There was a significant decrease in sCTX-1 from baseline in both treatment groups at month 1 and a significantly

greater reduction was observed with denosumab treatment compared with risedronate treatment: median (IQR) percentage change of − 77.7% (− 85.9%, − 67.6%) for denosumab and − 17.0% (− 36.8%, − 1.6%) for risedronate (p < 0.0001; Fig. 4). Median reductions in sCTX-1 at month 6 were also greater in the denosumab group compared with the risedronate group: median (IQR) percentage change of − 60.6% (− 77.0%, − 48.8%) for denosumab and Dabrafenib datasheet –22.5% (− 41.9%, 11.4%) for risedronate (p < 0.0001). The BMD mean percentage changes from baseline at month 12 by tertiles (< 0.23, ≥ 0.23 to < 0.37, and ≥ 0.37 ng/mL) of baseline sCTX-1 for each skeletal site are reported in Fig. 5. This additional analysis showed that subjects treated with denosumab, compared with risedronate, demonstrated significantly greater gains in lumbar spine BMD at month 12 at each tertile of baseline sCTX-1 (p < 0.01; Fig. 5). Significantly greater gains in total hip and femoral neck BMD were also observed among subjects in the middle and highest tertiles of baseline sCTX-1 (p < 0.01). At all sites the magnitude of the BMD gain was significantly more EGFR inhibitor pronounced in the middle and highest sCTX-1 tertiles (treatment-by-sCTX-1 tertile

interaction p-values < 0.01). The post-hoc analysis showed that nearly half of the enrolled population was at higher risk for fracture: 46.4% and 45.5% of risedronate- and denosumab-treated subjects, respectively. These higher-risk subjects demonstrated BMD gains that were consistent with findings in the overall population (Fig. 6). Overall, the subject incidences of AEs were 293 subjects Histidine ammonia-lyase (68.3%) in the risedronate group and

269 subjects (62.7%) in the denosumab group, with the most frequently experienced AEs (≥ 4% in either treatment group [risedronate, denosumab]) being hypertension (2.6%, 4.2%), arthralgia (4.4%, 4.0%), nasopharyngitis (4.2%, 3.5%), and constipation (5.1%, 3.3%). Most of the AEs in both groups were categorized as being either mild or moderate in severity (Table 2). SAEs were reported for 8.2% of risedronate-treated subjects and 7.7% of denosumab-treated subjects. There was no evidence of clustering of SAEs within any given system organ class or high-level group term in either treatment group. SAEs reported for ≥ 2 denosumab-treated subjects were osteoarthritis, radius fracture, cerebral ischemia, cerebrovascular accident, arthralgia, and atrial fibrillation; these SAEs were each experienced by 2 (0.5%) denosumab-treated subjects. In the risedronate treatment group, the most frequently reported SAEs (2 [0.5%] subjects each) were breast cancer and coronary artery stenosis; all other SAEs were experienced at an incidence of 1 subject each. One death due to cardiac arrest was reported in a risedronate-treated subject.