The clinical use of bone resorption markers in patients with malignant bone disease

Cancer. 2002 May 15;94(10):2521-33. doi: 10.1002/cncr.10522.


Background: Advanced tumors often metastasize to bone, resulting in a variety of skeletal complications. Bisphosphonates are potent inhibitors of osteoclast-mediated bone resorption that reduce the incidence and delay the onset of skeletal complications and reduce the need for radiation and surgery. Biochemical markers of bone resorption have been identified that can augment the imaging techniques used to diagnose bone metastases and assess response to bisphosphonate therapy.

Methods: In the current study, the available literature regarding bone resorption markers is reviewed and the clinical relevance of these data with respect to the treatment of bone metastases discussed.

Results: Urinary calcium and hydroxyproline have been widely used to assess bone metabolism, but do not appear to be well correlated with clinical outcome in patients with bone metastases. Several unique breakdown products of Type I collagen (including pyridinium crosslinks, pyridinoline, and deoxypyridinoline) and peptide-bound crosslinks (N-telopeptide and C-telopeptide) are more specific and sensitive markers of bone resorption. N-telopeptide and C-telopeptide have been identified as the most sensitive biochemical markers currently available for detecting bone metastases and for assessing response to therapy or disease progression.

Conclusions: To the author's knowledge markers of bone resorption have not yet been recommended for routine clinical use. However, further research is needed to define their potential role in the diagnosis of bone metastases, the assessment of disease progression and response to bisphosphonate therapy, and predict the rate of bone loss and the potential for fracture. Suppression of bone resorption markers in response to bisphosphonate therapy appears to correlate with clinical outcome in patients with both osteolytic and blastic bone lesions; therefore, the goal of bisphosphonate therapy should be to suppress markers of bone resorption.

Publication types

  • Review

MeSH terms

  • Biomarkers / analysis*
  • Biomarkers, Tumor / analysis
  • Bone Neoplasms / diagnosis*
  • Bone Neoplasms / drug therapy
  • Bone Neoplasms / secondary*
  • Bone Resorption / metabolism*
  • Diphosphonates / therapeutic use
  • Humans


  • Biomarkers
  • Biomarkers, Tumor
  • Diphosphonates