Bone equilibria and disruptions.

Osteoporosis is considered a disease of adulthood, but there is increasing recognition that poor bone density during childhood can have effects decades later. To understand the pathogenesis of osteoporosis, it is important to understand normal bone maintenance and remodeling, since disruptions of these processes lead to pathologic bone. Bone maintenance is a complex and highly regulated system, consisting of several homeostatic equilibria. This article highlights three homeostatic systems. The first, the interplay between the differentiation of osteoblasts from mesenchymal stem cells and osteoclasts from hematopoietic stem cells, is the most important. Estrogen has a direct effect on the system, and its absence is pivotal. The second is a lesser-known homeostasis that functions between bone and bone marrow adipose tissue, which can insidiously drive osteoporosis. Bone marrow adipose tissue acts as a regulator of bone metabolism, negatively affecting bone formation. The third homeostatic system covered is the microbiota-gut-bone axis, where the make-up of the gut microbiome can influence a balance between osteoblastic and osteoclastic T-cells. Understanding these systems has provided avenues of study for existing and future treatments. Key Concepts: (1)The balance between bone formation and bone resorption is driven by factors that initiate the differentiation of mesenchymal stem cells to osteoblasts and hematopoietic stem cells to osteoclasts.(2)Bone marrow adipose tissue is formed by adipocytes that are the result of diversion of mesenchymal stem cells from the osteoblastic differentiation pathway.(3)The health of the gut microbiome has direct effects on the bone homeostatic processes.