Predictive value of n-terminal telopeptide of type I collagen in patients with malignant osteolytic bone disease on bisphosphonates.

Abstract

e13047 Background: There is an urgent need for individualized treatment of patients with malignant bone disease (MBD), as the clinical benefit from bone-targeted therapies is moderate so far. As there is indirect evidence for N-terminal telopeptide of type I collagen (P1NP) to be involved in bisphosphonate resistance, we assessed the predictive value of P1NP for clinical outcome in patients with MBD receiving bisphosphonates. Methods: 70 patients with MBD were randomized to receive iv. pamidronate 60mg (n=35) or 90mg (n=35) for six 3-weekly cycles in a randomized, double-blind study (approved by the ethics committee). All patients had WHO pain score ≥2, modified WHO analgesic score ≥2, serum creatinine <350μmol/l, written informed consent. Median follow-up time is 14.8 years. Total serum P1NP concentrations were measured every three weeks by ELISA (gift from Roche Diagnostics, Basel). Baseline (continuous and categorical) P1NP concentrations were compared with pain response [visual analog scale (VAS), composite pain score (PPA)] and clinical outcome (skeletal-related events (SRE): Pathologic bone fracture, spinal cord compression, surgery to bone or radiation to bone) using Student's t, Wilcoxon rank-sum and log-rank test, respectively. The study has a power of 80% to detect a 20% difference in pain intensity (α=0.05, SD=15 mm on the VAS). Results: Patients with ≥20% pain reduction on the VAS had lower baseline P1NP concentrations as compared to patients with <20% VAS-response (146 vs. 323μg/L, p<0.0001). A negative correlation was found between baseline P1NP concentrations and maximum VAS-response (r= -0.59, p<0.0001) or PPA-response (r= -0.30, p=0.02) High baseline P1NP concentrations (highest tertile vs. lower two tertiles) were associated with a shorter duration of pain response (p<0.0001) and a shorter time interval to first SRE (p<0.008). Sensitivity for low baseline P1NP to predict freedom-from-SRE in the first year after treatment was 75%, specificity 82%. Conclusions: Serum P1NP has considerable predictive value for clinical outcome in patients with MBD receiving bisphosphonates. P1NP should be validated in studies with newer bone-targeted agents. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche