Bazedoxifene可能對停經後骨質疏鬆女性是安全的
作者：Laurie Barclay, MD
出處：WebMD醫學新聞
January 5, 2010 — 根據一項於11月/12月更年期（Menopause）期刊上的隨機分派、雙盲、安慰劑控制第三期臨床研究結果，選擇性雌激素受體調控藥物bazedoxifene對於停經後骨質疏鬆女性可能是安全的。
來自諾福克東維吉尼亞醫學院的David F. Archer醫師與其同事們寫到，雖然目前對停經後骨質疏鬆症的藥物治療已經被證實是有效的，但許多藥物仍然有安全性以及/或是耐受性的擔憂，這限制或阻礙了成功的長期治療。SERMs類藥物（選擇性雌激素受體調控藥物）是停經後骨質疏鬆一個有潛力的治療藥物，因為它具有混合型功能雌激素受體作用劑與拮抗劑的活性。
這項研究的目的在於評估bazedoxifene用於治療停經後骨質疏鬆對於子宮內膜、卵巢以及乳房的安全性。研究收納的是除了骨質疏鬆外，相對健康、年齡介於55~85歲之間的女性病患，這些病患被隨機分派接受每天使用bazedoxifene 20或40 mg、raloxifene 60 mg或是安慰劑，持續達三年。在24個月之間，這些參與者定期接受經陰道超音波及子宮內膜切片，以決定子宮內膜與卵巢安全性，整個試驗期間記錄產科與乳房相關不良反應。
在12或24個月時，根據可取得的753位參與者的經陰道超音波資料，組與組之間整體子宮內膜厚度與子宮內膜厚度超過5 mm以上的受試者比例並沒有顯著差異。在24個月時，試驗前後平均子宮內膜厚度，接受bazedoxifene 20 mg的女性為-0.07±0.11 mm，接受bazedoxifene 40 mg的女性為0.10±0.11 mm，接受raloxifene 60 mg的女性為0.16±0.12 mm，安慰劑組為-0.08±0.11 mm。
這些組別受試者發生子宮內膜異常的報告各為一例。使用bazedoxifene 20 mg的女性，沒有人發生子宮內膜惡性腫瘤，接受bazedoxifene 40 mg的女性有2例，接受raloxifene 60 mg的女性有2例，安慰劑組有3例。試驗前後，卵巢囊腫的數目與大小在各組之間並無臨床上重要差異。相較於raloxifene組，bazedoxifene組發生纖維囊腫乳房疾病的發生率顯著較低（P≦0.05）。
研究作者們寫到，停經後骨質疏鬆女性使用bazeoxifene與較佳的子宮內膜、卵巢、乳房安全性有關。進一步的臨床評估正在進行中，以確認bazeoxifene對於子宮與卵巢的長期安全性及效果。
這項研究的限制包括後續追蹤僅限兩年。
研究作者們的結論是，這項針對停經後骨質疏鬆症女性進行的研究發現支持過去bazeoxifene臨床前與臨床研究結果，這些研究結果證實bazeoxifene用於預防骨質流失以及降低骨折風險，且不會刺激子宮內膜、卵巢或是乳房的作用。根據這些研究結果，bazeoxifene是預防與治療停經後骨質疏鬆一個有潛力的治療選擇。
惠氏研究贊助這項試驗，提供撰寫文章的主編經費、雇用其中3位研究作者，且其他5位研究作者表示已無相關資金上的往來。
Bazedoxifene May Be Safe for Postmenopausal Women With Osteoporosis
By Laurie Barclay, MD
Medscape Medical News
January 5, 2010 — The selective estrogen receptor modulator bazedoxifene may be safe for postmenopausal women with osteoporosis, according to the results of a randomized, double-blind, placebo-controlled phase 3 trial reported in the November/December issue of Menopause.
"Although current pharmacologic options for postmenopausal osteoporosis have been shown to be effective, many are associated with safety and/or tolerability concerns that may limit or hinder successful long-term therapy," write David F. Archer, MD, from the Eastern Virginia Medical School in Norfolk, and colleagues. "As a class, SERMs [selective estrogen receptor modulators] are appealing therapeutic agents for postmenopausal osteoporosis because of their mixed functional estrogen receptor agonist and antagonist activities."
The objective of the study was to assess the endometrial, ovarian, and breast safety of bazedoxifene when used to treat postmenopausal osteoporosis. Otherwise healthy women with osteoporosis, aged 55 to 85 years, were randomly assigned to treatment with bazedoxifene 20 or 40 mg, raloxifene 60 mg, or placebo daily for 3 years. Through 24 months, participants had periodic transvaginal ultrasonography and endometrial biopsy to determine endometrial and ovarian safety, and gynecologic and breast-related adverse events were recorded throughout the study.
At 12 or 24 months, overall endometrial thickness and the percentage of participants with endometrial thickness greater than 5 mm were not significantly different among groups, based on 753 participants with available transvaginal ultrasonography data. At 24 months, changes in the mean endometrial thickness from baseline were –0.07 ± 0.11 mm for women receiving bazedoxifene 20 mg, 0.10 ± 0.11 mm for women receiving bazedoxifene 40 mg, 0.16 ± 0.12 mm for women receiving raloxifene 60 mg, and –0.08 ± 0.11 mm in the placebo group.
Each group had 1 report of endometrial hyperplasia. Endometrial carcinoma was reported in no women in the bazedoxifene 20-mg group, in 2 in the bazedoxifene 40-mg group, in 2 in the raloxifene 60-mg group, and in 3 in the placebo group. The groups did not differ in clinically important changes from baseline in the number or size of ovarian cysts. Compared with the raloxifene group, the bazedoxifene groups had a significantly lower incidence of fibrocystic breast disease (P ? .05).
"Bazedoxifene was associated with a favorable endometrial, ovarian, and breast safety profile in postmenopausal women with osteoporosis," the study authors write. "Further clinical evaluation is currently ongoing to confirm the long-term safety and efficacy of bazedoxifene on the uterus and ovary."
Limitations of this study include follow-up limited to 2 years.
"Findings from this study of postmenopausal women with osteoporosis support those of previous preclinical and clinical studies of bazedoxifene, which have demonstrated the efficacy of bazedoxifene in preventing bone loss and reducing the risk of fracture without stimulation of the endometrium, ovaries, or breast," the study authors conclude. "Based on these results, bazedoxifene represents a promising therapeutic option for the prevention and treatment of postmenopausal osteoporosis."
Wyeth Research sponsored this study, funded editorial support for the writing of the article, employs 3 of the study authors, and has disclosed various financial relationships with 5 other study authors.
Menopause. 2009;16:1109-1115.
