Efficacy and safety of drugs for Pagetʹs disease of bone

Pagetʹs disease of bone is characterized by an anarchic bone turnover starting with excessive resorption caused by structural and functional abnormalities involving osteoclasts. Calcitonin and bisphosphonates are now considered as the main therapeutic approaches for this disease. Daily parental administration of calcitonin to patients with Pagetʹs disease of bone results in a significant fall in serum alkaline phosphatase and urinary hydroxyproline levels. This treatment has also been reported to be effective in relieving clinical symptoms of the disease, mainly bone pain. The drawbacks of injectable calcitonin have stimulated interest in alternative routes of delivery. Substantial evidence of calcitonin bioavailability and bioefficacy equivalent to those of parenteral administration is currently available for only two alternative routes: nasal spray and rectal suppository. Since many results have been published showing a dramatic effect of several bisphosphonates in Pagetʹs disease of bone, nasal and rectal calcitonin are no longer considered as the treatments of choice in this condition. A major advantage of the use of bisphosphonates over calcitonin in Pagetʹs disease is that biochemical and histologic suppression of disease activity may persist for many years after the cessation of treatment. Oral etidronate and intravenous pamidronate have been extensively used and have provided satisfactory benefits to the patient. Since the risk/benefit ratio of alendronate does not appear to be completely positive, it is likely that the future of treatment of Pagetʹs disease of bone will be based on the oral formulation of the new bisphosphonates, including tiludronate, risedronate or dimethyl-pamidronate.