title: Clinical value of bone remodelling markers in patients with bone metastases treated with zoledronic acid.
abstract: BACKGROUND
  Bisphosphonates have an established role in the treatment of bone metastases from a variety of solid tumours. The objective response to anti-resorptive treatment cannot be evaluated by imaging techniques. A number of bone remodelling markers have been associated with bone metastases status; among them, urine and serum levels of N-terminal telopeptide of collagen type I (NTx) seem to have the best diagnostic accuracy. However, serum NTx has not yet been properly evaluated.
  
  
  METHODS
  Seventy-one consecutive patients with newly diagnosed skeletal metastases were enrolled in this prospective study. All of them were treated with zoledronic acid at 4 mg, every 3 or 4 weeks. Serum NTx and bone-isoform of alkaline phosphatase (BAP) were measured by enzyme-linked immunosorbent assays at baseline and every 2 months thereafter.
  
  
  RESULTS
  At baseline, serum NTx and BAP levels were significantly higher in patients with blastic than lytic bone lesions and in those with multiple rather than few bone site involvement. Forty-seven patients were followed for a median period of 139 days. Zoledronic acid resulted in a significant NTx reduction at first and second post-treatment evaluations (mean reduction of 43% at first evaluation); thereafter, mean NTx levels remained suppressed. In contrast, BAP levels did not show any significant changes. Bone disease progression resulted in a significant NTx elevation by an average of 69%. The initial response of NTx to zoledronic acid was correlated with the long-term clinical outcome of bone disease: patients with an initial NTx elevation had a significantly higher rate of bone disease progression compared to those with an initial NTx decline (66.7% versus 18.8%, p=0.001). Extraskeletal disease or bone irradiation did not influence NTx response.
  
  
  CONCLUSIONS
  Serum NTx appears to be a useful marker in monitoring patients with skeletal metastases, as it is correlated with the type and bulk of bone disease and reflects bone disease progression. It is also useful in monitoring bisphosphonate therapy, while the initial response to this therapy seems to bear a prognostic significance for bone disease outcome.
authors.affiliation: Second Department of Internal Medicine-Propaedeutic, Athens University Medical School, Attikon University Hospital, Athens, Greece. pectasid@otenet.gr
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Pectasides
authors.forename: Maria
authors.initials: M
authors.lastname: Nikolaou
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Farmakis
authors.forename: Ioannis
authors.initials: I
authors.lastname: Kanakis
authors.forename: Asimina
authors.initials: A
authors.lastname: Gaglia
authors.forename: Pantelis
authors.initials: P
authors.lastname: Kountourakis
authors.forename: Nikolaos K
authors.initials: NK
authors.lastname: Karamanos
authors.forename: Theofanis
authors.initials: T
authors.lastname: Economopoulos
authors.forename: Sotirios A
authors.initials: SA
authors.lastname: Raptis
mesh_terms: D000368:Aged; D000469:Alkaline Phosphatase / Q000097:blood; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000032:analysis*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary*; D016723:Bone Remodeling / Q000187:drug effects*; D003094:Collagen / Q000097:blood*; D024042:Collagen Type I; D004164:Diphosphonates / Q000627:therapeutic use*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000097:blood*; D000077211:Zoledronic Acid
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D024042:Collagen Type I; D004164:Diphosphonates; D007093:Imidazoles; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D000077211:Zoledronic Acid; D003094:Collagen; D000469:Alkaline Phosphatase