Fig. 1: A timeline of the evolution of our knowledge on bone marrow adipose tissue.

Pathologists noted in the 1880s that abundant adipocytes were found in the marrow of healthy older individuals. Bone marrow adipose tissue (BMAT) was speculated as a nutrient source for haematopoietic elements and a cushion for the skeleton⁹⁷. In the 1920s, certain blood disorders and heavy-metal intoxication were associated with florid-marrow adiposity and impaired haematopoiesis. The term ‘yellow marrow’ was designated to distinguish tissue from red haematopoietic marrow⁹⁸. An important report by Tavassoli and Crosby delineated anatomical and functional differences between yellow and red marrow and described, to our knowledge for the first time, the marrow adipocyte⁹⁹. In the latter part of the twentieth century, investigators noted that marrow ablation following chemotherapy or radiotherapy was associated with a fibrotic response and the appearance of large numbers of adipocytes¹⁰⁰. Similarly, others have reported that postmenopausal women with osteoporosis had abundant marrow adipocytes and decreased trabecular bone tissue⁷⁷. A seminal study on anorexia nervosa has noted an association between an increase in marrow adiposity and skeletal fragility¹⁰¹. With the advent of magnetic resonance spectroscopy and dual-energy CT imaging, a strong negative association between BMAT and bone quantity has been reported^102,103. BMAT was then postulated to regulate bone turnover by increasing bone resorption and suppressing bone formation^104,105. In vitro studies have confirmed that isolated skeletal stem cells could commit to either the adipocyte or bone lineage. Furthermore, activation of PPARγ shifted skeletal stem cells into an adipocyte-like phenotype. Some in vitro evidence showed that cold temperatures could induce expression of markers of thermogenesis in marrow adipocytes¹⁰⁶. Subsequent studies using in vivo models confirmed that lineage allocation enables early progenitors to shift between osteoblasts and adipocytes, providing another mechanism for altered bone remodelling after hormonal, nutritional or environmental injury¹⁰⁷. Ablation of BMAT in mice using global and conditional genetic deletions drives increased cortical and trabecular bone, in part because of the absence of growth factors secreted by marrow adipocytes^5,23. MALP, marrow adipogenic lineage precursor.