鲑鱼降钙素鼻喷雾剂用于已确诊骨质疏松症的绝经后妇女的随机试验：预防骨质疏松性骨折复发研究。PROOF研究组

A randomized trial of nasal spray salmon calcitonin in postmenopausal women with established osteoporosis: the prevent recurrence of osteoporotic fractures study. PROOF Study Group.

作者信息

Chesnut C H, Silverman S, Andriano K, Genant H, Gimona A, Harris S, Kiel D, LeBoff M, Maricic M, Miller P, Moniz C, Peacock M, Richardson P, Watts N, Baylink D

机构信息

University of Washington (CHC), Seattle, Washington, USA.

出版信息

Am J Med. 2000 Sep;109(4):267-76. doi: 10.1016/s0002-9343(00)00490-3.

DOI:10.1016/s0002-9343(00)00490-3

PMID:10996576

Abstract

PURPOSE

We conducted a 5-year, double-blind, randomized, placebo-controlled study to determine whether salmon calcitonin nasal spray reduced the risk of new vertebral fractures in postmenopausal women with osteoporosis.

SUBJECTS AND METHODS

A total of 1,255 postmenopausal women with established osteoporosis were randomly assigned to receive salmon calcitonin nasal spray (100, 200, or 400 IU) or placebo daily. All participants received elemental calcium (1,000 mg) and vitamin D (400 IU) daily. Vertebral fractures were assessed with lateral radiographs of the spine. The primary efficacy endpoint was the risk of new vertebral fractures in the salmon calcitonin nasal spray 200-IU group compared with the placebo group.

RESULTS

During 5 years, 1,108 participants had at least one follow-up radiograph. A total of 783 women completed 3 years of treatment, and 511 completed 5 years. The 200-IU dose of salmon calcitonin nasal spray significantly reduced the risk of new vertebral fractures by 33% compared with placebo [200 IU: 51 of 287, placebo: 70 of 270, relative risk (RR) = 0.67, 95% confidence interval (CI): 0.47- to 0.97, P = 0.03]. In the 817 women with one to five prevalent vertebral fractures at enrollment, the risk was reduced by 36% (RR = 0.64, 95% CI: 0.43- to 0.96, P = 0.03). The reductions in vertebral fractures in the 100-IU (RR = 0.85, 95% CI: 0.60- to 1.21) and the 400-IU (RR = 0.84, 95% CI: 0.59- to 1.18) groups were not significantly different from placebo. Lumbar spine bone mineral density increased significantly from baseline (1% to 1. 5%, P<0.01) in all active treatment groups. Bone turnover was inhibited, as shown by suppression of serum type-I collagen cross-linked telopeptide (C-telopeptide) by 12% in the 200-IU group (P <0.01) and by 14% in the 400-IU group (P<0.01) as compared with placebo.

CONCLUSION

Salmon calcitonin nasal spray at a dose of 200 IU daily significantly reduces the risk of new vertebral fractures in postmenopausal women with osteoporosis.

摘要

目的

我们进行了一项为期5年的双盲、随机、安慰剂对照研究，以确定鲑鱼降钙素鼻喷雾剂是否能降低绝经后骨质疏松症妇女发生新椎体骨折的风险。

受试者与方法

共有1255名已确诊骨质疏松症的绝经后妇女被随机分配，每天接受鲑鱼降钙素鼻喷雾剂（100、200或400国际单位）或安慰剂治疗。所有参与者每天均服用元素钙（1000毫克）和维生素D（400国际单位）。通过脊柱侧位X线片评估椎体骨折情况。主要疗效终点是200国际单位鲑鱼降钙素鼻喷雾剂组与安慰剂组相比发生新椎体骨折的风险。

结果

在5年期间，1108名参与者至少有一张随访X线片。共有783名女性完成了3年治疗，511名完成了5年治疗。与安慰剂相比，200国际单位剂量的鲑鱼降钙素鼻喷雾剂显著降低了33%的新椎体骨折风险[200国际单位组：287名中有51名发生骨折，安慰剂组：270名中有70名发生骨折，相对风险（RR）=0.67，95%置信区间（CI）：0.47至0.97，P = 0.03]。在入组时有1至5处椎体骨折的817名女性中，风险降低了36%（RR = 0.64，95%CI：0.43至0.96，P = 0.03）。100国际单位组（RR = 0.85，95%CI：0.60至1.21）和400国际单位组（RR = 0.84，95%CI：0.59至1.18）椎体骨折风险的降低与安慰剂组无显著差异。所有活性治疗组的腰椎骨密度均较基线显著增加（1%至1.5%，P<0.01）。骨转换受到抑制，与安慰剂相比，200国际单位组血清I型胶原交联端肽（C-端肽）抑制了12%（P <0.01），400国际单位组抑制了14%（P<0.01）。