Large observational studies have yielded conflicting results regarding whether the use of proton pump inhibitors (PPI) increases the risk of bone diseases. Here, we performed a meta-analysis to examine the link between PPI and risk of bone fractures, osteoporosis and bone mineral density (BMD) loss. We systematically performed a search for published reports on PubMed, EMBASE and the Cochrane Library. We considered articles published in English, and restricted the search to studies on human participants. Studies that reported adjusted Hazard ratio (HR) estimates with 95% confidence intervals (CI) for the associations of interest were included. Data from the articles which can be used to estimate standardized mean difference (SMD) were also obtained and utilized to assess the risk of BMD loss. Compared with patients not taking PPI, those taking PPI, had the increased risk of developing any-site fractures (HR: 1.30; 95%CI: 1.16 to 1.45), hip fracture (HR:1.22; 95%CI:1.15 to 1.31), spine fracture (HR:1.49; 95%CI:1.31 to 1.68), and osteoporosis (HR:1.23; 95%CI:1.06 to 1.42) based on a random model, but there was no correlation with developing BMD loss in the femoral (SMD: −0.27; 95%CI: −0.62 to 0.09), or in the spine (SMD: −0.06; 95%CI: −0.54 to 0.41). Results of this meta-analysis suggest that PPI may moderately increase the risk of any-site, hip, spine fracture. Due to the widespread use of PPI and the impact of fractures on human health, clinicians should carefully evaluate the patient condition before prescribing PPI therapy.