Zoledronic acid prevents pagetic-like lesions and accelerated bone loss in the p62^P394L mouse model of Paget's disease.

ABSTRACT: Paget's disease of bone (PDB) is an age-related metabolic bone disorder, characterised by focally increased and disorganised bone remodelling initiated by abnormal and hyperactive osteoclasts. The germline P392L mutation of SQSTM1 (encoding p62) is a strong genetic risk factor for PDB in humans, and the equivalent mutation in mice (P394L) causes a PDB-like disorder. However, it is unclear why pagetic lesions become more common with age. Here, we assessed the effect of the p62 P394L mutation on osteoclastogenesis and bone morphometry in relation to ageing, the natural history of lesion progression in p62^P394L mice and the effect of zoledronic acid (ZA) on lesion development. p62^P394L+/+ osteoclast precursors had increased sensitivity to RANKL (also known as TNFS

SUBMITTER: Daroszewska A 

PROVIDER: S-EPMC6177010 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature