Mechanisms of Disease: is osteoporosis the obesity of bone?

Osteoporosis results from decreased osteoblast function, increased osteoclast function and increased adiposity of the bone marrow with age. Regulation of the balance between fat and bone in the bone marrow is complex and involves genetic, hormonal and environmental influences. Here, Clifford Rosen outlines a hypothesis that skeletal fragility has its pathogenic roots in pleuripotent marrow stromal cells and their fate as either fat or bone cells. Osteoporosis and obesity, two disorders of body composition, are growing in prevalence. Interestingly, these diseases share several features including a genetic predisposition and a common progenitor cell. With aging, the composition of bone marrow shifts to favor the presence of adipocytes, osteoclast activity increases, and osteoblast function declines, resulting in osteoporosis. Secondary causes of osteoporosis, including diabetes mellitus, glucocorticoids and immobility, are associated with bone-marrow adiposity. In this review, we ask a provocative question: does fat infiltration in the bone marrow cause low bone mass or is it a result of bone loss? Unraveling the interface between bone and fat at a molecular and cellular level is likely to lead to a better understanding of several diseases, and to the development of drugs for both osteoporosis and obesity. Key Points Bone-marrow stromal cells can differentiate into adipocytes or osteoblasts Bone-marrow adiposity increases with age in mammalian species The function of fat in the bone marrow is unknown; it may be protective or detrimental Increased bone-marrow fat as detected by MRI might be associated with greater fracture risk The master controls over stem-cell lineage allocation are still not well defined