For instance, it has been reported that loss of knee cartilage is much greater in 50- to 79-year-old women than in age-matched men, which suggests that there are distinct effects of age and menopause. Such variation may be relevant to knee OA because bone changes, particularly subchondral bone, during the development of OA83,84. Because variable loss of bone mass has also been observed in astronauts during exposure to microgravity, the rate of bone loss is likely influenced by mechanical factors and the balance between anabolism and catabolism in a tissue. Although a genetic component is likely involved, loss of ovarian function after menopause leads to different rates of bone loss. One feature of this work, especially the studies of osteoporosis in human populations, is that the loss of bone density and structure is variable across individuals.