Osteoporosis is a condition in which bone resorption by osteoclasts overtakes bone formation by osteoblasts ; as a result, bone density is reduced, the bone microarchitecture is damaged, and the risk of fractures is increased. To date, the increase in bone resorption has been explained by a reduction in female hormones, which control the activity of osteoclasts. More recently, however, it has become clear that a reduction in male hormones from middle age onwards, increasing age, and an increase in oxidative stress related to lifestyle-related diseases can also activate osteoclasts and reduce osteoblast function. These changes lead to both qualitative and quantitative abnormalities in collagen, which is the major bone matrix protein. In contrast to microstructure and calcification levels, among other bone-density and bone-matrix factors, which are controlled by bone remodeling, the intermolecular cross-link formation of collagen, which regulates bone-material attributes, is a mechanism independent of bone remodeling. In other words, cross-link formation is controlled by the environment surrounding the bone matrix, comprising cellular functions, oxidative stress, carbonyl stress, and glycation level. Therefore, bone quality is regulated both by bone remodeling and by a remodeling-independent mechanism, and markers for evaluating bone quality should be established.