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Additionally, the aging population and prevalence of osteoporosis\u2010related fractures necessitate the further exploration of novel ways to augment osteogenesis in this special population. This review focuses on the current clinical modalities available, and the ongoing clinical and pre\u2010clinical research to promote osteogenesis in segmental bone defects, delayed unions, and osteoporosis. In summary, animal models of fracture repair are often small animals as historically significant large animal models, like the dog, continue to gain favor as companion animals. Small rodents have well\u2010documented limitations in comparing to fracture repair in humans, and few similarities exist. Study design, number of studies, and availability of funding continue to limit large animal studies. Osteoinduction with rhBMP\u20102 results in robust bone formation, although long\u2010term quality is scrutinized due to poor bone mineral quality. PTH 1\u201034 is the only FDA approved osteo\u2010anabolic treatment to prevent osteoporotic fractures. Limited to 2 years of clinical use, PTH 1\u201034 has further been plagued by dose\u2010related ambiguities and inconsistent results when applied to pathologic fractures in systematic human clinical studies. There is limited animal data of PTH 1\u201034 applied locally to bone defects. Gene therapy continues to gain popularity among researchers to augment bone healing. Non\u2010integrating viral vectors and targeted apoptosis of genetically modified therapeutic cells is an ongoing area of research. Finally, progenitor cell therapies and the content variation of patient\u2010side treatments (e.g., PRP and BMAC) are being studied. \u00a9 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. 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