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Predictors of osteoclast activity in sickle cell disease patients.
MedLine Citation:
PMID:  21546502     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Background. 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 sickle cell disease patients. Design and Methods. We examined tartrate-resistant acid phosphatase 5b concentrations in sickle cell disease patients 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 by the Bio-Plex suspension array system. Tricuspid regurgitation velocity, an indirect measure of systolic pulmonary artery pressure, was determined by echocardiography. Results. Tartrate-resistant acid phosphatase 5b concentrations were higher in 58 adult sickle cell disease patients than 22 controls (medians of 4.4 vs. 2.4 U/L, P=0.0001). Among sickle cell disease patients, 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), but not serum ferritin concentration. Frequent blood transfusions (>10 units in life time) were not associated with higher tartrate-resistant acid phosphatase 5b in multivariate analysis. There were strong correlations among tartrate-resistant acid phosphatase 5b, alkaline phosphatase and tricuspid regurgitation velocity (r>0.35, P<0.001). Conclusion. Sickle cell disease patients have increased osteoclast activity as reflected in serum tartrate-resistant acid phosphatase 5b concentrations. Our results may support a potential role of inflammation rather than increased iron stores in stimulating osteoclast activity in sickle cell disease patients. The positive relationships among tartrate-resistant acid phosphatase 5b, alkaline phosphatase and tricuspid regurgitation velocity raise the possibility of a common pathway in the pulmonary and bone complications of sickle cell disease.
Authors:
Mehdi Nouraie; Kevin Cheng; Xiaomei Niu; Evadne Moore-King; Margaret F Fadojutimi-Akinsi; Caterina P Minniti; Craig Sable; Sohail Rana; Niti Dham; Andrew Campbell; Gregory Ensing; Gregory J Kato; Mark T Gladwin; Oswaldo L Castro; Victor R Gordeuk
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-5-5
Journal Detail:
Title:  Haematologica     Volume:  -     ISSN:  1592-8721     ISO Abbreviation:  -     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-5-6     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0417435     Medline TA:  Haematologica     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Howard University, USA;
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