Less Zoledronate May Prevent Osteoporotic Fractures

BOSTON – An annual dose of zoledronate that has been reduced by 50% or even 80% appears to be as effective as the recommended 5-mg dose in increasing bone mineral density and decreasing markers of bone turnover in osteopenic postmenopausal women, according to Dr. Andrew Grey, who presented the findings at the annual meeting of the Endocrine Society.

"We know that annual administration of intravenous zoledronate (also known as zoldedronic acid) at the 5-mg dose is an effective treatment for preventing fractures and decreasing fractures in osteoporotic, postmenopausal women by 25%-70%, depending on the skeletal site. Such treatment also reduces the risk of dying after hip fracture by 30%. Yet we don’t know the optimum dosing schedule," said Dr. Grey of the University of Auckland (New Zealand). The results of this study are important because reducing the dose can result in significant cost savings as well as decrease the risk of dose-dependent side effects.

In this prospective, controlled trial, 180 osteopenic postmenopausal women were randomized to receive a single dose of placebo or 1 mg, 2.5 mg, or 5 mg of zoledronate. The women had never been treated with zoledronate or any other bisphosphonate medication. The women underwent bone mineral density (BMD) evaluations at baseline and then 12 months after treatment.

For the primary end point (change in lumbar spine BMD at 12 months), the BMD increased significantly in each of the zoledronate groups, compared with placebo (P less than .001 for each dose). Notably, the magnitude of change was comparable for each dose: 3.5% for the 1-mg group, 4% for the 2.5-mg group, and 3.6% for the standard 5-mg group.

Similar results were observed for increases in total hip BMD (2.7% for the 1-mg group, 3.6% for the 2.5-mg group, and 3.6% for the 5-mg group). All results were significantly different from those with placebo (P less than .001).

Dr. Gray also looked at treatment effects on two blood markers of bone resorption, including beta-CTx (beta C-terminal telopeptide) and P1NP (procollagen type 1 N-terminal peptide). At all doses for both bone markers, zoledronate led to significant decreases, compared with placebo (P less than .001). For beta-CTx, the results were –44% for the 1-mg dose, –68% for the 2.5-mg dose and –73% for the 5-mg dose. For P1NP, the reductions were 41% for the 1-mg dose, 58% for the 2.5-mg dose, and 64% for the 5-mg dose.

An acute phase reaction is a side effect of intravenous bisphosphonate use. Fever is the most commonly associated symptom, but occasionally patients experience a flulike syndrome consisting of fever, chills, flushing, myalgias, and bone pain and/or arthralgias. In this study, acute phase reaction occurred less frequently in the zoledronate low-dose 1-mg group (odds ratio, 2.8) compared with either of the higher-dose groups (OR, 8.7 for the 2.5-mg group and 7.4 for the 5-mg group).

"These results show that lower doses than are currently prescribed have substantial antiresorptive effects that approximate those of the 5-mg dose, and suggest that these lower doses will be effective in preventing fractures in people with osteoporosis. Clinical trials should be undertaken to confirm whether annual low doses of zoledronate prevent fractures," according to Dr. Gray.

Dr. Grey had nothing to disclose; he said that the study was funded by public funds.

BOSTON – An annual dose of zoledronate that has been reduced by 50% or even 80% appears to be as effective as the recommended 5-mg dose in increasing bone mineral density and decreasing markers of bone turnover in osteopenic postmenopausal women, according to Dr. Andrew Grey, who presented the findings at the annual meeting of the Endocrine Society.

"We know that annual administration of intravenous zoledronate (also known as zoldedronic acid) at the 5-mg dose is an effective treatment for preventing fractures and decreasing fractures in osteoporotic, postmenopausal women by 25%-70%, depending on the skeletal site. Such treatment also reduces the risk of dying after hip fracture by 30%. Yet we don’t know the optimum dosing schedule," said Dr. Grey of the University of Auckland (New Zealand). The results of this study are important because reducing the dose can result in significant cost savings as well as decrease the risk of dose-dependent side effects.

In this prospective, controlled trial, 180 osteopenic postmenopausal women were randomized to receive a single dose of placebo or 1 mg, 2.5 mg, or 5 mg of zoledronate. The women had never been treated with zoledronate or any other bisphosphonate medication. The women underwent bone mineral density (BMD) evaluations at baseline and then 12 months after treatment.

For the primary end point (change in lumbar spine BMD at 12 months), the BMD increased significantly in each of the zoledronate groups, compared with placebo (P less than .001 for each dose). Notably, the magnitude of change was comparable for each dose: 3.5% for the 1-mg group, 4% for the 2.5-mg group, and 3.6% for the standard 5-mg group.

Similar results were observed for increases in total hip BMD (2.7% for the 1-mg group, 3.6% for the 2.5-mg group, and 3.6% for the 5-mg group). All results were significantly different from those with placebo (P less than .001).

Dr. Gray also looked at treatment effects on two blood markers of bone resorption, including beta-CTx (beta C-terminal telopeptide) and P1NP (procollagen type 1 N-terminal peptide). At all doses for both bone markers, zoledronate led to significant decreases, compared with placebo (P less than .001). For beta-CTx, the results were –44% for the 1-mg dose, –68% for the 2.5-mg dose and –73% for the 5-mg dose. For P1NP, the reductions were 41% for the 1-mg dose, 58% for the 2.5-mg dose, and 64% for the 5-mg dose.

An acute phase reaction is a side effect of intravenous bisphosphonate use. Fever is the most commonly associated symptom, but occasionally patients experience a flulike syndrome consisting of fever, chills, flushing, myalgias, and bone pain and/or arthralgias. In this study, acute phase reaction occurred less frequently in the zoledronate low-dose 1-mg group (odds ratio, 2.8) compared with either of the higher-dose groups (OR, 8.7 for the 2.5-mg group and 7.4 for the 5-mg group).

"These results show that lower doses than are currently prescribed have substantial antiresorptive effects that approximate those of the 5-mg dose, and suggest that these lower doses will be effective in preventing fractures in people with osteoporosis. Clinical trials should be undertaken to confirm whether annual low doses of zoledronate prevent fractures," according to Dr. Gray.

Dr. Grey had nothing to disclose; he said that the study was funded by public funds.

BOSTON – An annual dose of zoledronate that has been reduced by 50% or even 80% appears to be as effective as the recommended 5-mg dose in increasing bone mineral density and decreasing markers of bone turnover in osteopenic postmenopausal women, according to Dr. Andrew Grey, who presented the findings at the annual meeting of the Endocrine Society.

"We know that annual administration of intravenous zoledronate (also known as zoldedronic acid) at the 5-mg dose is an effective treatment for preventing fractures and decreasing fractures in osteoporotic, postmenopausal women by 25%-70%, depending on the skeletal site. Such treatment also reduces the risk of dying after hip fracture by 30%. Yet we don’t know the optimum dosing schedule," said Dr. Grey of the University of Auckland (New Zealand). The results of this study are important because reducing the dose can result in significant cost savings as well as decrease the risk of dose-dependent side effects.

In this prospective, controlled trial, 180 osteopenic postmenopausal women were randomized to receive a single dose of placebo or 1 mg, 2.5 mg, or 5 mg of zoledronate. The women had never been treated with zoledronate or any other bisphosphonate medication. The women underwent bone mineral density (BMD) evaluations at baseline and then 12 months after treatment.

For the primary end point (change in lumbar spine BMD at 12 months), the BMD increased significantly in each of the zoledronate groups, compared with placebo (P less than .001 for each dose). Notably, the magnitude of change was comparable for each dose: 3.5% for the 1-mg group, 4% for the 2.5-mg group, and 3.6% for the standard 5-mg group.

Similar results were observed for increases in total hip BMD (2.7% for the 1-mg group, 3.6% for the 2.5-mg group, and 3.6% for the 5-mg group). All results were significantly different from those with placebo (P less than .001).

Dr. Gray also looked at treatment effects on two blood markers of bone resorption, including beta-CTx (beta C-terminal telopeptide) and P1NP (procollagen type 1 N-terminal peptide). At all doses for both bone markers, zoledronate led to significant decreases, compared with placebo (P less than .001). For beta-CTx, the results were –44% for the 1-mg dose, –68% for the 2.5-mg dose and –73% for the 5-mg dose. For P1NP, the reductions were 41% for the 1-mg dose, 58% for the 2.5-mg dose, and 64% for the 5-mg dose.

An acute phase reaction is a side effect of intravenous bisphosphonate use. Fever is the most commonly associated symptom, but occasionally patients experience a flulike syndrome consisting of fever, chills, flushing, myalgias, and bone pain and/or arthralgias. In this study, acute phase reaction occurred less frequently in the zoledronate low-dose 1-mg group (odds ratio, 2.8) compared with either of the higher-dose groups (OR, 8.7 for the 2.5-mg group and 7.4 for the 5-mg group).

"These results show that lower doses than are currently prescribed have substantial antiresorptive effects that approximate those of the 5-mg dose, and suggest that these lower doses will be effective in preventing fractures in people with osteoporosis. Clinical trials should be undertaken to confirm whether annual low doses of zoledronate prevent fractures," according to Dr. Gray.

Dr. Grey had nothing to disclose; he said that the study was funded by public funds.