Paget's disease of bone: clinical, pathogenetic and therapeutic aspects

Paget's disease of bone is a focal disorder of bone remodelling due to abnormally increased osteoclast-mediated bone resorption. It rarely presents before the age of 35 years and its prevalence increases with age affecting 2-5% of the population above 50 years, making Paget's disease the most common skeletal disorder after osteoporosis. Its aetiology is not known but available evidence favours an infection of genetically predisposed individuals with a paramyxovirus. Affected bones change in shape, size and direction causing considerable morbidity but the majority of patients are asymptomatic. In Paget's disease increased bone resorption is tightly linked to increased bone formation which are reflected in the proportional increases in biochemical indices of bone turnover. Because the primary abnormality lies in the osteoclasts, inhibitors of bone resorption are used for its therapy and bisphosphonates are currently the treatment of choice. These decrease bone turnover effectively and their effect lasts after stopping treatment. With available bisphosphonates clinical and biochemical, long-lasting, remissions can be obtained in the majority of patients. Symptomatic disease and preparation for orthopaedic surgery are no longer the only indication for treatment, but asymptomatic patients with localizations at sites likely to induce complications should be considered candidates for bisphosphonate therapy.