Zoledronic Acid Cuts Fractures at All Fracture-Risk Levels

TORONTO – Among postmenopausal women with osteoporosis, treatment with zoledronic acid had a similar effect on fracture reduction regardless of whether women had a low, intermediate, or high baseline fracture risk, based on a post-hoc analysis of nearly 3,900 women who received the agent in the drug's pivotal trial for fracture prevention.

The analysis showed that rates of vertebral fractures and total clinical fractures fell by roughly similar amounts, regardless of the women's baseline fracture risk, with annual injection of zoledronic acid during 3 years of treatment and follow-up.

The rate of hip fractures showed a greater reduction in women who entered the study in the lowest tertile for fracture risk relative to the placebo group than in women with intermediate or high risk, but this difference failed to reach statistical significance, Jane A. Cauley, Dr.P.H. said at the meeting.

The message is that postmenopausal women with osteoporosis should feel comfortable starting zoledronic acid treatment regardless of the severity of their fracture risk at baseline, said Dr. Cauley, professor of epidemiology at the University of Pittsburgh.

It is not necessary to target treatment to women with an especially elevated fracture risk, such as those with a high FRAX (Fracture Risk Assessment Tool) score, she explained.

The current analysis used data collected in the Health Outcomes and Reduced Incidence With Zoledronic Acid Once Yearly (HORIZON) pivotal fracture trial, which randomized 7,765 postmenopausal women to either an annual infusion with 5 mg zoledronic acid or placebo for 3 years (N. Engl. J. Med 2007;356:1809-22).

Assessment of the study's primary end point showed that annual treatment with zoledronic acid significantly cut the rate of vertebral and hip fractures as well as total clinical fractures.

To perform the post-hoc analysis, Dr. Cauley and her associates rated the baseline fracture risk of the 3,889 women randomized to receive zole-dronic acid using a modification of the Fracture Index developed for the Study of Osteoporotic Fractures (SOF) (Osteoporosis Int. 2001;12:519-28).

The modification calculated a woman's baseline fracture risk using five of the seven variables of the SOF tool available in the HORIZON records: age, femoral neck bone mineral density T score, clinical fracture history, weight, and smoking status. The two SOF tool elements not available were maternal history of hip fracture and the use of arms to stand from a chair.

Analyses by Dr. Cauley and her associates using SOF data showed that calculating a fracture risk score with the five elements had a 98% correlation with the seven-item score, as well as a 64% correlation with women's FRAX scores. To further confirm the validity of the modified SOF score, they calculated scores for the 3,876 women enrolled in the placebo arm of HORIZON.

During 3 years of follow-up, the rate of total fractures per 1,000 person-years was 30, 35, and 45, respectively, in the low-, intermediate-, and high-risk tertiles.

Overall, for every 1-point rise in the modified SOF score, the risk of a fracture among the placebo women during follow-up rose by 11%, a statistically significant difference.

HORIZON was supported by Novartis, the company that markets zoledronic acid. Dr. Cauley said that she has received research funding from and has served as a consultant to Novartis.

TORONTO – Among postmenopausal women with osteoporosis, treatment with zoledronic acid had a similar effect on fracture reduction regardless of whether women had a low, intermediate, or high baseline fracture risk, based on a post-hoc analysis of nearly 3,900 women who received the agent in the drug's pivotal trial for fracture prevention.

The analysis showed that rates of vertebral fractures and total clinical fractures fell by roughly similar amounts, regardless of the women's baseline fracture risk, with annual injection of zoledronic acid during 3 years of treatment and follow-up.

The rate of hip fractures showed a greater reduction in women who entered the study in the lowest tertile for fracture risk relative to the placebo group than in women with intermediate or high risk, but this difference failed to reach statistical significance, Jane A. Cauley, Dr.P.H. said at the meeting.

The message is that postmenopausal women with osteoporosis should feel comfortable starting zoledronic acid treatment regardless of the severity of their fracture risk at baseline, said Dr. Cauley, professor of epidemiology at the University of Pittsburgh.

It is not necessary to target treatment to women with an especially elevated fracture risk, such as those with a high FRAX (Fracture Risk Assessment Tool) score, she explained.

The current analysis used data collected in the Health Outcomes and Reduced Incidence With Zoledronic Acid Once Yearly (HORIZON) pivotal fracture trial, which randomized 7,765 postmenopausal women to either an annual infusion with 5 mg zoledronic acid or placebo for 3 years (N. Engl. J. Med 2007;356:1809-22).

Assessment of the study's primary end point showed that annual treatment with zoledronic acid significantly cut the rate of vertebral and hip fractures as well as total clinical fractures.

To perform the post-hoc analysis, Dr. Cauley and her associates rated the baseline fracture risk of the 3,889 women randomized to receive zole-dronic acid using a modification of the Fracture Index developed for the Study of Osteoporotic Fractures (SOF) (Osteoporosis Int. 2001;12:519-28).

The modification calculated a woman's baseline fracture risk using five of the seven variables of the SOF tool available in the HORIZON records: age, femoral neck bone mineral density T score, clinical fracture history, weight, and smoking status. The two SOF tool elements not available were maternal history of hip fracture and the use of arms to stand from a chair.

Analyses by Dr. Cauley and her associates using SOF data showed that calculating a fracture risk score with the five elements had a 98% correlation with the seven-item score, as well as a 64% correlation with women's FRAX scores. To further confirm the validity of the modified SOF score, they calculated scores for the 3,876 women enrolled in the placebo arm of HORIZON.

During 3 years of follow-up, the rate of total fractures per 1,000 person-years was 30, 35, and 45, respectively, in the low-, intermediate-, and high-risk tertiles.

Overall, for every 1-point rise in the modified SOF score, the risk of a fracture among the placebo women during follow-up rose by 11%, a statistically significant difference.

HORIZON was supported by Novartis, the company that markets zoledronic acid. Dr. Cauley said that she has received research funding from and has served as a consultant to Novartis.

TORONTO – Among postmenopausal women with osteoporosis, treatment with zoledronic acid had a similar effect on fracture reduction regardless of whether women had a low, intermediate, or high baseline fracture risk, based on a post-hoc analysis of nearly 3,900 women who received the agent in the drug's pivotal trial for fracture prevention.

The analysis showed that rates of vertebral fractures and total clinical fractures fell by roughly similar amounts, regardless of the women's baseline fracture risk, with annual injection of zoledronic acid during 3 years of treatment and follow-up.

The rate of hip fractures showed a greater reduction in women who entered the study in the lowest tertile for fracture risk relative to the placebo group than in women with intermediate or high risk, but this difference failed to reach statistical significance, Jane A. Cauley, Dr.P.H. said at the meeting.

The message is that postmenopausal women with osteoporosis should feel comfortable starting zoledronic acid treatment regardless of the severity of their fracture risk at baseline, said Dr. Cauley, professor of epidemiology at the University of Pittsburgh.

It is not necessary to target treatment to women with an especially elevated fracture risk, such as those with a high FRAX (Fracture Risk Assessment Tool) score, she explained.

The current analysis used data collected in the Health Outcomes and Reduced Incidence With Zoledronic Acid Once Yearly (HORIZON) pivotal fracture trial, which randomized 7,765 postmenopausal women to either an annual infusion with 5 mg zoledronic acid or placebo for 3 years (N. Engl. J. Med 2007;356:1809-22).

Assessment of the study's primary end point showed that annual treatment with zoledronic acid significantly cut the rate of vertebral and hip fractures as well as total clinical fractures.

To perform the post-hoc analysis, Dr. Cauley and her associates rated the baseline fracture risk of the 3,889 women randomized to receive zole-dronic acid using a modification of the Fracture Index developed for the Study of Osteoporotic Fractures (SOF) (Osteoporosis Int. 2001;12:519-28).

The modification calculated a woman's baseline fracture risk using five of the seven variables of the SOF tool available in the HORIZON records: age, femoral neck bone mineral density T score, clinical fracture history, weight, and smoking status. The two SOF tool elements not available were maternal history of hip fracture and the use of arms to stand from a chair.

Analyses by Dr. Cauley and her associates using SOF data showed that calculating a fracture risk score with the five elements had a 98% correlation with the seven-item score, as well as a 64% correlation with women's FRAX scores. To further confirm the validity of the modified SOF score, they calculated scores for the 3,876 women enrolled in the placebo arm of HORIZON.

During 3 years of follow-up, the rate of total fractures per 1,000 person-years was 30, 35, and 45, respectively, in the low-, intermediate-, and high-risk tertiles.

Overall, for every 1-point rise in the modified SOF score, the risk of a fracture among the placebo women during follow-up rose by 11%, a statistically significant difference.

HORIZON was supported by Novartis, the company that markets zoledronic acid. Dr. Cauley said that she has received research funding from and has served as a consultant to Novartis.