Purpose: Bone antiresorptive agents can significantly reduce bone turnover markers (BTM) in patients with advanced cancer. We evaluated association of changes in BTMs with overall survival (OS), disease progression (DP), and disease progression in bone (DPB) in patients with advanced cancer and bone metastases following denosumab or zoledronic acid treatment. Experimental Design: This is an integrated analysis of patient-level data from three identically designed, blinded, phase III trials with patients randomized to subcutaneous denosumab or intravenous zoledronic acid. Levels of the BTMs urinary N-telopeptide (uNTx) and serum bone-specific alkaline phosphatase (sBSAP) measured at study entry and month 3 were analyzed. OS, DP, and DPB were compared in patients with BTMs ≥ median versus < median based on month 3 assessments. Results: uNTx levels ≥ the median of 10.0 nmol/mmol at month 3 were associated with significantly reduced OS compared with levels < median (HR for death, 1.85; P < 0.0001). sBSAP levels ≥ median of 12.6 ng/mL were associated with significantly reduced OS compared with levels < median (HR, 2.44; P < 0.0001). uNTx and sBSAP levels ≥l median at month 3 were associated with significantly greater risk of DP (HR, 1.31; P < 0.0001 and HR, 1.71; P < 0.0001, respectively) and DPB (HR, 1.11; P = 0.0407 and HR, 1.27; P < 0.0001, respectively). Conclusions: BTM levels-median after 3 months of bone antiresorptive treatment were associated with reduced OS and increased risk of DP and DPB. Assessment of uNTx and sBSAP levels after bone antiresorptive therapy may add to identification of patients at risk for worse clinical outcomes.