In vitro osteoclast differentiation correlates with bone mineral density in Gaucher disease patients

ORMAZABAL, MAXIMILIANO; GONZALEZ, DIANA; BONDAR, CONSTANZA; OLIVERI, BEATRIZ; MUCCI, JUAN MARCOS; CRIVARO, ANDREA; ROZENFELD, PAULA

San Diego

Simposio; World Symposium 2018; 2018

Gaucher disease (GD) is caused by mutations on the gene encodingfor the lysosomal enzyme glucocerebrosidase. Bone alterations are themost disabling condition in Type I GD (GD1) patients. Bone alterationsin GD patients remain a chronic issue in spite of ERT treatment.Mechanisms leading to bone damage are poorly understood, butprevious reports suggest that osteoclasts are involved. Chitotriosidase(CHIT) is the most reliable and used biomarker in the follow up ofpatients, but its correlation with bone status has not been studied. Theaim of this work was to study osteoclast differentiation from patientsblood and to evaluate its correlation with CHIT activity levels andclinical parameters. PBMCs from treated patients and healthy controlswere cultured in the presence of M-CSF, and mature osteoclasts werecounted. BMD, blood CHIT activity and serum levels of CTX, BAP,and cytokines were evaluated in patients. We found that blood CHITactivity and osteoclast differentiation were significantly increasedin patients, but no correlation between these two parameters wasobserved. Osteoclast numbers but not CHIT, presented a negativecorrelation with BMD expressed as Z-score. CTX, BAP and serumcytokines related to bone dynamics were found altered in GD1patients. These results show for the first time a correlation betweenosteoclast differentiation and BMD in GD1 patients, further showingthe involvement of osteoclasts in the bone pathology of GD1. Ourresults also suggest that an altered immune response may play animportant role in bone damage