Genetic Determinants of Paget’s Disease of Bone

• Published in: Current osteoporosis reports Vol. 19; no. 3; pp. 327 - 337
• Main Authors: Makaram, Navnit S., Ralston, Stuart H.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01-06-2021
• Subjects: Epidemiology; Genetic Predisposition to Disease; Genetic Testing; Genetics (D Karasik and C Ackert-Bicknell; Genetics (D Karasik and C Ackert-Bicknell, Section Editors); Genome-Wide Association Study; Humans; Medicine; Medicine & Public Health; Orthopedics; Osteitis Deformans - genetics; Section Editors; Topical Collection on Genetics; multisystem proteinopathy; genetics; osteoclast; SQSTM1; Paget's disease of bone
• ISSN: 1544-1873; 1544-2241
• DOI: 10.1007/s11914-021-00676-w

Purpose of Review
To provide an overview of the role of genes and loci that predispose to Paget’s disease of bone and related disorders.
Recent Findings
Studies over the past ten years have seen major advances in knowledge on the role of genetic factors in Paget’s disease of bone (PDB). Genome wide association studies have identified six loci that predispose to the disease whereas family based studies have identified a further eight genes that cause PDB. This brings the total number of genes and loci implicated in PDB to fourteen. Emerging evidence has shown that a number of these genes also predispose to multisystem proteinopathy syndromes where PDB is accompanied by neurodegeneration and myopathy due to the accumulation of abnormal protein aggregates, emphasising the importance of defects in autophagy in the pathogenesis of PDB.
Summary
Genetic factors play a key role in the pathogenesis of PDB and the studies in this area have identified several genes previously not suspected to play a role in bone metabolism. Genetic testing coupled to targeted therapeutic intervention is being explored as a way of halting disease progression and improving outcome before irreversible skeletal damage has occurred.