Bone marrow

Bone marrow is the soft, spongy tissue within bones that contains the precursor cells that produce red blood cells, white blood cells, and platelets. Essentially, it's the "blood factory" and a vital part of the immune system, as it produces a significant portion of the cells of the innate and adaptive immune system. [1]

In adults, the greatest proportion of active hematopoiesis is concentrated in the bones of the axial skeleton, such as the pelvic bones, vertebrae, ribs, and sternum. This is clinically important: these areas are the most likely to yield material during aspiration and trephine biopsy, and it is there that the bone marrow is most often assessed for its "empty" or cellular content. [2]

Bone marrow works constantly: every day, the body must replace huge volumes of blood cells that age and deteriorate. The workload increases dramatically during infection, inflammation, blood loss, hemolysis, and after chemotherapy, so the bone marrow is forced to rapidly switch between the production modes of different cell lines. [3]

The central idea of modern hematology is this: it's not just the "bone marrow volume" that matters, but the conditions in which hematopoietic stem cells live and divide. These conditions are created by vessels that support stromal cells, neural influences, and a multitude of signaling molecules, which together are called the bone marrow microenvironment or niche. [4]

Table 1. Red and yellow bone marrow: what they are and how they differ

Sign	Red bone marrow	Yellow bone marrow
The main role	Hematopoiesis and maturation of blood cells	Energy reserves, bone marrow adipose tissue
Cellular composition	Many hematopoietic cells and progenitor cells	Predominantly fat cells and stromal elements
Where is it most often located in an adult?	Axial skeleton, proximal parts of some long bones	Diaphyses of many long bones
Clinical significance	Suffers from leukemia, aplasia, myelofibrosis	May change with chronic diseases and systemic stress

[5]

How bone marrow is structured: vessels, stroma, and hematopoiesis "working zones"

Bone marrow is more than just "cells in a bone cavity." It has an architecture: bone trabeculae, a network of blood vessels, specialized sinusoidal capillaries that release mature cells into the bloodstream, and supportive stromal tissue. [6]

An important part of the structure is the perivascular zones surrounding the vessels. Many hematopoietic stem cells and their immediate "neighbors" are located near the vessels, regulating their division, maturation, and migration. This organization explains why the distribution of cells and their release into the bloodstream changes during inflammation and stressful situations. [7]

In addition to blood cells, the bone marrow contains many non-hematopoietic cells: mesenchymal stromal cells, osteoblastic lineages, fat cells, vascular endothelium, macrophages, and nerve fibers. They secrete signaling molecules and "tune" blood cell production, sometimes accelerating it, sometimes keeping stem cells dormant. [8]

Bone marrow adipose tissue is not simply a "filler." Recent studies suggest that fat cells may influence hematopoiesis, injury repair, and age-related changes, although the mechanisms are context-dependent and are still being actively studied. [9]

Table 2. The main components of the bone marrow microenvironment and their role

Component	Example of functions	Why is this important for the disease?
Sinusoidal vessels and endothelium	Release of mature cells into the blood, signals for stem cells	With inflammation and tumors, the “patency” and regulation changes
Mesenchymal stromal cells	Support and signals for hematopoietic cells	Stromal abnormalities may impair hematopoietic recovery
Bone marrow fat cells	Metabolic support, niche impact	Associated with age-related changes and recovery from stress
Nerve fibers of the bone marrow	Regulation of cell migration and egress rhythms	Disorders can alter the mobilization of cells into the blood
Macrophages and other niche immune cells	"Tuning" the maturation and removal of defective cells	Inflammation can switch hematopoiesis into an unfavorable mode

[10]

Hematopoiesis and immunity: what cells does bone marrow make and how does it regulate the balance?

Hematopoiesis begins with hematopoietic stem cells, which are capable of self-renewal and simultaneously give rise to all blood cell lineages. Intermediate precursors and maturing cells then form, gradually acquiring specialized functions and entering the bloodstream. [11]

The balance of cell production is constantly being adjusted: bacterial infections typically increase neutrophil production, viral loads and certain immune responses alter lymphocyte composition, and blood loss accelerates red blood cell and platelet production. From a patient's perspective, this manifests itself as changes in a complete blood count, and from a physician's perspective, it provides clues as to "where to look for the problem." [12]

The bone marrow is where some key immune cells, including B lymphocytes, form and mature, and where precursor cells are trained and selected to reduce the risk of defective and potentially dangerous clones. When these processes are disrupted, the risk of immunodeficiencies, autoimmune reactions, and clonal blood disorders increases. [13]

Modern biology emphasizes that the "quality of hematopoiesis" depends not only on the hematopoietic cells themselves, but also on niche signals. Therefore, two patients with similar blood test results may have different causes: one may have a stem cell defect, while the other may have an inflammatory restructuring of the microenvironment. [14]

Table 3. What bone marrow produces and how it is reflected in blood tests

Cell line	Main function	Typical consequences of deficiency
Red blood cells	Oxygen transport	Anemia, weakness, shortness of breath, tachycardia
Neutrophils	Rapid response to bacterial infection	Frequent infections, risk of severe complications
Lymphocytes	Adaptive immunity, immune memory	Susceptibility to viruses and some bacteria
Platelets	Primary hemostasis and bleeding control	Bruises, petechiae, bleeding, nosebleeds
Monocytes and macrophages	Phagocytosis and regulation of inflammation	Impaired control of inflammation and tissue repair

[15]

Age-related changes and recovery from stress

In children, bone marrow is predominantly "red" and actively produces hematopoiesis, but some areas are gradually replaced by fatty tissue. This process is natural and is even reflected in magnetic resonance imaging (MRI) images, where the water-to-fat ratio changes predictably with age. [16]

With age, both stem cells and the niche change: damage accumulates, the inflammatory environment changes, and support signals are disrupted. As a result, the balance of hematopoiesis can shift, clonal changes occur more frequently, and the likelihood of certain blood diseases increases, especially in the presence of additional risk factors. [17]

Following severe stress, such as massive blood loss or intensive care, the bone marrow can restructure itself to more quickly restore blood cells. The literature describes mechanisms of niche adaptation to acute stress and attempts to therapeutically influence microenvironmental signals to accelerate hematopoiesis recovery after myeloablation, i.e., bone marrow suppression. [18]

A separate clinical topic is bone marrow "reconversion," when the proportion of hematopoietic tissue in areas typically rich in fat increases. This may be an adaptation, for example, in chronic anemia, smokers, obesity, and certain other conditions, and requires careful interpretation of imaging studies to avoid mistaking physiological changes for a tumor process. [19]

Table 4. Age and stress: how bone marrow changes and what it means

Situation	What happens in the bone marrow	Practical significance
Childhood	Active hematopoiesis predominates	Blood tests are sensitive to deficiencies and infections
Adulthood	More fatty tissue in the bone area	The "reserve" is reduced, but adaptation is maintained
Old age	The niche is changing, clonal changes are growing	Higher risk of certain blood diseases and anemia
Acute blood loss and severe stress	Activation of hematopoiesis and restructuring of niche signals	Iron, B12, folate and inflammation control are important
After chemotherapy and radiation	Temporary or long-term suppression of hematopoiesis	Growth factors, transfusions, and sometimes transplantation are required.

[20]

Bone marrow diseases: not a list of diagnoses, but 5 typical syndromes

Clinically, it's not the "names of diseases" that are most often seen, but rather syndromes. The first syndrome is hematopoietic insufficiency: red blood cells, white blood cells, and platelets decrease in various combinations. This occurs with aplastic anemia, deficiencies, drug-induced bone marrow damage, severe infections, and tumor infiltration of the bone marrow. [21]

The second syndrome is clonal cell overproduction, when the bone marrow produces too many cells of one lineage or creates an abnormal clone. This is typical of myeloproliferative and some other clonal diseases, as well as leukemias, where normal hematopoiesis is displaced by tumor cells. [22]

The third syndrome is "abnormal" cell maturation, when the bone marrow appears to be functioning, but the cells are formed defectively and quickly die. This is characteristic of myelodysplastic syndrome, which often combines anemia, neutropenia, and thrombocytopenia of varying severity with an increased risk of transformation into acute leukemia. [23]

The fourth syndrome is the replacement of normal bone marrow by fibrous tissue or tumor infiltration, which disrupts the architecture and impairs cell release into the blood. These conditions often include an enlarged spleen, severe weakness, sweating, weight loss, and characteristic changes in blood tests, but the diagnosis is confirmed morphologically. [24]

The fifth syndrome is infectious complications and bleeding as a direct consequence of neutropenia and thrombocytopenia. These are not "minor symptoms," but rather the cause of hospitalization and life-threatening complications, so if a bone marrow problem is suspected, risk assessment is carried out quickly. [25]

Table 5. Blood test and symptoms: what bone marrow problems are most often behind the picture

What is the person complaining about?	What does a blood test show?	Common directions for searching for the cause
Weakness, shortness of breath, pallor	Low hemoglobin	Iron and B12 deficiency, chronic inflammation, aplasia, clonal diseases
Frequent infections, fever without cause	Low neutrophils	Drug effects, viral infections, aplasia, clonal diseases
Bruises, petechiae, bleeding gums and nose	Low platelets	Immune thrombocytopenia, aplasia, bone marrow infiltration
Simultaneous anemia, neutropenia and thrombocytopenia	Pancytopenia	Aplastic anemia, myelodysplastic syndrome, infiltration, severe infections
Very high white blood cells or atypical cells	Leukocytosis and blast forms	Leukemia, severe reaction to infection, clonal processes

[26]

Diagnosis and treatment: from tests to transplantation

Diagnosis almost always begins with a complete blood count and peripheral blood smear, as these are the primary indicators of the disorder. Biochemistry, inflammation indicators, iron, B12, and folate metabolism, hemolysis markers, and tests specifically targeting the underlying clinical hypothesis are then added. [27]

If tests suggest a primary bone marrow lesion, an aspiration and trephine biopsy are performed. Aspiration yields liquid material for cell evaluation, while trephine biopsy produces a tissue core for assessing cellularity, fibrosis, and infiltration. These procedures are typically performed from the ilium and are often performed together because they complement each other. [28]

Modern morphology is rarely limited to the microscope. For many blood diseases, immunophenotyping with flow cytometry, cytogenetics, and molecular diagnostics are added, as they determine the disease subtype, prognosis, and choice of therapy, including targeted drugs and indications for hematopoietic stem cell transplantation. [29]

Treatment depends on the mechanism. In hematopoietic failure, addressing the underlying cause, discontinuing toxic medications, treating infections, and supporting with blood transfusions are important. Clonal diseases are treated with drug therapy, including chemotherapy, targeted therapies, and immune-based drugs. For some conditions, hematopoietic stem cell transplantation remains the only potentially curative treatment. [30]

Hematopoietic stem cell transplantation can be autologous, using the patient's own cells, or allogeneic, using cells from a donor. Indications depend on the diagnosis, stage, response to treatment, and risk of complications, and current practical guidelines are regularly updated by specialized professional societies. [31]

Table 6. What are the differences between the main methods of bone marrow examination?

Method	What does it evaluate best?	What is it most often used for?
General blood test and smear	The final "release" of bone marrow into the blood, atypical cells	Primary screening and diagnostic referral
Bone marrow aspiration	Morphology of individual cells and percentages	Leukemia, myelodysplastic syndrome, infections, treatment response assessment
Bone marrow trephine biopsy	Tissue architecture, cellularity, fibrosis, infiltration	Myelofibrosis, lymphoma infiltration and metastases, aplasia
Flow cytometry	Immune cell profile	Accurate classification of leukemia and lymphoma
Cytogenetics and molecular tests	Genetic changes	Prognosis, choice of targeted therapy, decision on transplantation

[32]

Table 7. Main directions of treatment of bone marrow diseases

Situation	Basic measures	Specific therapy according to indications
Anemia due to deficiencies	Correction of iron, B12, folates	Treatment of the cause of deficiency and blood loss
Aplastic anemia	Prevention of infections, transfusions as indicated	Immunosuppressive therapy or hematopoietic stem cell transplantation
Leukemia	Support, prevention of complications	Chemotherapy, targeted therapy, sometimes transplantation
Myelodysplastic syndrome	Support, transfusions, growth factors as indicated	Course-modifying drug regimens, transplantation in selected patients
Myelofibrosis and infiltration	Symptomatic therapy, correction of cytopenias	Targeted drugs, transplantation in selected patients

[33]