The bone-fat interface: basic and clinical implications of marrow adiposity

Abstract

Obesity and osteoporosis are two of the most common chronic disorders of the 21st century. Both are accompanied by significant morbidity. The only place in the mammalian organism where bone and fat lie adjacent to each other is in the bone marrow. Marrow adipose tissue is a dynamic depot that probably exists as both constitutive and regulated compartments. Adipocytes secrete cytokines and adipokines that either stimulate or inhibit adjacent osteoblasts. The relationship of marrow adipose tissue to other fat depots is complex and might play very distinct parts in modulation of metabolic homoeostasis, haemopoiesis, and osteogenesis. Understanding of the relationship between bone and fat cells that arise from the same progenitor within the bone marrow niche provides insight into the pathophysiology of age-related osteoporosis, diabetes, and obesity.

Figure 1. Bone–fat interactions in the bone marrow microenvironment

The bone marrow microenvironment includes osteoblasts, bone lining cells, pre-osteoblasts, pre-adipocytes, endothelial cells, reticuloendothelial cells that might be the earliest progenitor for mesenchymal stromal cells, osteoclasts that resorb bone, haematopoietic cells, haematopoietic progenitor cells, and, within the bone matrix, osteocytes. The communication between osteocytes and bone lining cells and osteoblasts organises the bone remodelling process. Mesenchymal stromal cells can differentiate into pre-osteoblasts or pre-adipocytes and these early cells can be plastic. The haematopoietic progenitors are intimately associated with the endosteal osteoblasts, and both are involved in blood cell differentiation. Bone lining cells are fibroblast-like cells; their function is not known, although it is likely these cells become osteoblasts, and express markers of osteoblasts and osteocytes. These cells could become adipocytes in response to injury. Dotted lines indicate hypothesised pathways; solid lines indicate known pathways. Pre-OB=pre-osteoblasts. EC=endothelial cells. RE=reticuloendothelial cells. MSCs=mesenchymal stromal cells. HC=haematopoietic cell. HP=haematopoietic progenitor. Adapted from DiGirolamo and colleagues,7 by permission of Macmillan Publishing Ltd.

Figure 2

Osmium tetroxide (OsO4) staining of bone marrow fat visualized by microcomputed tomography. Representative images from the tibia show that compared to normal diet (Control, left panel), marrow adiposity is increased only marginally by high fat diet (HFD, right panel).