Markers of bone turnover in Gaucher disease: modeling the evolution of bone disease.

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.

Type II and VI collagen in nasal and articular cartilage and the effect of IL-1alpha on the distribution of these collagens.

The distribution of type II and VI collagen was immunocytochemically investigated in bovine articular and nasal cartilage. Cartilage explants were used either fresh or cultured for up to 4 weeks with or without interleukin 1alpha (IL-1alpha). Sections of the explants were incubated with antibodies for both types of collagen. Microscopic analyses revealed that type II collagen was preferentially localized in the interchondron matrix whereas type VI collagen was primarily found in the direct vicinity of the chondrocytes. Treatment of the sections with hyaluronidase greatly enhanced the signal for both types of collagen. Also in sections of explants cultured with IL-1alpha a higher level of labeling of the collagens was found. This was apparent without any pre-treatment with hyaluronidase. Under the influence of IL-1alpha the area positive for type VI collagen that surrounded the chondrocytes broadened. Although the two collagens in both types of cartilage were distributed similarly, a remarkable difference was the higher degree of staining of type VI collagen in articular cartilage. Concomitantly we noted that digestion of this type of cartilage hardly occurred in the presence of IL-1alpha whereas nasal cartilage was almost completely degraded within 18 days of culture. Since type VI collagen is known to be relatively resistant to proteolysis we speculate that the higher level of type VI collagen in articular cartilage is important in protecting cartilage from digestion.