Procollagen type I N-propeptide is a predictor of skeletal morbidity in patients with malignant osteolytic bone disease on bisphosphonates

Abstract

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. 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. 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). 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.