Project 1

Clinical condition: Osteoporosis

Introduction:

The word ‘osteoporosis’ means ‘porous bone.’ It is a disease that weakens bones, and if you have it, you are at a greater risk for sudden and unexpected bone fractures. Osteoporosis implies that you have less bone mass and strength. The disease frequently creates with practically no side effects or pain, and it is usually not discovered until the weakened bones cause painful fractures. A large portion of these are cracks of the hip, wrist and spine. It is common in older women but even men can develop the condition.

(Picture attached by the name: Osteoporosis)

(Picture attached by the name: Mechanism of osteoporosis)

Symptoms:

• Getting short in height
• Changes in posture like stooping or bending forward
• Shortness if breath due to compressed disc
• Bone fracture
• Lower back pain

(Picture attached by the name: Osteoporosis effect)

Endocrine system:

It consistes of glands and hormones secreted by the gland. Endocrine system produces and regulates chemical substances called hormones. Other than endocrine glands, brain, heart, liver, skin, etc. produce and release hormones.

The primary endocrine glands are

• Pituitary gland: Located below the brain.
• Pineal gland: Located below the corpus callosum, in the middle of the brain.
• Thyroid gland: Located at the base of the neck.
• Parathyroid gland: Located in front of the neck, below the larynx.
• Pancreas- Islets of Langerhans: Located across the back of the abdomen, behind the stomach.
• Thymus: Located in the upper part of the chest.
• Adrenal gland: Located on top of each kidney.
• Ovaries (in females): Located on both sides of the uterus, below the opening of the fallopian tubes.
• Testis (in males): Located in a pouch called scrotum that hangs suspended outside the male body.
• Placenta: It is a structure that develops in the uterus during pregnancy.

Organ involved: Hormonal imbalance in parathyroid hormone and calcitonin in endocrine gland, specially thyroid gland and parathyroid gland. (Picture attached by the name: Organs involved)

In thyroid glands, calcitonine is released when level of calcium ions in blood raises above a certain point. Its main function is to reduce the concentration of calcium ions in blood by aiding absorption into matrix of bone.

In parathyroid glands, parathyroid hormones are released and are involved in calcium ion homeostasis. It stimulates osteoclast activity within the bone matrixto release free calcium ions in bloodstream.

Parathyroid and Thyroid problems: Hyperparathyroidism is caused due to increase in the level of parathyroid hormone and can cause osteoporosis as excess hormones extract calcium from bones. Parathyroid hormone and calcitonin produced are essential for bone resorption. Imbalance in hormones results in osteoporosis. (Picture attached by the name: Process of osteoporosis)

Diagnostic technique: Bone mineral density (BMD) tests also known as dual-energy X-ray absorptiometry (DEXA or DXA) scans. In order to detect vertebral osteoporosis CT scan procedure is done. (Picture attached by the name: DXA Scan)

Bone mineral density test determines whether a person has osteoporosis or not. It is a disorder characterized by bones that are more fragile and more likely to break. The test uses X-rays to measure how many grams of calcium and other bone minerals are present in bone segment.

Bone mineral density testing is mainly done to:

• Check whether there is a decrease in bone density before the bone is broken
• Determines whether there is any rosk of breaking bones or fracture
• Confirms the diagnosis of osteoporosis
• Monitors treatment for osteoporosis (Picture attached by the name: Bone density test)

There are few limitations realted to bone mineral density testing:

• Results may not be accurate in people who have structural abnormalities in their spines, such as severe arthritis, previous spinal surgeries or scoliosis.
• It uses X-rays and the amount of radiation exposure is usually less. Still pregnant women should avoid these tests.
• Lack of information about the cause since it can confirm that the person has low bone density but it cannot tell the exact reason for this cause.

(Picture attached by the name: Screening process)

Surgical techniques:

• Vertebroplasty: It is an outpatient procedure for stabilizing compression fractures in the spine. Bone cement is injected into back bones (vertebrae) that have cracked or broken, often because of osteoporosis. The cement hardens, stabilizing the fractures and supporting the spine. For people with severe, disabling pain caused by a compression fracture, vertebroplasty can relieve pain, increase mobility and reduce the use of pain medication.
• Kyphoplasty: It also injects special cement into the vertebrae and then in the next step it uses special balloons to create spaces within the vertebrae which are then filled with bone cement. It can correct spinal deformity and restore lost height.

Treatment: Bisphosphonates, Anabolic agents, etc. Also includes exercise, vitamin and mineral supplements, and medications.

• Bisphosphonates: These are considered as antiresorptive drugs as they stop the bone from reabsorbing bone tissue. The side effects include symptoms like fever, headache, heatburn, impaired function in kidneys, etc. Taking these medications for a long period of time increases the risk of serious side effects.
• Anabolic agents: It helps in building bones in people who suffer from osteoporosis.

Recent advancement:

1. Antibody therapy

• Sclerostin inhibitor: Romosozumab
• RANKL inhibitor: Denosub
• DKK-1 inhibitor

2. Antiserotonin therapy

3. Stem cells therapy

• Mesenchymal stem cells
• Hematopoietic stem cells

4. Cathepsin K inhibitors: Odanocatib

5. Biomaterials

• Chitosan biopolymers
• Strontium modified calcium phosphate cement (SrCPC)
• Titanium coated with calcium phosphate
• Titanium coated with collagen type 1
• Titanium polycaprolactone magnesium composite
• Titanium calcium phosphate

Case Study:

Topic: A case of male osteoporosis: A 37 year old man with mutiple vertebral compression fractures

Abstract:

A 37-year-old man was presented with multiple vertebral compression fractures for several years following termination of testosterone replacement therapy for presumed constitutional delay in growth and puberty. The patient was ultimately diagnosed with hyposmia or Kallmann syndrome. It also states the role of androgens in the acquisition of bone mass during puberty and its maintenance thereafter. Provides specific strategies for patients with hypogonadism and high risk for fragility fractures. His lower back pain was increasing and had a history for the past 4 months.

Radiographic examination of the spine disclosed diffuse osteopenia with moderate wedging of several mid-thoracic vertebrae along with severe compression fractures of T11, T12, and L1 (80%–90% vertebral height loss). There was a 10% superior endplate collapse at L5. Dual-energy X-ray absorptiometry (DXA) scan of the skeleton reported a -score of −6.9 at the lumbar vertebrae (L2–L4), −3.3 at the femoral neck, and −4.1 at the total hip. The figure attached below (Case study table 1).

Three weeks later a CT scan was performed on his spine as he was stooping due to lower back pain. A CT scan of the spine disclosed a new L3 compression fracture, with 75% loss of height, along with an interval progression of the L5 superior endplate collapse (from 10% to 40% loss of height). The T11-L1 fractures remained unchanged. The figure attached below (Saggital view).

While convalescing, his application for teriparatide use was approved and treatment was initiated. Skeletal response to the drug was monitored using osteocalcin and procollagen type 1 N-terminal propeptide (P1NP) serum levels as surrogate markers of bone formation. The figure attached below (Changes in serum level).

After completing 24 months of teriparatide treatment, he was switched over to sequential treatment with denosumab (Prolia™) 60 mg s/c q6 months. A repeat DXA scan performed on May 2015 (following two doses of denosumab) showed improvement of the bone mineral density at the lumbosacral spine, femoral neck, and total hip [ score of −5 (from −6.9), −3.3 (from −3.3), and −3.9 (from −4.1). The figure attached below (After 2 years table 2).

Result:

He has been doing well since then, and while continuing with calcium, vitamin D, testosterone, and denosumab therapy, he has remained pain-free and has not sustained further fractures.

Reference:

Hindawi Journal: A case of male osteoporosis: A 37 year old man with mutiple vertebral compression fractures

Suhaib Radi and Andrew C. Karaplis

Part B

The type of bone the skull belongs to is the flat bone.

Flat bones have a flattened and broad surface. They are made up of a layer of spongy bone between two thin layers of compact bone. They are flat in shape and not rounded. They are mainly thin, flattened and slightly curved. They have marroe but do not have bone marrow cavity. It covers the skull and protects the brain. It also provides support to the face.

Bones are made up of bone matrix. The components in matrix are both organic and inorganic. Matrix of bone is laid by osteoblasts as collagen or osteoid. Osteoid is hardened with inorganic salts like calcium and phosphate and the chemicals released from the osteoblasts by a method called mineralization.

The basic microscopic unit of bone is an osteon or Haversian system. Osteons are cylindrical in shape and can measure length upto several millimeters and diameter around 0.2 mm.

Each osteon consists of a lamellae of compact bone tissue surrounded by a central canal or Haversian canal containing the bone’s blood supplies. The boundary of an osteon is called the cement line. It can be classified as woven bone and lamellar bone.

Woven bone: It is woven due to criss crossappearance of the fibrous matrix. It is found on the growing ends of an immature skeleton and at the site of a healing fracture in adults. They are mechanically weak but forms pretty quickly. It is mechanically weak as it has a high proportion of osteocytes. During deveopment of bones Woven bone is replaced by lamellar bone. (Picture attached by name: Woven bone)

Lamellar bone: It makes up the cortical bone in the skeleton. When the lamellar bone is loose, it is called trabecular bone which gets its name due to the spongy pattern displayed in an X-ray. In trabecular bone are filled with active bone marrow. (Picture attached by the name: Lamellar bone)

Blood supply takes place in long bones. The sources of supplying blood to the long bone are

• Nutrient artery system: It originates from major system arteries and it is a high pressure system. It enters the cortex with the help of the nutrient foramen and then migrates into the medullary canal. It is branched into ascending and descending branches. It is then further branched out into arterioles and supply the inner 2/3 of bone inside the Haversian system.
• Metaphyseal-epiphyseal system: It emerges from the periarticular plexus which is found around the joint area of a long bone.
• Periosteal system: It is a low pressure system. It is connected through Haversian and Volkmann canals which supplies 1/3 of bone to the outer portion of the bone. It is a part of the osteon structure of the cortex.

Remodelling of bones occur at different sites in the body where bone experiences growth, stress, breaks or microfractures. Around 20% of all bone tissue are replaced annually by process of remodelling.

There are five main steps involved in bone remodelling and new bone formation. These are

• Activation: Sites of remodelling are attracted to preosteoclasts which then fuses to form multinucleated osteoclasts.
• Resorption: Osteoclasts then dig out a cavity in spongy bone or in compact bone known as resorption pit. Calcium is then released into the blood for different functions in the body. Osteoclasts then disappear.
• Reversal: Mesenchymal stem cells appear around the resorption pit where they proliferate and differentiate into preosteoblasts.
• Formation: Then it matures into osteoblasts and release osteoid at the site to form a new nonmineralised matrix which is then mineralised with calcium and phosphorous.
• Quiescence: It is the site with resting lining cells. It remains dormant until the next cycle.

Reference: ACTIVITY 3D: HEALTHY BONE REMODELING – THE OSTEO BLASTER/CLASTER WHEEL

Bone implant is a surgical process used to transplant or implant bones to repair or rebuild the damaged bone. Most of the bone implants are made up of metal and used as devices for surgical procedures.

In order for the treatment of broken bone in skull, a surgical procedure known as cranioplasty is done. It is surgically done to repair the broken or defective bone in skull occured due to injury. There are different kinds of cranioplasties but most of them involve in lifting the scalp and restoring the contour of the skull with the original skull piece or a custom contoured graft made from material such as:

• Titanium plate
• Synthetic bone substitute
• Any solid biomaterial which is a prefabricated customised implant to match the exact shape and contour of the skull

Before performing cranioplasty, the doctor needs to know about the different health conditions of the patient like if the patient is allergic to any medications or other substances.

Cranioplasty is recommended by many doctors when there is any injury in skull. Its benefits includes

• It provides protection to the skull and brain
• It improves neuroligical functions for some patients
• It helps in aesthetics as a noticeable defect in skull can affect a person's appearance and their confidence
• It can reduce headaches caused due to injury