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Segmental bone loss increases the probability of non\u2010union. Though grafting can be an effective treatment for segmental bone loss, autografting is limited for large defects since a limited amount of bone is available for harvest. Parathyroid hormone (PTH) is a key regulator of calcium homeostasis in the body and plays an important role in bone metabolism. Presently PTH is FDA approved for use as an anabolic treatment for osteoporosis. The anabolic effect PTH has on bone has led to research on its use for bone regeneration applications. Numerous studies in animal models have indicated enhanced fracture healing as a result of once daily injections of PTH. Similarly, in a human case study, non\u2010union persisted despite treatment attempts with internal fixation, external fixation, and autograft in combination with BMP\u20107, until off label use of PTH1\u201084 was utilized. Use of a biomaterial scaffold to locally deliver PTH to a defect site has also been shown to improve bone formation and healing around dental implants in dogs and drill defects in sheep. Thus, PTH may be used to promote bone regeneration and provide an alternative to autograft and BMP for the treatment of large segmental defects and non\u2010unions. This review briefly summarizes the unmet clinical need for improved bone regeneration techniques and how PTH may help fill that void by both systemically and locally delivered PTH for bone regeneration applications. \u00a9 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. 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