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... Show moreContext: 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. (J Clin Endocrinol Metab 96: 2194-2205, 2011) Show less
