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The aim of this study was to assess the effects of zoledronic acid and raloxifene on bone turnover markers.This multicenter, randomized, double-blind study involved 110 postmenopausal women with low bone mineral density who received either a single intravenous infusion of zoledronic acid 5 mg or 6 months of daily oral raloxifene 60 mg. The primary efficacy variable was change from baseline in the bone resorption marker urine N-telopeptide of type I collagen. The secondary efficacy variable was change from baseline in the bone formation marker serum bone-specific alkaline phosphatase. Analysis time points were at 2, 4, and 6 (primary) months.At 6 months, zoledronic acid produced a significantly greater reduction than did raloxifene in urine N-telopeptide of type I collagen (P < 0.001). Zoledronic acid also yielded significantly greater decreases in urine N-telopeptide of type I collagen at 2 and 4 months and in serum bone-specific alkaline phosphatase at all time points (P < 0.001 vs raloxifene for all comparisons). Both treatments were well tolerated. More adverse events occurred in the zoledronic acid group; these were primarily transient postdose symptoms that occurred within the first 3 days after the infusion.Zoledronic acid demonstrated significantly greater decreases in bone turnover markers than did raloxifene in postmenopausal women with low bone mass.