Nagatoya Katsuyuki, Nishimoto Kazuhiko, Shibahara Nobuhisa, Takahashi Toshikazu, Kanehara Hironori, Ueno Nobuyuki, Yasuda Hideaki, Okada Shigeki, Ueda Haruhiko, Hirai Kei, Inoue Toru
Blood Purification Center, Osaka Medical College Hospital, Takatsuki, Japan.
Department of Laboratory Medicine, Osaka Rosai Hospital, 1179-3 Nagasone-cho, Sakai, Osaka, 591-8025, Japan.
Clin Exp Nephrol. 2015 Oct;19(5):939-46. doi: 10.1007/s10157-014-1065-z. Epub 2014 Dec 11.
Postmenopausal women with end-stage renal failure are at an increased risk of fracture because of the effects of secondary hyperparathyroidism and postmenopausal osteoporosis. In the present study, we investigated the feasibility of using raloxifene to prevent fractures in postmenopausal women with end-stage renal failure on hemodialysis.
This study was conducted using a multicenter, single-arm, prospective design. Raloxifene was administered to postmenopausal women aged ≥50 years who were on maintenance hemodialysis and met any of the following criteria after a 24-week run-in period: an alkaline phosphatase level (bone formation marker) of ≥6.18 µkat/L (≥370 U/L), a bone-specific alkaline phosphatase (BAP; bone formation marker) level of ≥0.59 µkat/L (≥35.4 U/L), or a bone-derived tartrate-resistant acid phosphatase (TRACP-5b; bone resorption marker) level of ≥4.2 U/L.
A total of 48 individuals were eligible for study inclusion. Of them, 30 individuals participated in this study. The BAP levels were significantly decreased at week 4, but returned to the baseline levels at week 24. Similarly, the TRACP-5b levels were significantly decreased at week 4, but returned to the baseline levels at week 24. The serum calcium value decreased consistently after the start of raloxifene therapy. The intact parathyroid hormone (iPTH) levels were likely increased at week 4. The ratio of BAP to iPTH levels and the ratio of TRACP-5b to iPTH levels both showed significant decreases over time. During the raloxifene therapy, no thrombosis or other drug-related adverse events developed.
The study results indicated that raloxifene can transiently reduce the levels of bone metabolism markers and might be useful for preventing fractures in postmenopausal women with end-stage renal failure, although raloxifene use over the long term may not have adequate efficacy in the absence of appropriate concomitant active vitamin D therapy.
绝经后终末期肾衰竭女性因继发性甲状旁腺功能亢进和绝经后骨质疏松症的影响，骨折风险增加。在本研究中，我们调查了使用雷洛昔芬预防接受血液透析的绝经后终末期肾衰竭女性骨折的可行性。
本研究采用多中心、单臂、前瞻性设计。对年龄≥50岁、接受维持性血液透析且在24周导入期后符合以下任何一项标准的绝经后女性给予雷洛昔芬：碱性磷酸酶水平（骨形成标志物）≥6.18微卡特/升（≥370单位/升）、骨特异性碱性磷酸酶（BAP；骨形成标志物）水平≥0.59微卡特/升（≥35.4单位/升）或骨源性抗酒石酸酸性磷酸酶（TRACP-5b；骨吸收标志物）水平≥4.2单位/升。
共有48人符合研究纳入标准。其中，30人参与了本研究。BAP水平在第4周时显著下降，但在第24周时恢复到基线水平。同样，TRACP-5b水平在第4周时显著下降，但在第24周时恢复到基线水平。雷洛昔芬治疗开始后血清钙值持续下降。完整甲状旁腺激素（iPTH）水平在第4周时可能升高。BAP与iPTH水平之比以及TRACP-5b与iPTH水平之比均随时间显著下降。在雷洛昔芬治疗期间，未发生血栓形成或其他药物相关不良事件。
研究结果表明，雷洛昔芬可短暂降低骨代谢标志物水平，可能有助于预防绝经后终末期肾衰竭女性骨折，尽管在缺乏适当的活性维生素D联合治疗的情况下，长期使用雷洛昔芬可能没有足够的疗效。
