Six-Year Zoledronic Acid Regimen Maintains BMD

TORONTO — Patients who continued annual treatment with zoledronic acid for 6 years had significantly better bone mineral density and fewer morphometric vertebral fractures than did patients who received 3 years of treatment and then stopped, in a controlled study with more than 1,200 patients.

Six continuous years of annual zoledronic acid treatment also proved safe, making continued treatment with this bisphosphonate formulation an option for patients who might benefit, said Dennis M. Black, Ph.D., professor of epidemiology and biostatistics at the University of California, San Francisco.

“After 3 years, it might be beneficial for some women, particularly those at high vertebral fracture risk, to continue zoledronic acid for an additional 3 years,” he said.

“These new findings show that continued treatment with zoledronic acid for 6 years continues to maintain bone mass and reduced vertebral fracture risk with no change to its favorable safety profile compared with discontinuation of treatment after 3 years,” Dr. Black said in a written statement.

On the other hand, the decision to continue bisphosphonate treatment long term must be individualized, he said. It may be possible to identify women who would benefit from a drug holiday.

The new zoledronic acid findings came from an extension of the Health Outcomes and Reduced Incidence With Zoledronic Acid Once Yearly (HORIZON) Pivotal Fracture Trial, which compared a single, annual infusion of zoledronic acid with placebo in postmenopausal women with osteoporosis during 3 years of treatment (N. Engl. J. Med. 2007;356:1809–22). D

Dr. Black and his associates randomized 1,233 women who completed the zoledronic acid arm of the study to either continue with another 3 years of annual infusions of 5 mg zoledronic acid or switch to placebo.

Their average age was 76, and about 55% had a femoral neck T score of less than −2.5.

At the end of the study, the percent change in femoral neck bone mineral density, compared with the level at entry into the study, averaged 1% higher in patients treated with zoledronic acid, a statistically significant difference in the study's primary end point.

Femoral neck bone mineral density in the zoledronic acid–treated patients increased by an average of 1.4% over their baseline 6 years earlier (when they started on the drug), compared with those who switched off the bisphosphonate after 3 years, also a statistically significant difference.

The rate of morphometric vertebral fractures during the 3 years of the new study totaled 6% in the patients on placebo and 3% in those on zoledronic acid, a statistically significant difference.

The HORIZON trial was funded by Novartis, which markets zoledronic acid (Aclasta).

Dr. Black said that he has served as a consultant and done teaching for Amgen Inc. and Nycomed, and that he has received research contracts from Amgen, Merck & Co., Novartis, and Roche/Genentech.

TORONTO — Patients who continued annual treatment with zoledronic acid for 6 years had significantly better bone mineral density and fewer morphometric vertebral fractures than did patients who received 3 years of treatment and then stopped, in a controlled study with more than 1,200 patients.

Six continuous years of annual zoledronic acid treatment also proved safe, making continued treatment with this bisphosphonate formulation an option for patients who might benefit, said Dennis M. Black, Ph.D., professor of epidemiology and biostatistics at the University of California, San Francisco.

“After 3 years, it might be beneficial for some women, particularly those at high vertebral fracture risk, to continue zoledronic acid for an additional 3 years,” he said.

“These new findings show that continued treatment with zoledronic acid for 6 years continues to maintain bone mass and reduced vertebral fracture risk with no change to its favorable safety profile compared with discontinuation of treatment after 3 years,” Dr. Black said in a written statement.

On the other hand, the decision to continue bisphosphonate treatment long term must be individualized, he said. It may be possible to identify women who would benefit from a drug holiday.

The new zoledronic acid findings came from an extension of the Health Outcomes and Reduced Incidence With Zoledronic Acid Once Yearly (HORIZON) Pivotal Fracture Trial, which compared a single, annual infusion of zoledronic acid with placebo in postmenopausal women with osteoporosis during 3 years of treatment (N. Engl. J. Med. 2007;356:1809–22). D

Dr. Black and his associates randomized 1,233 women who completed the zoledronic acid arm of the study to either continue with another 3 years of annual infusions of 5 mg zoledronic acid or switch to placebo.

Their average age was 76, and about 55% had a femoral neck T score of less than −2.5.

At the end of the study, the percent change in femoral neck bone mineral density, compared with the level at entry into the study, averaged 1% higher in patients treated with zoledronic acid, a statistically significant difference in the study's primary end point.

Femoral neck bone mineral density in the zoledronic acid–treated patients increased by an average of 1.4% over their baseline 6 years earlier (when they started on the drug), compared with those who switched off the bisphosphonate after 3 years, also a statistically significant difference.

The rate of morphometric vertebral fractures during the 3 years of the new study totaled 6% in the patients on placebo and 3% in those on zoledronic acid, a statistically significant difference.

The HORIZON trial was funded by Novartis, which markets zoledronic acid (Aclasta).

Dr. Black said that he has served as a consultant and done teaching for Amgen Inc. and Nycomed, and that he has received research contracts from Amgen, Merck & Co., Novartis, and Roche/Genentech.

TORONTO — Patients who continued annual treatment with zoledronic acid for 6 years had significantly better bone mineral density and fewer morphometric vertebral fractures than did patients who received 3 years of treatment and then stopped, in a controlled study with more than 1,200 patients.

Six continuous years of annual zoledronic acid treatment also proved safe, making continued treatment with this bisphosphonate formulation an option for patients who might benefit, said Dennis M. Black, Ph.D., professor of epidemiology and biostatistics at the University of California, San Francisco.

“After 3 years, it might be beneficial for some women, particularly those at high vertebral fracture risk, to continue zoledronic acid for an additional 3 years,” he said.

“These new findings show that continued treatment with zoledronic acid for 6 years continues to maintain bone mass and reduced vertebral fracture risk with no change to its favorable safety profile compared with discontinuation of treatment after 3 years,” Dr. Black said in a written statement.

On the other hand, the decision to continue bisphosphonate treatment long term must be individualized, he said. It may be possible to identify women who would benefit from a drug holiday.

The new zoledronic acid findings came from an extension of the Health Outcomes and Reduced Incidence With Zoledronic Acid Once Yearly (HORIZON) Pivotal Fracture Trial, which compared a single, annual infusion of zoledronic acid with placebo in postmenopausal women with osteoporosis during 3 years of treatment (N. Engl. J. Med. 2007;356:1809–22). D

Dr. Black and his associates randomized 1,233 women who completed the zoledronic acid arm of the study to either continue with another 3 years of annual infusions of 5 mg zoledronic acid or switch to placebo.

Their average age was 76, and about 55% had a femoral neck T score of less than −2.5.

At the end of the study, the percent change in femoral neck bone mineral density, compared with the level at entry into the study, averaged 1% higher in patients treated with zoledronic acid, a statistically significant difference in the study's primary end point.

Femoral neck bone mineral density in the zoledronic acid–treated patients increased by an average of 1.4% over their baseline 6 years earlier (when they started on the drug), compared with those who switched off the bisphosphonate after 3 years, also a statistically significant difference.

The rate of morphometric vertebral fractures during the 3 years of the new study totaled 6% in the patients on placebo and 3% in those on zoledronic acid, a statistically significant difference.

The HORIZON trial was funded by Novartis, which markets zoledronic acid (Aclasta).

Dr. Black said that he has served as a consultant and done teaching for Amgen Inc. and Nycomed, and that he has received research contracts from Amgen, Merck & Co., Novartis, and Roche/Genentech.