Mean percent changes from baseline in biochemical markers LDK378 chemical structure of the bone formation marker serum BAP, and the bone resorption markers serum TRACP-5b, urinary DPD/CRN, urinary NTX/CRN, and urinary CTX/CRN were generally comparable in the two treatment groups. Bone resorption markers started to decrease from 1 month after the first treatment of study drug while the bone formation marker started to decrease from 3 months after the first treatment of study drug. The

reductions were maintained to the 12-month time point in both treatment groups (Fig. 3). The mean percent change from baseline in urinary NTX/CRN and urinary CTX/CRN levels showed a statistically significant decrease in the 2.5 mg once-daily group compared with the 75 mg once-monthly group throughout the treatment period (at 1, 3, 6, 9, 12 months, and at the end of the study [M12, LOCF]). The results of the subgroup analysis showed that the mean percent changes from baseline MK0683 mw in (L2–L4) BMD at the end of the study (M12, LOCF) were similar between treatment groups in each subgroup of the biochemical markers (Table 2). The mean percent changes from baseline in (L2–L4) BMD at the end of the study (M12, LOCF) were generally higher in both treatment groups for the subgroup of subjects with higher baseline

values of biochemical markers. Thoracic vertebra and lumbar spine X-ray images were taken at baseline and at the end of the study. The frequency of new vertebral fractures (including aggravation Cyclic nucleotide phosphodiesterase of prevalent fractures) at the end of the study (M12, LOCF) was 1.2% (5/410 subjects) in the 2.5 mg once-daily group and 1.3% (5/393 subjects)

in the 75 mg once-monthly group. The difference between treatment groups was 0.1% (95% CI, − 1.48% to 1.59%) and, thus, the effects of both treatment regimens were similar. Safety and tolerability were evaluated using the safety analysis set. The frequency of AEs was similar between the two groups: 82.2% (352/428 subjects) in the 2.5 mg once-daily group and 86.5% (365/422 subjects) in the 75 mg once-monthly group. In both groups, the majority of AEs were mild to moderate and the most common AE was nasopharyngitis (Table 3). The incidence of mild/moderate/severe AEs was 75.5%/6.3%/0.5% in the 2.5 mg once-daily group and 77.7%/8.1%/0.7% in the 75 mg once-monthly group. The incidence of AEs counted as non-vertebral fractures was 3.0% (13/428 subjects) in the 2.5 mg once-daily group and 2.1% (9/422 subjects) in the 75 mg once-monthly group, but these were considered to be unrelated to the study drug. Furthermore, no cases of AEs associated with non-traumatic atypical fracture of the subtrochanteric or mid-shaft of the femur were observed. The frequency of AEs associated with gastrointestinal symptoms was 26.2% (112/428 subjects) in the 2.5 mg once-daily group and 30.