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Zoledronate limits fracture risk in older women with osteopenia

Women aged at least 65 years with osteopenia were shown to be less at risk for fragility fracture when treated with zoledronate vs. placebo, according to study results reported at the American Society for Bone and Mineral Research Annual Meeting and published simultaneously in The New England Journal of Medicine.

“The need to establish treatment efficacy in osteopenia has become more pressing, given the clinical trend to base intervention decisions on absolute fracture risk,” Ian. R. Reid, MD, of the department of medicine at Faculty of Medical and Health Sciences, University of Auckland, and colleagues wrote. “Zoledronate (also known as zoledronic acid) has characteristics that make it attractive for use in women who have osteopenia. It is administered by intravenous injection at intervals of 1 year or longer, it is preferred over oral bisphosphonates by a majority of patients and it has had a satisfactory safety profile.”

The researchers enrolled 2,000 women from Auckland, New Zealand, to take part in a randomized, double-blind, placebo-controlled trial. Those selected were aged at least 65 years (mean age, 71 years) and had a T score of –1 to –2.5 at the total hip or femoral neck.

Participants were enrolled from 2009 to 2011 and randomly assigned to a 5 mg injection of zoledronate every 18 months for 6 years or saline injections at the same intervals. Participants were followed throughout the 6 years of the treatment process, with the final follow-up occurring in January 2018. Primary endpoint was time to first fragility fracture. Participants self-reported fractures, and events that required hospitalization were confirmed by medical records.

The researchers reported 227 fragility fractures in 190 of the women from the placebo group and 131 fractures in 122 women in the zoledronate group (zoledronate group HR = 0.63; 95% CI, 0.5-0.79). The placebo group had 276 symptomatic fractures in 214 women compared with 185 in 163 women in the zoledronate group (zoledronate group HR = 0.73; 95% CI, 0.6-0.9). Fewer vertebral fractures (25 in 23 women) were observed in the zoledronate group vs. the placebo group (64 fractures in 49 women; zoledronate group HR = 0.45; 95% CI, 0.27-0.73). Fewer nonvertebral fractures were observed in the zoledronate group (108 fractures in 101 women) compared with the placebo group (178 fractures in 148 women; zoledronate group HR = 0.66; 95% CI, 0.51-0.85); difference in nonvertebral hip fractures between the groups was not statistically significant.

When accounting for exclusionary factors such as baseline risk for hip fracture, the zoledronate group maintained a lower risk for fragility fracture (HR = 0.6; 95% CI, 0.39-0.91) vs. the placebo group, according to the results.

“Our results address an important knowledge gap identified in the recently published American College of Physicians guidelines on osteoporosis, which stated that ‘current evidence is limited for a treatment benefit for women aged 65 years or older with osteopenia,’” the researchers wrote. “Zoledronate has a sustained duration of action, with bone turnover markers still suppressed by almost half 5 years after a single infusion. ... The reduction in the risk of fractures observed in the current trial suggests that annual administration may be unnecessary for maximal efficacy in the prevention of fractures and that even longer intervals between doses should be considered.” – by Phil Neuffer

Reference:

Reid I, et al. Abstract LB-1166. Presented at: American Society for Bone and Mineral Research Annual Meeting; Sept. 28-Oct. 1, 2018; Montreal.

Disclosures: Reid reports he has received grants from the Health Research Council of New Zealand; nonfinancial support from Novartis, which supplied trial medication; grants and personal fees from Amgen and Merck; and personal fees from Eli Lilly and Novartis. Please see the study for all other authors’ relevant financial disclosures.

Women aged at least 65 years with osteopenia were shown to be less at risk for fragility fracture when treated with zoledronate vs. placebo, according to study results reported at the American Society for Bone and Mineral Research Annual Meeting and published simultaneously in The New England Journal of Medicine.

“The need to establish treatment efficacy in osteopenia has become more pressing, given the clinical trend to base intervention decisions on absolute fracture risk,” Ian. R. Reid, MD, of the department of medicine at Faculty of Medical and Health Sciences, University of Auckland, and colleagues wrote. “Zoledronate (also known as zoledronic acid) has characteristics that make it attractive for use in women who have osteopenia. It is administered by intravenous injection at intervals of 1 year or longer, it is preferred over oral bisphosphonates by a majority of patients and it has had a satisfactory safety profile.”

The researchers enrolled 2,000 women from Auckland, New Zealand, to take part in a randomized, double-blind, placebo-controlled trial. Those selected were aged at least 65 years (mean age, 71 years) and had a T score of –1 to –2.5 at the total hip or femoral neck.

Participants were enrolled from 2009 to 2011 and randomly assigned to a 5 mg injection of zoledronate every 18 months for 6 years or saline injections at the same intervals. Participants were followed throughout the 6 years of the treatment process, with the final follow-up occurring in January 2018. Primary endpoint was time to first fragility fracture. Participants self-reported fractures, and events that required hospitalization were confirmed by medical records.

The researchers reported 227 fragility fractures in 190 of the women from the placebo group and 131 fractures in 122 women in the zoledronate group (zoledronate group HR = 0.63; 95% CI, 0.5-0.79). The placebo group had 276 symptomatic fractures in 214 women compared with 185 in 163 women in the zoledronate group (zoledronate group HR = 0.73; 95% CI, 0.6-0.9). Fewer vertebral fractures (25 in 23 women) were observed in the zoledronate group vs. the placebo group (64 fractures in 49 women; zoledronate group HR = 0.45; 95% CI, 0.27-0.73). Fewer nonvertebral fractures were observed in the zoledronate group (108 fractures in 101 women) compared with the placebo group (178 fractures in 148 women; zoledronate group HR = 0.66; 95% CI, 0.51-0.85); difference in nonvertebral hip fractures between the groups was not statistically significant.

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When accounting for exclusionary factors such as baseline risk for hip fracture, the zoledronate group maintained a lower risk for fragility fracture (HR = 0.6; 95% CI, 0.39-0.91) vs. the placebo group, according to the results.

“Our results address an important knowledge gap identified in the recently published American College of Physicians guidelines on osteoporosis, which stated that ‘current evidence is limited for a treatment benefit for women aged 65 years or older with osteopenia,’” the researchers wrote. “Zoledronate has a sustained duration of action, with bone turnover markers still suppressed by almost half 5 years after a single infusion. ... The reduction in the risk of fractures observed in the current trial suggests that annual administration may be unnecessary for maximal efficacy in the prevention of fractures and that even longer intervals between doses should be considered.” – by Phil Neuffer

Reference:

Reid I, et al. Abstract LB-1166. Presented at: American Society for Bone and Mineral Research Annual Meeting; Sept. 28-Oct. 1, 2018; Montreal.

Disclosures: Reid reports he has received grants from the Health Research Council of New Zealand; nonfinancial support from Novartis, which supplied trial medication; grants and personal fees from Amgen and Merck; and personal fees from Eli Lilly and Novartis. Please see the study for all other authors’ relevant financial disclosures.

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