臨床婦人科産科71巻1号

2017年01月発行

合併増大号　今月の臨床 性ステロイドホルモン研究の最前線と臨床応用 選択的性ステロイドホルモン受容体修飾薬

選択的エストロゲン受容体修飾薬（SERM）

著者： 竹内靖博¹

所属機関： ¹虎の門病院内分泌センター

ページ範囲：P.115 - P.120

●SERMは非ホルモン構造のエストロゲン受容体修飾薬である．

●ラロキシフェンとバゼドキシフェンは骨組織ではエストロゲン・アゴニストとして，乳腺や子宮ではアンタゴニストとして作用する．

●閉経後骨粗鬆症治療薬としてSERMであるラロキシフェンとバゼドキシフェンは，長期にわたる骨密度の上昇と椎体骨折の抑制効果を示す．

参考文献

1）Riggs BL, et al : Selective estrogen-receptor modulators : mechanisms of action and applicationto clinical practice. N Engl J Med 348 : 618─629, 2003

2）Saito M, et al : Raloxifene ameliorates detrimental enzymatic and nonenzymatic collagen cross-links and bone strength in rabbits with hyperhomocysteinemia. Osteoporos Int 21 : 655─666, 2010

3）Walsh BW, et al : The effects of hormone replacement therapy and raloxifene on C-reactive protein and homocysteine in healthy postmenopausal women : a randomized, controlled trial. J Clin Endocrinol Metab 85 : 214─218, 2000

4）Ettinger B, et al : Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene : results from a 3-year randomized clinical trial. Multiple Outcomes of Raloxifene Evaluation（MORE） Investigators. JAMA 282 : 637─645, 1999

5） Delmas PD, et al : Efficacy of raloxifene on vertebral fracture risk reduction in postmenopausal women with osteoporosis : four-year results from a randomized clinical trial. J Clin Endocrinol Metab 87 : 3609─3617, 2002

6）Silverman SL, et al : Efficacy of bazedoxifene in reducing new vertebral fracture risk in postmenopausal women with osteoporosis : results from a 3-year, randomized, placebo-, and active-controlled clinical trial. J Bone Miner Res 23 : 1923─1934, 2008

7）Siris ES, et al : Skeletal effects of raloxifene after 8 years : results from the continuing outcomes relevant to Evista（CORE） study. J Bone Miner Res 20 : 1514─1524, 2005

8）Iikuni N, et al : Safety and effectiveness profile of raloxifene in long-term, prospective, postmarketing surveillance. J Bone Miner Metab 30 : 674─682, 2012

9）Palacios S, et al : A 7-year randomized, placebo-controlled trial assessing the long-term efficacy and safety of bazedoxifene in postmenopausal women with osteoporosis : effects on bone density and fracture. Menopause 22 : 806─813, 2015

10）Maricic M, et al : Early effects of raloxifene on clinical vertebral fractures at 12 months in postmenopausal women with osteoporosis. Arch Intern Med 162 : 1140─1143, 2002

11）Seeman E, et al : Anti-vertebral fracture efficacy of raloxifene : a meta-analysis. Osteoporos Int 17 : 313─316, 2006

12）Kanis JA, et al : Effect of raloxifene on the risk of new vertebral fracture in postmenopausal women with osteopenia or osteoporosis : a reanalysis of the Multiple Outcomes of Raloxifene Evaluation trial. Bone 33 : 293─300, 2003

13）Barrett-Connor E, et al : Effects of raloxifene on cardiovascular events and breast cancer in postmenopausal women. N Engl J Med 355 : 125─137, 2006

14）Kaufman JM, et al : An evaluation of the Fracture Risk Assessment Tool（FRAX®） as an indicator of treatment efficacy : the effects of bazedoxifene and raloxifene on vertebral, nonvertebral, and all clinical fractures as a function of baseline fracture risk assessed by FRAX®. Osteoporos Int 24 : 2561─2569, 2013

15）Delmas PD, et al : Severity of prevalent vertebral fractures and the risk of subsequent vertebral and nonvertebral fractures : results from the MORE trial. Bone 33 : 522─532, 2003

16）Cadarette SM, et al : Relative effectiveness of osteoporosis drugs for preventing nonvertebral fracture. Ann Intern Med 148 : 637─646, 2008

17）Nakamura T, et al : Effect of raloxifene on clinical fractures in Asian women with postmenopausal osteoporosis. J Bone Miner Metab 24 : 414─418, 2006

18）Scharla S, et al : Skeletal pain in postmenopausal women with osteoporosis : prevalence and course during raloxifene treatment in a prospective observational study of 6 months duration. Curr Med Res Opin 22 : 2393─2402, 2006

19）Yoh K, et al : Quality of life in raloxifene-treated Japanese women with postmenopausal osteoporosis : a prospective, postmarketing observational study. Curr Med Res Opin 28 : 1757─1766, 2012

20）Grady D, et al : Effect of Raloxifene on all-cause mortality. Am J Med 123 : 469. e1─7, 2010

21）Cauley JA, et al : Continued breast cancer risk reduction in postmenopausal women treated with raloxifene : 4-year results from the MORE trial. Multiple outcomes of raloxifene evaluation. Breast Cancer Res Treat 65 : 125─134, 2001

22）Takeuchi Y, et al : Safety of 3-year raloxifene treatment in Japanese postmenopausal women aged 75 years or older with osteoporosis : a postmarketing surveillance study. Menopause 22 : 1134─1137, 2015