Proosteoclastogenic state in patients with Gaucher Disease: correlation with bone pathology

BONDAR C; OLIVERI B; CRIVARO A; ORMAZABAL M; MUCCI J; ROZENFELD P

Congreso; Congreso SAIC; 2016

.Gaucher disease is the most frequent lysosomal storage disease. This autosomic recessive disease is caused by mutations on the gene encoding for the lysosomal enzyme glucocerebrosidase, that leads to the accumulation of its substrate, glucosylceramide. Clinical manifestations include anemia, hepatosplenomegaly and bone alterations. In spite of treatment, bone alterations in Gaucher patients persist. Chitotriosidase is the most reliable biomarker used in the follow up of the disease, although its correlation with bone status has not been studied. The aim of our work was to study the proosteoclastogenic potential in patients and to evaluate its correlation with chitotriosidase activity levels and clinical parameters. To evaluate the proosteoclastogenic state, PBMC from patients under Enzyme Replacement Therapy were obtained by ficoll gradient and cultured in the presence of M-CSF. Mature osteoclasts were defined as multinucleated TRAP positive cells. On the other hand, total and column z-score was evaluated in patients as well as serum levels of CTX and chitotriosidase. As expected, serum chitotriosidase activity was higher in patients. We also found that osteoclast differentiation was increased in patients. However, no correlation between osteoclasts and serum chitotriosidase was observed. Osteoclast levels presented a negative correlation with z-score (both total and column) while a positive correlation with CTX was observed. In conclusion, our results show for the first time a correlation between osteoclast differentiation and bone clinical parameters in Gaucher disease, but not with chitotriosidase. In addition, these results support the involvement of osteoclasts in the bone pathology of Gaucher disease.