Document Detail

Predictors of osteoclast activity in patients with sickle cell disease.
MedLine Citation:
PMID:  21546502     Owner:  NLM     Status:  MEDLINE    
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 patients with sickle cell disease.
DESIGN AND METHODS: 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.
RESULTS: 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<0.001).
CONCLUSIONS: Patients with sickle cell disease have increased osteoclast activity as reflected by 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. 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.
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; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural     Date:  2011-05-05
Journal Detail:
Title:  Haematologica     Volume:  96     ISSN:  1592-8721     ISO Abbreviation:  Haematologica     Publication Date:  2011 Aug 
Date Detail:
Created Date:  2011-08-03     Completed Date:  2011-12-07     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  0417435     Medline TA:  Haematologica     Country:  Italy    
Other Details:
Languages:  eng     Pagination:  1092-8     Citation Subset:  IM    
Center for Sickle Cell Disease and Department of Medicine, Howard University, 1840 7th Street NW, Washington, DC 20001, USA.
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MeSH Terms
Acid Phosphatase / blood
Anemia, Sickle Cell / metabolism*
Biological Markers / blood
Case-Control Studies
Isoenzymes / blood
Middle Aged
Osteoclasts / metabolism*
Reference Values
Grant Support
1R01 HL079912-02/HL/NHLBI NIH HHS; 1ZIAHL006016.//PHS HHS; 2 R25 HL003679-08/HL/NHLBI NIH HHS; 2M01 RR10284-10/RR/NCRR NIH HHS; Z01 CL008098-01/CL/CLC NIH HHS; Z01 CL008098-02/CL/CLC NIH HHS; ZIA HL006016-01/HL/NHLBI NIH HHS; ZIA HL006016-02/HL/NHLBI NIH HHS
Reg. No./Substance:
0/Biological Markers; 0/Isoenzymes; EC 3.1.3.-/tartrate-resistant acid phosphatase; EC Phosphatase

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