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, Dennis M. Black, Ph.D., said at the annual meeting of the American Society for Bone and Mineral Research.

“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,” said Dr. Black, professor of epidemiology and biostatistics at the University of California, San Francisco. “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,” he 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.

With the new finding, zoledronic acid joins other bisphosphonates, such as alendronate, shown to prevent loss of bone density when the drug is continued after several years of treatment. In a prior report, continuing treatment with alendronate for 5 years following an initial 5 years of treatment led to less bone density loss than in patients who switched from alendronate to placebo (JAMA 2006;296:2927-38). The same alendronate study failed to show that continued bisphosphonate treatment led to a reduced rate of morphometric vertebral fractures, compared with stopping alendronate.

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).

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 two treatment arms showed no significant difference in their rates of nonvertebral fractures. Continued zoledronic acid treatment also led to reduced blood levels of a marker of bone turnover compared with the patients who received placebo injections.

Six years of annual zoledronic acid treatment appeared safe, with no excess of adverse events or serious adverse events compared with the patients on 3 years of placebo. The researchers looked especially closely at cardiovascular events; the only significant, between-treatment difference was in new hypertensive adverse events, which occurred significantly more often in the patients who received placebo for 3 years.

The HORIZON Pivotal Fracture 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.

Copyright (c) 2010 Elsevier Global Medical News. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.

多伦多(EGMN)—加州大学旧金山分校流行病学和统计学教授Black博士在美国骨矿学会年会上报告称，连续6年接受每年1次唑来膦酸注射剂治疗的患者，其骨密度显著高于接受3年治疗后停药的患者，椎体骨折发生率也较低，并且具有良好的安全性。

 

此前研究表明，合用唑来膦酸和阿仑膦酸钠5年后再继续用药5年的患者，比用安慰剂替代阿仑膦酸钠的患者骨密度丢失较小。而阿仑膦酸钠的类似研究却未见继续服用阿仑膦酸钠患者比停药者椎体骨折发生率减少现象。

 

研究者将已完成为期3年的唑来膦酸与安慰剂对照研究(HORIZON-PFT)的1,233名唑来膦酸组女性随机分为两组，分别继续接受每年1次5 mg的唑来膦酸或安慰剂，试验周期为3年，主要终点为股骨颈骨密度变化百分率。受试者平均年龄为76岁，约55%的患者股骨颈T score值小于–2.5。

 

试验结束时与入组时相比，唑来膦酸组股骨颈骨密度变化率平均提高1%，具有统计学显著差异；与6年前基线水平相比平均提高1.4%，与用药3年后改换为安慰剂的患者相比，也具有统计学显著差异。此外，3年研究期间椎体骨折发生率安慰剂组为6%，唑来膦酸组为3%，两者具有统计学显著差异；两组间非椎体骨折发生率无显著差异。唑来膦酸组与安慰剂组相比，血液骨转换指标水平降低。研究还表明，连续6年接受唑来膦酸治疗是安全的，与后3年接受安慰剂治疗的患者相比，未见更多的不良反应事件或严重不良反应事件，而后3年接受安慰剂治疗的患者高血压不良事件发生率显著较多。

 

研究表明，与接受唑来膦酸治疗3年后停药相比，连续6年接受治疗可继续保持骨密度和减少椎体骨折风险，且具有良好的安全性，可使椎体骨折高危女性从中受益。

 

HORIZON-PFT由唑来膦酸制造商诺华制药资助。研究者声明获得多家医药公司经济资助。

 

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