Changes in bone resorption and vascular endothelial growth factor after a single zoledronic acid infusion in cancer patients with bone metastases from solid tumours

Daniele Santini, Bruno Vincenzi, Rosemary A. Hannon, Janet E. Brown, Giordano Dicuonzo, Silvia Angeletti, Annalisa La Cesa, Robert E. Coleman, Giuseppe Tonini, Alfredo Budillon, Michele Caraglia, Ingunn Holen

Research output: Contribution to journalArticle

Abstract

Zoledronic acid (Zometa, ZOL) is increasingly used to treat tumour-induced bone disease, and is also reported to have antiangiogenic properties in vivo. In this study, we have investigated the correlations between changes in the proangiogenic cytokine, vascular endothelial growth factor (VEGF), and markers of bone resorption in a cohort of patients with metastatic bone disease, following a single infusion of ZOL. Twenty-four consecutive selected cancer patients with scintigraphic and radiographic evidence of bone metastases were treated for the first time with a single infusion of 4 mg ZOL. Patients were considered ineligible if they had received any steroid therapy, radiotherapy, chemotherapy, immunotherapy or haemopoietic growth factors in the 4 weeks before or during the study period. Circulating levels of VEGF and β crosslinked type I collagen C-telopeptide (βCTX) were measured at base-line and at 1, 2, 7 and 21 days following ZOL infusion. The majority of our patients (23/24) developed a significant reduction in circulating levels of βCTX at just 1 day after the single zoledronic acid infusion, median percentage decrease 67.05% (95% CI, 52.39%; 76.27%). This reduction persisted at all following time points in almost all subjects in our patient population (day 2, 95.8%; day 7, 100%; day 21, 91.7%). The median decrease at day 2 was 85.67% (95% CI, 78.23%; 90.16%); at day 7, 67.38% (95% CI, 67.38%; 86.98); and at day 21, 76.89% (95% CI, 35.00%; 83.16%). Moreover, a linear regression model with variance analysis demonstrated a statistically significant correlation between median VEGF and βCTX circulating levels at each of the time points (1, 2, 7 and 21 days after ZOL infusion). The present work demonstrates that a single infusion of ZOL was able to induce a rapid and long lasting decrease of βCTX plasma levels in the majority (23/24) of the included cancer patients. Furthermore, we found that there is a correlation between the levels of VEGF and βCTX following ZOL treatment. Future clinical trials should be designed to prospectively evaluate the prognostic role of reduction of βCTX and VEGF in response to ZOL to predict clinical and skeletal outcome.

Original languageEnglish
Pages (from-to)1351-1357
Number of pages7
JournalOncology Reports
Volume15
Issue number5
Publication statusPublished - May 2006

Keywords

  • Angiogenesis
  • Bone metastases
  • Marker of bone resorption
  • Zoledronic acid

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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    Santini, D., Vincenzi, B., Hannon, R. A., Brown, J. E., Dicuonzo, G., Angeletti, S., La Cesa, A., Coleman, R. E., Tonini, G., Budillon, A., Caraglia, M., & Holen, I. (2006). Changes in bone resorption and vascular endothelial growth factor after a single zoledronic acid infusion in cancer patients with bone metastases from solid tumours. Oncology Reports, 15(5), 1351-1357.