Single-Dose Zoledronic Acid Rapidly Improves Bone Markers

TORONTO — A single intravenous dose of zoledronic acid reduced markers of bone resorption in postmenopausal women more rapidly and to a greater extent than did weekly oral alendronate, Dr. Kenneth Saag reported in a poster session at a world congress on osteoporosis.

Zoledronic acid is the most powerful of the available bisphosphonates, and its long duration of effect now has been shown in a multicenter double-blind trial that randomized 118 women aged 45–79 years to a single infusion of 5 mg zoledronic acid or 70 mg weekly oral alendronate for 24 weeks. Patients receiving IV zoledronic acid also received oral placebo, and those receiving oral alendronate also received IV placebo.

In the zoledronic acid group, mean urine cross-linked N-telopeptide of type I collagen (NTx) fell from 46.1 to 15.2 nmol bone collagen equivalent (BCE)/mmol creatinine at 1 week, while the level of this marker of bone turnover fell from 45.8 to 35.5 nmol BCE/mmol creatinine in the alendronate group at 1 week. The greater reduction in urine NTx with zoledronic acid was significant and persisted throughout the 24 weeks of the study, according to Dr. Saag of the division of rheumatology, University of Alabama, Birmingham.

Levels of bone-specific alkaline phosphatase (BSAP) also decreased from baseline through week 24 in both groups. While reductions in BSAP levels were significantly greater in the zoledronic acid group at week 12, levels in both groups were within the premenopausal range of 6.2–12.8 ng/mL.

Overall, 91% of patients in the zoledronic acid group and 86% of those in the alendronate group experienced an adverse event. During the first 3 days after drug initiation, flulike symptoms led to a greater frequency of adverse events in the zoledronic acid group than in the alendronate group (64% vs. 37%), but after 3 days the adverse event rates were similar in the two groups, Dr. Saag said.

Serious adverse events were reported by two patients in the zoledronic acid group (one report of osteoarthritis and one of chest pain) and by three patients in the alendronate group (one report of patella fracture and two of osteoarthritis). None of the reports was considered to be related to the treatment.

Patient preferences for the treatments also were analyzed, with study participants expressing a “strong preference” for the single infusion compared with the weekly regimen (66% vs. 20%), Dr. Robert Lindsay noted in another poster session at the meeting, which was sponsored by the International Osteoporosis Foundation.

Even among patients who experienced adverse events during the 3 days after the infusion, 74% expressed an overall preference for the single-dose treatment, according to Dr. Lindsay of the clinical research center, Helen Hayes Hospital, West Haverstraw, N.Y.

The study was funded by Novartis Pharma AG, Basel, Switzerland.

TORONTO — A single intravenous dose of zoledronic acid reduced markers of bone resorption in postmenopausal women more rapidly and to a greater extent than did weekly oral alendronate, Dr. Kenneth Saag reported in a poster session at a world congress on osteoporosis.

Zoledronic acid is the most powerful of the available bisphosphonates, and its long duration of effect now has been shown in a multicenter double-blind trial that randomized 118 women aged 45–79 years to a single infusion of 5 mg zoledronic acid or 70 mg weekly oral alendronate for 24 weeks. Patients receiving IV zoledronic acid also received oral placebo, and those receiving oral alendronate also received IV placebo.

In the zoledronic acid group, mean urine cross-linked N-telopeptide of type I collagen (NTx) fell from 46.1 to 15.2 nmol bone collagen equivalent (BCE)/mmol creatinine at 1 week, while the level of this marker of bone turnover fell from 45.8 to 35.5 nmol BCE/mmol creatinine in the alendronate group at 1 week. The greater reduction in urine NTx with zoledronic acid was significant and persisted throughout the 24 weeks of the study, according to Dr. Saag of the division of rheumatology, University of Alabama, Birmingham.

Levels of bone-specific alkaline phosphatase (BSAP) also decreased from baseline through week 24 in both groups. While reductions in BSAP levels were significantly greater in the zoledronic acid group at week 12, levels in both groups were within the premenopausal range of 6.2–12.8 ng/mL.

Overall, 91% of patients in the zoledronic acid group and 86% of those in the alendronate group experienced an adverse event. During the first 3 days after drug initiation, flulike symptoms led to a greater frequency of adverse events in the zoledronic acid group than in the alendronate group (64% vs. 37%), but after 3 days the adverse event rates were similar in the two groups, Dr. Saag said.

Serious adverse events were reported by two patients in the zoledronic acid group (one report of osteoarthritis and one of chest pain) and by three patients in the alendronate group (one report of patella fracture and two of osteoarthritis). None of the reports was considered to be related to the treatment.

Patient preferences for the treatments also were analyzed, with study participants expressing a “strong preference” for the single infusion compared with the weekly regimen (66% vs. 20%), Dr. Robert Lindsay noted in another poster session at the meeting, which was sponsored by the International Osteoporosis Foundation.

Even among patients who experienced adverse events during the 3 days after the infusion, 74% expressed an overall preference for the single-dose treatment, according to Dr. Lindsay of the clinical research center, Helen Hayes Hospital, West Haverstraw, N.Y.

The study was funded by Novartis Pharma AG, Basel, Switzerland.

TORONTO — A single intravenous dose of zoledronic acid reduced markers of bone resorption in postmenopausal women more rapidly and to a greater extent than did weekly oral alendronate, Dr. Kenneth Saag reported in a poster session at a world congress on osteoporosis.

Zoledronic acid is the most powerful of the available bisphosphonates, and its long duration of effect now has been shown in a multicenter double-blind trial that randomized 118 women aged 45–79 years to a single infusion of 5 mg zoledronic acid or 70 mg weekly oral alendronate for 24 weeks. Patients receiving IV zoledronic acid also received oral placebo, and those receiving oral alendronate also received IV placebo.

In the zoledronic acid group, mean urine cross-linked N-telopeptide of type I collagen (NTx) fell from 46.1 to 15.2 nmol bone collagen equivalent (BCE)/mmol creatinine at 1 week, while the level of this marker of bone turnover fell from 45.8 to 35.5 nmol BCE/mmol creatinine in the alendronate group at 1 week. The greater reduction in urine NTx with zoledronic acid was significant and persisted throughout the 24 weeks of the study, according to Dr. Saag of the division of rheumatology, University of Alabama, Birmingham.

Levels of bone-specific alkaline phosphatase (BSAP) also decreased from baseline through week 24 in both groups. While reductions in BSAP levels were significantly greater in the zoledronic acid group at week 12, levels in both groups were within the premenopausal range of 6.2–12.8 ng/mL.

Overall, 91% of patients in the zoledronic acid group and 86% of those in the alendronate group experienced an adverse event. During the first 3 days after drug initiation, flulike symptoms led to a greater frequency of adverse events in the zoledronic acid group than in the alendronate group (64% vs. 37%), but after 3 days the adverse event rates were similar in the two groups, Dr. Saag said.

Serious adverse events were reported by two patients in the zoledronic acid group (one report of osteoarthritis and one of chest pain) and by three patients in the alendronate group (one report of patella fracture and two of osteoarthritis). None of the reports was considered to be related to the treatment.

Patient preferences for the treatments also were analyzed, with study participants expressing a “strong preference” for the single infusion compared with the weekly regimen (66% vs. 20%), Dr. Robert Lindsay noted in another poster session at the meeting, which was sponsored by the International Osteoporosis Foundation.

Even among patients who experienced adverse events during the 3 days after the infusion, 74% expressed an overall preference for the single-dose treatment, according to Dr. Lindsay of the clinical research center, Helen Hayes Hospital, West Haverstraw, N.Y.

The study was funded by Novartis Pharma AG, Basel, Switzerland.