title: Path Analysis Identifies Receptor Activator of Nuclear Factor-κB Ligand, Osteoprotegerin, and Sclerostin as Potential Mediators of the Tophus-bone Erosion Relationship in Gout.
abstract: OBJECTIVE
  To determine the relationship between tophus, erosion and bone remodeling factors in gout.
  
  
  METHODS
  Computed tomography bone erosion and circulating bone factors were measured in adults with tophaceous gout. Multiple regression modeling and path analysis were used to determine predictors of erosion.
  
  
  RESULTS
  Tophus number, Māori or Pacific ethnicity, creatinine, receptor activator of nuclear factor-κB ligand (RANKL), osteoprotegerin (OPG), and sclerostin were independently associated with erosion. Path analysis showed a direct effect of tophus number on erosion, partially mediated through OPG, RANKL, and sclerostin.
  
  
  CONCLUSIONS
  Tophus number is strongly associated with bone erosion in gout. Circulating RANKL, OPG, and sclerostin are potential mediators of tophus-related erosion.
authors.affiliation: From the Bone and Joint Research Group, the Department of Medicine, the Department of Anatomy with Radiology, and the Department of Molecular Medicine and Pathology, University of Auckland; and the Department of Radiology, Auckland District Health Board, Auckland, New Zealand.A. Chhana, PhD, Bone and Joint Research Group, Department of Medicine, University of Auckland; O. Aati, MHSc, Bone and Joint Research Group, Department of Medicine, University of Auckland; G.D. Gamble, MSc, Bone and Joint Research Group, Department of Medicine, University of Auckland; K.E. Callon, BSc, Bone and Joint Research Group, Department of Medicine, University of Auckland; A. Horne, MBChB, Bone and Joint Research Group, Department of Medicine, University of Auckland; I.R. Reid, MBChB, MD, FRACP, Bone and Joint Research Group, Department of Medicine, University of Auckland; J. Cornish, PhD, Bone and Joint Research Group, Department of Medicine, University of Auckland; N. Dalbeth, MBChB, MD, FRACP, Bone and Joint Research Group, Department of Medicine, University of Auckland; A.J. Doyle, MBChB, Department of Anatomy with Radiology, University of Auckland, and Department of Radiology, Auckland District Health Board; M. Roger, MBChB, Department of Radiology, Auckland District Health Board; F.M. McQueen, MD, FRACP, Department of Molecular Medicine and Pathology, University of Auckland.
authors.forename: Ashika
authors.initials: A
authors.lastname: Chhana
authors.affiliation: From the Bone and Joint Research Group, the Department of Medicine, the Department of Anatomy with Radiology, and the Department of Molecular Medicine and Pathology, University of Auckland; and the Department of Radiology, Auckland District Health Board, Auckland, New Zealand.A. Chhana, PhD, Bone and Joint Research Group, Department of Medicine, University of Auckland; O. Aati, MHSc, Bone and Joint Research Group, Department of Medicine, University of Auckland; G.D. Gamble, MSc, Bone and Joint Research Group, Department of Medicine, University of Auckland; K.E. Callon, BSc, Bone and Joint Research Group, Department of Medicine, University of Auckland; A. Horne, MBChB, Bone and Joint Research Group, Department of Medicine, University of Auckland; I.R. Reid, MBChB, MD, FRACP, Bone and Joint Research Group, Department of Medicine, University of Auckland; J. Cornish, PhD, Bone and Joint Research Group, Department of Medicine, University of Auckland; N. Dalbeth, MBChB, MD, FRACP, Bone and Joint Research Group, Department of Medicine, University of Auckland; A.J. Doyle, MBChB, Department of Anatomy with Radiology, University of Auckland, and Department of Radiology, Auckland District Health Board; M. Roger, MBChB, Department of Radiology, Auckland District Health Board; F.M. McQueen, MD, FRACP, Department of Molecular Medicine and Pathology, University of Auckland.
authors.forename: Opetaia
authors.initials: O
authors.lastname: Aati
authors.affiliation: From the Bone and Joint Research Group, the Department of Medicine, the Department of Anatomy with Radiology, and the Department of Molecular Medicine and Pathology, University of Auckland; and the Department of Radiology, Auckland District Health Board, Auckland, New Zealand.A. Chhana, PhD, Bone and Joint Research Group, Department of Medicine, University of Auckland; O. Aati, MHSc, Bone and Joint Research Group, Department of Medicine, University of Auckland; G.D. Gamble, MSc, Bone and Joint Research Group, Department of Medicine, University of Auckland; K.E. Callon, BSc, Bone and Joint Research Group, Department of Medicine, University of Auckland; A. Horne, MBChB, Bone and Joint Research Group, Department of Medicine, University of Auckland; I.R. Reid, MBChB, MD, FRACP, Bone and Joint Research Group, Department of Medicine, University of Auckland; J. Cornish, PhD, Bone and Joint Research Group, Department of Medicine, University of Auckland; N. Dalbeth, MBChB, MD, FRACP, Bone and Joint Research Group, Department of Medicine, University of Auckland; A.J. Doyle, MBChB, Department of Anatomy with Radiology, University of Auckland, and Department of Radiology, Auckland District Health Board; M. Roger, MBChB, Department of Radiology, Auckland District Health Board; F.M. McQueen, MD, FRACP, Department of Molecular Medicine and Pathology, University of Auckland.
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Gamble
authors.affiliation: From the Bone and Joint Research Group, the Department of Medicine, the Department of Anatomy with Radiology, and the Department of Molecular Medicine and Pathology, University of Auckland; and the Department of Radiology, Auckland District Health Board, Auckland, New Zealand.A. Chhana, PhD, Bone and Joint Research Group, Department of Medicine, University of Auckland; O. Aati, MHSc, Bone and Joint Research Group, Department of Medicine, University of Auckland; G.D. Gamble, MSc, Bone and Joint Research Group, Department of Medicine, University of Auckland; K.E. Callon, BSc, Bone and Joint Research Group, Department of Medicine, University of Auckland; A. Horne, MBChB, Bone and Joint Research Group, Department of Medicine, University of Auckland; I.R. Reid, MBChB, MD, FRACP, Bone and Joint Research Group, Department of Medicine, University of Auckland; J. Cornish, PhD, Bone and Joint Research Group, Department of Medicine, University of Auckland; N. Dalbeth, MBChB, MD, FRACP, Bone and Joint Research Group, Department of Medicine, University of Auckland; A.J. Doyle, MBChB, Department of Anatomy with Radiology, University of Auckland, and Department of Radiology, Auckland District Health Board; M. Roger, MBChB, Department of Radiology, Auckland District Health Board; F.M. McQueen, MD, FRACP, Department of Molecular Medicine and Pathology, University of Auckland.
authors.forename: Karen E
authors.initials: KE
authors.lastname: Callon
authors.affiliation: From the Bone and Joint Research Group, the Department of Medicine, the Department of Anatomy with Radiology, and the Department of Molecular Medicine and Pathology, University of Auckland; and the Department of Radiology, Auckland District Health Board, Auckland, New Zealand.A. Chhana, PhD, Bone and Joint Research Group, Department of Medicine, University of Auckland; O. Aati, MHSc, Bone and Joint Research Group, Department of Medicine, University of Auckland; G.D. Gamble, MSc, Bone and Joint Research Group, Department of Medicine, University of Auckland; K.E. Callon, BSc, Bone and Joint Research Group, Department of Medicine, University of Auckland; A. Horne, MBChB, Bone and Joint Research Group, Department of Medicine, University of Auckland; I.R. Reid, MBChB, MD, FRACP, Bone and Joint Research Group, Department of Medicine, University of Auckland; J. Cornish, PhD, Bone and Joint Research Group, Department of Medicine, University of Auckland; N. Dalbeth, MBChB, MD, FRACP, Bone and Joint Research Group, Department of Medicine, University of Auckland; A.J. Doyle, MBChB, Department of Anatomy with Radiology, University of Auckland, and Department of Radiology, Auckland District Health Board; M. Roger, MBChB, Department of Radiology, Auckland District Health Board; F.M. McQueen, MD, FRACP, Department of Molecular Medicine and Pathology, University of Auckland.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Doyle
authors.affiliation: From the Bone and Joint Research Group, the Department of Medicine, the Department of Anatomy with Radiology, and the Department of Molecular Medicine and Pathology, University of Auckland; and the Department of Radiology, Auckland District Health Board, Auckland, New Zealand.A. Chhana, PhD, Bone and Joint Research Group, Department of Medicine, University of Auckland; O. Aati, MHSc, Bone and Joint Research Group, Department of Medicine, University of Auckland; G.D. Gamble, MSc, Bone and Joint Research Group, Department of Medicine, University of Auckland; K.E. Callon, BSc, Bone and Joint Research Group, Department of Medicine, University of Auckland; A. Horne, MBChB, Bone and Joint Research Group, Department of Medicine, University of Auckland; I.R. Reid, MBChB, MD, FRACP, Bone and Joint Research Group, Department of Medicine, University of Auckland; J. Cornish, PhD, Bone and Joint Research Group, Department of Medicine, University of Auckland; N. Dalbeth, MBChB, MD, FRACP, Bone and Joint Research Group, Department of Medicine, University of Auckland; A.J. Doyle, MBChB, Department of Anatomy with Radiology, University of Auckland, and Department of Radiology, Auckland District Health Board; M. Roger, MBChB, Department of Radiology, Auckland District Health Board; F.M. McQueen, MD, FRACP, Department of Molecular Medicine and Pathology, University of Auckland.
authors.forename: Mark
authors.initials: M
authors.lastname: Roger
authors.affiliation: From the Bone and Joint Research Group, the Department of Medicine, the Department of Anatomy with Radiology, and the Department of Molecular Medicine and Pathology, University of Auckland; and the Department of Radiology, Auckland District Health Board, Auckland, New Zealand.A. Chhana, PhD, Bone and Joint Research Group, Department of Medicine, University of Auckland; O. Aati, MHSc, Bone and Joint Research Group, Department of Medicine, University of Auckland; G.D. Gamble, MSc, Bone and Joint Research Group, Department of Medicine, University of Auckland; K.E. Callon, BSc, Bone and Joint Research Group, Department of Medicine, University of Auckland; A. Horne, MBChB, Bone and Joint Research Group, Department of Medicine, University of Auckland; I.R. Reid, MBChB, MD, FRACP, Bone and Joint Research Group, Department of Medicine, University of Auckland; J. Cornish, PhD, Bone and Joint Research Group, Department of Medicine, University of Auckland; N. Dalbeth, MBChB, MD, FRACP, Bone and Joint Research Group, Department of Medicine, University of Auckland; A.J. Doyle, MBChB, Department of Anatomy with Radiology, University of Auckland, and Department of Radiology, Auckland District Health Board; M. Roger, MBChB, Department of Radiology, Auckland District Health Board; F.M. McQueen, MD, FRACP, Department of Molecular Medicine and Pathology, University of Auckland.
authors.forename: Fiona M
authors.initials: FM
authors.lastname: McQueen
authors.affiliation: From the Bone and Joint Research Group, the Department of Medicine, the Department of Anatomy with Radiology, and the Department of Molecular Medicine and Pathology, University of Auckland; and the Department of Radiology, Auckland District Health Board, Auckland, New Zealand.A. Chhana, PhD, Bone and Joint Research Group, Department of Medicine, University of Auckland; O. Aati, MHSc, Bone and Joint Research Group, Department of Medicine, University of Auckland; G.D. Gamble, MSc, Bone and Joint Research Group, Department of Medicine, University of Auckland; K.E. Callon, BSc, Bone and Joint Research Group, Department of Medicine, University of Auckland; A. Horne, MBChB, Bone and Joint Research Group, Department of Medicine, University of Auckland; I.R. Reid, MBChB, MD, FRACP, Bone and Joint Research Group, Department of Medicine, University of Auckland; J. Cornish, PhD, Bone and Joint Research Group, Department of Medicine, University of Auckland; N. Dalbeth, MBChB, MD, FRACP, Bone and Joint Research Group, Department of Medicine, University of Auckland; A.J. Doyle, MBChB, Department of Anatomy with Radiology, University of Auckland, and Department of Radiology, Auckland District Health Board; M. Roger, MBChB, Department of Radiology, Auckland District Health Board; F.M. McQueen, MD, FRACP, Department of Molecular Medicine and Pathology, University of Auckland.
authors.forename: Anne
authors.initials: A
authors.lastname: Horne
authors.affiliation: From the Bone and Joint Research Group, the Department of Medicine, the Department of Anatomy with Radiology, and the Department of Molecular Medicine and Pathology, University of Auckland; and the Department of Radiology, Auckland District Health Board, Auckland, New Zealand.A. Chhana, PhD, Bone and Joint Research Group, Department of Medicine, University of Auckland; O. Aati, MHSc, Bone and Joint Research Group, Department of Medicine, University of Auckland; G.D. Gamble, MSc, Bone and Joint Research Group, Department of Medicine, University of Auckland; K.E. Callon, BSc, Bone and Joint Research Group, Department of Medicine, University of Auckland; A. Horne, MBChB, Bone and Joint Research Group, Department of Medicine, University of Auckland; I.R. Reid, MBChB, MD, FRACP, Bone and Joint Research Group, Department of Medicine, University of Auckland; J. Cornish, PhD, Bone and Joint Research Group, Department of Medicine, University of Auckland; N. Dalbeth, MBChB, MD, FRACP, Bone and Joint Research Group, Department of Medicine, University of Auckland; A.J. Doyle, MBChB, Department of Anatomy with Radiology, University of Auckland, and Department of Radiology, Auckland District Health Board; M. Roger, MBChB, Department of Radiology, Auckland District Health Board; F.M. McQueen, MD, FRACP, Department of Molecular Medicine and Pathology, University of Auckland.
authors.forename: Ian R
authors.initials: IR
authors.lastname: Reid
authors.affiliation: From the Bone and Joint Research Group, the Department of Medicine, the Department of Anatomy with Radiology, and the Department of Molecular Medicine and Pathology, University of Auckland; and the Department of Radiology, Auckland District Health Board, Auckland, New Zealand.A. Chhana, PhD, Bone and Joint Research Group, Department of Medicine, University of Auckland; O. Aati, MHSc, Bone and Joint Research Group, Department of Medicine, University of Auckland; G.D. Gamble, MSc, Bone and Joint Research Group, Department of Medicine, University of Auckland; K.E. Callon, BSc, Bone and Joint Research Group, Department of Medicine, University of Auckland; A. Horne, MBChB, Bone and Joint Research Group, Department of Medicine, University of Auckland; I.R. Reid, MBChB, MD, FRACP, Bone and Joint Research Group, Department of Medicine, University of Auckland; J. Cornish, PhD, Bone and Joint Research Group, Department of Medicine, University of Auckland; N. Dalbeth, MBChB, MD, FRACP, Bone and Joint Research Group, Department of Medicine, University of Auckland; A.J. Doyle, MBChB, Department of Anatomy with Radiology, University of Auckland, and Department of Radiology, Auckland District Health Board; M. Roger, MBChB, Department of Radiology, Auckland District Health Board; F.M. McQueen, MD, FRACP, Department of Molecular Medicine and Pathology, University of Auckland.
authors.forename: Jillian
authors.initials: J
authors.lastname: Cornish
authors.affiliation: From the Bone and Joint Research Group, the Department of Medicine, the Department of Anatomy with Radiology, and the Department of Molecular Medicine and Pathology, University of Auckland; and the Department of Radiology, Auckland District Health Board, Auckland, New Zealand.A. Chhana, PhD, Bone and Joint Research Group, Department of Medicine, University of Auckland; O. Aati, MHSc, Bone and Joint Research Group, Department of Medicine, University of Auckland; G.D. Gamble, MSc, Bone and Joint Research Group, Department of Medicine, University of Auckland; K.E. Callon, BSc, Bone and Joint Research Group, Department of Medicine, University of Auckland; A. Horne, MBChB, Bone and Joint Research Group, Department of Medicine, University of Auckland; I.R. Reid, MBChB, MD, FRACP, Bone and Joint Research Group, Department of Medicine, University of Auckland; J. Cornish, PhD, Bone and Joint Research Group, Department of Medicine, University of Auckland; N. Dalbeth, MBChB, MD, FRACP, Bone and Joint Research Group, Department of Medicine, University of Auckland; A.J. Doyle, MBChB, Department of Anatomy with Radiology, University of Auckland, and Department of Radiology, Auckland District Health Board; M. Roger, MBChB, Department of Radiology, Auckland District Health Board; F.M. McQueen, MD, FRACP, Department of Molecular Medicine and Pathology, University of Auckland. n.dalbeth@auckland.ac.nz.
authors.forename: Nicola
authors.initials: N
authors.lastname: Dalbeth
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D019485:Bone Morphogenetic Proteins / Q000097:blood*; D016723:Bone Remodeling; D001842:Bone and Bones / Q000000981:diagnostic imaging*; D004164:Diphosphonates / Q000627:therapeutic use; D005260:Female; D005819:Genetic Markers; D006073:Gout / Q000097:blood* / Q000000981:diagnostic imaging / Q000188:drug therapy; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D053244:Osteoprotegerin / Q000097:blood*; D053245:RANK Ligand / Q000097:blood*; D000077211:Zoledronic Acid
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D019485:Bone Morphogenetic Proteins; D004164:Diphosphonates; D005819:Genetic Markers; D007093:Imidazoles; D053244:Osteoprotegerin; D053245:RANK Ligand; C422903:SOST protein, human; D000077211:Zoledronic Acid
keywords: BONE; EROSION; GOUT; OPG; RANKL; SCLEROSTIN