Clinical benefit of zoledronic acid for the prevention of skeletal complications in patients with prostate cancer based on history of skeletal complications

Bone metastases are a major cause of morbidity for men with prostate cancer. Complications of bone metastases include pain, fractures, and spinal cord compression. Although they appear osteoblastic by radiographic imaging, most bone metastases are characterized by excess osteoclast number and activity. In addition, pathologic osteoclast activation is associated with increased risk of skeletal complications. Zoledronic acid, a potent inhibitor of osteoclast activity, differentiation, and survival, decreases the risk of skeletal complications in men with androgen-independent prostate cancer and bone metastases. Other bisphosphonates, including pamidronate and clodronate, seem to be ineffective in this setting. The reduction in risk of skeletal complications with zoledronic acid must be weighed against potential adverse effects. Additional studies are needed to determine the optimal timing, schedule, and duration of treatment in men with bone metastases as well as the potential role of bisphosphonates in other settings including the prevention of bone metastases.

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Bone turnover markers as predictive tools for skeletal complications in men with metastatic prostate cancer treated with zoledronic acid

The Prostate ◽

10.1002/pros.20917 ◽

2009 ◽

Vol 69 (6) ◽

pp. 624-632 ◽

Cited By ~ 31

Author(s):

Michael Lein ◽

Kurt Miller ◽

Manfred Wirth ◽

Lothar Weißbach ◽

Christoph May ◽

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Keyword(s):

Prostate Cancer ◽

Zoledronic Acid ◽

Bone Turnover ◽

Bone Turnover Markers ◽

Metastatic Prostate Cancer ◽

Predictive Tools ◽

Skeletal Complications ◽

Turnover Markers

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Effects of Denosumab versus Zoledronic Acid in Patients with Castration-Resistant Prostate Cancer and Bone Metastases

Oncology & Hematology Review (US) ◽

10.17925/ohr.2012.08.2.94 ◽

2012 ◽

Vol 08 (02) ◽

pp. 94 ◽

Cited By ~ 1

Author(s):

Neal Shore ◽

Carsten Goessl ◽

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Keyword(s):

Prostate Cancer ◽

Zoledronic Acid ◽

Bone Metastases ◽

Human Monoclonal Antibody ◽

Bone Destruction ◽

Comprehensive Treatment ◽

Castration Resistant Prostate Cancer ◽

Efficacy Analysis ◽

Castration Resistant ◽

Skeletal Complications

Progression of castration-resistant prostate cancer often leads to bone metastases, increasing the risk of skeletal-related events (SREs). The use of antiresorptive therapies such as denosumab, a human monoclonal antibody and zoledronic acid (ZA), a bisphosphonate, reduces bone destruction by inhibiting osteoclast function and survival. In 2002, ZA was approved for the prevention of skeletal complications in patients with bone disease from myeloma or bone metastases from solid tumors including prostate cancer. Recently, efficacy analysis demonstrated superiority of denosumab to ZA for the prevention or delay of SREs in 1,901 patients with prostate cancer and bone metastases, significantly delaying the time to first SRE and time to first and subsequent SRE compared to ZA. Decreases in bone turnover markers were greater with denosumab, mirroring the reduction in SREs. The reported incidence of adverse events were similar between denosumab and ZA. Advanced prostate cancer patients require long-term disease management where maintenance of overall bone health is an essential component of a comprehensive treatment program.

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