Unraveling the mystery of Gaucher bone density pathophysiology

ROZENFELD PA; CRIVARO, A.; ORMAZABAL, M.; MUCCI JM; BONDAR C; DELPINO MV

MOLECULAR GENETICS AND METABOLISM

ACADEMIC PRESS INC ELSEVIER SCIENCE

Lugar: Amsterdam; Año: 2021

1096-7192

Gaucher disease (GD) is caused by pathogenic mutations in GBA1, the gene that encodes the lysosomal enzymeβ-glucocerebrosidase. Despite the existence of a variety of specific treatments for GD, they cannot completelyreverse bone complications. Many studies have evidenced the impairment in bone tissue of GD, and molecularmechanisms of bone density alterations in GD are being studied during the last years and different reportsemphasized its efforts trying to unravel why and how bone tissue is affected. The cause of skeletal densityaffection in GD is a matter of debates between research groups. and there are two opposing hypotheses trying toexplain reduced bone mineral density in GD: increased bone resorption versus impaired bone formation. In thisreview, we discuss the diverse mechanisms of bone alterations implicated in GD revealed until the present, alongwith a presentation of normal bone physiology and its regulation. With this information in mind, we discusseffectiveness of specific therapies, introduce possible adjunctive therapies and present a novel model for GDassociated bone density pathogenesis. Under the exposed evidence, we may conclude that both sides of thebalance of remodeling process are altered. In GD the observed osteopenia/osteoporosis may be the result ofcontribution of both reduced bone formation and increased bone resorption