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Paget's disease of bone: evidence for complex pathogenetic interactions
Pui Yan Jenny Chung1, Wim Van Hul
1Department of Medical Genetics, University of Antwerp, Antwerp, Belgium.
Seminars in Arthritis and Rheumatism
|October 1, 2011
Summary
Paget's disease of bone (PDB) involves genetic factors and environmental influences, like viruses. Understanding these genetic links, particularly in osteoclastogenesis and autophagy, can help identify at-risk individuals for early detection and treatment.
Area of Science:
- Bone Biology and Metabolic Diseases
- Genetics and Molecular Biology
- Pathogenesis of Bone Disorders
Background:
- Paget's disease of bone (PDB) is a common metabolic bone disorder characterized by abnormal bone remodeling.
- Its etiology remains incompletely understood, with current research exploring both genetic and environmental factors.
- PDB affects Caucasians over 55, with a prevalence of 2-5%.
Purpose of the Study:
- To review current knowledge on the etiology, clinical aspects, and treatment of Paget's disease of bone.
- To discuss the role of genetic variations and environmental factors in PDB pathogenesis.
- To highlight the importance of understanding genetic backgrounds for early detection and treatment.
Main Methods:
- Literature search of the PubMed database.
- Keywords included PDB, genetic factors (SQSTM1, VCP, RANK, OPG), viruses, and treatment modalities (bisphosphonates, denosumab).
- Review and synthesis of existing research on PDB etiology and pathogenesis.
Main Results:
- Genetic polymorphisms in genes regulating osteoclastogenesis (e.g., OPG, RANK) are associated with PDB risk.
- Mutations in SQSTM1 were previously the only known cause, but polymorphisms in other genes are now identified.
- Disturbances in autophagy, involving SQSTM1 and VCP, may also contribute to PDB risk.
- Environmental factors, including viral infections, are implicated in PDB development.
Conclusions:
- Elucidating the genetic basis of PDB is crucial for understanding its pathogenesis.
- Identifying genetic risk factors and potential viral roles can lead to early detection strategies.
- This knowledge may enable timely intervention and treatment for individuals at risk of PDB.
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