Compact bone makes up approximately 80% of the human skeletal mass. This study examines the effect of estrogen deficiency on compact bone turnover and associated geometrical structural adaptation over a 31-month period in a large animal model. Twenty-seven skeletally mature sheep were divided into control (n ¼ 16) and ovariectomy group (OVX, n ¼ 11). Animals were administered five different fluorochrome dyes to label intracortical bone turnover, and sacrificed at 31 months. Compact bone samples were analyzed for cortical geometry, intracortical turnover at five time points, resorption cavities, porosity, and compressive strength. Intracortical bone turnover was significantly increased in OVX, which demonstrated seasonal variation. Cross-sectional area in OVX was significantly greater than control and was associated with an increased section modulus. Intracortical porosity was significantly increased in OVX, however, there was no significant difference in ultimate compressive strength between the groups. Our results demonstrate increased intracortical bone turnover, resportion spaces, and porosity in OVX, without adversely affecting compressive strength. Our results also support the hypothesis of geometrical adaptation of compact bone in response to estrogen deficiency. These results suggest an early structural compensatory response in compact bone, despite increased intracortical turnover. Keywords: compact bone; estrogen; ovine; bone turnover; bone geometry Bone strength depends not only on material properties, but also on structural properties. The structural properties of bone depend on size and shape, as well as its microarchitecture.1 Adding mass away from the center of the bone, periosteal apposition, can dramatically affect a bone's ability to resist bending and torsion. It has been estimated that an increase of 10% in periosteal diameter would lead to a 50% increase in axial compressive strength and a 70% increase in bending strength.2 These parameters are important considerations in the pathophysiology of skeletal diseases such as osteoporosis and fracture.In this study, we used an ovariectomy sheep model to study the effects of estrogen deficiency on compact bone over a 31-month period. The sheep has been used previously as an animal model for studying bone turnover, porosity, and biomechanical aspects of osteoporosis. [3][4][5] Similarities between the hormone profiles of ewes and women, a comparable metabolic rate, and commensurate bone remodeling cycles support the use of the ovine model of postmenopausal osteoporosis. [6][7][8] We have previously demonstrated an increase compact bone turnover and porosity in an ovine model of osteoporosis during the initial 12-months postovariectomy without adversely affecting biomechanical properties.5 Conversely, we have also demonstrated a significant reduction in the biomechanical properties of trabecular bone associated with increased turnover. 9 Here we examine the effect of estrogen deficiency on compact bone geometry, intracortical remodeling, por...