Although mechanical loading is known to influence trabecular bone adaptation, the role of specific loading parameters requires further investigation. Previous studies demonstrated that the number of loading cycles and loading duration modulate the adaptive response of trabecular bone in a rabbit model of applied loading. In the current study, we investigated the influence of load magnitude on the adaptive response of trabecular bone using the rabbit model. Cyclic compressive loads, producing peak pressures of either 0.5 or 1.0 MPa, were applied daily (5 days/week) at 1 Hz and 50 cycles/day for 4 weeks post-operatively to the trabecular bone on the lateral side of the distal right femur, while the left side served as an nonloaded control. The adaptive response was characterized by microcomputed tomography and histomorphometry. Bone volume fraction, bone mineral content, tissue mineral density, and mineral apposition rate (MAR) increased in loaded limbs compared to the contralateral control limbs. No load magnitude dependent difference was observed, which may reflect the critical role of loading compared to the operated, nonloaded contralateral limb. The increased MAR suggests that loading stimulated new bone formation rather than just maintaining bone volume. The absence of a dose-dependent response of trabecular bone observed in this study suggests that a range of load magnitudes should be examined for biophysical therapies aimed at augmenting current treatments to enhance long-term fixation of orthopedic devices. Keywords: trabecular bone; bone adaptation; rabbit; microcomputed tomography; mechanical stimulation Mechanical loading plays a central role in skeletal development and maintenance via both modeling and remodeling processes. 1-3 Throughout life the skeleton adapts by changing bone mass and architecture to the functional demands placed on it by mechanical stimuli. In cortical bone, loading must be dynamic rather than static to elicit an anabolic response 4 and adaptive remodeling is preferentially responsive to short periods of strain change. 5 For example, high-magnitude strains, varied by regulating the applied load 6-8 and strain rate, 9 enhanced cortical bone mass.Age-related bone loss, disuse-related bone loss, bone healing, and osseointegration around implants are all intimately coupled with the mechanical loading environment in trabecular bone. Despite the importance of studies on cortical diaphyseal bone adaptation to mechanical loading, prevention and treatment of osteoporosis and osteoarthritis requires investigation of trabecular bone adaptation. In addition, important questions remain concerning trabecular bone functional adaptation to a variety of loading parameters.Well-controlled and minimally invasive experimental models of loading in trabecular bone have been difficult to develop. [10][11][12][13] In vivo intermittent compressive loading via a hydraulic bone chamber stimulated bone matrix synthesis in trabecular bone of the canine tibial and femoral metaphyses. 14 While clearl...