Cartilage

 forms the supporting framework of certain organs, the articulating surfaces of bones, and the
greater part of the fetal skeleton, although most of that will be replaced by bone
 a nonvascular, strong, and somewhat pliable structure composed of a firm matrix of
proteoglycans, whose main glycosaminoglycans are chondroitin-4-sulfate and chondroitin-6-
sulfate
 There are three types of cartilage in the body
o hyaline cartilage
o elastic cartilage, and;
o fibrocartilage

Cellular Components of Cartilage

 Chondrocytes
 are the cells responsible for cartilage formation, and they are crucial for the
process of endochondral ossification
 are housed individually in small spaces known as lacunae.
 Chondroblasts
 contribute to the formation of the extracellular matrix and are the precursors of
the chondrocytes
 chondroblasts and chondrogenic cells are located in the perichondrium

Perichondrium

 is a layer of dense irregular connective tissue that surrounds the cartilage.

 has an outer fibrous layer and an inner chondrogenic layer.
o The outer fibrous layer, although poor in cells, is composed mostly of fibroblasts and
collagen fibers.
o The inner cellular or chondrogenic layer is composed of chondroblasts and
chondrogenic cells. It gives rise to chondroblasts, cells that are responsible for secreting
the cartilage matrix. It is from this layer that the cartilage may grow appositionally.

Hyaline Cartilage

 surrounded by a well-defined perichondrium.

 The type II collagen fibers of the matrix of this cartilage are mostly very fine and are, therefore,
fairly well masked by the surrounding glycosaminoglycans giving the matrix a smooth, glassy
appearance
 This cartilage is located in areas like the articulating surfaces of most bones, the C rings of the
trachea, and the laryngeal, costal, and nasal cartilages, among others
Elastic Cartilage

 also possesses a perichondrium.

 The matrix, in addition to the type II collagen fibers, contains a wealth of coarse elastic fibers
that impart to it a characteristic appearance.
 This cartilage is located in areas like the epiglottis, external ear and ear canal, and some of the
smaller laryngeal cartilages.

Fibrocartilage

 it has no perichondrium.
 the chondrocytes are smaller and are usually oriented in parallel longitudinal rows.
 The matrix of this cartilage contains a large number of thick type I collagen fiber bundles
between the rows of chondrocytes.
 present in only a few places, namely, in some symphyses, the eustachian tube, intervertebral
(and some articular) discs, and certain areas where tendons insert into bone

Bone

Functions:

o support,
o protection,
o mineral storage and;
o hemopoiesis.

 It is hard and rigid because of mineralization of the extracellular matrix. Bone also serves as
a reservoir for calcium.

 Bone has a rich vascular supply (unlike cartilage).

  Bone is a vascular connective tissue consisting of cells and calcified extracellular materials,
known as the matrix. The calcified matrix is composed of

o 65% minerals (mostly calcium hydroxyapatite crystals)

o 35% organic matter (type I collagen, sulfated glycoproteins, and proteoglycans)
including bound water.

The presence of these crystals makes bone the body’s storehouse of calcium,
phosphate, and other inorganic ions.

Type of Bones

 Spongy bone (also known as cancellous or trabecular bone)

 Compact bone

Spongy or Cancellous Bone

 has large, open spaces surrounded by thin, anastomosing plates of bone.

 The large spaces are marrow spaces, and the plates of bones are trabeculae composed of
several layers or lamellae.
 Location: enlarged ends (epiphyses) of the long bones, the ribs, the shoulder blades, the flat
bones of the skull, and a variety of short, flat bones elsewhere in the skeleton.

Compact Bone

 much denser than cancellous bone. Its spaces are much reduced in size, and its lamellar
organization is much more precise and thicker
 It is composed of cylindrical units, known as osteon (Haversian systems),
 An osteon is composed of concentric rings of bone (lamellae) surrounding a central channel.

The marrow cavity is lined by an endosteum composed of osteoprogenitor cells (previously

known as osteogenic cells), osteoblasts, and occasional osteoclasts.

The periosteum covering the outer surface of compact bone is composed of an

o outer fibrous layer consisting mainly of collagen fibers and populated by fibroblasts.
o The inner osteogenic layer consists of some collagen fibers and mostly osteoprogenitor
cells and their progeny, the osteoblasts

Cells of Bone

Bone possesses four types of cells: osteoprogenitor cells, osteoblasts, osteocytes, and osteoclasts.

Osteoprogenitor cells
  give rise to osteoblasts under the influence of transforming growth factor-β and bone
morphogenic protein.
o TGF-β is a multifunctional set of peptides that controls proliferation, differentiation, and
other functions in many cell types.
 under hypoxic conditions, osteoprogenitor cells become chondrogenic cells; therefore, these
two cells are really the same cell that expresses different factors under differing oxygen tension

Osteoblasts

 elaborate bone matrix, become surrounded by the matrix they synthesized, and calcify the
matrix via matrix vesicles that they release.
 When osteoblasts are dormant, they lose much of their protein synthetic machinery and
resemble osteoprogenitor cells.
 Osteoblasts function not only in the control of bone matrix mineralization but also in the
formation, recruitment, and maintenance of osteoclasts as well as for the initiation of bone
resorption
 Osteoblasts possess parathyroid receptors on their cell membrane, and in the presence of
parathormone, they release macrophage colony– stimulating factor that induces the formation
of osteoclast precursors.

Osteocytes

 Are osteoblasts trapped in the matrix that they have synthesized.

 Two transcription factors have been implicated in the transformation of osteoblasts to
osteocytes, namely, Cbfa1/Runx2 and osterix. Both of these factors are essential for the normal
development of mammalian skeleton.
 As the differentiation occurs, the membrane-bound alkaline phosphatase is no longer
expressed.
 They occupy lacunae, lenticular-shaped spaces, and possess long osteocytic processes that are
housed in tiny canals or tunnels known as canaliculi.
 Osteocytes are responsible for the maintenance of bone.
 Their cytoplasmic processes contact and form gap junctions with processes of other osteocytes
within canaliculi; thus, these cells sustain a communication network.
 Large population of osteocytes are able to respond to blood calcium levels as well as to
calcitonin and parathormone, released by the thyroid and parathyroid glands, respectively.
 Thus, osteocytes are responsible for the short-term calcium and phosphate homeostasis of the
body

Osteoclasts,

 large, multinucleated cells derived from monocyte precursors are responsible for the
resorption of bone.
 As they remove bone, they appear to occupy a shallow cavity, Howship’s lacuna
(subosteoclastic compartment)
 Osteoclasts have four regions:
o the basal zone, housing nuclei and organelles of the cell;
 o the ruffled border, composed of finger-like processes that are suspended in the
subosteoclastic compartment where the resorption of bone is actively proceeding:
o the vesicular zone, housing numerous vesicles that ferry material out of the cell and
into the cell from the subosteoclastic compartment; and
o the clear zone, where the osteoclast forms a seal with the bone, isolating the
subosteoclastic compartment from the external milieu.
 The osteoclast cell membrane also possesses calcitonin receptors;
o when calcitonin is bound to the receptors, these cells become inhibited; they stop
bone resorption, leave the bone surface, and dissociate into individual cells or
disintegrate and are eliminated by macrophages.
o Cooperation between osteoclasts and osteoblasts is responsible not only for the
formation, remodeling, and repair of bone but also for the long-term maintenance
of calcium and phosphate homeostasis of the body.

Since bone, unlike cartilage, is a vascular hard tissue whose blood vessels penetrate and perforate it,
canaliculi eventually open into channels known as haversian canals, housing the blood vessels, in order
to exchange cellular waste material for nutrients and oxygen and to convey nutrients, hormones, and
other necessary substances to and from the osteocytes.

• Each haversian canal with its surrounding lamellae of bone containing canaliculi radiating to it
from the osteocytes trapped in the lacunae is known as an osteon or haversian canal system.
• Haversian canals, which more or less parallel the longitudinal axis of long bones, are connected
to each other by Volkmann’s canals.

The bony lamellae of compact bone are organized into four lamellar systems: external and internal
circumferential lamellae, interstitial lamellae, and the osteons

Osteogenesis is the process of bone formation. This will synthesize bone matrix in the periphery of
mesenchymal cells continue to differentiate into osteoblast. After that the bone differentiate & replace
by the mature lamellar bone.

Histogenesis of bone occurs via either intramembranous or endochondral ossification.

• Intramembranous ossification
• arises in a richly vascularized mesenchymal membrane where mesenchymal cells
differentiate into osteoblasts (possibly via osteoprogenitor cells),
• Intramembranous ossification is the process of bone development from fibrous membrane
which begin to elaborate bone matrix, thus forming trabeculae of bone
o As more and more trabeculae form in the same vicinity, they will become
interconnected.
o As they fuse with each other, they form cancellous bone, the peripheral regions of
which will be remodeled to form compact bone.
o The surfaces of these trabeculae are populated with osteoblasts.
o Frequently, an additional cell type, the osteoclast, may be present.
 o These large, multinucleated cells derived from monocyte precursors are found in
shallow depressions on the trabecular surface (Howship’s lacunae) and function to
resorb bone.
o It is through the integrated interactions of these cells and osteoblasts that bone is
remodeled.
• The region of the mesenchymal membrane that does not participate in the ossification process
will remain the soft tissue component of bone (i.e., periosteum, endosteum)
• Newly formed bone is called primary or woven bone, since the arrangement of collagen fibers
lacks the precise orientation present in older bone. The integrated interaction between
osteoblasts and osteoclasts will act to replace the woven bone with secondary or mature bone.

Endochondral Ossification

o the process by which growing cartilage is systematically replaced by bone to form the growing
skeleton. This process occurs at three main sites: the physis, the epiphysis, and the cuboidal bones
of the carpus and tarsus.
 Reserve Zone- Storage site for lipids, glycogen, proteoglycan
 Proliferative Zone- Proliferating chondrocytes leading to longitudinal growth
 Hypertrophic Zone-Site of chondrocyte maturation
-Within the hypertrophic zone, the chondrocytes go through a transformation process. The
chondrocyte mature and prepare a matrix for calcification; then they degenerate which
allows calcium release for calcification of the matrix.
 Primary Spongiosa-Site for mineralization to form woven bone
-Vascular invasion occurs
 Secondary Spongiosa-Internal modeling with the replacement of fiber bone with lamellar
bone
-External modeling with funnelization

 Five steps can summarize endochondral ossification:

1. Mesenchymal cells differentiate into chondrocytes and form the cartilage model for
bone
2. Chondrocytes near the center of the cartilage model undergo hypertrophy and alter
the contents of the matrix they secrete, enabling mineralization
3. Chondrocytes undergo apoptosis due to decreased nutrient availability; blood
vessels invade and bring osteogenic cells
4. Primary ossification center forms in the diaphyseal region of the periosteum called
the periosteal collar
5. Secondary ossification centers develop in the epiphyseal region after birth

 Reserve Zone
o Storage site for lipids, glycogen, proteoglycan 
 Proliferative Zone
o Proliferating chondrocytes leading to longitudinal growth
  Hypertrophic Zone
o Site of chondrocyte maturation
o Within the hypertrophic zone, the chondrocytes go through a transformation
process. The chondrocyte mature and prepare a matrix for calcification; then they
degenerate which allows calcium release for calcification of the matrix. 
 Primary Spongiosa
o Site for mineralization to form woven bone
o Vascular invasion occurs
 Secondary Spongiosa
o Internal modeling with the replacement of fiber bone with lamellar bone
o External modeling with funnelization
Five steps can summarize endochondral ossification:
1. Mesenchymal cells differentiate into chondrocytes and form the cartilage model for bone
2. Chondrocytes near the center of the cartilage model undergo hypertrophy and alter the
contents of the matrix they secrete, enabling mineralization
3. Chondrocytes undergo apoptosis due to decreased nutrient availability; blood vessels
invade and bring osteogenic cells
4. Primary ossification center forms in the diaphyseal region of the periosteum called the
periosteal collar
5. Secondary ossification centers develop in the epiphyseal region after birth
Paget's Disease of Bone
Paget's disease of bone is a chronic disease of the skeleton. In healthy bone, a process
called remodeling removes old pieces of bone and replaces them with new, fresh bone.
Paget’s disease causes this process to shift out of balance, resulting in new bone that is
abnormally shaped, weak, and brittle. 

Description
Paget's disease can affect any bone in the skeleton. It appears most often in the
spine, pelvis, long bones of the limbs, and skull. It can be present in just one bone or
in several bones. It can affect the entire bone or just part of it.
Bone Remodeling
In normal bone, a process called remodeling takes place every day. Bone is absorbed and
then reformed in response to the normal stresses on the skeleton. More specifically:
 Cells of the bone called "osteoclasts" absorb bone.
 Cells of the bone called "osteoblasts" make new bone.
In Paget's disease, osteoclasts are more active than osteoblasts. This means that there is
more bone absorption than normal. The osteoblasts try to keep up by making new bone,
but they overreact and make excess bone that is abnormally large, deformed, and fits
together haphazardly.
(Left) Microscopic view of large, plump osteoclasts (OCL) resorbing bone. The divots in the
bone indicate that the osteoclasts are active. (Right) The disordered mosaic pattern of Pagetoid
bone.
Normal bone has a tight overlapping structure, like a well-constructed brick wall. Bone
afflicted by Paget's disease has an irregular mosaic pattern, as though the bricks were
just dumped in place. The end result is bones that are large and dense, but weak and
brittle. The bone is prone to fractures, bowing, and deformities.
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TREATMENT

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DISEASES & CONDITIONS

Bone Tumor

Cause
The cause of Paget’s disease is not known, but doctors have identified a number of risk
factors that make someone more likely to develop the disease. These include:
 Genetics. Paget’s disease tends to run in families. In as many as 25 to 40 percent of
cases, another relative will also have the disease.
 Age. Paget's disease occurs only rarely in people under 40 years of age. It is more
common as people age.
 Ancestry. It is more common in people of Anglo-Saxon descent and those who live
in certain geographic areas, such as the United States, England, Australia, New
Zealand, and Western Europe. It is not common in Scandinavia, China, Japan, or
India.
  Environmental factors. Some studies suggest that certain environmental exposures
may play a role in the development of Paget's disease. This has not been proven
definitively, however.
While there are no known ways to prevent Paget's disease from occurring, eating a
healthy diet with sufficient calcium and vitamin D, and getting regular exercise, are
important components in maintaining skeletal health and joint mobility.

Symptoms
Many people with Paget's disease do not have any symptoms at all. The disease is often
first discovered when x-rays are taken for another reason or when routine blood work
indicates an elevated blood serum alkaline phosphatase level.

Paget’s Disease of Bone - Symptoms and Treatment - OrthoInfo - AAOS. (2017). Aaos.org.

https://orthoinfo.aaos.org/en/diseases--conditions/pagets-disease-of-bone#:~:text=Paget’s

%20disease%20of%20bone%20is,shaped%2C%20weak%2C%20and%20brittle.

What is osteoporosis?

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 means that you have less
bone mass and strength. The disease often develops without any
symptoms or pain, and it is usually not discovered until the weakened
bones cause painful fractures. Most of these are fractures of the hip,
wrist and spine.
Who gets osteoporosis?

About 200 million people are estimated to have osteoporosis throughout

the world. In the U.S., the figure is about 54 million people. Although
osteoporosis occurs in both men and women, women are four times
more likely to develop the disease than men. There are currently about
two million men in the U.S. who have osteoporosis and some 12 million
more who are at risk of developing the condition.

After age 50, one in two women and one in four men will have an
osteoporosis-related fracture in their lifetimes. Another 30% have low
bone density that puts them at risk of developing osteoporosis. This
condition is called osteopenia.

Osteoporosis is responsible for more than two million fractures each

year, and this number continues to grow. There are steps you can take to
prevent osteoporosis from ever occurring. Treatments can also slow the
rate of bone loss if you do have osteoporosis.
What causes osteoporosis?

Researchers understand how osteoporosis develops even without

knowing the exact cause of why it develops. Your bones are made of
living, growing tissue. The inside of healthy bone looks like a sponge.
This area is called trabecular bone. An outer shell of dense bone wraps
around the spongy bone. This hard shell is called cortical bone.

When osteoporosis occurs, the "holes" in the "sponge" grow larger and
more numerous, which weakens the inside of the bone. Bones support
the body and protect vital organs. Bones also store calcium and other
minerals. When the body needs calcium, it breaks down and rebuilds
bone. This process, called bone remodeling, supplies the body with
needed calcium while keeping the bones strong.

Up until about age 30, you normally build more bone than you lose.
After age 35, bone breakdown occurs faster than bone buildup, which
causes a gradual loss of bone mass. If you have osteoporosis, you lose
bone mass at a greater rate. After menopause, the rate of bone
breakdown occurs even more quickly.

SYMPTOMS AND CAUSES

What are the symptoms of osteoporosis?
Usually, there are no symptoms of osteoporosis. That is why it is
sometimes called a silent disease. However, you should watch out for
the following things:

 Loss of height (getting shorter by an inch or more).

 Change in posture (stooping or bending forward).
 Shortness of breath (smaller lung capacity due to compressed
disks).
 Bone fractures.
 Pain in the lower back.

Osteoporosis: Symptoms, Causes, Tests & Treatment. (2020). Cleveland Clinic.

https://my.clevelandclinic.org/health/diseases/4443-osteoporosis

Osteopetrosis is a rare bone disease that may present in one of three distinct forms (Table 1).
Osteopetrosis tarda, the most benign form, presents in adulthood and is often diagnosed
incidentally on routine radiographs, whereas the two more malignant variants, osteopetrosis
congenita and marble bone disease, present in infancy and childhood. In all three forms, the
main features are pathologic alteration of osteoclastic bone resorption and thickening of cortical
and lamellar bones

Carolino, J., Perez, J. A., & Anca Popa. (2021). Osteopetrosis. American Family

Physician, 57(6), 1293. https://www.aafp.org/afp/1998/0315/p1293.html

‌
Osteomalacia is the name of a condition where bones become soft and weak. This means they
can bend and break more easily than normal.
The most common cause is not having enough vitamin D.
Rickets is the name of a similar condition that affects childre

NHS Choices. (2021). Overview - Rickets and osteomalacia.

https://www.nhs.uk/conditions/rickets-and-osteomalacia/

‌
What is chondrosarcoma?
Chondrosarcoma is a type of bone cancer that develops in cartilage cells. Cartilage is
the specialized, gristly connective tissue that is present in adults and the tissue from
which most bones develop. Cartilage plays an important role in the growth process.
There are many different types of cartilage that are present throughout the body.
Chondrosarcoma primarily affects the cartilage cells of the femur (thighbone), arm,
pelvis, or knee. Although less often, other areas (such as the ribs) may be affected.

Chondrosarcoma is the second most common type of primary bone cancer. A primary
bone cancer is one that starts from bone. This is opposed to starting in another organ
and then spreading to the bone. This type of cancer rarely affects individuals under age
20. The risk continues to rise until age 75. The incidence between males and females is
equal.

What causes chondrosarcoma?

The exact cause of chondrosarcoma is not known. There may be a genetic or
chromosomal component that makes certain individuals more open to this type of
malignancy. Chondrosarcomas have been observed as a late consequence of radiation
therapy for other cancers. 

Chondrosarcoma. (2021). https://www.hopkinsmedicine.org/health/conditions-and-

diseases/sarcoma/chondrosarcoma#:~:text=Chondrosarcoma%20is%20a%20type

%20of,role%20in%20the%20growth%20process.