Bone marrow fat (BMF) is an adipose tissue located within the skeletal cavity that constitutes a significant portion of the adult body’s total fat mass. For many years, scientists viewed this tissue as merely inert filler, occupying space not taken up by blood-producing cells. This historical perspective has changed, as BMF is now recognized as a highly active and unique metabolic organ. Modern research shows that BMF adipocytes actively participate in biological processes, regulating both local bone health and distant systemic energy balance. BMF is established as a distinct and important component of the endocrine and skeletal systems.
Structure and Types of Bone Marrow Fat
Bone marrow fat is a distinct, heterogeneous depot classified into two main types based on its location and responsiveness.
Constitutive Bone Marrow Fat (cBMF)
Constitutive Bone Marrow Fat (cBMF) develops early in life and is primarily found in the distal limbs, or appendicular skeleton. This type is relatively stable and consists of larger adipocytes that are less metabolically active. The presence of cBMF generally remains constant, even when facing acute changes in nutritional status.
Regulated Bone Marrow Fat (rBMF)
Regulated Bone Marrow Fat (rBMF) is highly dynamic and found mainly in the axial skeleton, such as the vertebrae and pelvis. rBMF exhibits high plasticity, changing volume and metabolic activity rapidly in response to environmental or physiological stimuli. This depot is sensitive to factors like cold exposure, fasting, and hormonal shifts, allowing it to rapidly expand or contract. The molecular signature of BMF is distinct from both white adipose tissue (WAT) and brown adipose tissue (BAT), possessing unique functional properties that allow it to operate within the specialized bone microenvironment.
Essential Metabolic Roles in Hematopoiesis
Bone marrow fat is an integral component of the hematopoietic niche where blood cell production occurs. The adipocytes within this niche provide essential metabolic support directly to hematopoietic stem cells (HSCs). This support is achieved through the localized release of energy substrates and signaling molecules.
The adipocytes release free fatty acids (FFAs) into the marrow space through lipolysis. These FFAs serve as fuel for the HSCs, which rely heavily on fatty acid oxidation (FAO) for maintaining their long-term function and quiescent state. HSCs utilize specialized proteins, such as CD36, to import these FFAs, ensuring a steady energy supply for their survival and self-renewal.
BMF adipocytes also secrete paracrine factors that directly influence the fate of blood-producing cells. They regulate HSC proliferation and differentiation by secreting supportive cytokines, including Stem Cell Factor (SCF), which is necessary for stem cell survival.
Systemic Endocrine Function and Communication
Bone marrow fat functions as an active endocrine organ, releasing adipokines that communicate with distant tissues throughout the body. The adipocytes secrete molecules such as leptin and adiponectin, which enter the systemic circulation. This endocrine output links the internal metabolic status of the bone to whole-body energy homeostasis.
Adiponectin, a hormone associated with improved insulin sensitivity and anti-inflammatory effects, is produced by BMF. Studies have shown that BMF can be a major source of circulating adiponectin, particularly during states of negative energy balance like caloric restriction or anorexia nervosa. During these conditions, BMF often expands, and its increased adiponectin secretion helps support systemic metabolic function.
Leptin, which regulates appetite and energy expenditure, is also secreted by BMF adipocytes. The levels of these adipokines, along with inflammatory cytokines, can influence peripheral organs, including the liver and muscle tissue. This systemic communication highlights how changes in BMF volume and activity, triggered by metabolic shifts, can have far-reaching effects on overall energy balance and health.
Relationship with Bone Health and Disease
The expansion or contraction of bone marrow fat is closely linked to bone mass and the progression of various diseases. There is an inverse relationship between BMF volume and bone mineral density (BMD): as BMF increases, bone mass often decreases. This is evident in age-related conditions like osteoporosis, where the marrow cavity accumulates fat.
This inverse relationship is attributed to shared progenitor cells, the mesenchymal stem cells (MSCs), which can differentiate into either bone-forming osteoblasts or fat-storing adipocytes. In conditions such as aging or chronic inflammation, the MSC lineage commitment shifts, favoring the production of adipocytes over osteoblasts.
BMF is also implicated in metabolic disorders, often expanding in conditions like obesity and Type 2 diabetes. This BMF expansion contributes to disease pathology by altering the local environment with increased fatty acid availability and a shift in adipokine secretion profiles. Changes in BMF are also linked to the progression of certain hematologic malignancies, such as leukemia and multiple myeloma, where the adipocytes may provide a protective niche for cancer cell survival and proliferation.