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Purpose: Osteoporosis is a pathologic condition characterized by low bone mass and changes in the microarchitecture of the bone tissue. Although compromised bone strength and increased susceptibility to fracture have been established, little is known regarding the process of bone regeneration in osteoporotic conditions. Accordingly, this study sought to evaluate the intramembranous bone regeneration process in an ovariectomized rat model following the establishment of calvarial subcritical-size defects (sCSDs). Materials and Methods: Calvarial sCSDs were established in rats that had been ovariectomized (Ovx) or sham-operated 2 months previously and left to heal, unfilled, for 6 months. Bone regeneration was assessed by radiographic, densitometric, histologic, and histometric analyses. Results: Radiologic and histologic analyses showed reduced new bone formation in calvarial sCSDs in Ovx animals in comparison to sham animals. Densitometric analysis of radiologic images and histometric analysis showed significant quantitative differences between groups that converged to substantiate reduced bone regeneration in Ovx animals. Conclusions: The intramembranous ossification process is impaired in the Ovx rat model. This may suggest an impairment of the bone regeneration process in clinical conditions of postmenopausal osteoporosis and highlight the requirement for selective bone regenerative strategies in affected patients. © 2012 by Quintessence Publishing Co Inc.