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Joerger, M. et al.

M. Joerger, A. Templeton, D. Köberle, H. Engler, W.F. Riesen, B. Thürlimann,

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

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.[1]

References

Procollagen type I N-propeptide is a predictor of skeletal morbidity in patients with malignant osteolytic bone disease on bisphosphonates. Joerger, M., Templeton, A., Köberle, D., Engler, H., Riesen, W.F., Thürlimann, B. Cancer Chemother. Pharmacol. (2011) [Pubmed]

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