• Redness
• Swelling
• Heat
• Pain
• Loss of Function

1. What Is the Main Cause of Inflammation in the Body?

There are many causes of inflammation that is triggered by the body’s immune system:

• Injury such as a splinter, scrapes, trauma, or any damage caused by a foreign object.
• Pathogens, including viruses, bacteria, parasites, or fungi
• Chemicals such as glucose, fatty acids, chemical irritants (e.g., acids), toxins, and alcohol
• Radiation such as sunburns
• Biological such as damaged cells in the body

2. What Happens During Inflammation?

Inflammation involves the contribution of different immune cells which release substances known as inflammatory mediators, including hormones such as histamine and bradykinin [1].

These inflammatory mediators induce vasodilation (dilatation of the vessels) which promotes the blood flow in the injured tissue and the recruitment of inflammatory cells (neutrophils, monocytes, and endothelial cells) to the site of injury.

The vasodilatation and the blood rush into the injured tissue result in redness and heat which are 2 signs of acute inflammation.

The pain associated with inflammation is caused by the irritation of local nerves by the inflammatory mediators.

These inflammatory cells have specific roles during acute inflammation:

• Neutrophils initiate the phagocytosis and killing of pathogens to decontaminate the wound, while also promoting cell proliferation and angiogenesis.
• Monocytes also contribute to the phagocytosis and killing of pathogens, and become macrophages, which remove dead cells, and support cell proliferation and tissue restoration following injury.
• Endothelial cells are the building blocks for vessels, and during wound healing, these cells generate new vessels (angiogenesis) to satisfy the metabolic demands of the highly proliferative healing tissue. 

Depending on the site of injury, a transitory loss of function can be observed due to tissue damage, swelling, or pain during inflammation.

3. How long Does Inflammation Last For?

Inflammation can be acute lasting for a few days (2-3 days) or chronic which lasts for a longer time until the insult is resolved.

What Are the Outcomes of Inflammation?

The resolution of acute inflammation (initial inflammation) depends on the causes and the extent of tissue damage. It is characterized by the following outcomes:

• Complete repair of the injured tissue and without scars
• Resolution of the inflammation with the formation of a scar or fibrosis
• Formation of an abscess
• Chronic inflammation if the initial inflammation persists and remains unresolved

The complete repair of the injured tissue or the formation of scars is mediated by a process known as wound healing.

Wound healing is a natural reaction of our body to tissue damage and involves crosstalk between different cells, cytokines, inflammatory mediators, and the vascular system to repair the damaged tissue.

4. What Are the Most Common Inflammatory Diseases?

The most common inflammatory diseases are associated with chronic mediated inflammation which includes the following diseases [2]:

• Rheumatoid Arthritis
• Cardiovascular diseases
• Inflammatory Bowel Disease (IBD) 
• Allergic Asthma
• Chronic obstructive pulmonary disease (COPD)
• Diabetes
• Chronic Kidney Disease
• Cancer

4.1. Rheumatoid Arthritis

Rheumatoid arthritis is due to a local chronic inflammation that results in the infiltration of immune cells into the joints and the release of inflammatory mediators such as cytokines.

4.2. Cardiovascular diseases

Atherosclerosis is associated with a chronic inflammation that leads to heart diseases such as stroke, and myocardial infarction.

4.3. Inflammatory Bowel Disease (IBD)

Inflammatory Bowel Disease (IBD) is a group of chronic inflammatory disorders affecting the bowels that are caused by ulcerative colitis (inflammation of the colon due to ulcer) or Crohn’s disease.

4.4. Allergic Asthma

Allergic asthma is due to the inflammation of the airways caused by the inhalation of an allergen which results in their swelling and tightening affecting breathing.

4.5. Chronic obstructive pulmonary disease (COPD)

COPD is a chronic inflammatory lung disease due to the exposure of the airways to harmful particles or gases causing inflammation that obstruct airflow in the lung leading to breathing difficulties.

4.6. Diabetes

One of the characteristics of diabetes is the infiltration of immune cells, such as macrophages, into pancreatic tissue, and their release of pro-inflammatory molecules responsible for inflammation.

4.7. Chronic Kidney Disease (CDK)

Chronic kidney disease or chronic kidney failure is a progressive loss of the function of the kidney resulting from the accumulation of body wastes and fluids in the blood.

One of the causes of chronic kidney disease is the inflammation of the glomeruli that filter blood for the elimination of waste and fluids in urine.

4.8. Cancer

Chronic inflammation is one of the characteristics of different types of cancer from various origins (Prostate, hepatic, colorectal, ovarian, pancreatic, and lung cancers).

4.9. Neurodegenerative diseases

Neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease are associated with the production of proinflammatory molecules by the brain resident immune cells and microglia which cause brain damage.

5. What Is the Difference Between Inflammation and Infection?

Infections cause inflammation which is a natural process by which the body’s immune system fights against pathogens, including bacteria, viruses, fungi, or parasites.

6. How Do You Get Rid of Inflammation in the Body?

Unlike acute inflammation, chronic inflammation can last for a longer period, and therefore, requires management and treatment through lifestyle changes or medications [3].

6.1. Lifestyle changes

6.1.1. Diet

A diet rich in glucose and processed food rich in saturated fat and trans fats promotes inflammation leading to cardiovascular diseases and type 2 diabetes. Hence, a low glucose diet and avoiding processed food can prevent inflammation.

A diet rich in vegetables and fish oils, nuts, mung bean, green and black teas, and certain species (e.g., ginger, turmeric) can prevent or reduce inflammation as they contain antioxidants and polyphenols which have anti-inflammatory properties.

6.1.2. Physical Activity

In addition to weight loss associated with exercising, physical activity also results in energy consumption with reduces the levels of proinflammatory molecules in the body.

6.2. Medications

The most used anti-inflammatory medications include nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids. 

Nonsteroidal anti-inflammatory drugs (NSAIDs) such as naproxen, ibuprofen, and aspirin, alleviate pain by inhibiting the function of the enzyme cyclooxygenase (Cox) involved in the synthesis of the proinflammatory molecules, prostaglandins.

Corticosteroids are prescribed for some inflammatory conditions such as arthritis, asthma, systemic lupus, and sarcoidosis.

Conclusion

Acute inflammation is a natural process by which the body’s immune system responds to injuries and infections. Acute inflammation takes a few days to resolve, leading to a complete repair of damaged tissues, fibrosis (scars), formation of an abscess, or chronic inflammation.

Chronic inflammation can be associated with several inflammatory diseases such as rheumatoid arthritis, allergic asthma, cancer, diabetes, cardiovascular diseases, chronic kidney disease, COPD, inflammatory bowel disease, and neurodegenerative diseases.

The treatment of chronic inflammation includes lifestyle changes, physical activity, and medications using anti-inflammatory drugs such as NSAIDs and corticosteroids.

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• Osteoporosis
• Paget’s Disease
• Rickets and Osteomalacia
• Osteogenesis Imperfecta
• Bone Tumors

1. What is Bone Made of?

The bone is a hard connective tissue (support and connect tissues) that contains a honey-comb shaped structure made of a mineralized matrix and bone cells [1].

1.1. What Are the Bone Cells and Their Functions?

There are 4 types of bone cells: osteoblasts, osteocytes, osteoclasts, and bone lining cells.

• What Are Osteoblasts?

Osteoblasts are cells that have a cuboidal shape (resembling a cube) found on the surface of bones where they produce components of the mineralized matrix including a specific type of collagen known as ossein, proteoglycans, and cell attachment proteins.

Osteoblasts are also involved in the mineralization of the bone by promoting the deposition of calcium and phosphorus to form the bone mineral hydroxyapatite crystals (bone minerals).

• What Are osteoclasts?

Osteoclasts are a type of phagocytes (engulfing cells) involved in the resorption of the bone that allows its remodeling during growth or mechanical stress.

The resorption of bone is a mechanism by which the bone tissue is broken down into minerals and their transfer to the blood.

• What Are Osteocytes?

Osteocytes are oblate-shaped cells that are widely distributed within the bone where they mainly act as mechanical stress sensors (mechanoreceptors).

They also contribute to the resorption of the bone tissue through a mechanism similar to the one of osteoclast known as osteocytic osteolysis and which involves the secretion of a protein known as sclerostin.

• What Are Bone Lining Cells?

Bone Lining Cells are elongated cells found on the surface of the bone where the protect the bone tissue from resorption.

1.2. What Is the Mineralized Matrix of the Bone?

The mineralized matrix of the bone is made up of deposited hydroxyapatite crystals, ossein, proteoglycans (glycosylated proteins), and cell attachment proteins. This matrix is what makes the bonne hard [2].

2. What Is Osteoporosis?

This disease is characterized by bone fragility and an increased risk of fractures due to the weakening of the bone structure and a low bone mass [3].

2.1. What Is the Difference Between Type 1 and Type 2 Osteoporosis?

Type 1 osteoporosis is called primary osteoporosis that is due to the loss of bone structure and mass associated with age, while secondary osteoporosis (Type 2 Osteoporosis) is associated with specific diseases and medications.

2.2. What Causes Osteoporosis?

The causes of osteoporosis depend on the type of osteoporosis, primary or secondary.

Primary osteoporosis is due to an age-related imbalance between the production of new bone and bone tissue resorption.

At an old age, our body capacity to form new bone is significantly reduced, while the resorption of bone tissue continues.

Secondary osteoporosis is associated with the following diseases and medications:

• Genetic Diseases such as cystic fibrosis and idiopathic hypercalciuria.

Osteoporosis associated with cystic fibrosis is due to the malabsorption of calcium and vitamin D, while Osteoporosis related to idiopathic hypercalciuria is due to the reduction in renal retention of calcium caused by renal failure.

• Hyperparathyroidism

This disorder is characterized by an increased secretion of the parathyroid hormone (Parathyrin) which regulates calcium concentration in the serum through its action on the bone, intestine, and kidneys.

• Intestinal Disorders such as celiac disease, biliary cirrhosis, Chron’s disease, or ulcerative colitis or alcoholic cirrhosis. Intestinal disorders are associated with malabsorption of calcium and phosphorus.

• Anorexia Nervosa

• Hormonal Imbalance such as estrogens or testosterone deficiency during adolescence associated with disorders that affect the onset of puberty (e.g., Turner syndrome or Kallmann syndrome)

• Tumors such as tumors of the pituitary gland or adrenal glands can increase the resorption of bone tissue that is mediated by increased glucocorticoids production.

• Autoimmune and Allergic Disorders such as lupus and rheumatoid arthritis.

• Medications such as glucocorticoids for the treatment of chronic inflammation, antiepileptic drugs, and cyclosporine, or tacrolimus for the prevention of organ transplant rejection.

2.3. What Are the First Signs of Osteoporosis?

The first signs of osteoporosis are a broken bone and a stooped posture (forward bending) due to fracture in the spine leading to difficulties in supporting own weight.

3. Paget’s Disease of Bone

This disease is characterized by alterations in the formation of new bones particularly the spine, skull, and leg bones associated with increased activity of osteoclasts involved in the resorption of bone tissue [4].

3.1. What Causes Paget’s Disease?

Although there is a strong familial predisposition, no genetic alterations have been associated with Paget’s disease.

The causes for this disease are unknown and potential involvement of a viral infection with measles has been proposed [5].

3.2. What Are the Symptoms of Paget’s Disease of Bone?

Although in most cases no symptoms are observed with this disease, symptoms are associated with deformities, fractures, and pain due to the production of bones with disorganized structures.

4. Rickets and Osteomalacia

Both rickets and osteomalacia are due to a deficiency in vitamin D in children (rickets) or in adults (osteomalacia) [6].

Vitamin D is essential in facilitating the mineralization of the bone by ensuring that sufficient concentrations of calcium and phosphorus are available.

Symptoms of rickets manifest with bone deformities such as bowed legs, pain, and large forehead while osteomalacia manifests with pain, bone fragility, and muscle weakness.

5. Osteogenesis Imperfecta

This genetic disease is also known as brittle bone disease characterized by bones that break easily. It is caused by mutations in the genes that encode collagen type I necessary for the formation of the bone tissue [7].

Depending on the severity of the disease, the symptoms manifest as follows:

• Short stature
• Bone malformations (long bones)
• Curved spine, blue color of the eye whites (sclerae)
• Loose joints
• Misshapen or brittle teeth
• Compression of the spine vertebrates
• Hearing loss
• Deformed hip
• Muscle weakness.

6. Bone Tumors

Bone tumors can be benign (noncancerous) such as osteochondroma or malignant such as osteosarcoma and Ewing’s sarcoma

• Osteochondroma

This benign tumor is characterized by an overgrowth of cartilage or bone near the growth plate.

Most osteochondromas do not manifest with symptoms; however, complications such as fractures, mechanical joint issues, and bone deformity can be caused by the tumor.

• Osteosarcoma

Osteosarcoma is a bone cancer mostly found in children and young adults and is caused by the malignant transformation of bone cells and supportive cells in the bone tissue.

It develops in the bones around the knee, the thigh, the tibia, and near the shoulder.  It manifests with pain, swelling, and fractures [7].

• Ewing’s sarcoma

Ewing’s sarcoma is an aggressive tumor of the bone or soft tissue also associated with malignant transformation of bone cells and supportive cells in the bone tissue [8]. It is mainly associated with adolescents and young adults.

This tumor develops in the bones of the leg, feet, arms, hands, spine, chest, pelvis, and skull but can also be found in other parts of the body in a form of soft tissue. It manifests with symptoms such as swelling, fever, pain, and fractures.

Conclusion

Most bone diseases are due to alterations of the balance between bone formation and bone tissue resorption associated with bone cells, and with calcium, phosphorus, and vitamin D deficiencies.

In certain cases, the cause of the bone disease is associated with benign or cancerous tumors that arise from the bone cells or the soft tissue.

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