This was a 12-month, phase III, multicenter, randomized, double-blind, parallel group, active comparator controlled study in Japanese patients with involutional osteoporosis. Diagnosis of osteoporosis was based on the presence or absence of fragility fracture and BMD measurements specified in the “Guideline for the Diagnosis of Primary Osteoporosis (2000 Revised Version)” established by the Japanese Society for Bone and Mineral Research GSI-IX in vitro [20] and [21]. Individuals eligible for this study were ambulatory Japanese male and female subjects aged ≥ 50 years who were diagnosed with osteoporosis, based on the criteria for primary osteoporosis of the Japanese Society for Bone and

Mineral Research [20] and [21]. Primary osteoporosis was defined by the presence of a fragility fracture and BMD < 80% of the ‘young adult mean’ (20 to 44 years of age), or BMD < 70% of the ‘young adult mean’ in the absence of a detectable fragility fracture [21]. In the case of female subjects, ≥ 2 years must have passed since menopause.

The main exclusion criteria were factors which affect 3-Methyladenine mouse efficacy evaluation; secondary osteoporosis and any other disease causing decreased bone mass or affecting lumbar spine BMD (including severe scoliosis of the spine, fracture or severe deformation in any of the L2–L4 lumbar vertebrae, or a spinal X-ray image suggesting severe bone sclerosis [calcification] in any of the L2–L4 lumbar vertebrae); Morin Hydrate administration of bisphosphonate within 24 weeks before the first dose of the study

drug; administration of any drug affecting bone metabolism such as SERMs, vitamin D3 and vitamin K2 preparations, and calcitonin analogs, etc. within 8 weeks before the first dose of the study drug. In addition, any subject judged by the attending physician to be unsuitable to participate in the study was also excluded. The study was performed at 60 study sites in Japan between February 2010 and August 2011 in accordance with the ethical principles set out in the Declaration of Helsinki and the ICH Harmonized Tripartite Guideline for Good Clinical Practice, and was approved by the Institutional Review Boards at each study site in line with local regulations. Prior to study registration, all subjects were given a full explanation of the study procedures and provided written informed consent. Subjects fulfilling the inclusion/exclusion criteria were eligible for the study and were randomized (in a ratio of 1:1) to receive risedronate 75 mg once-monthly or risedronate 2.5 mg once-daily. Matching 2.5 mg and 75 mg placebo tablets were administered to maintain double blindness throughout the study. Subjects were instructed to take a single 75 mg risedronate tablet or 75 mg placebo tablet on the same calendar day each month and a single 2.5 mg risedronate tablet or 2.5 mg placebo tablet at the designated time on every day.