Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Palle Juul-Jensens Boulevard 165, 8200, Aarhus N, Denmark.
Osteoporos Int. 2019 May;30(5):995-1002. doi: 10.1007/s00198-018-04833-3. Epub 2019 Jan 17.
Treatment with zoledronic acid 5 mg maintained bone turnover markers in the premenopausal range, increased lumbar spine bone mineral density, and maintained hip bone mineral density in women previously treated with odanacatib 50 mg weekly.
The development of odanacatib (ODN), a cathepsin K inhibitor, for treatment of osteoporosis was discontinued due to an increased risk of cardiovascular events. As the treatment is considered reversible, participants from the LOFT trial in Aarhus, Denmark, were offered treatment with zoledronic acid (ZOL).
Sixty-seven postmenopausal women were treated with ZOL 5 mg and followed for 12 months. Of these, 39 had received ODN for 7 years and 28 had received placebo for 5 years and ODN for 2 years. Bone turnover markers (BTM) were measured 3, 6, and 12 months after ZOL, and DXA of spine and hip were performed at time of ZOL treatment and after 12 months.
Within the entire study population, BMD at the lumbar spine increased by 2.8 ± 0.9% (mean ± SEM) (p < 0.01) from baseline to month 12. There was no significant change in BMD at the total hip (p = 0.17) or femoral neck (p = 0.39). There was no difference in the changes in BMD from baseline to 12 months between the two groups at any site (p ≥ 0.20 for all). CTX increased by 107 ± 9% (p < 0.001), PINP by 102 ± 16% (p < 0.001), osteocalcin by 32 ± 6% (p = 0.001) and BSAP by 79 ± 37% (p = 0.001) between 3 and 12 months after ZOL. At month 12, BTM were still within the premenopausal reference range. S-25-hydroxyvitamin D increased (p = 0.059), while PTH (p = 0.007) and eGFR (p = 0.014) decreased during the year following ZOL administration.
Treatment with ZOL 5 mg maintained BTMs in the premenopausal range and prevented bone loss in women previously treated with ODN.
唑来膦酸 5mg 的治疗使绝经前范围内的骨转换标志物保持稳定，增加了腰椎骨密度，并保持了先前用odanacatib 50mg 每周治疗的女性的髋部骨密度。
由于心血管事件风险增加，odanacatib（ODN）的开发（一种组织蛋白酶 K 抑制剂）被停止用于治疗骨质疏松症。由于该治疗被认为是可逆的，丹麦奥胡斯 LOFT 试验的参与者被提供唑来膦酸（ZOL）治疗。
67 名绝经后妇女接受 ZOL 5mg 治疗并随访 12 个月。其中 39 人接受 ODN 治疗 7 年，28 人接受安慰剂治疗 5 年和 ODN 治疗 2 年。在 ZOL 治疗后 3、6 和 12 个月测量骨转换标志物（BTM），并在 ZOL 治疗时和 12 个月后进行腰椎和髋部 DXA。
在整个研究人群中，腰椎骨密度从基线到 12 个月时增加了 2.8±0.9%（平均值±SEM）（p<0.01）。总髋部（p=0.17）或股骨颈（p=0.39）的骨密度无显著变化。两组在任何部位从基线到 12 个月的骨密度变化无差异（p≥0.20 所有）。CTX 增加了 107±9%（p<0.001），PINP 增加了 102±16%（p<0.001），骨钙素增加了 32±6%（p=0.001），BSAP 增加了 79±37%（p=0.001）在 ZOL 后 3 至 12 个月之间。在 12 个月时，BTM 仍处于绝经前参考范围。S-25-羟维生素 D 增加（p=0.059），而 PTH（p=0.007）和 eGFR（p=0.014）在 ZOL 给药后一年中下降。
唑来膦酸 5mg 的治疗使绝经前范围内的 BTM 保持稳定，并防止了先前用 ODN 治疗的女性的骨质流失。
