Osteoclast differentiation correlates with bone mineral density in Gaucher disease patients

J.M. MUCCI; CRIVARO A.; BONDAR, C.; ORMAZABAL, M.; CECI, R.; OLIVERI, B.; ROZENFELD, P.

San Diego

Congreso; 14th Annual Lysosomal Disease Network WORLDSymposium; 2018

Gaucher disease (GD) is caused by mutations on the gene encoding for the lysosomal enzymeglucocerebrosidase. Bone alterations are the most disabling condition in Type I GD (GD1) patients. Bone alterations in GD patients remain a chronic issue in spite of ERT treatment. Mechanisms leading to bone damage are poorly understood, but previous reports suggest that osteoclasts are involved. Chitotriosidase (CHIT) is the most reliable and used biomarker in the follow up of patients, but its correlation with bone status has not been studied. The aim of this work was to study osteoclast differentiation from patients blood and to evaluate its correlation with CHIT activity levels and clinical parameters. PBMCs from treated patients and healthy controls were cultured in the presence of M-CSF, and mature osteoclasts were counted. BMD, blood CHIT activity and serum levels of CTX, BAP, and cytokines were evaluated in patients. We found that blood CHIT activity and osteoclast differentiation were significantly increased in patients, but no correlation between these two parameters was observed. Osteoclast numbers but not CHIT, presented a negative correlation with BMD expressed as Z-score. CTX, BAP and serum cytokines related to bone dynamics were found altered in GD1 patients. These results show for the first time a correlation between osteoclast differentiation and BMD in GD1 patients, further showing the involvement of osteoclasts in the bone pathology of GD1. Our results also suggest that an altered immune response may play an important role in bone damage.