Fracture healing remains a significant clinical challenge, with delayed union and nonunion occurring in 5-10% of all fractures and contributing to prolonged disability, muscle atrophy, and substantial healthcare costs. While calcium, vitamin D₃, and early mobilization are routinely recommended, few affordable adjuncts directly target the energy-dependent processes underlying bone and muscle repair. Creatine monohydrate, a widely used supplement with a well-established safety profile, has demonstrated benefits in skeletal muscle energetics, hypertrophy, and recovery through enhanced phosphocreatine stores and ATP availability. Preclinical evidence suggests potential effects on bone metabolism through improved cellular energetics and modulation of oxidative stress pathways. This literature review synthesizes interdisciplinary evidence assessing whether oral creatine monohydrate supplementation positively impacts healing outcomes following fracture diagnosis. A systematic search of PubMed, Cochrane, Embase and related databases yielded studies across preclinical and human models. Studies were screened by authors Sierra H Jones, Samuel Majka, Dylan Johnson, Dillon Sorensen, Andrew Dong, and Rayna Carlson with conflict resolution by Sierra H Jones. Evidence consistently supports creatine as a low-cost, well-tolerated supplement with adequate absorption and bioavailability. Across the included literature, findings demonstrate that creatine supplementation may benefit muscle preservation during immobilization, with robust benefits observed during post-immobilization rehabilitation following disuse atrophy. Creatine improves bone geometric properties predictive of bending strength under mechanical loading, though effects on bone mineral density remain inconsistent. Additionally, creatine may indirectly affect bone fracture healing through metabolic amplification via increased intracellular phosphocreatine availability, which serves as a rapidly mobilizable energy buffer during high ATP demand. Under certain conditions, creatine has been shown to enhance mTOR/P70S6K anabolic signaling and modulate AMPK activity, though these effects are context-dependent and have not been demonstrated in bone tissue. The creatine kinase/phosphocreatine system is essential for osteoblast energy metabolism and differentiation, with phosphocreatine promoting mineralization via SIRT1/FOXO1/PGC-1α signaling and suppressing oxidative stress in vitro, though direct evidence linking oral creatine supplementation to bone tissue creatine accumulation is lacking. Critically, no studies directly evaluate creatine supplementation in fracture healing populations, and no data exist regarding time to radiographic union or functional recovery. Targeted trials should evaluate creatine's impact on time to radiographic union, functional recovery milestones, and patient-reported outcomes in both operatively and non-operatively managed fractures.
