Paget's disease of bone: there's more than the affected skeletal--a clinical review and suggestions for the clinical practice.
OBJECTIVE
New acquisitions have been recently obtained on molecular pathogenesis, genetics and treatment of the Paget's disease of bone. Utmost importance to the skeletal manifestations of this disease has been given, even though extraskeletal abnormalities have been reported over the years. Consequently, the clinical aspects of extraskeletal complications have been less extensively investigated. This review will focus primarily on epidemiological, clinical and diagnostic features of skeletal and extra-skeletal clinical manifestations and will include either the hypotheses or new findings on their underlying molecular pathophysiology. A practical suggestion for an optimal management path of Paget's disease of bone is given.


RESULTS
It has been revealed that osteoblasts and osteocytes participate in impaired bone remodeling; in a North American study on pagetic patients, the survival rate was better than expected; the frequency of neurological complications and hearing loss could be different than previously reported; and somatically acquired mutations of SQSTM1/p62 gene have been found in both the diseased bone and tumor samples from sporadic patients with Paget's disease of bone.


CONCLUSIONS
Through an improved and more complete clinical characterization the 'old' complications could be better managed and new ones could emerge as entities potentially associated with Paget's disease.
Regional Center for Hereditary Endocrine Tumors, Department of Internal Medicine, University of Florence, Florence, Italy.
Alberto
A
Falchetti
Laura
L
Masi
Maria Luisa
ML
Brandi
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D006801:Humans; D009154:Mutation; D010001:Osteitis Deformans / Q000235:genetics / Q000473:pathology*; D010006:Osteoblasts / Q000473:pathology; D000071456:Sequestosome-1 Protein
D048868:Adaptor Proteins, Signal Transducing; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein