Prospective evaluation of the peptide-bound collagen type I cross-links N-telopeptide and C-telopeptide in predicting bone metastases status

Purpose: The objective assessment of bone metastases is currently based on serial changes in skeletal survey. We performed a prospective study to determine whether a correlation exists between the biochemical markers of bone turnover and x-ray evaluation of bone metastases in patients with or without bisphosphonate therapy, and whether bone markers are influenced by extraskeletal disease. Patients and Methods: Patients with either bone or extraskeletal metastases were consecutively enrolled and World Health Organization response criteria were applied for both bone and extraosseous disease every 3 to 4 months. Serum levels of bone-specific alkaline phosphatase (B-AP) and C-telopeptide (ICTP) and urine levels of N-telopeptide (NTX) were measured monthly. The data were analyzed by generalized estimation equation regression. Results: We studied 97 patients with bone metastases (52 also with extraskeletal metastases) and 26 with extraosseous disease only. Median time on study was 153 days, and 281 objective evaluations (171 in bone) were performed. With bisphosphonates (49 patients receiving pamidronate and three receiving clodronate), percent change from levels without therapy was 47% for NTX (P < .001) and 69% for B-AP (P = .008). With disease progression in bone, percent change from mean levels during stable disease was 152% for NTX (P < .001) and 144% for ICTP (P < .001) regardless of bisphosphonate therapy. NTX had the highest positive predictive value (71%) for the diagnosis of bone metastases progression. Extraskeletal disease had no significant effect on bone markers. Conclusion: Urinary NTX may be a valuable bone marker to assess the antiresorptive effect of bisphosphonate therapy and to evaluate the progression of bone metastases.