Finally, based on the included criteria and excluded criteria, 11 literatures [16-26] were included in this meta-analysis. significantly decreased the risk of non-vertebral fracture but increased the risk of SAE related to infection in the postmenopausal women with osteoporosis or low BMD. However, no difference between the safety of denosumab and bisphosphonates was found. strong class=”kwd-title” Keywords: Denosumab, osteoporosis, postmenopausal women, meta-analysis Introduction Osteoporosis is a GOAT-IN-1 common disease characterized by a systemic impairment of bone mass, strength, and microarchitecture which increases the propensity of fragility fractures [1]. There is higher prevalence of osteoporosis among postmenopausal women and the elderly [2]. Approximately 30% of all postmenopausal women in the United States and Europe have osteoporosis [3]. In Korea, the prevalence of osteoporosis has been reported to be 31% in postmenopausal women aged 45-64 years, 53% in those aged 65-74 years [4]. Shao et al. [5] reported that the prevalence of osteoporosis was as much as 60% in postmenopausal Chinese women. The treatment of osteoporosis and prevention of osteoporotic fractures consist of non-drug and drug therapy [6]. Drug therapy of osteoporosis is based on the knowledge of mechanisms of bone turnover and the manipulation of the cellular components of bone turnover in recruitment, activation and apoptosis [7]. Bisphosphonates is one of the drugs that are currently available for postmenopausal osteoporosis by inhibiting bone turnover [8]. Denosumab is a fully human monoclonal antibody to receptor activator of nuclear factor-B ligand (RANKL) [9]. RANKL is a cytokine member of the tumour necrosis factor family that is the principal final mediator of osteoclastic bone resorption [10]. It is the key molecule responsible for the bone loss observed in osteoporosis [11]. By binding to RANKL and preventing its binding to the RANK receptors on the surface of osteoclasts and osteoclast precursors, denosumab inhibits the development, activation and survival of osteoclasts [12]. Although denosumab had been recommended as one of the clinical medicines by American Association of Clinical Endocrinologists (AACE) [13], it is lack of large sample size studies to perfectly evaluate the effectiveness and safety of denosumab. Therefore, we performed a meta-analysis to assess the safety of denosumab in postmenopausal women with osteoporosis or low bone mineral density (BMD). Materials and methods Search strategy A systematic literature search without language restriction was conducted up to January, 2014 by using the electronic databases such as PubMed, Embase, GOAT-IN-1 Springer link, Cochrane library. The key words included denosumab, osteoporosis, postmenopausal women, and low bone mineral density. Furthermore, paper literatures were retrieved by manual search. Review articles and reference lists of retrieved Figure 1. Literature search and study selection.articles were also inspected to find additional eligible studies. Open in a separate window Figure 1 Literature search and study selection. Study selection Studies that met the following criteria were included in the meta-analysis: (1) the studies were randomized controlled trials; (2) the subjects were the postmenopausal women with osteoporosis or low BMD; (3) the studies were designed to compare the safety of denosumab with placebo or bisphosphonates; (4) one of the following risk indicators must be included: any adverse events (AAE), serious adverse event (SAE), SAE related to infection, non-vertebral fracture, neoplasm/cancer and deaths. Studies were excluded if they were (1) animal studies; (2) studies that had unavailable data or lack of enough data; (3) reviews, letters and comments; (4) repeated publication articles. Data extraction and quality assessment Two evaluators independently selected studies and extracted data. Discrepancies were resolved by discussion with a third investigator. For each study, GOAT-IN-1 the following information was extracted: the first author name, year of publication, region, age of subjects, number of subjects, dosage of denosumab and outcomes. Study quality was assessed using the 6-item instrument developed by Jadad et al [13]. The studies with the score from 3 to 5 5 are high quality studies. According to Cochrane Library Handbook [14], risk assessment tool in RevMan 5.1 was used to evaluate the risk of bias Rabbit Polyclonal to PDK1 (phospho-Tyr9) in the following factors: random sequence generation, allocation concealment, blinding of participants and staff, blinding of outcome assessment, incomplete data of outcome, selective reporting and so on. Statistical analysis The risk indicators of AAE, SAE, SAE related to infection, fractures, neoplasm/cancer and deaths were used to assess the safety of denosumab in the postmenopausal women with osteoporosis.
