Latest developments in Paget's disease of bone.

Area of Science:

• Bone biology and genetics
• Metabolic bone diseases
• Rheumatology

Background:

• Paget's disease of bone (PDB) is characterized by increased osteoclastic resorption and disorganized bone formation.
• It affects up to 1% of the UK population, with many cases undiagnosed, often presenting as musculoskeletal pain or complications like deformity and nerve compression.
• Genetic predisposition is linked to variants in genes regulating osteoclast function, notably SQSTM1, with environmental factors also playing a role.

Purpose of the Study:

• To summarize the understanding of Paget's disease of bone, including its pathophysiology, diagnosis, and management.
• To highlight the role of genetic factors, particularly SQSTM1 variants, in disease predisposition.
• To emphasize the efficacy of bisphosphonates, specifically zoledronic acid, in managing PDB symptoms and progression.

Main Methods:

• Review of literature on Paget's disease of bone, focusing on genetic factors, clinical presentation, diagnostic methods, and treatment strategies.
• Analysis of diagnostic approaches including X-ray, radionuclide bone scan, and genetic testing for SQSTM1.
• Evaluation of treatment outcomes with bisphosphonates, particularly intravenous zoledronic acid.

Main Results:

• Paget's disease of bone involves focal increases in bone resorption and disorganized formation, leading to symptoms like pain and complications.
• Pathogenic variants in SQSTM1 are strongly associated with PDB predisposition.
• Intravenous zoledronic acid is the preferred bisphosphonate for suppressing abnormal bone turnover and treating PDB.
• Genetic testing can identify individuals with early or asymptomatic disease, who may benefit from prophylactic zoledronic acid treatment.

Conclusions:

• Paget's disease of bone requires accurate diagnosis through imaging and genetic testing, especially for individuals with a family history.
• Management focuses on bisphosphonates, with zoledronic acid being the treatment of choice for symptomatic disease and potentially for early intervention.
• Understanding the genetic basis, particularly SQSTM1, aids in identifying at-risk individuals and guiding prophylactic treatment strategies to improve disease outcomes.