• Shruti GOCHHWAL

Bone Diseases

When it comes to our bones, the most common misconception is that bones are inert, non-living things.

Surprisingly, contrary to this belief, bones are highly organized tissues that are composed of two bone cells and extracellular matrix which is subdivided into organic substances, like collagen and proteins, and inorganic substances like calcium and phosphorus.

Bones are continuously activated to remodel in response to stress, growth, old age and injury.

Collectively, bone diseases are conditions in which one’s skeletal system gets damaged, becomes weak and is more prone to fractures. It usually destroys the density, strength and structure of bones, making them brittle and weak.

In order to understand the various bone diseases, you must first learn about bone activities that have clinical relevance in the formation of these disorders.

Bone Growth and Remodelling

The chemical process of bone growth and remodelling is the same.

The only difference is that bone growth usually occurs at the tip of bones during the growing age. On the other hand, bone remodelling is the reshaping of bones which occurs when bones get damaged, broken or during old age.

Whenever bones grow or get remodeled, the reaction is always coupled. This is to ensure that when old or damaged bone cells get destroyed, at the same time new cells are added to maintain and improve the structure.

The coupling action is carried out by the two bone cell -: osteoclast and osteoblasts.

  1. Osteoclast is responsible for destroying old and damaged bone cells by a process called resorption. It is the only cell capable of breaking down mineralised bones.

  2. Osteoblast cells are responsible for the formation of new bone cells.

Coincidentally, the activation of the osteoclast cells depends on the osteoblast cells.

Here’s why:

The release of RANK-L is responsible for the production of osteoclasts but RANK-L is activated when PTH hormone binds to the receptor activators present in osteoblasts.

Once this happens, the activated osteoclast now fuses and matures to form bone resorbing cells and migrate to the surface of old or damaged bones.

These cells create an acidic environment and also release an enzyme called cathepsin K which is capable of dissolving the inorganic matrix of the bone.

This process is known as resorption and the reaction causes a release of calcium and phosphorus into the blood.

This next step is almost like recycling.

After resorption is complete, the osteoclast cells become inactive by the release of OPG, a decoy that is capable of replacing RANK-L but has completely different effects as it inhibits the activity of osteoclast cells.

Now the osteoblast cells start secreting a substance called osteoid seam.

Osteoid seam absorbs the calcium and phosphorus that was released back into the blood and deposits them back into the bone again to form new bone cells.

When does bone formation and bone resorption take place?

Bone formation takes place when there is high serum calcium ion levels in the blood. Thus, the bones absorb this calcium by bone formation.

This is why vitamin D is good for bone formation as it absorbs calcium in the blood and increases the levels.

On the other hand, when there is low serum calcium ion in the blood, the bones start to release calcium ions by the process of resorption.

Credits: wikimedia common Caption: Bone remodelling

Types Of Bone Diseases

  1. Osteoporosis:

This is a condition where the osteoclast breaks down bones faster than the formation of new bones by osteoblast cells is known as osteoporosis.

This means that more bone would be resorbed than formed, which results in the lowering of the bone mass and bone density. Thus, this condition makes bones fragile and very prone to fractures.

Women during menopause are more prone to osteoporosis.

The reason being that estrogen is capable of creating a decoy called OPG to replace RANK-L but instead of increasing production, OPG decreases maturation of osteoclasts, thus reducing resorption.

However, in menopausal women, the levels of estrogen decrease which will in turn increase resorption and thus making them more prone to osteoporosis.

This is why postmenopausal osteoporosis is the most common type. Another common type is senile osteoporosis, where around old age, the osteoblasts just lose it’s ability to form bones and thus is out-functioned by osteoclast cells.

Other factors that increase osteoporosis is the consumption of drugs and alcohol that lowers the serum calcium ions in the blood. Due to this decrease, we have learnt that it promotes resorption and therefore increasing the activity of osteoclast cells.

Physical inactivity and diseases like Cushing’s syndrome, Turner’s syndrome and diabetes mellitus are also known to increase the risk of osteoporosis.

Symptoms of osteoporosis usually do not occur until a fracture.

The common fractures are femoral neck fractures, vertebral fractures and distal radius fractures.

Treatment and Diagnosis

Osteoporosis is usually diagnosed by testing the bone density with a dexa scan.

It is usually treated with biphosphonate or recombinant PTH in order to activate and increase osteoblast activity.

Another effective treatment is the use of hydrochlorothiazide, a diuretic that increases calcium ion levels in the blood and leads to bone formation.

Credits: unsplash             Caption: bone fracture due to osteoporosis

  1. Paget’s disease : This disease results in weak and misshapen bones that cause fractures and nerve compression.

The mechanism of Paget’s disease is quite similar but yet is the reverse of osteoporosis. There’s an excessive amount of bone resorption but also followed by disorganised, rapid bone growth.

This occurs in three steps:

  1. First the osteoclast starts to demineralize and resorb aggressively in an uncontrollable manner upto at least 20 times more than normal. This phase is known as the lytic phase.

  2. The second phase is known as the mixed phase. Where there’s a combination of the lytic phase and the blastic phase. During the blastic phase, there’s a rapid and disorganised new bone formation by an unusually large number of osteoblasts.

  3. The last phase is known as the sclerotic phase. Here the bone formation by osteoblast cells exceeds bone resorption by osteoclast cells.

This causes a decrease in calcium and phosphorus in the blood during bone formation and as a result, it will form structurally disorganised weak bones.

Symptoms: Over time the irregular shaped bones and apply pressure and damage nerve cells and cause pain. If Paget’s disease occurs in the skull it leads to the face structure getting disfigured, this is known as leontiasis and the person’s face would appear lion-like. The bones could also impinge on the auditory or optic nerve and cause hearing and vision loss, respectively.

Other symptoms are excessive curvature of the spine, lower limb muscle weakness and pelvic asymmetry.

Diagnosis of Paget’s disease can be done by

  1. x-rays can used to detect for lesions during the lytic phase or check it unusual thick bones in

  2. bone biopsy

  3. testing levels of alkaline phosphatase

Treatment can be done by administering antiresorptive drugs like biphosphonate or by surgical removal of excess deformed bones.

Pain-killers are given to relieve the pain caused by nerve strain.

Credits: Wikimedia common Caption : Rheumatoid Arthritis

  1. Rheumatoid Arthritis

Any condition which involves inflammation of the joints is known as arthritis. There are various types of arthritis. Rheumatoid Arthritis is a joint inflammation caused due to autoimmune problems.

So essentially, in this specific case, the body is attacking itself.

A joint typically consists of two bones that are held close to each other, tip to tip. The tip of each bone is covered with articular cartilage that acts like a cushion to prevent rubbing of the bones by allowing it to smoothly glide against each other.

One common type of joint is known as the synovial joint. It has a fibrous joint capsule which is lined inside with a synovial membrane. The synovial membrane cells secretes a jelly-like fluid that helps lubricate the joints and is known as synovial fluid. The joint has a supply of blood and lymphatic vessel linings to help these cells function.

This autoimmune disease occurs when the white blood cells of the immune system move into the joint and release a chemical substance called cytokines.

The cytokines attack the cells of the synovial membrane.

Due to this, the synovial cells proliferate and release harmful substances.

The synovial membrane also grows new blood vessels and forms a thick area called a pannus.

The pannus destroys areas of the cartilage and bones as the T cells present in the blood vessels stimulate RANK-L which in turn stimulates osteoclast cells to breakdown bones and damage the articular cartilage.

The inflamed joint stimulates fluid build up and causes the joint to swell.

Eventually, if this condition is not treated, the two bones will get fused together and grow as one bone. The loss of joint will restrict movement

Treatment: There are medications to reduce inflammation and slow down joint damage but there is no cure for Rheumatoid Arthritis.

These medications are non-steroidal anti-inflammatory drugs or anti-rheumatic drugs.

Sometimes, a joint replacement procedure known as arthroplasty is recommended.

  1. Osteoarthritis

This condition is similar to rheumatoid arthritis where the articular cartilage gets destroyed but osteoarthritis is not an autoimmune disease and is more associated to physical factors and old age.

The progressive loss of the articular cartilage leads to friction created Between the two bones and eventually leading up to inflammation.

There are chondrocyte cells present in the articular cartilage that is responsible for maintaining any activity that is related to the cartilage. The cells produce and are surrounded by type 2 collagen cells (protein that provides structural support) and proteoglycans which make the cartilage.

Chondrocytes in healthy people regulate a balance between the breakdown of old cartilage through degradative enzymes and production of new cartilage through synthetic enzymes.

Osteoarthritis occurs when some factors increase the activity of degradative enzymes leading to a net loss of articular cartilage.

When this happens, chondrocytes will try to make up for the loss and produce more cartilage. Eventually, it wouldn’t be able to keep up and lose its function. The death of chondrocyte cells is known as apoptosis.

The biggest factors known to increase these activities are mostly linked to old age. Other factors are injury and inflammation of joints, mechanical stress and obesity.

Symptoms of osteoarthritis include stiffness and pain toward the start and end of the day.

Treatment

Patients are advised to exercise and lose weight. They are also recommended to join physiotherapy.

Pain killers and relievers are used to ease out joint pains.

Other options include joint replacement surgery and hyaluronic acid injections

Credits: foter  Caption: Swollen ankle due to gout

  1. Gout: It is a disease in which uric acid crystals are deposited into joints.

The main cause of gout is hyperuricemia which is a condition when there is too much uric acid in the blood.

The main source of uric acid in the blood is due to breakdown purines and pyrimidines, one of the main components of all living tissues (DNA) and proteins.

Thus, uric acid is the wastage produced during the breakdown of purine and pyrimidines. Uric acid is usually excreted out of the body in the form of urine.

However, in the case of hyperglycemia, uric acid stays in the body. It gets converted into urate ion and then goes to bind with a sodium ion, forming monosodium urate crystals.

Crystal formation is either due to increase in consumption of purine-rich foods (shellfish and red meat) or due to increase in the production of purine in the body.

Another way uric acid crystals get accumulated is when the kidneys resorbs it excessively due to dehydration or consumption of alcohol.

Once the crystals get deposited, the joints get red, swollen and inflamed.

It usually affects the big toe, knees, ankles and wrist, causing a sensation as if the joint is burning on fire.

This inflammation is due to the white blood cells that migrate to the joints and release cytokines to eliminate excess uric acid.

Treatment includes medications that can reduce the pain and diuretics to reduce uric acid build. Uric acid can also be drained out from joints.

It is important to stay hydrated, active and avoid high purine content foods. There are also medications to decrease uric acid levels.

Gout can be diagnosed either by symptoms of acute joint swelling, a blood test to check for uric acid levels or directly detecting uric acid crystals in the joints by extracting the fluid in the joints and testing it for crystals.

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