Fat's loss is bone's gain

Osteoporosis, characterized by low bone mass and structural deterioration of bone tissue with an increased susceptibility to fractures, is a major public health threat to the elderly. Bone mass homeostasis in adults is maintained locally by the balance between osteoblastic bone formation and osteoclastic bone resorption. Haploinsufficiency of PPARγ, a key transcription factor implicated previously in adipogenesis, lipid metabolism, and glucose homeostasis, has now been shown to promote osteogenesis through enhanced osteoblast formation (see the related article beginning on page 846). These findings support a reciprocal relationship between the development of bone and fat, and may prompt further exploration of the PPAR pathway as a potential target for intervention in osteoporosis. Osteoclast and osteoblast: the yin and yang that control skeletal homeostasis In vertebrates, bones undergo a process of continual renewal throughout life. This process, called bone remodeling, can be viewed as a balance between osteoblastmediated bone formation and osteoclastmediated bone resorption (1). Osteoclasts are specialized cells derived from the monocyte/macrophage lineage that degrade extracellular bone matrix (2). On the other hand, mesenchyme-derived osteoblasts rebuild the resorbed bone by elaborating matrix that subsequently undergoes mineralization (3). An imbalance between the two arms of bone remodeling is associated with diseases including rheumatoid