Bone Mineral Density and Dickkopf-1 in Adolescents with Non-deletional Hemoglobin H Disease

Background: Low bone mineral density (BMD) is prevalent in individuals with β-thalassemia which might be related to increased circulating dickkopf-1 (Dkk-1). These data are limited in α-thalassemia. Objectives: To evaluate the prevalence of low BMD in adolescents with non-deletional hemoglobin (Hb) H disease. Additionally, we aimed to examine the association between serum Dkk-1 concentration and BMD. Methods: : Participant medical records were reviewed. The lumbar spine (LS) and total body (TB) BMD were measured and converted into height-adjusted z-scores. Serum Dkk-1, osteocalcin and C-telopeptide of type-I collagen (CTX) concentrations were also analyzed. Results: : Thirty-seven participants (59% female, 86% Tanner stage ≥2, 95% regularly transfused) had mean age 14.6 ± 3.2 years, and average pretransfusion Hb and ferritin concentrations of 8.8 ± 1.0 g/dL and 958 ± 513 ng/mL, respectively. No participants had experienced fracture. The prevalence of low LSBMD and TBBMD was 42% and 17%, respectively. LSBMD z-score was lower in males vs. females (p-value = 0.029). LSBMD and TBBMD z-scores were correlated positively with BA, Tanner stage, and BMI, and negatively with Dkk-1 (p-values <0.05). Dkk-1 was correlated positively with history of delayed puberty, and negatively with transfusion interval (p-values = 0.038). Osteocalcin and CTX did not correlate with BMD or Dkk-1. Multiple regression analysis showed Dkk-1 inversely associated with TBBMD z-score adjusting for confounders (p-value = 0.009). Conclusions: : We demonstrated a high prevalence of low BMD in adolescents with non-deletional Hb H disease. Moreover, Dkk-1 inversely associated with TBBMD suggesting it may serve as bone biomarker in thalassemia.