Additionally, it has been postulated that the RANKL–RANK interaction may

modify immune responses in specific tissues such as the skin, potentially through an effect on the intensity of the inflammatory response, rather than through an immunosuppressive effect [31, 32]. In a dose-ranging study of denosumab in buy Adriamycin healthy postmenopausal women, no clinically meaningful differences in overall lymphocyte counts, T cells, or B cells were observed in learn more subjects treated with denosumab [33]. In the phase 3 international, double-blind pivotal trial demonstrating fracture reduction efficacy of denosumab in postmenopausal women with osteoporosis (Fracture Reduction Evaluation of Denosumab in Osteoporosis every 6 Months (FREEDOM)], the overall incidence of adverse events and serious adverse events was similar between denosumab- and placebo-treated subjects; however, some numeric imbalances in specific events were reported, including serious adverse events of infections involving the skin [8]. To better understand the potential influence of RANKL inhibition on infections, we examined the incidence and types of infections as well as details of individual cases among participants in the pivotal phase

3 denosumab fracture trial, which www.selleckchem.com/products/Staurosporine.html represents 10,826 patient-years of exposure to denosumab. Materials and methods Subjects and database Adverse events and serious adverse events of infections

as reported in the denosumab pivotal phase 3 fracture trial were examined. The study design and primary results of the study have been previously reported [8]. Briefly, PIK-5 it was a 3-year multicenter, international, randomized, double-blind, placebo-controlled study in 7,808 postmenopausal women with osteoporosis. Subjects received placebo or denosumab subcutaneously 60 mg every 6 months (Q6M). The study was conducted in accordance with the Declaration of Helsinki, and the protocol was approved by an institutional review board or ethics committee for each study site. All subjects provided written informed consent. Safety was assessed through adverse event reporting for all women who received at least one dose of investigational product (3,876 placebo and 3,886 denosumab). Information about adverse events was collected by investigators at each study visit. The investigator’s verbatim description of an adverse event was converted into standardized terminology based on the Medical Dictionary for Regulatory Activities (MedDRA) version 11 and entered in the safety database as preferred terms. Adverse events and serious adverse events were defined according to regulatory criteria: an adverse event was defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.