Predictors of osteoclast activity in patients with sickle cell disease

• Published in: Haematologica (Roma) 2011-08, Vol.96 (8), p.1092-1098
• Main Authors: Nouraie, Mehdi, Cheng, Kevin, Niu, Xiaomei, Moore-King, Evadne, Fadojutimi-Akinsi, Margaret F, Minniti, Caterina P, Sable, Craig, Rana, Sohail, Dham, Niti, Campbell, Andrew, Ensing, Gregory, Kato, Gregory J, Gladwin, Mark T, Castro, Oswaldo L, Gordeuk, Victor R
• Format: Article
• Language: English
• Subjects: Acid Phosphatase - blood; Adult; Anemia, Sickle Cell - metabolism; Anemias. Hemoglobinopathies; Biological and medical sciences; Biomarkers - blood; Case-Control Studies; Diseases of red blood cells; Female; Hematologic and hematopoietic diseases; Humans; Isoenzymes - blood; Male; Medical sciences; Middle Aged; Original; Osteoclasts - metabolism; Reference Values; Tartrate-Resistant Acid Phosphatase
• ISSN: 0390-6078; 1592-8721
• DOI: 10.3324/haematol.2011.042499

Bone changes are common in sickle cell disease, but the pathogenesis is not fully understood. Tartrate-resistant acid phosphatase (TRACP) type 5b is produced by bone-resorbing osteoclasts. In other forms of hemolytic anemia, increased iron stores are associated with osteoporosis. We hypothesized that transfusional iron overload would be associated with increased osteoclast activity in patients with sickle cell disease. We examined tartrate-resistant acid phosphatase 5b concentrations in patients with sickle cell disease and normal controls of similar age and sex distribution at steady state. Serum tartrate-resistant acid phosphatase 5b concentration was measured using an immunocapture enzyme assay and plasma concentrations of other cytokines were assayed using the Bio-Plex suspension array system. Tricuspid regurgitation velocity, an indirect measure of systolic pulmonary artery pressure, was determined by echocardiography. Tartrate-resistant acid phosphatase 5b concentrations were higher in 58 adults with sickle cell disease than in 22 controls (medians of 4.4 versus 2.4 U/L, respectively; P=0.0001). Among the patients with sickle cell disease, tartrate-resistant acid phosphatase 5b independently correlated with blood urea nitrogen (standardized beta=0.40, P=0.003), interleukin-8 (standardized beta=0.30, P=0.020), and chemokine C-C motif ligand 5 (standardized beta=-0.28, P=0.031) concentrations, but not with serum ferritin concentration. Frequent blood transfusions (>10 units in life time) were not associated with higher tartrate-resistant acid phosphatase 5b levels in multivariate analysis. There were strong correlations among tartrate-resistant acid phosphatase 5b, alkaline phosphatase and tricuspid regurgitation velocity (r>0.35, P