Influence of Chronic Therapies on Bone Mineral Density In Children with Sickle Cell Anemia.

Children with sickle cell anemia (SCA) have increased risk of developing osteoporosis at a young age. Neither the etiology nor the prevalence of osteoporosis in this population is well understood. Chronic therapies, such as hydroxyurea (HU) or chronic red blood cell transfusions (CRBCT) are used to prevent and/or treat acute and chronic complications in children with SCA. However, little is known about the effects of these treatment modalities on bone mineral density (BMD). The current study aimed to explore in detail, the patho-physiology of bone mineral metabolism in 3 groups of pediatric patients; those receiving either HU or PRBC or supportive care only.

The main objectives of this study were 1) to determine the prevalence of osteoporosis in children with SCA, 2) to determine if differences exist between the 3 groups with regards to bone mineral density. Other aims were to assess trends in markers of bone metabolism and other inflammatory markers in relation to treatment modalities and bone mineral density.

Children with SCA ≥ age 10 years receiving HU or CRBCT or supportive care were considered for eligibility for this cross sectional study. Patients were excluded if they were on chronic daily steroids, had a history of avascular hip necrosis, or were non-ambulatory. Data collected included demographic information, body composition, pubertal staging, clinical markers of disease severity (pain crises, episodes acute chest syndrome etc), bone mineral density (DEXA z-scores, Hologic), and biochemical markers of bone metabolism (calcium, phosphorous, alkaline phosphatase, parathyroid hormone, urine Ca/Cr ratio, osteocalcin, osteoprogerin, and urine N-telopeptide and RANK-L ligand).

Thirty five children with SCA (Hb-SS) were included in the study. The mean age was 14 years (range 10–21 years) and 31% (11) were males. Fifteen children were on CRBCT, 12 patients were taking HU and 8 were receiving supportive care only. There were no differences in age, sex, body mass index and Tanner staging between these groups. All patients were found to be vitamin D deficient (serum 25(OH) vitamin D < 30ng/ml). Overall 11 (31%) patients had osteoporosis as defined by z-score of less than -2.0. Patients on CRBCT had a lower prevalence rate of osteoporosis (20%) and increased BMD than both the supportive group (38%) and the HU (42%) group (Table 1). However, there was no significant difference in vitamin D status, markers of bone turnover and hyperresorption among these three groups. In addition, there was no correlation between BMD and disease severity (pain crises, episodes acute chest syndrome etc), Vitamin D status and markers of bone resorption.

The prevalence of osteoporosis in our cohort of children with SCA is 31%. To our knowledge, this is the first study to evaluate BMD in children with SCA according to various modalities of treatment. CRBCT group had a lower prevalence of osteoporosis and increased BMD compared to the other 2 groups. This; however, was not statistically significant which could be due to a small sample size. The decrease in BMD in our cohort was not related to advancing age, pubertal status, vitamin D deficiency, and bone hyperresorption or disease severity suggesting abnormal bone formation as the underlying mechanism. Larger studies are needed to identify the difference in BMD amongst these treatment groups.

No relevant conflicts of interest to declare.