title: Markers of bone turnover in Gaucher disease: modeling the evolution of bone disease.
abstract: BACKGROUND
  Gaucher disease (GD) is a lysosomal storage disorder characterized by abundant presence of macrophages. Bone complications and low bone density are believed to arise from enhanced bone resorption mediated through macrophage-derived factors.
  
  
  OBJECTIVE
  The objective of the study was to investigate the relationship between bone turnover and bone complications in GD.
  
  
  METHODS
  This was a retrospective cohort study and review of the literature.
  
  
  METHODS
  Forty adult type I GD patients were included in the study.
  
  
  METHODS
  Levels of the bone-resorption marker, type 1 collagen C-terminal telopeptide, and two bone-formation markers, N-terminal propeptide of type 1 procollagen and osteocalcin, were investigated in relation to clinical bone disease, measures of overall disease severity, and imaging data representing bone marrow infiltration.
  
  
  RESULTS
  Osteocalcin was decreased in 50% of our patients (median 0.35 nmol/liter, normal 0.4-4.0), indicating a decrease of bone formation. Type 1 collagen C-terminal telopeptide and N-terminal propeptide of type 1 procollagen were within the normal range for most patients. Osteocalcin concentration was negatively correlated to measures of overall disease severity and positively correlated with imaging data (correlation coefficient 0.423; P = 0.025), suggesting a relation with disease severity. A review of the literature revealed variable outcomes on bone resorption markers but more consistent abnormalities in bone formation markers. Two of three reports conclude that bone-formation parameters increase in response to enzyme therapy, but none describes an effect on bone-resorption markers.
  
  
  CONCLUSIONS
  In contrast to earlier hypotheses, we propose that in GD patients, primarily a decrease in bone formation causes an imbalance in bone remodeling.
authors.affiliation: Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
authors.forename: L
authors.initials: L
authors.lastname: van Dussen
authors.forename: P
authors.initials: P
authors.lastname: Lips
authors.forename: V E
authors.initials: VE
authors.lastname: Everts
authors.forename: N
authors.initials: N
authors.lastname: Bravenboer
authors.forename: I D C
authors.initials: ID
authors.lastname: Jansen
authors.forename: J E M
authors.initials: JE
authors.lastname: Groener
authors.forename: M
authors.initials: M
authors.lastname: Maas
authors.forename: J A K
authors.initials: JA
authors.lastname: Blokland
authors.forename: J M F G
authors.initials: JM
authors.lastname: Aerts
authors.forename: C E M
authors.initials: CE
authors.lastname: Hollak
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001862:Bone Resorption / Q000097:blood*; D024042:Collagen Type I / Q000097:blood*; D018450:Disease Progression; D005260:Female; D005776:Gaucher Disease / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood*; D010012:Osteogenesis; D010455:Peptides / Q000097:blood*; D011347:Procollagen / Q000097:blood*; D012189:Retrospective Studies; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; D024042:Collagen Type I; D010455:Peptides; D011347:Procollagen; C052929:collagen type I trimeric cross-linked peptide; D015675:Osteocalcin