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Conditional depletion of IGF-I produced in osteoblasts or osteocytes inhibits the bone anabolic effect of mechanical loading. Here, we determined the role of endocrine IGF-I for the osteogenic response to mechanical loading in young adult and old female mice with adult, liver-specific IGF-I inactivation (LI-IGF-I<jats:sup>\u2212\/\u2212<\/jats:sup>mice, serum IGF-I reduced by \u224870%) and control mice. The right tibia was subjected to short periods of axial cyclic compressive loading three times\/wk for 2 wk, and measurements were performed using microcomputed tomography and mechanical testing by three-point bending. In the nonloaded left tibia, the LI-IGF-I<jats:sup>\u2212\/\u2212<\/jats:sup>mice had lower cortical bone area and increased cortical porosity, resulting in reduced bone mechanical strength compared with the controls. Mechanical loading induced a similar response in LI-IGF-I<jats:sup>\u2212\/\u2212<\/jats:sup>and control mice in terms of cortical bone area and trabecular bone volume fraction. In fact, mechanical loading produced a more marked increase in cortical bone mechanical strength, which was associated with a less marked increase in cortical porosity, in the LI-IGF-I<jats:sup>\u2212\/\u2212<\/jats:sup>mice compared with the control mice. In conclusion, liver-derived IGF-I regulates cortical bone mass, cortical porosity, and mechanical strength under normal (nonloaded) conditions. However, despite an \u223c70% reduction in circulating IGF-I, the osteogenic response to mechanical loading was not attenuated in the LI-IGF-I<jats:sup>\u2212\/\u2212<\/jats:sup>mice.<\/jats:p>","DOI":"10.1152\/ajpendo.00107.2016","type":"journal-article","created":{"date-parts":[[2016,5,25]],"date-time":"2016-05-25T03:59:56Z","timestamp":1464148796000},"page":"E138-E144","source":"Crossref","is-referenced-by-count":11,"title":["Liver-derived IGF-I regulates cortical bone mass but is dispensable for the osteogenic response to mechanical loading in female mice"],"prefix":"10.1152","volume":"311","author":[{"given":"Johan","family":"Svensson","sequence":"first","affiliation":[{"name":"Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara H.","family":"Windahl","sequence":"additional","affiliation":[{"name":"Centre for Bone and Arthritis 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