Endochondral Ossification

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Endochondral Ossification

• Most bones form this way!

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Endochondral Ossification - The general plan
Cartilage is formed
Cartilage calcifies
Cartilage matrix deteriorates
Cartilage is replaced by bone tissue
Bone grows
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A. Development of the Hyaline Cartilage Model

• Hyaline cartilage model is generated that has the
  shape of the future bone
• The model enlarges using interstitial growth

Interstitial growth growing from the inside out
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Perichondrium coating of cartilage
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B. Bone Collar Formation

• The diaphyseal perichondrium becomes
  vascularized and osteoprogenitor cells arise
• The periosteal osteoblasts deposit bone around
  the periphery of the diaphysis forming a bone
  collar
• The perichondrium is now a periosteum

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Once bone cells appear you have periosteum!
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C. Loss of Cartilage in the Central Diaphysis
? The cartilage matrix becomes calcified
RIP cartilage!
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D. Deposition of Bone in the Central Diaphysis

• During the 3rd month, a periosteal bud invades
  the mid-diaphysis
• Includes nerves, arteries, veins, lymphatic
  vessels, osteoclasts, osteoblasts and red marrow
  elements
• Osteoblasts in the periosteal bud deposit bone
  matrix over the spicules of deteriorating
  cartilage matrix
• This is called a primary center of ossification

As bone expands it has to break down
cartilage! Cartilage near the ends keeps growing
to lengthen the bone
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Osteoclasts break down and reorganize the bone
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E. Formation of the Medullary Cavity
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F. Ossification of the Epiphysis

• At various times after birth, the epiphysis
  ossify
• These are called secondary centers of
  ossification

? What do you think the sequence of steps for
ossification of the epiphysis will be?
One difference-no medullary cavity formed!
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• Hyaline cartilage remains in two places
• Articular cartilage
• Epiphyseal plate

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Bone growth through life
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Growing bone

• Long bones lengthen by interstitial growth of the
  epiphyseal plate cartilage
• Long bones thicken by appositional growth
  (outside in)

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Epiphyseal plate is living cartilage It can
grow (Sometimes called growth plate)
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Androgens Cause closure of the epiphyseal
growth plates Ends bone growth
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Quiet, inactive side
Bone growth at the growth plate
Cartilage
(growing)
Bone
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• Growth (proliferation) zone
• Mitosis of cartilage cells
• Hypertrophic zone
• Cartilage cells enlarge
• Calcification zone
• Cartilage cells die
• Matrix is calcified
• Ossification zone
• Bone formation

Epiphyseal side
Cells younger active proliferation
Older hypertrophied cells
Diaphyseal side
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• Growth of Bones in Diameter
• appositional growth (addition of tissue to the
  surface)
• involves periosteal osteoblasts

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Bone formation disorders
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Disorders related to osteogenesis Osteogenesis
Imperfecta production of defective or inadequate
type 1 collagen
Deceased synthesis of collagen Bone fragility,
fractures easily Short stature Scoliosis Fractures
common, healing normal
Why are the bones so fragile?
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Achondroplastic Dwarfism

• Genetic disorder
• Gene defect in Fibroblast growth factor receptor
• 75 new mutation in parents gene (normal stature
  parents)
• Deficiency of cell proliferation
• Disproportionate dwarfism (normal trunk,
  shortened limbs)

Munchkins of Oz
Tom Thumb, Lavinia Bump
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Hormones involved in the regulation of bone growth
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Bone growth hormones

• Growth hormone
• Comes from anterior pituitary
• Stimulates the cartilage cells in the epiphyseal
  growth plate
• Thyroid hormone
• Comes from thyroid gland
• Modulates the activity of growth hormone
• Ensures bone has proper proportions
• Estrogen and progesterone
• Increase in adolescence
• Stimulate bone growth
• Ends growth of bones by closing epiphyseal plate

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Hormonal Regulation of Bone Growth
Growth Hormone

• Pathway
• GH released by anterior pituitary
• Liver (other tissues also) produces insulin like
  growth factors (IGF)

• Effects - Mitogenic
• chondroblasts
• osteoblasts

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Hypersecretion of GH
Hyposecretion of GH
Dwarfism
Pituitary dwarf -The sister on the left is 1 ½
years older but 18 cm shorter
Gigantism
Pituitary giant - Robert Wadlow 8 feet 11
inches, 475 lbs.
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Thyroid Hormone (T3. T4)
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• Thyroid Gland Anatomy
• Anterior neck
• Inferior to the thyroid cartilage
• 2 lateral lobes connected by an isthmus

• Hypothalamus Pituitary
• Hypothalamus secretes TRH
• Pituitary secretes TSH
• Thyroid secretes T3, T4
• Release regulated by a negative feedback
  mechanism

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• Effects of Thyroid hormone on growth
• Modulates growth hormone activity
• Stimulates osteoblasts

• Other effects
• Increases metabolic rate
• Increases mitochondrial activity
• Stimulates carbohydrate, protein, and lipid
  metabolism

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Juvenile Hypothyroidism (endemic cretinism)

• Effects
• Mental retardation
• Growth stunting
• Delayed or absent sexual maturity

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• Estrogen/Testosterone
• At puberty, stimulates osteoblasts
• At the end of growth, stimulates closure of the
  epiphyseal plate

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Nutritional requirements of skeletal growth

• Vitamins A, C, B12 D
• Minerals
• Calcium
• Phosphorous
• Fluoride
• Magnesium
• Iron
• Weight-bearing exercise