Paget‘s disease - advances in treatment

Paget‘s disease is the second most common metabolic disorder of the skeleton. It is a chronic condition which requires long-term, if not lifetime, treatment. Due to a primary disorder at the level of osteoclast clones, the treatment involves drugs inhibiting their action or reducing their number. Historically, the first agent to have been used was synthetic salmon calcitonin. Until recently, the treatment of Paget‘s disease included either oral bisphosphonates given in multiples of the daily doses used in osteoporosis treatment or intravenous bisphosphonates administered repeatedly at several month intervals. In the autumn of 2005, the latest therapeutic approach using a single, once-yearly short infusion of zolendronate was introduced which has been available in the Czech Republic since January 2006. The HORIZON-TOP study compared the effect of 30 mg of oral risedronate, the most widely used reference agent so far, given daily for two months with that of a once-yearly, 15-minute infusion of 5 mg zolendronate. The study demonstrated that, at six months, a therapeutic response was achieved in 96 % of patients on zolendronate compared to 74.3 % of patients on risedronate (p = 0.001). Alkaline phosphatase (ALP) returned to normal in 88.6 % on zolendronate compared to only 57.9 % of those on risedronate. In addition, zolendronate exhibited a substantially shorter median time to therapeutic response (64 vs. 79 days, p = 0.001). The study extension (a median of 190 days) demonstrated that the therapeutic response was lost in 26 % of pateints treated with risedronate but only in 1 % of those treated with zolendronate. The patients treated with the new approach showed a significantly better quality of life than those treated conventionally with risedronate.

Keywords: Paget‘s disease, osteoclasts, bisphosphonates, risedronate, zolendronate