Proton pump inhibitors (PPIs) are commonly prescribed in conjunction with other drugs as a preventative measure. Their primary function is acid suppression; as such, they subsequently hold back intestinal calcium absorption. By this mechanism, chronic use of PPIs is suggested to induce osteoporosis, a condition that gradually increases bone fragility and is associated with high suffering and morbidity rates. Additionally, PPI administration amongst elderly patients for more than one year has been shown to have an increased risk for hip fractures. This current review consists of literature searches from PubMed and the National Library of Medicine (USA). It analyzes factors such as age, race, gender, menopausal status, lifestyle, medical conditions, and polypharmacy, which may induce osteoporosis, and explores the mechanism of how PPIs may trigger osteoporosis development and/or progression. Clinicians should be cautious of severe osteoporosis as a potential consequence of PPI use, and be aware that it can be mitigated by the appropriate selection of pharmacological therapies and modalities.