Osteoporosis is a widespread problem, which frequently has devastating health consequences through its association with fragility fractures. The total number of fractures, and hence the cost to society, will increase dramatically over the next 50 years as a result of demographic changes in the number of elderly people. Thus, prevention of osteoporosis by identifying risk factors or risk indicators, as well as the development of new treatment strategies, are major issues. Recent data suggest that homocysteine (Hcy), folate, vitamin B6 and vitamin B12 affect bone metabolism, bone quality and fracture risk in humans. Since circulating Hcy depends on folate, vitamin B6 and vitamin B12, Hcy could be suitable as a risk indicator for micronutrient-deficiency-related osteoporosis. Initial experimental results indicate that Hcy is not only a risk indicator, but also a player in bone metabolism. Moreover, existing data open speculation that folate, vitamin B6 and vitamin B12 act not only via Hcy-dependent pathways, but also via Hcy-independent pathways. However, more studies are needed to clarify the mechanistic role of Hcy, folate, vitamin B6 and vitamin B12 in bone metabolism.