Proton pump inhibitors are the most effective drugs for the treatment of acid-dependent diseases. For a long time, proton pump inhibitors have been considered to be completely safe drugs both for short-term and long-term use. A number of modern clinical studies note that when prescribing proton pump inhibitors in high doses for a long time, the possibility of side effects should be taken into account. The purpose of the review is to study the effect of prolonged use of proton pump inhibitors on the condition of bone tissue and the risk of osteoporotic fractures. Materials and methods. A search was conducted in the PubMed and Scopus information databases for publications on the safety of using proton pump inhibitors, including sources published before December 1, 2023, with an emphasis on the influence of proton pump inhibitors on bone tissue and the possible risk of fractures. Results. According to numerous studies, prolonged use of proton pump inhibitors is associated with an increased risk of fractures of the hip, vertebrae and the wrist. An increased risk of fractures may be associated with hypergastrinemia and hypochlorhydria (due to inhibition of acid secretion by proton pump inhibitors), and electrolyte disorders (hypocalcemia). Conclusions. All the pros and cons of prescribing proton pump inhibitors in patients with a history of fractures associated with osteoporosis should be carefully considered. In the curation of comorbid/multimorbid patients, proton pump inhibitors should be used if medically required for as short duration as possible and at the minimum effective dose to relieve symptoms.