Purpose: Prolotherapy is a therapeutic method that involves injecting an irritant substance into injured areas of tendons, ligaments, and articular spaces. It has a wide application in orthopedic fields, including arthritis, tendinopathies, and back pain. Protocol of injection varies extensively based on the pathological condition. This review aims to discuss orthopedic applications of prolotherapy and its related outcomes, intending to introduce more specific injection protocols in each field. Methods: In a narrative review of literature, various musculoskeletal indications and contraindications of prolotherapy, as well as the method and location of injection, solution type, procedure intervals and frequencies, outcomes and side effects are investigated to reveal all aspects of the current knowledge about this new approach. Results: Chronic back pain, osteoarthritis, and tendinopathies are considered the most common indications for prolotherapy. Protocol of injection varies from one condition to another. The actual concentration of administered dextrose ranges from 12.5% to 25%. Results of the different studies indicate that prolotherapy could have a pleasing effect on improving patient’s pain and functional outcomes. No severe complication has been mentioned in previous investigations. Conclusion: Prolotherapy is a new therapeutic option that can be suggested as an effective method in recalcitrant musculoskeletal conditions.
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