新西兰奥克兰大学Mark J. Bolland团队研究了50~60岁女性少量使用唑来膦酸盐预防骨折的疗效。相关论文于2025年1月16日发表在《新英格兰医学杂志》上。

唑来膦酸盐每12至18个月给药一次，可预防老年女性骨折，但其对骨密度和骨转换的影响持续5年以上。少量服用唑来膦酸盐是否可以预防绝经后早期妇女的椎体骨折尚不清楚。

研究组进行了一项为期10年的前瞻性、双盲、随机、安慰剂对照试验，招募早期绝经后妇女（50至60岁），其腰椎、股骨颈或髋关节的骨密度T评分低于0且高于-2.5（评分-1或更高通常表示骨密度正常）。参与者被随机分配到基线时和5年时接受5 mg剂量的唑来膦酸盐给药（唑来膦酸盐-唑来膦酸盐组），基线时接受5 mg剂量的唑来膦酸盐和5年后接受安慰剂给药（唑来膦酸盐-安慰剂组），或基线和5年都接受安慰剂给药（安慰剂-安慰剂组）。在基线、5年和10年时获得脊柱X线照片。主要终点是形态计量学椎体骨折（半定量评估），定义为椎体高度与基线X线照片上所见的椎体高度至少有20%的变化。次要终点是脆性骨折、任何骨折和主要骨质疏松性骨折。

在1054名基线时平均年龄为56.0岁的女性中，1003名（95.2%）完成了10年的随访。唑来膦酸盐-唑来膦酸盐组22名女性（6.3%）、唑来膦酸盐-安慰剂组23名女性（6.6%）和安慰剂-安慰剂组39名女性（11.1%）发生了新的形态计量学骨折（相对风险，唑来膦酸盐-唑来膦酸盐与安慰剂-安慰剂，0.56[95%置信区间{CI}，0.34至0.92；P=0.04]；唑来膦酯盐-安慰剂与安慰剂-安慰剂，0.59[95%CI，0.36至0.97；P=0.08]）。当唑来膦酸盐-唑来膦酸盐组与安慰剂-安慰剂组进行比较时，脆性骨折、任何骨折和主要骨质疏松性骨折的相对风险分别为0.72（95%CI，0.55至0.93）、0.70（95%CI，0.56至0.88）和0.60（95%CI，0.42至0.86），当唑来磷酸盐-安慰剂组与安慰剂-安慰剂组进行比较时分别为0.79（95%CI-0.61至1.02）、0.77（95%CI0.62至0.97）和0.71（95%CI/0.51至0.99）。

研究结果表明，试验开始10年后，在基线和5年时服用唑来膦酸盐，可有效预防绝经后早期妇女的形态计量学椎体骨折。

附：英文原文

Title: Fracture Prevention with Infrequent Zoledronate in Women 50 to 60 Years of Age

Author: Mark J. Bolland, Zaynah Nisa, Anna Mellar, Chiara Gasteiger, Veronica Pinel, Borislav Mihov, Sonja Bastin, Andrew Grey, Ian R. Reid, Greg Gamble, Anne Horne

Issue&Volume: 2025-01-16

Abstract:

BACKGROUND

Zoledronate prevents fractures in older women when administered every 12 to 18 months, but its effects on bone density and bone turnover persist beyond 5 years. Whether infrequent zoledronate administration would prevent vertebral fractures in early postmenopausal women is unknown.

METHODS

We conducted a 10-year, prospective, double-blind, randomized, placebo-controlled trial involving early postmenopausal women (50 to 60 years of age) with bone mineral density T scores lower than 0 and higher than 2.5 (scores of 1 or higher typically indicate normal bone mineral density) at the lumbar spine, femoral neck, or hip. Participants were randomly assigned to receive an infusion of zoledronate at a dose of 5 mg at baseline and at 5 years (zoledronate–zoledronate group), zoledronate at a dose of 5 mg at baseline and placebo at 5 years (zoledronate–placebo group), or placebo at both baseline and 5 years (placebo–placebo group). Spinal radiographs were obtained at baseline, 5 years, and 10 years. The primary end point was morphometric vertebral fracture, which was assessed semiquantitatively and defined as at least a 20% change in vertebral height from that seen on the baseline radiograph. Secondary end points were fragility fracture, any fracture, and major osteoporotic fracture.

RESULTS

Of 1054 women with a mean age of 56.0 years at baseline, 1003 (95.2%) completed 10 years of follow-up. A new morphometric fracture occurred in 22 women (6.3%) in the zoledronate–zoledronate group, in 23 women (6.6%) in the zoledronate–placebo group, and in 39 women (11.1%) in the placebo–placebo group (relative risk, zoledronate–zoledronate vs. placebo–placebo, 0.56 [95% confidence interval {CI}, 0.34 to 0.92; P=0.04]; and zoledronate–placebo vs. placebo–placebo, 0.59 [95% CI, 0.36 to 0.97; P=0.08]). The relative risk of fragility fracture, any fracture, and major osteoporotic fracture was 0.72 (95% CI, 0.55 to 0.93), 0.70 (95% CI, 0.56 to 0.88), and 0.60 (95% CI, 0.42 to 0.86), respectively, when zoledronate–zoledronate was compared with placebo–placebo and 0.79 (95% CI, 0.61 to 1.02), 0.77 (95% CI, 0.62 to 0.97), and 0.71 (95% CI, 0.51 to 0.99), respectively, when zoledronate–placebo was compared with placebo–placebo.

CONCLUSIONS

Ten years after trial initiation, zoledronate administered at baseline and 5 years was effective in preventing morphometric vertebral fracture in early postmenopausal women.

DOI: NJ202501163920308

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2407031