Men's Osteoporosis Support Group5-mg zoledronate effective for two years J Clin Endocrinol Metab. 2009 Feb;94(2):538-44. Epub 2008 Dec 2. The antiresorptive effects of a single dose of zoledronate persist for two years: a randomized, placebo-controlled trial in osteopenic postmenopausal women. Grey A and others. PMID: 1905000. This study was a double-blind, randomized, placebo-controlled trial lasting two years and involving 50 postmenopausal women with osteopenia. The intervention group received a single 5-mg dose of zoledronate (Zometa). The effectiveness and length of action of the medication were measured with biochemical markers of bone turnover and bone mineral density (BMD) tests. Each of the four bone turnover markers was reduced by at least 38% throughout the study (P<0.0001 for each marker). Mean BMD in the zoledronate group increased by 5.7% at the lumbar spine, 3.9% at the proximal femur and 1.7% at the total body. The authors note that, "Between-groups differences in markers of bone turnover and bone mineral density were similar at 12 and 24 months." [Editor's emphasis] They also noted mild secondary hyperparathyroidism during the study. They concluded, "The antiresorptive effects of a single 5-mg dose of zoledronate are sustained for at least 2 yr." Editor's comments. Here is a recent Update regarding the bone turnover rate when once-yearly zoledronate was given to postmenopausal women for three consecutive years. This study by Recker RR and others used a different measurement criteria, activation frequency, and found a 71% reduction in bone turnover after three years. The greater difference may be due to the multiple doses over the three years compared to only one dose in two years for the Grey and others study. Or the two measurement methods may not be comparable. The current recommendation for treatment of osteoporosis with IV zoledronate is a single 5-mg IV dose yearly. But the duration of action hasn't been fully evaluated currently. The authors suggest in the full article that further studies to evaluate antifracture effectiveness after dose intervals of at least 18 months may be warranted. So look for studies in the future that evaluate the maximum interval that IV zoledronate can be given and still afford antifracture efficacy. A single dose every 18-24 months would save money and be more convenient for those who, for whatever reason, were unable to use medications that require a more frequent dose. I've seen estimates of the cost of a single zoledronate dose of from $800 to $1,200, so increasing the dosing interval could save quite a bit of money. They note that risedronate (Actonel) was effective at reducing fracture rates when associated with smaller effects on bone turnover rates and BMD than shown in the Grey and others study. So there is reason to expect the 18-24 months zoledronate dose will reduce fracture risk, too. In the full article the authors describe the effect on bone turnover markers in greater detail. At three months the decreases were very substantial at 50-80% reductions compared to baseline. At 12 months the reductions were from 40-60%. They also note that the results of the phase III zoledronate study by Black and others, discussed in this Update, found 5.9, 4.7 and 3.9% increases in BMD at the lumbar spine, total hip, and femoral neck, respectively, compared to 5.7, 3.9 and 3.9% in the current study. The Black and others study had given two doses of zoledronate, and yet got nearly identical increases in BMD when compared to the Grey and others study which had given a single dose. Baring some unforeseen future findings, it appears we could expect to see longer dosing intervals, possibly up to 2 years, for IV zoledronate in the future.
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