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Duration of suppression of bone turnover following treatment with zoledronic acid in men with metastatic castration-resistant prostate cancer


Aim: Zoledronate is approved for use every 3 weeks in men with bone metastases from castrate-resistant prostate cancer (CRPC) but the basis for such frequency is unclear. Methods: In men with bone metastasis from CRPC we measured the markers of bone turnover – urine and serum telopeptides before the first injection of zoledronate and at four 3-weekly intervals thereafter. Men received further zoledronate treatment after 12 weeks, or earlier if the telopeptides did not meet predefined adequate suppression. The primary end point was the proportion of evaluable subjects with suppressed telopeptides at 12 weeks. Exploratory analyses evaluated predictors of bone turnover suppression and quality-of-life. Results: 31 patients were enrolled. Median age was 70 (range: 53–86) years. 65%, (95% CI: 46–81%) had suppressed telopeptides at 12 weeks. Prior skeletal-related events, chemotherapy, bone surgery and higher baseline levels of telopeptides were associated with shorter duration of telopeptides. Conclusion: 12-weekly zoledronate suppresses bone turnover in the majority of men with bone metastasis from CRPC.

The bisphosphonate zoledronic acid (ZA) has been shown to maintain bone density in men receiving androgen deprivation therapy for prostate cancer and in men without bone metastases. This can be achieved with a 4 mg intravenous dose given annually [1]. In men with castrate-resistant prostate cancer (CRPC) and bone metastases, ZA given every 3 weeks has been demonstrated to delay time to first skeletal-related event (SRE defined as pathologic fracture, spinal cord compression, requirement for radiation therapy or surgery to bone, or change in antineoplastic therapy to treat bone pain) [2,3]. Treatment with ZA has no effect on progression-free or overall survival and is associated with potentially serious side effects including renal impairment, hypocalcemia and osteonecrosis of the jaw.

Click here to read the full article in Future Science OA.