RT Journal Article T1 Risk of fragility fracture is aggravated during bone regeneration processes in osteoporotic sheep A1 Toscano Angulo, Juan J. A1 Mora Macías, Juan A1 Blázquez-Carmona, Pablo A1 Morgaz, Juan A1 Navarrete Calvo, Rocío A1 Domínguez Abascal, Jaime AB Bone regeneration processes are associated with a systemic skeletal change in bonequality, increasing the risk of fragility fractures. This condition may be aggravated inosteoporotic patients due to their limited osteogenic capacity. This work evaluates theimpairment of the bone quality in osteoporotic sheep during a bone regeneration process.It provides a deeper understanding about the complex multiscale dynamics ofbone mineral density, microstructure and chemical composition across different bonetissues, locations and time pointsOsteoporosis was induced in fifteen Merino sheep. A critical-size defect was thencreated in the sheep’s right hind metatarsus and subsequently regenerated usingdistraction osteogenesis. The animals were randomly sacrificed during bone regeneration,either on days 40 or 100 after surgery. Computed tomography, micro-computedtomography and chemical composition analyses were conducted on different bonetissues (cortical, trabecular and woven) at several skeletal locations (the operatedmetatarsus, the contralateral one and the iliac crest) to assess the individual bonequality changes relative to the non-osteoporotic time pointAfter osteoporosis induction, the trabecular tissue experienced a 6.4% reduction inthe bone mineral density, while no significant changes were reported in cortical tissuequality. During bone regeneration, the operated bone increased significantly the woven ossification whilst the cortical mineral density decreased by 18.7%. Simultaneously, an early deterioration in the microstructure and chemical composition of the trabecular bone was observed in the iliac crest, persisting over time in non-operated trabecular regionsOsteoporosis causes uneven degradation to trabecular tissue quality across different bone locations. Furthermore, the bone regeneration process via bone transport in osteoporotic subjects leads to a systemic skeletal disorder that further impairs the bone quality, surpassing the damage caused by osteoporosis alone. This impairment appears to be intensified by the pre-existing osteoporotic condition PB Public Library of Science SN 1932-6203 (electrónico) YR 2025 FD 2025-05 LK https://hdl.handle.net/10272/25511 UL https://hdl.handle.net/10272/25511 LA eng NO Toscano-Angulo JJ, Mora-Macías J, Blázquez-Carmona P, Morgaz J, Navarrete-Calvo R, Domínguez J, et al. (2025) Risk of fragility fracture is aggravated during bone regeneration processes in osteoporotic sheep. PLoS One 20(5): e0319910. https://doi.org/10.1371/ journal.pone.0319910 NO This study was supported by theMICIU (Ministry of Science, Innovation and Universities of the Spanish Government) and ERPF/EU (European Regional Development Fund of the European Union) via Grant PID 2023-148828OB-I00 funded by MICIU/AEI/10.13039/501100011033 and by the ERDF/EU, received by Esther Reina-Romo and Juan Mora-Macías DS Repositorio Institucional de la Universidad de Huelva RD 30 may 2026