An inverse relationship between osteoarthritis and osteoporosis has been debated over years. The microstructure of the femoral heads from postmenopausal osteoarthritic and osteoporotic women was evaluated with micro-CT. Significant differences were observed in microstructural parameters between them. Different microstructure might relate to the opposite bone defects in osteoarthritis and osteoporosis. Introduction: This study was undertaken to verify the inverse relationship between osteoarthritis (OA) and osteoporosis (OP) by comparing the structural and mechanical indices. Methods: Femoral head specimens were obtained from 17 postmenopausal women (OA, n=8; OP, n=9) during hip surgery. The microstructural parameters were measured with micro-CT. Mechanical test was performed after bone cube scanning. Results: Significant difference in bone volume fraction (BV/TV) and trabecular thickness was noted between OA and OP groups. Structure model index decreased in OA, and increased in OP. The higher apparent density (AD) and lower material density (MD) were also shown in OA. Different from OP, positive correlation were noted between connectivity density and mechanical indices in OA. In OA group, BV/TV was associated with Young's modulus and AD, while trabecular number was the only parameter that correlated with MD. However, in OP group, only BV/TV correlated with yield strength, AD, and MD. Conclusions: We observed the difference in microstructure between postmenopausal women with OA and OP, which might relate to the opposite bone defects in OA and OP. BV/TV might play an important role in mechanical properties of the subchondral bone in either OA or OP. © 2009 International Osteoporosis Foundation and National Osteoporosis Foundation.