Definition |
Bisphosphonates have been used to inhibit osteoclast-mediated bone resorption in CRPC and have proven to be highly effective in reducing bone pain. 643 patients who had CRPC [862] with bone metastases were randomised to receive zoledronic acid, 4 or 8 mg every 3 weeks for 15 consecutive months, or placebo. At 15 and 24 months of follow-up, patients treated with 4 mg zoledronic acid had fewer skeletal-related events(SREs) compared to the placebo group (44% vs. 33%, P = 0.021) and fewer pathological fractures (13.1% vs.22.1%, P = 0.015). Furthermore, the time to first SRE was longer in the zoledronic acid group, thus improving QoL. Patients were initially randomised to 4 or 8 mg of zoledronic acid, but the 8 mg dosage was later modified to 4 mg due to toxicity. The toxicity (e.g., jaw necrosis) of these drugs,especially aminobisphosphonate, must always be kept in mind. Patients should have a dental examination before starting bisphosphonate therapy. The risk of jaw necrosis is increased by a history of trauma, dental surgery or dental infection, as well as long-term intravenous bisphosphonate administration.No survival benefit has been seen in any prospective trial with bisphosphonates.
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