Calcified Tissue International

, Volume 81, Issue 5, pp 341–351 | Cite as

The Use of Bone Markers in a 6-Week Study to Assess the Efficacy of Oral Clodronate in Patients with Metastatic Bone Disease

  • J. E. Brown
  • E. V. McCloskey
  • J. A. Dewar
  • J. J. Body
  • D. A. Cameron
  • A. N. Harnett
  • M. Ruutu
  • O. P. Purohit
  • R. Tähtelä
  • R. E. Coleman
Article

Abstract

Biochemical markers of bone metabolism are strongly associated with skeletal complications in metastatic bone disease. The bisphosphonate clodronate reduces skeletal morbidity by inhibiting bone resorption. This study investigated the use of bone markers to assess the efficacy of oral clodronate across a range of clinically relevant doses. There were 125 patients with metastatic bone disease randomized to daily oral clodronate (800, 1,600, 2,400 and 3,200 mg) or placebo in a double-blind, multicenter study. Urinary N-terminal telopeptide of type I collagen (U-NTX), serum C-terminal telopeptide of type I collagen (S-CTX), urinary calcium (U-Ca), and bone alkaline phosphatase were measured weekly for a 6-week treatment period. Doses of ≥1,600 mg clodronate produced mean reductions of >40% in U-NTX, S-CTX and U-Ca, all significantly different from placebo (P = 0.0015, 0.001, 0.0036, respectively), after 6 weeks. Evaluation of least significant changes in markers suggested that the commonly used 1,600 mg dose was most appropriate for breast cancer patients. However, this dose was suboptimal for other (mainly prostate cancer) patients, who showed better response to 2,400 mg. The number of adverse events in the treatment arms was not significantly different from that in placebo, but a higher number of patients had diarrhea in the 3,200 mg arm and withdrew from the study. This trial is the first to explore the dose-response relationship of clodronate in oncology using specific markers of bone turnover. It has confirmed that the 1,600 mg dose is safe and effective for breast cancer patients but may be suboptimal for the other tumors studied.

Keywords

Clodronate Metastatic bone disease Urinary N-terminal cross-linking telopeptide of type I collagen Serum C-terminal cross-linking telopeptide of type I collagen Bone alkaline phosphatase 

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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • J. E. Brown
    • 1
    • 9
  • E. V. McCloskey
    • 2
  • J. A. Dewar
    • 3
  • J. J. Body
    • 4
  • D. A. Cameron
    • 5
  • A. N. Harnett
    • 6
  • M. Ruutu
    • 7
  • O. P. Purohit
    • 1
  • R. Tähtelä
    • 8
  • R. E. Coleman
    • 1
  1. 1.Academic Unit of Clinical OncologyWeston Park Hospital University of SheffieldSheffieldUK
  2. 2.Metabolic Bone UnitUniversity of SheffieldSheffieldUK
  3. 3.Department of OncologyNinewells HospitalDundeeUK
  4. 4.Department of OncologyInstitut Jules BordetBrusselsBelgium
  5. 5.Department of OncologyWestern General HospitalEdinburghUK
  6. 6.Norfolk and Norwich University HospitalNorwichUK
  7. 7.Department of OncologyMaria HospitalHelsinkiFinland
  8. 8.Mehiläinen Oy LaboratoriopalvelutHelsinkiFinland
  9. 9.Cancer Research UK Clinical Center in LeedsJIF Building, St. James’s University HospitalLeedsUK

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