Impairment of Bone Health in Pediatric Patients with Hemolytic Anemia

Introduction Sickle cell anemia and thalassemia result in impaired bone health in both adults and youths. Children with other types of chronic hemolytic anemia may also display impaired bone health. Study Design To assess bone health in pediatric patients with chronic hemolytic anemia, a cross-sectional study was conducted involving 45 patients with different forms of hemolytic anemia (i.e., 17 homozygous sickle cell disease and 14 hereditary spherocytosis patients). Biochemical, radiographic and anamnestic parameters of bone health were assessed. Results Vitamin D deficiency with 25 OH-vitamin D serum levels below 20 ng/ml was a common finding (80.5%) in this cohort. Bone pain was present in 31% of patients. Analysis of RANKL, osteoprotegerin (OPG) and osteocalcin levels indicated an alteration in bone modeling with significantly elevated RANKL/OPG ratios (control: 0.08+0.07; patients: 0.26+0.2, P = 0.0007). Osteocalcin levels were found to be lower in patients compared with healthy controls (68.5+39.0 ng/ml vs. 118.0+36.6 ng/ml, P = 0.0001). Multiple stepwise regression analysis revealed a significant (P<0.025) influence of LDH (partial r2 = 0.29), diagnosis of hemolytic anemia (partial r2 = 0.05) and age (partial r2 = 0.03) on osteocalcin levels. Patients with homozygous sickle cell anemia were more frequently and more severely affected by impaired bone health than patients with hereditary spherocytosis. Conclusion Bone health is impaired in pediatric patients with hemolytic anemia. In addition to endocrine alterations, an imbalance in the RANKL/OPG system and low levels of osteocalcin may contribute to this impairment

Clinical characteristics, parameters of disease activity and bone health.

<p>Mean ± SD, (range) are displayed. Followed by the number of patients examined if different from total number. (Pubic hair stage SDS (PH SDS), testicular volume/breast development stage SDS (TV/breast stage SDS), Lactate dehydrogenase (LDH), bilirubin (bili), reticulocytes (retic), 25-OH vitamin D (25-OH Vit D), 1,25-(OH)₂ vitamin D (1,25-OH Vit D), serum alkaline phosphatase (SAP), bone alkaline phosphatase (BAP), parathyroid hormone (PTH), urinary N-terminal telopeptide (NTX), urinary deoxypyridinoline (DPD), urinary calcium:creatinine ratio (Ca:Crea), osteocalcin, insulin-like growth factor 1 SDS (IGF-1 SDS), receptor activator of nuclear factor kappa-B (RANKL), osteoprotegerin (OPG) and dual-energy X-ray absorptiometry (DXA) Z-Score) were assessed. P-values refer to Kruskal Vallis test (HBSS vs Spherocytosis vs Healthy controls) if values are available for all 3 groups, or to Wilcoxon-two-sample test if values are available for HBSS and Spherocytosis only (in cursive).</p><p>Clinical characteristics, parameters of disease activity and bone health.</p

Serum levels of 25-OH vitamin D levels positively correlate with calcium to creatinine ratio in urine (<i>P</i> = 0.03, r = 0.36) in patients with hemolytic anemia.

<p>The predicted values based on bivariate regression are indicated as solid line.</p

Serum 25-OH vitamin D levels are significantly lower in patients who report bone pain (back pain and/or knee pain with exercise) than in patients without reported bone pain (left).

<p>Statistically significant differences between the groups, determined via Mann-Whitney test, are indicated with asterisks (*: <i>P</i><0.05).</p