral density and/or fractures were measured at baseline and during/after cessation of treatment.

Results - A total of 923 articles were identified. After screening and critical appraisal, ten articles (n=16-43, mean/ median age 3.9-11.2 years) were eligible for quantitative analysis. Five studies showed deficient 25-OHD and/or 1,25(OH)₂D levels, ranging from 8.5-46 ng/ml and 12.3-75 pg/ml, respectively. In all these cases, levels were already deficient at baseline.

No studies adressed the predicitive value of vitamin D on fracture risk. All studies except one investigating BMD found decreased BMD Z-scores both at baseline and at follow-up, ranging from 0.70- -2.3 and -0.21- -2.4. Only four studies assessed the relation between vitamin D status and low BMD, of which just two corrected for possible confounders. Of these studies, one reported a positive correlation of serum 25-OHD at follow-up and subtotal body BMD (R=0.39-0.42, p<0.03), whereas the others found no relation.

Conclusion - Based on the available evidence consisting of small studies, deficient vitamin D serum concentration cannot be conceived to be a predictor of impaired BMD and fractures during and after cessation of treatment in children with hematological malignancies. However, one studie reported a positive correlation and both vitamin D levels and BMD were often decreased, implying a relation. Larger studies addressing vitamin D as an independent risk factor should be conducted.