Quantitative information about bone tissue-level loading is essential for understanding bone mechanical behavior. We made microfinite element models of a healthy and osteoporotic human femur and found that tissue-level strains in the osteoporotic femoral head were 70% higher on average and less uniformly distributed than those in the healthy one. INTRODUCTION: Bone tissue stresses and strains in healthy load-adapted trabecular architectures should be distributed rather evenly, because no bone tissue is expected to be overloaded or unused. In this study, we evaluate this paradigm with the use of microfinite element (microFE) analyses to calculate tissue-level stresses and strains for the human femur. Our objectives were to quantify the strain distribution in the healthy femur, to investigate to what extent this distribution is affected by osteoporosis, to determine if osteoporotic bone is simply bone adapted to lower load levels, and to determine the "safety factor" for trabecular bone. MATERIALS AND METHODS: microFE models of a healthy and osteoporotic proximal femur were made from microcomputed tomography images. The models consisted of over 96 and 71 million elements for the healthy and osteoporotic femur, respectively, and represented their internal and external morphology in detail. Stresses and strains were calculated for each element and their distributions were calculated for a volume of interest (VOI) of trabecular bone in the femoral head. RESULTS: The average tissue-level principal strain magnitude in the healthy VOI was 304 +/- 185 microstrains and that in the osteoporotic VOI was 520 +/- 355 microstrains. Calculated safety factors were 8.6 for the healthy and 4.9 for the osteoporotic femurs. After reducing the force applied to the osteoporotic model to 59%, the average strain compared with that of the healthy femur, but the SD was larger (208 microstrains). CONCLUSIONS: Strain magnitudes in the osteoporotic bone were much higher and less uniformly distributed than those in the healthy one. After simulated joint-load reduction, strain magnitudes in the osteoporotic femur were very similar to those in the healthy one, but their distribution is still wider and thus less favorable.