Paget‘s disease of bone - new therapeutic options

Paget‘s disease of bone is the second most common metabolic bone disease. It is a chronic condition which requires long-term, if not

life-long, treatment, and it decreases the quality of life. The disease aetiology remains unclear; however, it most likely results from

a combination of a viral infection and an underlying genetic predisposition. The disease is most commonly detected on an incidental

radiological or biochemical finding. Given the primary disorder at osteoclast level, the treatment is based on drugs inhibiting osteoclast

action or reducing their number. Until recently, the treatment for Paget‘s disease involved both calcitonin and oral bisphosphonates given

in multiples of daily doses used in the treatment of osteoporosis, or intravenous bisphosphonates administered repeatedly at severalmonth

intervals. The major progress so far has been the therapeutic use of zoledronate in a short infusion once yearly. The HORIZON-TOP

study compared the effect of 30 mg of oral risedronate, the so far most widely used reference agent, given daily for two months to that

of a 15-minute infusion of 5 mg of zoledronate given once-yearly. The study demonstrated that, at six months, a therapeutic response

was achieved in 96 % of patients on zoledronate compared to 74.3 % of patients on risedronate (p = 0.001). Alkaline phosphatase (ALP)

returned to normal in 88.6 % of patients on zoledronate compared to a mere 57.9 % of those on risedronate. Moreover, zoledronate

exhibited a substantially shorter median of time to therapeutic response of 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 those treated with risedronate compared to a mere 1 % of

those treated with zoledronate. The once-yearly administration of intravenous bisphosphonate ensures not only a 100 % compliance

with treatment but also a substantially better quality of life of patients with Paget‘s disease.

Keywords: Paget‘s disease, bisphosphonates, zoledronate.