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Osteocyte apoptosis is spatially and temporally linked to bone fatigue‐induced microdamage and to subsequent intracortical remodeling. Specifically, osteocytes surrounding fatigue microcracks in bone undergo apoptosis, and those regions containing apoptotic osteocytes co‐localize exactly with areas subsequently resorbed by osteoclasts. Here we tested the hypothesis that osteocyte apoptosis is a key controlling step in the activation and/or targeting of osteoclastic resorption after bone fatigue. We carried out in vivo fatigue loading of ulna from 4‐ to 5‐mo‐old Sprague‐Dawley rats treated with an apoptosis inhibitor (the pan‐caspase inhibitor Q‐VD‐OPh) or with vehicle. Intracortical bone remodeling and osteocyte apoptosis were quantitatively assessed by standard histomorphometric techniques on day 14 after fatigue. Continuous exposure to Q‐VD‐OPh completely blocked both fatigue‐induced apoptosis …