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- Rama Nada

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- Mousa Al-Abbadi

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Bones, Joints and Soft tissue tumors

Before we start: the first 8 minutes was recalling to Dr.Mousa’s duties, go over them

in the slides.

Wherever you see * refer to the page index at the bottom of the page (things that

are written by red in the index are not mentioned by the doctor but may help you in

understanding)

These are the objects that well discuss in the coming 8 lectures:

1-Remember the basic structure & function of bone

2-Congenital diseases of bone and cartilage

3-Metabolic disorders of bone

4-Paget disease of bone*

5-Fractures

6- Osteonecrosis

7- Osteomyelitis**

8- Bone tumors and tumor-like conditions

9-Arthritis**: (very common diseases)

– Osteoarthritis; RA; Juvenile Idiop A

– Seronegative Spondyloarthropathies

– Infectious arthritis; Lyme arthritis

– Crystal-induced arthritis (such as: gout and pseudogout***)

10-Joint tumors & tumorlike conditions (not common conditions)

11- Soft tissue tumors:

– Adipose tissue; fibrous tissue; skeletal muscle

– Smooth muscle; tumors of uncertain origin

Relax you don’t need to understand or to memorize them here, you’ll

do that over lectures.

*It is a localized disorder of bone remodeling

**inflammation conditions

***It’s important to differentiate between them later (there is a question about them in the exam)

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Important note pathologists should not make diagnoses for bone

diseases or tumors based on pathological features only, instead they

should first corelate these pathological features with clinical data. For

example: woven bones in adult femur indicate a pathological condition,

you may think that is an osteogenic sarcoma but when you know from

the patient history that he/she has a fracture recently you’ll know that

they are present normally as a part of repair.

Bone functions:

1- Provide a Mechanical support; a problem in a patient’s bone impair

his/her mechanical support.

2- Forces transmission; forces and weights are balanced by bones, from

the skull on the shoulders and upper limbs then the thoraces, the pelvic

and the lower limbs. For example: impairment in the hip bone imbalance

the patient’s walk.

3- Protection; your skull protects your brain from hits

4- Mineral homeostasis*; control your calcium phosphorus metabolism.

Problems in the factors that are related to mineral homeostasis, such as:

parathyroid hormones (hyperparathyroidism) and vitamin D (vitamin D

deficiency/ rickets), can cause many problems in bones.

5- Haematopoiesis; most of your blood elements** are synthesized from

stem cells in the bone marrow especially in the long bones, so problems

in the bones affect blood elements.

*bones act as reservoir for minerals that are important to our body such as calcium and phosphate. A

certain concentration of calcium or other minerals inside the blood should be maintained, so when the

body needs calcium, calcium will be mobilized from the bone to increase calcium blood level. On the

other hand, if you increase your intake of calcium, more deposition of calcium inside the bone occurs.

**Red blood cells, white blood cells and platelets

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Bone structure

Matrix Cells

Bone structure:

The balance between osteoblasts and osteoclasts:

In the childhood the activity of osteoblasts are higher than it for

osteoclasts (bone formation more than bone resorption), they reach the

peak of their activity in the early adulthood, from that period up to the

4th decade they activity of osteoblasts still higher than it for osteoclasts

but not as much as before, at the 4th decade of age the activity for both

types of cells are in homeostasis (nearly equal), but after that the activity

for osteoblasts decrease while it increases for osteoclasts, so bones

resorption more than bones formation, that leads to what we call

osteoporosis especially in women post-menopausal.

How to prevent or delay osteoporosis?

You can decrease osteoporosis by controlling your lifestyle (increase

your activity) and food (get species with large amount of minerals), more

exposure to sun light (vitamin D) and

there are some drugs that can help.

A beneficial picture from Robbins book

(not from the slides):

Osteoid 35%:

organic type I collagen

and glycosaminoglycans

& other proteins

Minerals 65%:

One of them is Inorganic

hydroxyapatite which

make your bones hard,

decrease in it results in

soft bones (pathological

condition)

Osteoblasts:

forms bone

and forms

the osteoid

Osteoclasts:

Specialized

multinucleated

macrophages,

derived from

circulating

monocytes,

responsible for

bone resorption

Osteocytes:

mature bone

cells (mature

osteoblasts),

these cells

have many

processes

(dendrites like

structures)

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This picture shows the paracrine molecular

mechanism that regulate osteoclast formation

and function. Osteoclasts are derived from the

same mononuclear cells that differentiate into

macrophages. Osteoblasts (stromal cells)

membrane associated RANK ligand binds to its

receptor RANK located on the cell surface of

osteoclasts precursors. This interaction causes

the precursor cells to produce functional

osteoclasts. Osteoblasts also secrete

osteoprotegerin (OPG), which act as “decoy”

receptor for RANK ligand, preventing it from

binding the RANK receptor on osteoclast

precursors. Consequently. OPG prevents bone

resorption by inhibiting osteoclast

differentiation.

Pay attention to these pieces of information:

-The homeostasis between osteoblasts and osteoclasts in bones

remodelling is a continuous and dynamic complex process even in adult

mature skeleton, even in the microscopic level the intensity decreases

with age but it won’t stop never until die.

- Peak bone mass is reached in early adulthood after completion of

skeletal growth, then it decreases in the 4th decade. Remember that this

decrement differs from person to person according to factors mentioned

earlier.

-Bone Resorption > bone formation on 4th decade

The things that increase (+) osteoclasts (decrease the bone mass) are

Pth,IL-1 and steroids (given for a long time to treat immunological

diseases, so these patients suffer from decrease in the bone mass and

osteoporosis). And the things that decrease (-) osteoclasts (decrease

bone resorption) are BMPs (bone morphogenic proteins) and sex

hormones (oestrogen and test.)

Some people suggest that we can treat osteoporosis in females by giving

oestrogen hormone, but there are risks, such as: thromboembolism

especially if the patient suffer from hypertension, so they use

alternatives.

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There are two types of bone: woven bones and lamellar bones

Woven bones are hyperactive, haphazard bones, they are replaced by

lamellar bones in adults (remodelling process). The present of woven

bones in adults is abnormal and indicates a pathological condition, such

as: fracture and osteogenic sarcoma.

The bone matrix is synthesized in one of two histologic forms, woven or

lamellar. Woven bone (pic A) is produced more rapidly, such as during

fetal development or fracture repair, but the haphazard arrangement of

collagen fibers imparts less structural integrity than the parallel collagen

fibers in slowly produced lamellar bone (pic B)

Lamellar has less cells and they are osteocytes (less active). on the other

hand, woven has osteoblasts which are more active.

The picture show osteoclasts,

multinucleated giant cells, they

resorb bone. Look to the

osteoclastic bite (it’s the space

between osteoclasts and the bone)

The picture show osteoblasts,

where they synthesized osteoid

(the pink material), either during

growth or fracture repair.

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Remember: bone formation occurs by osteoblasts then remodelling

occurs by osteoclasts

Long bone structure:

Its composed of two epiphyses at proximal and distal end and a

diaphysis (shaft) between them, between epiphysis and metaphysis

there is a layer of hyaline cartilage called growth plate/ epiphysial line,

it’s totally ossified in the adulthood (after you complete your skeleton

maturation. The area between the growth plate and the diaphysis called

metaphysis.

Its important to know the structure as there are certain diseases

especially tumors occurs particularly in metaphysis or diaphysis and so

on.

Hematopoietic process

occurs in red bone

marrow in the diaphysis.

Flat bones, such as:

sternum and skull differ

in shape than long bones.

The picture shows the steps of

long bone formation by a process

called endochondral ossification

The picture shows the steps of flat

bone formation by a process

called intramembranous

ossification.

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Now lets start with pathology:

The first type of disorders is congenital disorders.

These disorders are born with the infant and divided into two major

groups:

-Dysostosis: it is characterized by abnormal condensation and migration

of mesenchyme during growth, it results from genetic abnormalities

(mutation) in homeobox genes, and stimulated by cytokines and its

receptors, they are not common but they can occur:

1- Aplasia; means no growth. For example:

aplasia in the distal phalanx or aplasia in

tibia (the patient doesn’t have tibia)

2- Supernumerary digits; here the patient have

additional one or more digit.

3- Syndactaly and craniosynostosis; in Syndactaly

digits are fused together and need a separation

surgery, while in craniosynostosis abnormal

formation for the skull sutures (missing sutures or

abnormal) they affect brain growth.

The picture shows the histology of

articulating cartilage (growth plate),

look to the:

chondrocytes

subchondral plate

bone marrow

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-Dysplasia

Dysplasia in neoplasia means a precursor for malignancy. However in

congenital disorders it means disorganized bone and cartilage results

from genetic mutation which control the development and remodelling,

some of them are common and some are not and they don’t considered

a premalignant condition. (it will be continued in the next lecture

insallah).

Pay attention to the pictures the doctor said that there will be

questions about them in the exam.

Sorry for any mistake

Best of luck 😉

“if you want to go fast go alone, but if you want to go far go together”