A phase III clinical trial of monthly minodronate in the treatment of Chinese postmenopausal women with osteoporosis
Hao Zhang1,
Ya-nan Huo2,
Ya-wei Zhang3,
Zhi-feng Cheng4,
Xiao-jing Wang5,
Jun Chen6,
Qi-fu Li7,
Xin-hua Xiao8,
Li-zhen Lan9,
Xin-long Ma10,
Liu-jun Fu11,
Xiao-pan Chen12,
Ling-qing Yuan13,
Fang-jiang Xu14,
Li You15,
Jin- luo Cheng16,
Dun Hong17,
Fei Hua18,
Li Mao19,
Guo-xi Jin20,
Guan-feng Yao21,
Ya-jun Bing22,
Gui-jie Xie23,
Ying Yang24,
Jin Xu25,
Ying Zhang26,
Wei Zhang27,
Yue Ding28,
Guo-ping Cai29,
Hui-min Zhou30,
Cheng-yun Liu31,
Jian-xiang Zhang32,
Zhong-min Zhao32,
Bu-jun Zhuang32,
Xiao Cheng33,
Zhen-lin Zhang1
1 Department of Osteoporosis and Bone Diseases, Shanghai Clinical Research Center of Bone Diseases, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China
2 Department of Endocrinology, Jiangxi Provincial People’s Hospital Affiliated to Nanchang University, Nanchang 337099, China
3 Department of Endocrinology, Pingxiang People’s Hospital, Pingxiang 337000, China
4 Department of Endocrinology, The Fourth Hospital of Harbin Medical University, Harbin 150001, China
5 Department of Endocrinology, Yuncheng Central Hospital of Shanxi Medical University, Yuncheng 140000, China
6 Department of orthopedics, Chongqing University Three Gorges Hospital, Chongqing 401147, China
7 Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
8 Department of Endocrinology, The First Affiliated Hospital of University of South China, Hengyang 421001, China
9 Department of General Practice, First Hospital of Shanxi Medical University, Taiyuan 030001, China
10 Department of orthopedics, Tianjin Hospital, Tianjin 300211, China
11 Department of Endocrinology, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang 471003, China
12 Department of Endocrinology, The First Affiliated Hospital of Hainan Medical University, Haiko 570102, China
13 Department of Endocrinology, The Second Xiangya Hospital of Central South University, Changsha 410011, China
14 Department of Endocrinology, Linyi Central Hospital, Linyi 276003, China
15 Shanghai General Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China
16 Department of Endocrinology, The Second People’s Hospital of Changzhou, Changzhou 213003, China
17 Department of orthopedics, Taizhou Hospital of Zhejiang Province, Taizhou 317000, China
18 Department of Endocrinology, The First People’s Hospital of Changzhou, Changzhou 225000, China
19 Department of Endocrinology, The Affiliated Huaian No. 1 People’s Hospital of Nanjing Medical University, Huaian 223300, China
20 Department of Endocrinology, The First Affiliated Hospital of Bengbu Medical University, Bengbu 510110, China
21 Department of orthopedics, The Second Affiliated Hospital of Shantou University Medical College, Shantou 515041, China
22 Department of Geriatrics, Gansu Provincial Hospital of TCM, Lanzhou 730050, China
23 Department of orthopedics, The People’s Hospital of Chizhou, Chizhou 247000, China
24 Department of gynecology, Yantai Yuhuangding Hospital, Yantai 650001, China
25 Department of Endocrinology, Shandong Provincial Hospital, Jinan 250022, China
26 Department of Endocrinology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, China
27 Department of Endocrinology, The First Affiliated Hospital of Shandong First Medical University, Shandong Provincial Qianfoshan Hospital, Jinan 250014, China
28 Department of orthopedics, Sun Yat-sen Memorial Hospital Sun Yat-sen University, Guangzhou 510120, China
29 Department of orthopedics, Jinshan Hospital of Fudan University, Shanghai 200540, China
30 Department of Endocrinology, The first hospital of Hebei medical university, Shijiazhuang 300402, China
31 Department of Geriatrics, Union hospital Tongji college Huazhong University of Science and Technology, Wuhan 430030, China
32 Department of Technical Development, Shandong New Time Pharmaceutical Co., Ltd, Linyi 273499, China
33 Office of the Clinical Trial Institution, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China
Correspondence to: Xiao Cheng: 1322193118@qq.com, Zhen-lin Zhang: zhangzl@sjtu.edu.cn,
DOI: 10.1038/s41401-025-01661-0
Received: 15 April 2025
Accepted: 24 August 2025
Advance online: 1 October 2025
Abstract
To date, monthly oral bisphosphonates have not been available in China. In this randomized, double blind, positive-controlled, multicenter phase III clinical trial, we compared the efficacy and safety of monthly minodronate versus weekly alendronate in the treatment of Chinese postmenopausal women with osteoporosis. A total of 548 participants were screened across 31 study centers, of which 330 participants were randomized into two groups: the experimental group (n = 165) received oral minodronate (50 mg/tablet once every four weeks) and alendronate placebo (once weekly), while the positive control group (n = 165) received oral alendronate (70 mg/tablet once weekly) and minodronate placebo (once every four weeks) for a duration of 48 weeks. The bone mineral density (BMD) of the lumbar spine, femoral neck and total hip were measured using dual-energy X-ray absorptiometry (DXA) at baseline and at 24 and 48 weeks. At the end of treatments, the experimental group exhibited a mean increase (SD) in BMD above the baseline at the lumbar spine, femoral neck and total hip of 4.61% (4.613%), 3.04% (4.034%) and 3.40% (3.569%), respectively, compared with those of 4.55% (3.753%), 1.86% (3.592%) and 2.30% (4.838%) in the control group. All improvements from the baseline in the two groups were statistically significant. The monthly minodronate did not cause new safety risks compared with alendronate. This study demonstrates that monthly minodronate administration is non-inferior to weekly alendronate in terms of therapeutic efficacy, while maintaining a comparable safety profile. Furthermore, the monthly dosing schedule of minodronate may significantly enhance medication adherence among osteoporosis patients, potentially improving long-term treatment outcomes.
Keywords:
postmenopausal osteoporosis; Chinese women; minodronate; alendronate; bone mineral density; bone turnover markers
