title: Procollagen type I N-propeptide is a predictor of skeletal morbidity in patients with malignant osteolytic bone disease on bisphosphonates.
abstract: BACKGROUND
  There is an urgent need for individualized treatment of malignant bone disease (MBD), as the clinical benefit from bone-targeted therapies is moderate. We assessed the predictive value of the bone formation marker procollagen type I N-propeptide (PINP) for skeletal morbidity in patients with MBD receiving pamidronate.
  
  
  METHODS
  Seventy patients with advanced MBD were randomized to receive pamidronate 60 mg (n = 35) or 90 mg (n = 35) every 3 weeks for six cycles in a double-blind study. PINP was analyzed at baseline and before each administration of pamidronate, using a validated ELISA. Serum PINP concentrations were compared with pain response (visual analog scale VAS, composite pain score) and skeletal morbidity (skeletal-related events, SRE) using Student's T-test, Wilcoxon rank-sum and log-rank test, respectively.
  
  
  RESULTS
  Patients with ≥20% pain reduction in the VAS had lower baseline PINP concentrations when compared to patients with <20% VAS response (P < 0.0001). A high baseline serum PINP concentration (highest tertile versus lower two tertiles) was significantly associated with a shorter duration of pain response (P < 0.0001) and a shorter time interval to first SRE (P < 0.008). Sensitivity of a low baseline PINP serum concentration for freedom from SRE at 1 year from randomization was 75% (15 out of 20 patients), while specificity was 82% (27 out of 33 patients).
  
  
  CONCLUSIONS
  Serum PINP has been shown to be a significant predictor for skeletal morbidity in patients with MBD on pamidronate treatment. Prospective validation of PINP in patients with MBD to assess the prognosis or individualize bone-targeted treatment is justified.
authors.affiliation: Department of Oncology and Hematology, Cantonal Hospital, Rorschacherstr. 95, 9007 St. Gallen, Switzerland. markus.joerger@kssg.ch
authors.forename: M
authors.initials: M
authors.lastname: Joerger
authors.forename: A
authors.initials: A
authors.lastname: Templeton
authors.forename: D
authors.initials: D
authors.lastname: Köberle
authors.forename: H
authors.initials: H
authors.lastname: Engler
authors.forename: W F
authors.initials: WF
authors.lastname: Riesen
authors.forename: B
authors.initials: B
authors.lastname: Thürlimann
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D001859:Bone Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000473:pathology / Q000556:secondary; D001842:Bone and Bones / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D024042:Collagen Type I / Q000378:metabolism*; D004164:Diphosphonates / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D010014:Osteolysis / Q000175:diagnosis* / Q000188:drug therapy / Q000473:pathology; D010146:Pain / Q000503:physiopathology; D000077268:Pamidronate; D010446:Peptide Fragments / Q000097:blood*; D011237:Predictive Value of Tests; D011347:Procollagen / Q000097:blood*; D011446:Prospective Studies
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D024042:Collagen Type I; D004164:Diphosphonates; D010446:Peptide Fragments; D011347:Procollagen; C047202:procollagen Type I N-terminal peptide; D000077268:Pamidronate