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

Michael Lein, Kurt Miller, Manfred Wirth, Lothar Weissbach, Christoph May, Katja Schmidt, Ulrike Haus, Mark Schrader, Klaus Jung
Prostate 2009 May 1, 69 (6): 624-32

BACKGROUND: Bone turnover markers are helpful to diagnose bone metastases. The aim of this study was to evaluate the usefulness of these markers in prostate cancer patients with bone metastases before and during the treatment with zoledronic acid as predictive and monitoring tools of skeletal-related events (SRE).

METHODS: One hundred seventeen prostate cancer patients with bone metastases and treated with zoledronic acid (4 mg every 4 weeks) were examined. Fifty-six patients were with and 61 patients without SRE during a 60-week study. Total and bone-specific alkaline phosphatase, and amino-terminal procollagen propeptides of type-I-collagen (PINP), cross-linked N-terminal (NTx), cross-linked C-terminal telopeptides of type-I-collagen (ICTP), and C-terminal telopeptides of type-I-collagen as well as prostate-specific antigen (PSA) were measured before and 12, 24, 36, 48, and 60 weeks after starting treatment.

RESULTS: Higher baseline concentrations were observed in the SRE group. The bone markers except for ICTP and tALP decreased to 20-80% of the baseline values at week 12 after the drug administration showing a generally higher decline in the non-SRE group except for NTx. At all time points during treatment higher and increasing concentrations of bone markers were observed in the SRE group compared with non-SRE group. Cox regression models with clinical data and bone markers showed the baseline NTx concentration as predictor of SREs. During the study, percentage changes of PINP and ICTP were most indicative for SREs.

CONCLUSIONS: Bone markers are useful tools to predict and diagnose SRE in prostate cancer patients with bone metastases under receiving zoledronic acid therapy.

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