4% vs 52.9%, respectively; P = 0.17), and serious Metabolism inhibitor adverse events of infections were reported in 3.4% of placebo subjects and 4.1% of denosumab subjects (P = 0.14) [8]. About 40% of the serious adverse events of infection (41.3% with placebo and 44.7% with denosumab) were of mild or moderate severity, although they met the regulatory definition of “serious adverse events.” Usually, the “serious” definition was applied due to hospitalization of the subject. The number of subjects discontinuing the study as a result of adverse events of infection was low and similar SHP099 between treatment groups

(four placebo, three denosumab; Table 1). No increased risk for fatal infections was observed with denosumab (six placebo, six denosumab; Table 1). Table 1 Summary of adverse events and serious adverse events of infection   Placebo (N = 3,876), n (%) Denosumab (N = 3,886), n (%) P value Adverse events of infections 2,108 (54.4) 2,055 (52.9) 0.1721 Serious adverse events of infection 133 (3.4) 159 (4.1) 0.1399 Serious opportunistic

infection 3 (<0.1) 4 (0.1) 0.7130 AEs of infection leading to study discontinuation 4 (0.1) 3 (<0.1) 0.6979 Fatal infections 6 (0.2) 6 (0.2) 0.9787 Serious adverse events of infections over GDC-0449 price time The incidence of serious adverse events of infection across the 3 years of study was examined. The rate of infection did not change with increasing duration of denosumab exposure (Table 2). The rates of known bacterial, viral, and fungal infections also did not increase with duration of denosumab exposure (Table 2). Table 2 Incidence of serious adverse events of infections by year of study and microbial classification   Year 1 Year 2 Year 3 Incidence of serious adverse events of infection by year        Placebo 42 (1.1%) 49 (1.3%) 47 (1.4%)  Denosumab 55 (1.4%) 58 (1.6%) 54 (1.5%) Positively identified bacterial infections        Placebo 10 (0.3%) 12 (0.3%)

10 (0.3%)  Denosumab 13 (0.3%) 15 (0.4%) 19 (0.5%) Positively identified viral infections        Placebo 0 (0.0%) 1 (<0.1%) 5 (0.1%)  Denosumab 2 (0.1%) 4 (0.1%) 2 (0.1%) Positively identified fungal infections        Placebo 1 (<0.1%) 0 (0.0%) 0 (0.0%) PD184352 (CI-1040)  Denosumab 1 (<0.1%) 0 (0.0%) 1 (<0.1%) Opportunistic infections Serious adverse events of opportunistic infections were prospectively identified as events of interest. The incidence of serious adverse events of opportunistic infections was low and similar in the placebo (three [<0.1%]) and denosumab (four [0.1%]) groups [8]. No clear pattern in the type of infections was observed. In the placebo group, all three subjects had tuberculosis (preferred terms of tuberculosis or pulmonary tuberculosis) and one event was fatal. In the denosumab group, the opportunistic infections were tuberculosis (two subjects), aspergillosis of the face, and disseminated herpes zoster.