Predictors of osteoclast activity in patients with 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

Research output: Contribution to journalArticle

9 Citations (Scopus)

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. 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 tartrateresistant 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 tartrateresistant 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.

Original languageEnglish (US)
Pages (from-to)1092-1098
Number of pages7
JournalHaematologica
Volume96
Issue number8
DOIs
StatePublished - Aug 2011
Externally publishedYes

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Sickle Cell Anemia
Osteoclasts
Tricuspid Valve Insufficiency
Acid Phosphatase
Bone and Bones
Alkaline Phosphatase
Iron
Serum
CC Chemokines
Sex Distribution
Iron Overload
Blood Urea Nitrogen
Hemolytic Anemia
Age Distribution
Enzyme Assays
Ferritins
Tartrate-Resistant Acid Phosphatase
Interleukin-8
Blood Transfusion
Pulmonary Artery

Keywords

  • Bone turnover
  • Inflammation
  • Osteoclast activity
  • Pulmonary complications
  • Sickle cell disease
  • TRACP 5b

ASJC Scopus subject areas

  • Hematology

Cite this

Nouraie, M., Cheng, K., Niu, X., Moore-King, E., Fadojutimi-Akinsi, M. F., Minniti, C. P., ... Gordeuk, V. R. (2011). Predictors of osteoclast activity in patients with sickle cell disease. Haematologica, 96(8), 1092-1098. https://doi.org/10.3324/haematol.2011.042499

Predictors of osteoclast activity in patients with sickle cell disease. / 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.

In: Haematologica, Vol. 96, No. 8, 08.2011, p. 1092-1098.

Research output: Contribution to journalArticle

Nouraie, M, Cheng, K, Niu, X, Moore-King, E, Fadojutimi-Akinsi, MF, Minniti, CP, Sable, C, Rana, S, Dham, N, Campbell, A, Ensing, G, Kato, GJ, Gladwin, MT, Castro, OL & Gordeuk, VR 2011, 'Predictors of osteoclast activity in patients with sickle cell disease', Haematologica, vol. 96, no. 8, pp. 1092-1098. https://doi.org/10.3324/haematol.2011.042499
Nouraie M, Cheng K, Niu X, Moore-King E, Fadojutimi-Akinsi MF, Minniti CP et al. Predictors of osteoclast activity in patients with sickle cell disease. Haematologica. 2011 Aug;96(8):1092-1098. https://doi.org/10.3324/haematol.2011.042499
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. / Predictors of osteoclast activity in patients with sickle cell disease. In: Haematologica. 2011 ; Vol. 96, No. 8. pp. 1092-1098.
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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. 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 tartrateresistant 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 tartrateresistant 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.",
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AU - Nouraie, Mehdi

AU - Cheng, Kevin

AU - Niu, Xiaomei

AU - Moore-King, Evadne

AU - Fadojutimi-Akinsi, Margaret F.

AU - Minniti, Caterina P.

AU - Sable, Craig

AU - Rana, Sohail

AU - Dham, Niti

AU - Campbell, Andrew

AU - Ensing, Gregory

AU - Kato, Gregory J.

AU - Gladwin, Mark T.

AU - Castro, Oswaldo L.

AU - Gordeuk, Victor R.

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N2 - 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 tartrateresistant 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 tartrateresistant 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.

AB - 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 tartrateresistant 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 tartrateresistant 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.

KW - Bone turnover

KW - Inflammation

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KW - Pulmonary complications

KW - Sickle cell disease

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