Predictive value of bone resorption and formation markers in cancer patients with bone metastases receiving the bisphosphonate zoledronic acid

Robert E. Coleman, Pierre Major, Allan Lipton, Janet E. Brown, Ker Ai Lee, Matthew Smith, Fred Saad, Ming Zheng, Yong Jiang Hei, John Seaman, Richard Cook

Research output: Contribution to journalArticlepeer-review

420 Scopus citations

Abstract

Purpose: Three large, randomized trials of patients with bone metastases recently demonstrated that zoledronic acid reduces the risk of skeletal-related events. These trials provide an opportunity for investigating the correlation between bone metabolism and clinical outcome during bisphosphonate therapy. Patients and Methods: Urinary measurements of N-telopeptide (Ntx) and serum bone alkaline phosphatase (BAP) were obtained in 1,824 bisphosphonate-treated patients-1,462 with zoledronic acid (breast, 490; prostate, 411; myeloma, 210; non-small-cell lung, 183; other, 168) and 362 with pamidronate (breast, 254; myeloma, 108). This exploratory cohort analysis grouped patients by baseline and most recent levels of Ntx as low (< 50 nmol/mmol creatinine), moderate (50 to 99 nmol/mmol creatinine), or high (≥ 100 nmol/mmol creatinine), and BAP as low (< 146 U/L) or high (≥ 146 U/L). The relative risks for negative clinical outcomes were estimated for each group using multiple-event and Cox regression models with time-varying covariates. Results: Patients with high and moderate Ntx levels had 2-fold increases in their risk of skeletal complications and disease progression compared with patients with low Ntx levels (P < .001 for all). High Ntx levels in each solid tumor category were associated with a 4- to 6-fold increased risk of death on study, and moderate Ntx levels a 2- to 4-fold increased risk compared with low Ntx levels (P < .001 for all). Bone alkaline phosphatase also showed some correlation with risk of negative clinical outcomes. Conclusion: The bone resorption marker Ntx provides valuable prognostic information in patients with bone metastases receiving bisphosphonates.

Original languageEnglish (US)
Pages (from-to)4925-4935
Number of pages11
JournalJournal of Clinical Oncology
Volume23
Issue number22
DOIs
StatePublished - Dec 1 2005

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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