CONTEXT: 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. DESIGN: This was a retrospective cohort study and review of the literature. PATIENTS: Forty adult type I GD patients were included in the study. OUTCOME MEASURES: 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.
CONTEXT: 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. DESIGN: This was a retrospective cohort study and review of the literature. PATIENTS: Forty adult type I GDpatients were included in the study. OUTCOME MEASURES: 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 GDpatients, primarily a decrease in bone formation causes an imbalance in bone remodeling.
Authors: Pramod K Mistry; Jun Liu; Li Sun; Wei-Lien Chuang; Tony Yuen; Ruhua Yang; Ping Lu; Kate Zhang; Jianhua Li; Joan Keutzer; Agnes Stachnik; Albert Mennone; James L Boyer; Dhanpat Jain; Roscoe O Brady; Maria I New; Mone Zaidi Journal: Proc Natl Acad Sci U S A Date: 2014-03-17 Impact factor: 11.205
Authors: L van Dussen; E J Hendriks; J E M Groener; R G Boot; C E M Hollak; J M F G Aerts Journal: J Inherit Metab Dis Date: 2014-05-16 Impact factor: 4.982
Authors: Gertjan Kramer; Wouter Wegdam; Wilma Donker-Koopman; Roelof Ottenhoff; Paulo Gaspar; Marri Verhoek; Jessica Nelson; Tanit Gabriel; Wouter Kallemeijn; Rolf G Boot; Jon D Laman; Johannes P C Vissers; Timothy Cox; Elena Pavlova; Mary Teresa Moran; Johannes M Aerts; Marco van Eijk Journal: FEBS Open Bio Date: 2016-07-30 Impact factor: 2.693
Authors: Ravi S Kamath; Elena Lukina; Nora Watman; Marta Dragosky; Gregory M Pastores; Elsa Avila Arreguin; Hanna Rosenbaum; Ari Zimran; Rasha Aguzzi; Ana Cristina Puga; Andrea M Norfleet; M Judith Peterschmitt; Daniel I Rosenthal Journal: Skeletal Radiol Date: 2014-05-10 Impact factor: 2.199