Osteoporosis Clinical Center and Research Program, University of Wisconsin, Madison, WI 53705, USA.
J Bone Miner Res. 2012 Aug;27(8):1821-9. doi: 10.1002/jbmr.1602.
The Oral Calcitonin in Postmenopausal Osteoporosis (ORACAL) study was a randomized, double-blind, double-dummy, active- and placebo-controlled, multiple-dose, phase 3 study to assess the efficacy and safety of oral recombinant calcitonin for treatment of postmenopausal osteoporosis. A total of 565 women age 46 to 86 (mean 66.5) years were randomized (4:3:2) to receive oral recombinant salmon calcitonin (rsCT) tablets (0.2 mg/d) plus placebo nasal spray, synthetic salmon calcitonin (ssCT) nasal spray (200 IU/d) plus placebo tablets, or placebo (placebo tablets plus placebo nasal spray), respectively for 48 weeks. All women received calcium (≥1000 mg/d) and vitamin D (800 IU/d). Women randomized to oral rsCT had a mean ± SD percent increase from baseline in lumbar spine bone mineral density (BMD) (1.5% ± 3.2%) that was greater than those randomized to ssCT nasal spray (0.78% ± 2.9%) or placebo (0.5% ± 3.2%). Lumbar spine BMD change in those receiving nasal calcitonin did not differ from placebo. Oral rsCT treatment also resulted in greater improvements in trochanteric and total proximal femur BMD than ssCT nasal spray. Reductions in bone resorption markers with oral rsCT were greater than those observed in ssCT nasal spray or placebo recipients. Approximately 80% of subjects in each treatment group experienced an adverse event, the majority of which were mild or moderate in intensity. Gastrointestinal system adverse events were reported by nearly one-half of women in all treatment groups and were the principal reason for premature withdrawals. Less than 10% of women experienced a serious adverse event and no deaths occurred. Overall, oral rsCT was superior to nasal ssCT and placebo for increasing BMD and reducing bone turnover. Oral rsCT was safe and as well tolerated as ssCT nasal spray or placebo. Oral calcitonin may provide an additional treatment alternative for women with postmenopausal osteoporosis.
绝经后骨质疏松症的口服降钙素（ORACAL）研究是一项随机、双盲、双模拟、阳性和安慰剂对照、多剂量、3 期研究，旨在评估口服重组鲑鱼降钙素治疗绝经后骨质疏松症的疗效和安全性。共有 565 名年龄在 46 至 86 岁（平均 66.5 岁）的女性被随机（4:3:2）分为三组，分别接受口服重组鲑鱼降钙素（rsCT）片剂（0.2mg/d）+安慰剂鼻腔喷雾、合成鲑鱼降钙素（ssCT）鼻腔喷雾（200IU/d）+安慰剂片剂，或安慰剂（安慰剂片剂+安慰剂鼻腔喷雾）治疗，疗程均为 48 周。所有女性均接受钙（≥1000mg/d）和维生素 D（800IU/d）治疗。随机接受口服 rsCT 的女性腰椎骨密度（BMD）从基线的平均增加百分比（1.5%±3.2%）大于随机接受 ssCT 鼻腔喷雾（0.78%±2.9%）或安慰剂（0.5%±3.2%）的女性。接受鼻腔降钙素治疗的女性的腰椎 BMD 变化与安慰剂无差异。口服 rsCT 治疗还导致转子间和全股骨近端 BMD 的改善大于 ssCT 鼻腔喷雾。口服 rsCT 降低骨吸收标志物的作用大于 ssCT 鼻腔喷雾或安慰剂组。每个治疗组约有 80%的受试者发生不良事件，大多数为轻度或中度。所有治疗组近一半的女性报告胃肠道系统不良事件，这是提前退出的主要原因。不到 10%的女性发生严重不良事件，无死亡病例。总体而言，口服 rsCT 优于鼻腔 ssCT 和安慰剂，可增加 BMD 并降低骨转换率。口服 rsCT 安全且耐受性与 ssCT 鼻腔喷雾或安慰剂相当。口服降钙素可能为绝经后骨质疏松症女性提供另一种治疗选择。
