Distal radius fracture strength has been quantified using in vitro biomechanical testing. These tests are frequently performed using one of two methods: (1) load is applied directly to the embedded isolated radius or (2) load is applied through the hand with the wrist joint intact. Fracture loads established using the isolated radius method are consistently 1.5 to 3 times greater than those for the intact wrist method. To address this discrepancy, a validated finite element modeling procedure was used to predict distal radius fracture strength for 22 female forearms under boundary conditions simulating the isolated radius and intact wrist method. Predicted fracture strength was highly correlated between methods (r = 0.94; p < 0.001); however, intact wrist simulations were characterized by significantly reduced cortical shell load carriage and increased stress and strain concentrations. These changes resulted in fracture strength values less than half those predicted for the isolated radius simulations (2274 ± 824 N for isolated radius, 1124 ± 375 N for intact wrist; p < 0.001). The isolated radius method underestimated the mechanical importance of the trabecular compartment compared to the more physiologically relevant intact wrist scenario. These differences should be borne in mind when interpreting the physiologic importance of mechanical testing and simulation results.