The dose of 50 mg dose was selected based on the pharmacokinetics study (data not shown) that demonstrated monthly bone exposure comparable to daily 1 mg would require 42- to 56-mg single monthly doses because of lower absorption with larger single doses. Randomization was performed using a computerized system. Subjects were instructed to take their tablet on arising and 30 min before food with plain water. All subjects received daily calcium (610 mg) and vitamin

D (400 IU) supplementation once a day after the evening meal. Compliance with the study treatment was assessed through medication diaries and by counting residual medication supplies. Study outcomes The primary endpoint of the study was the test of the noninferiority of the mean percent change from

baseline in the lumbar spine (L2–L4) BMD at 12 months of Selleck JNK-IN-8 treatment with the study medication. Secondary endpoints of the study included mean percent change from baseline in the total hip BMD, relative changes in bone turnover markers, and the occurrence of new morphometric vertebral and nonvertebral fractures. Assessment learn more of BMD The lumbar spine (L2–L4) and the total hip were measured by dual-energy X-ray absorptiometry (DXA) at baseline and at 3, 6, 9, and 12 months to determine BMD. All 31 study centers involved in this trial were equipped with a Hologic QDR series for BMD measurements. A central facility (Department of Nuclear Liothyronine Sodium Medicine, Kawasaki Medical School, Okayama, Japan by T. Sone) performed quality assurance of the longitudinal adjustment. The DXA machines were adjusted for differences and each machine was calibrated with standardized phantoms. Assessment

of bone turnover Serum and urine samples were collected at baseline and 1, 3, 6, 9, and 12 months for measurement of bone turnover markers, including urine type I collagen N-telopeptide (NTX; this website Osteomark, Inverness Medical Japan Co., Ltd., Tokyo, Japan), urine deoxypyridinoline (DPD; Osteolinks “DPD”; Quidel Corporation, San Diego, CA, USA) after acid hydrolysis, serum bone-specific alkaline phosphatase (BALP; AccessR OstaseR; Beckman Coulter, Inc., Brea, CA, USA), serum osteocalcin (BGP-IRMA; Mitsubishi Chemical Medience Corporation, Tokyo, Japan), serum Ca (Iatrofine Ca II; Mitsubishi Chemical Medience Corporation), and serum intact parathyroid hormone (PTH; ECLusys “PTH”; Roche Diagnostics K.K., Tokyo, Japan). Serum 25-hydroxyvitamin D (25(OH)D 125I RIA Kit; DiaSorin Inc., Saluggia, Italy) was also determined at baseline. When possible, the samples for each subject were collected around the same time of day to avoid the influence of daily fluctuations. Assessment of vertebral fractures Lateral radiographs of the thoracic and lumbar spine were taken at the screening visit to determine the presence of prevalent fractures. Subjects were enrolled based on a visual assessment of prevalent fractures in T4 to L4.