Single, IV-Dose Zoledronic Acid Bests Alendronate on Resorption 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 demonstrated 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 intravenous zoledronic acid also received oral placebo, and those receiving oral alendronate also received intravenous 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 decreased from 45.8 to 35.5 nmol BCE/mmol creatinine in the alendronate group at 1 week. This relative change from baseline in NTx was significantly different between the two groups, and the greater reduction in urine NTx with zoledronic acid 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 BASP levels were significantly greater in the zoledronic acid group at week 12, levels in both groups were within the premenopausal range of 6.2 to 12.8 ng/mL.

Overall, a comparable proportion of patients in each treatment arm reported adverse events, with 91% of those in the zoledronic acid group and 86% of those in the alendronate group experiencing any 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 compared with the alendronate group (64% versus 37%), but after 3 days the adverse event rates were similar in the two groups, Dr. Saag reported.

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 in the alendronate group (one patella fracture and two reports of osteoarthritis). None were considered to be treatment related.

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% versus 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 following 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.

Early on, zoledronicgroup patients were more likely to have adverse events associated with flulike symptoms. DR. SAAG

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 demonstrated 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 intravenous zoledronic acid also received oral placebo, and those receiving oral alendronate also received intravenous 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 decreased from 45.8 to 35.5 nmol BCE/mmol creatinine in the alendronate group at 1 week. This relative change from baseline in NTx was significantly different between the two groups, and the greater reduction in urine NTx with zoledronic acid 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 BASP levels were significantly greater in the zoledronic acid group at week 12, levels in both groups were within the premenopausal range of 6.2 to 12.8 ng/mL.

Overall, a comparable proportion of patients in each treatment arm reported adverse events, with 91% of those in the zoledronic acid group and 86% of those in the alendronate group experiencing any 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 compared with the alendronate group (64% versus 37%), but after 3 days the adverse event rates were similar in the two groups, Dr. Saag reported.

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 in the alendronate group (one patella fracture and two reports of osteoarthritis). None were considered to be treatment related.

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% versus 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 following 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.

Early on, zoledronicgroup patients were more likely to have adverse events associated with flulike symptoms. DR. SAAG

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 demonstrated 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 intravenous zoledronic acid also received oral placebo, and those receiving oral alendronate also received intravenous 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 decreased from 45.8 to 35.5 nmol BCE/mmol creatinine in the alendronate group at 1 week. This relative change from baseline in NTx was significantly different between the two groups, and the greater reduction in urine NTx with zoledronic acid 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 BASP levels were significantly greater in the zoledronic acid group at week 12, levels in both groups were within the premenopausal range of 6.2 to 12.8 ng/mL.

Overall, a comparable proportion of patients in each treatment arm reported adverse events, with 91% of those in the zoledronic acid group and 86% of those in the alendronate group experiencing any 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 compared with the alendronate group (64% versus 37%), but after 3 days the adverse event rates were similar in the two groups, Dr. Saag reported.

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 in the alendronate group (one patella fracture and two reports of osteoarthritis). None were considered to be treatment related.

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% versus 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 following 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.

Early on, zoledronicgroup patients were more likely to have adverse events associated with flulike symptoms. DR. SAAG