Purpose: Usage of dental implants has become common for the treatment of edentulous patients, but concerns exist over the use of implants in patients where orofacial bone loss occurs. In the present study, the osseointegration of implants in rabbits under osteoporosis-like (OP-like) conditions simulating several clinically relevant conditions is reported. Materials and Methods: Forty rabbits were divided into 4 groups of 10. Three groups of animals received daily intramuscular injections of glucocorticoids (7.5 mg/kg) for 8 weeks to induce OP-like conditions either before, simultaneous to, or after implant placement. Results: The injections of glucocorticoids resulted in cortical thinning, irregular trabecular patterns, and impaired extracellular (ECM) matrix formation and mineralization. Although interfacial strength (8.5 ± 1.3 MPa for the control group; 9.3 ± 4.0 to 10.1 ± 4.0 MPa for the experimental groups) was apparently not affected in this limited sample cohort (n = 3 per group), statistically significant decreases (P .05) in implant-bone contact were observed in animals with OP-like conditions (49% ± 10% for the control group; 24% ± 16% to 42% ± 16% for the experimental groups). Discussion: Histologic features characteristic of OP-like conditions were observed in each experimental group. ECM expression also appeared to be altered and compromised in all animals with OP-like conditions, which may affect long-term biomechanical stability of the implants. Conclusion: OP-like conditions affect the osseointegration characteristics of implants, but long-term biomechanical stability under forces of mastication is unknown as yet.