Fat and bone.

Body weight is a principal determinant of bone density and fracture risk, and adipose tissue mass is a major contributor to this relationship. In contrast, some recent studies have argued that "fat mass after adjustment for body weight" actually has a deleterious effect on bone, but these analyses are confounded by the co-linearity between the variables studied, and therefore have produced misleading results. Mechanistically, fat and bone are linked by a multitude of pathways, which ultimately serve the function of providing a skeleton appropriate to the mass of adipose tissue it is carrying. Adiponectin, insulin/amylin/preptin, leptin and adipocytic estrogens are all likely to be involved in this connection. In the clinic, the key issues are that obesity is protective against osteoporosis, but underweight is a major preventable risk factor for fractures.