title: Predictors of osteoclast activity in patients with sickle cell disease.
abstract: 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.
  
  
  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.
authors.affiliation: Center for Sickle Cell Disease and Department of Medicine, Howard University, 1840 7th Street NW, Washington, DC 20001, USA. snouraie@howard.edu
authors.forename: Mehdi
authors.initials: M
authors.lastname: Nouraie
authors.forename: Kevin
authors.initials: K
authors.lastname: Cheng
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Niu
authors.forename: Evadne
authors.initials: E
authors.lastname: Moore-King
authors.forename: Margaret F
authors.initials: MF
authors.lastname: Fadojutimi-Akinsi
authors.forename: Caterina P
authors.initials: CP
authors.lastname: Minniti
authors.forename: Craig
authors.initials: C
authors.lastname: Sable
authors.forename: Sohail
authors.initials: S
authors.lastname: Rana
authors.forename: Niti
authors.initials: N
authors.lastname: Dham
authors.forename: Andrew
authors.initials: A
authors.lastname: Campbell
authors.forename: Gregory
authors.initials: G
authors.lastname: Ensing
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Kato
authors.forename: Mark T
authors.initials: MT
authors.lastname: Gladwin
authors.forename: Oswaldo L
authors.initials: OL
authors.lastname: Castro
authors.forename: Victor R
authors.initials: VR
authors.lastname: Gordeuk
mesh_terms: D000135:Acid Phosphatase / Q000097:blood; D000328:Adult; D000755:Anemia, Sickle Cell / Q000378:metabolism*; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000097:blood; D008297:Male; D008875:Middle Aged; D010010:Osteoclasts / Q000378:metabolism*; D012016:Reference Values; D000071681:Tartrate-Resistant Acid Phosphatase
chemical_list: D015415:Biomarkers; D007527:Isoenzymes; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase