Bone Mineral Density in Children with Sickle Cell Disease (SCD) Is Low and Not Related to Disease Severity, Vitamin D Status, or Bone Hyperresorption
Authors: Chapelon Emeline , Garabedian Michele , Brousse Valentine , Souberbielle Jean-Claude , Bresson Jean-Louis , De Montalembert Mariane 
Published: April 2020

Abstract
Background: SCD is characterized by HbS polymerization, chronic hemolytic anemia, and recurrent acute painful episodes. Recent data have established that SCD patients have chronic inflammation, with endothelium activation related to hypoxia/reoxygenation cycles and reperfusion injury, increased inflammatory markers, and enhanced endothelium adhesion of red cells and leukocytes. The bone is a key target of SCD, being the site of both acute events (painful crises and infections) and chronic changes. Osteopenia and osteoporosis are reported in 30 to 40% of adults with SCD. By analogy with thalassemia, bone marrow hyperplasia secondary to chronic anemia has been hypothesized to be a causative factor. The prevalence of low bone mineral density (BMD) is not known in children.
Aim: We assessed BMD in a cohort of SCD children and looked for correlations between BMD and age, gender, SCD severity, growth and pubertal development, serum vitamin D, calcium intake, and markers of bone turnover.
Methods: Fifty-three children (45 SS, 4 SC, 4 Sb-thalassemia), 27 females, and 26 males, with a mean age of 12.8±2.4 y (9–19 y) were enrolled between 2002 and 2006. They originated from: West and Central Africa (n=41), the Caribbean (n=8), North Africa (n=3), and Brazil (n=1). We assessed height; weight; sexual maturation (Tanner); number of hospitalizations and of painful crises and of transfusions in the last 3 years; calcium intake; steady-state hemoglobin (Hb) and leukocyte count; calcemia, phosphatemia, calciuria/creatinuria; 25-OH D and PTH concentrations; osteocalcin, urinary deoxypyridinolin (DPD) and C-terminal component of pro-collagen type I (CTX). BMD was assessed using a dual X-ray absorptiometry (DXA).
Results: In the overall population, mean lumbar spine z-score was −1.1±1.3 (−3.9–1.8), females had non-significantly lower values (−1.42±0.29) than males (−0.77±0.28). In prepubertal children, lumbar spine z-score was lower in females (−1.74±0.27) than in males (−0.53±0.31) (p=0.01). BMD did not correlate with hospitalization and transfusion episodes, Hb, or leukocytes counts. Hb and leukocyte count were inversely correlated (p=0.02) and leukocytosis was correlated to the number of hospitalizations (p&lt;0.0001). Vitamin D deficiency (25-OH D&lt;10 ng/ml) was found in 72% of patients and secondary hyperparathyroidism (PTH&gt;46 pg/ml) in 38%. BMD was not related to calcium intake, vitamin D status, osteocalcin, or bone resorption markers. The normal or low osteocalcin and CTX values argue against increased bone resorption as the cause of the low BMD. Mean serum IGF concentrations measured in 7 children were low (134±98 ng/ml)
Conclusion: A slight decrease of BMD was observed in SCD children, starting before puberty and being more marked in females. This low BMD was not related to the disease severity or to bone hyperresorption, suggesting that biphosphonates would be unhelpful. Neither was it related to vitamin D deficiency. The most likely cause is abnormal bone formation. Future research should focus on the mechanisms involved, with the goal of preventing osteoporosis in adults with SCD.