Kaap 309: Skeletal system II (Bone formation + clinical correlations)

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Cells of bone tissue

Cell Type

Description

Main Function

Osteogenic cells

Stem cells found in the periosteum and endosteum

Divide to form new osteoblasts (the “bone builders”)

Osteoblasts

Matrix-synthesizing cells

Build bone by secreting osteoid → responsible for bone growth

Osteocytes

Mature bone cells trapped in lacunae

Maintain bone matrix and communicate with other cells to direct remodeling

Osteoclasts

Bone-resorbing cells (large, multinucleated)

Break down (resorb) bone matrix during growth, repair, and remodeling

<table style="min-width: 215px;"><colgroup><col style="min-width: 25px;"><col style="min-width: 25px;"><col style="width: 165px;"></colgroup><tbody><tr><th colspan="1" rowspan="1"><p><strong>Cell Type</strong></p></th><th colspan="1" rowspan="1"><p><strong>Description</strong></p></th><th colspan="1" rowspan="1" colwidth="165"><p><strong>Main Function</strong></p></th></tr><tr><td colspan="1" rowspan="1"><p><strong>Osteogenic cells</strong></p></td><td colspan="1" rowspan="1"><p><strong>Stem cells</strong> found in the periosteum and endosteum</p></td><td colspan="1" rowspan="1" colwidth="165"><p>Divide to form new <strong>osteoblasts</strong> (the “bone builders”)</p></td></tr><tr><td colspan="1" rowspan="1"><p><strong>Osteoblasts</strong></p></td><td colspan="1" rowspan="1"><p><strong>Matrix-synthesizing cells</strong></p></td><td colspan="1" rowspan="1" colwidth="165"><p><strong>Build bone</strong> by secreting osteoid → responsible for <strong>bone growth</strong></p></td></tr><tr><td colspan="1" rowspan="1"><p><strong>Osteocytes</strong></p></td><td colspan="1" rowspan="1"><p><strong>Mature bone cells</strong> trapped in lacunae</p></td><td colspan="1" rowspan="1" colwidth="165"><p><strong>Maintain bone matrix</strong> and communicate with other cells to direct remodeling</p></td></tr><tr><td colspan="1" rowspan="1"><p><strong>Osteoclasts</strong></p></td><td colspan="1" rowspan="1"><p><strong>Bone-resorbing cells</strong> (large, multinucleated)</p></td><td colspan="1" rowspan="1" colwidth="165"><p><strong>Break down (resorb)</strong> bone matrix during growth, repair, and remodeling</p></td></tr></tbody></table><p></p>
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Formation of the Skeleton

  • All bones begin as fibrous connective tissue or hyaline cartilage models.

  • Ossification begins around week 8 in utero.

  • Two types of bone formation:

    1. Intramembranous ossification → forms flat bones (skull, clavicle)

    2. Endochondral ossification → forms most bones (long bones)

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Intramembranous Ossification

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Intramembranous Ossification

  1. Mesenchymal cells cluster

around a vessel and become

osteoblasts

  1. Osteoblasts secrete osteoid

and an ossification center

forms in fibrous connective

tissue.

1. Osteoblasts grow and continue

to secrete osteoid

2. Trapped osteoblasts now

become osteocytes

<ol><li><p>Mesenchymal cells cluster</p></li></ol><p>around a vessel and become</p><p>osteoblasts</p><ol start="2"><li><p>Osteoblasts secrete osteoid</p></li></ol><p>and an ossification center</p><p>forms in fibrous connective</p><p>tissue.</p><p></p><p>1. Osteoblasts grow and continue</p><p>to secrete osteoid</p><p>2. Trapped osteoblasts now</p><p>become osteocytes</p><p></p>
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Intramembranous Ossification

1. Osteoid continues to form

around vessels, forming an

immature spongy bone

2. Mesenchyme adheres to the

external surface and becomes

the periosteum

1. Immature spongy bone

near the periosteum is

remodeled and replaced

with compact bone

2. Central immature spongy

bone matures

<p>1. Osteoid continues to form</p><p>around vessels, forming an</p><p>immature spongy bone</p><p>2. Mesenchyme adheres to the</p><p>external surface and becomes</p><p>the periosteum</p><p></p><p>1. Immature spongy bone</p><p>near the periosteum is</p><p>remodeled and replaced</p><p>with compact bone</p><p>2. Central immature spongy</p><p>bone matures</p><p></p>
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Endochondral Ossification (I)

  1. Mesenchymal cells specialize into osteoblasts

  2. Perichondrium becomes periosteum

  3. Osteoblasts secrete osteoid, creating a bone collar

  4. Chondrocytes left within hypertrophy and become the primary ossification center

Cartilage model

<ol><li><p><strong>Mesenchymal cells</strong> specialize into <strong>osteoblasts</strong></p></li><li><p><strong>Perichondrium</strong> becomes <strong>periosteum</strong></p></li><li><p><strong>Osteoblasts</strong> secrete <strong>osteoid</strong>, creating a <strong>bone collar</strong></p></li><li><p><strong>Chondrocytes</strong> left within hypertrophy and become the <strong>primary ossification center</strong></p></li></ol><p><strong>Cartilage model</strong></p>
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Endochondral Ossification (II)

  1. Chondrocytes from the primary ossification center ossify surrounding cartilage

  2. Chondrocytes die and the matrix begins to dissolve

  3. Cavities are now formed within the model

  4. Remaining cartilage (ends) stay healthy and grow rapidly to elongate the model

<ol><li><p><strong>Chondrocytes</strong> from the <strong>primary ossification center</strong> ossify surrounding cartilage</p></li><li><p><strong>Chondrocytes</strong> die and the <strong>matrix begins to dissolve</strong></p></li><li><p><strong>Cavities</strong> are now formed within the model</p></li><li><p><strong>Remaining cartilage (ends)</strong> stay healthy and grow rapidly to <strong>elongate the model</strong></p></li></ol><p></p>
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Endochondral Ossification (III)

  1. Cavities are invaded by the periosteal bud

    • Nutrient a/v/n, red marrow elements, osteoprogenitor cells, osteoclasts

  2. Osteoclasts partially erode the cartilage matrix

  3. Osteoprogenitor cells become osteoblasts(spongy bone formation!)

<ol><li><p><strong>Cavities</strong> are invaded by the <strong>periosteal bud</strong></p><ul><li><p>Nutrient a/v/n, red marrow elements, osteoprogenitor cells, osteoclasts</p></li></ul></li><li><p><strong>Osteoclasts</strong> partially erode the <strong>cartilage matrix</strong></p></li><li><p><strong>Osteoprogenitor cells</strong> become <strong>osteoblasts</strong> → <em>(spongy bone formation!)</em></p></li></ol><p></p>
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Endochondral Ossification (IV)

1. Osteoclasts break down the newly formed spongy bone and open the cavity

2. The epiphyses stay as cartilage ends through birth (growing rapidly)

3. After birth, secondary ossification centers develop at epiphyses

– Short bones only have primary

– Irregular bones have multiple ossification centers

<p>1. <strong>Osteoclasts</strong> break down the newly formed <strong>spongy bone</strong> and open the cavity</p><p>2. The <strong>epiphyses</strong> stay as <strong>cartilage ends </strong>through birth (growing rapidly)</p><p>3. After birth, <strong>secondary ossification centers </strong>develop at epiphyses</p><p>– Short bones only have <strong>primary</strong></p><p>– Irregular bones have <strong>multiple ossification centers</strong></p><p></p>
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Endochondral Ossification (V)

  1. Secondary ossification mimics that of primary except the spongy bone remains and no cavity is formed

  2. The space between the diaphysis and epiphysis is the epiphyseal plate and is hyaline cartilage

<ol><li><p><strong>Secondary ossification</strong> mimics that of <strong>primary</strong> except the <strong>spongy bone remains </strong>and <strong>no cavity</strong> is formed</p></li><li><p>The space between the <strong>diaphysis</strong> and <strong>epiphysis</strong> is the epiphyseal plate and is <strong>hyaline cartilage</strong></p></li></ol><p></p>
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<p>Postnatal growth - length</p>

Postnatal growth - length

At the epiphyseal plate:

  1. Proliferation zone: chondrocytes divide

  2. Hypertrophic zone: older chondrocytes enlarge

  3. Calcification zone: matrix calcifies; chondrocytes die

  4. Ossification zone: new bone forms

<p>At the <strong>epiphyseal plate</strong>:</p><ol><li><p><strong>Proliferation zone:</strong> chondrocytes divide</p></li><li><p><strong>Hypertrophic zone:</strong> older chondrocytes enlarge</p></li><li><p><strong>Calcification zone:</strong> matrix calcifies; chondrocytes die</p></li><li><p><strong>Ossification zone:</strong> new bone forms</p></li></ol><p></p><p></p>
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Postnatal growth - width

  • Completed through appositional growth

  • Osteoblasts in the periosteum secrete bone matrix to the external bone surface

  • Osteoclasts on the endosteal surface remove bone

<ul><li><p>Completed through <strong>appositional</strong> <strong>growth</strong></p></li><li><p><strong>Osteoblasts</strong> in the <strong>periosteum</strong> secrete bone matrix to the <strong><mark data-color="#c1ff97" style="background-color: rgb(193, 255, 151); color: inherit;">external bone surface</mark></strong></p></li><li><p><strong>Osteoclasts</strong> on the <strong><mark data-color="#ff7676" style="background-color: rgb(255, 118, 118); color: inherit;">endosteal surface</mark> </strong>remove bone</p></li></ul><p></p>
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Remodeling bone

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Hormonal influence

  • Role of calcium in the body

    • Homeostasis for maintaining resting membrane potentials

  • 99% of the body’s calcium is stored in bone matrix

    • Hormones maintain a level of 9–11 mg/dL in the blood

  • Key hormones: Parathyroid hormone, Calcitriol, Calcitonin

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Hormonal influence

  1. hypercalcemia

  2. hypocalcemia

<ol><li><p>hypercalcemia</p></li><li><p>hypocalcemia</p></li></ol><p></p>
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Parathyroid Hormone

secreted by the parathyroid glands

  • Stimulate the osteoclasts to promote bone resorption

  • Promotes calcium reabsorption by the kidneys

  • Promotes final step of calcitriol synthesis in the kidneys

  • Inhibits collagen synthesis by osteoblasts

<p><strong>secreted by the parathyroid glands</strong></p><ul><li><p>Stimulate the <strong>osteoclasts</strong> to promote <strong>bone resorption</strong></p></li><li><p>Promotes <strong>calcium</strong> <strong>reabsorption</strong> by the kidneys</p></li><li><p>Promotes <strong>final</strong> step of <strong>calcitriol</strong> <strong>synthesis</strong> in the kidneys</p></li><li><p>Inhibits <strong>collagen</strong> synthesis by <strong>osteoblasts</strong></p></li></ul><p></p>
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Calcitriol & Calcitonin

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Mechanical stress influence

Wolff’s Law: the body adapts to the forces placed upon it

<p><strong>Wolff’s Law:</strong> the body adapts to the forces placed upon it</p><p></p>
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Fractures

Type

Description

Non-displaced

Ends in normal position (Broken but still in place)

Displaced

Ends out of alignment (Broken and shifted out of place)

Incomplete

Not fully broken through

Complete

Fully broken

Closed (simple)

Skin intact (Break on the inside)

Open (compound)

Skin penetrated (Break open to the outside)


<table style="min-width: 212px;"><colgroup><col style="width: 187px;"><col style="min-width: 25px;"></colgroup><tbody><tr><th colspan="1" rowspan="1" colwidth="187"><p>Type</p></th><th colspan="1" rowspan="1"><p>Description</p></th></tr></tbody></table><table style="min-width: 213px;"><colgroup><col style="width: 188px;"><col style="min-width: 25px;"></colgroup><tbody><tr><td colspan="1" rowspan="1" colwidth="188"><p><strong>Non-displaced</strong></p></td><td colspan="1" rowspan="1"><p>Ends in normal position (Broken but still in place)</p></td></tr></tbody></table><table style="min-width: 214px;"><colgroup><col style="width: 189px;"><col style="min-width: 25px;"></colgroup><tbody><tr><td colspan="1" rowspan="1" colwidth="189"><p><strong>Displaced</strong></p></td><td colspan="1" rowspan="1"><p>Ends out of alignment (Broken and shifted out of place)</p></td></tr></tbody></table><table style="min-width: 215px;"><colgroup><col style="width: 190px;"><col style="min-width: 25px;"></colgroup><tbody><tr><td colspan="1" rowspan="1" colwidth="190"><p><strong>Incomplete</strong></p></td><td colspan="1" rowspan="1"><p>Not fully broken through </p></td></tr></tbody></table><table style="min-width: 217px;"><colgroup><col style="width: 192px;"><col style="min-width: 25px;"></colgroup><tbody><tr><td colspan="1" rowspan="1" colwidth="192"><p><strong>Complete</strong></p></td><td colspan="1" rowspan="1"><p>Fully broken </p></td></tr></tbody></table><table style="min-width: 218px;"><colgroup><col style="width: 193px;"><col style="min-width: 25px;"></colgroup><tbody><tr><td colspan="1" rowspan="1" colwidth="193"><p><strong>Closed (simple)</strong></p></td><td colspan="1" rowspan="1"><p>Skin intact (Break on the inside)</p></td></tr></tbody></table><table style="min-width: 221px;"><colgroup><col style="width: 196px;"><col style="min-width: 25px;"></colgroup><tbody><tr><td colspan="1" rowspan="1" colwidth="196"><p><strong>Open (compound)</strong></p></td><td colspan="1" rowspan="1"><p>Skin penetrated (Break open to the outside)</p></td></tr></tbody></table><p><br></p>
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Four stages for traumatic (acute) fracture healing

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Osteoporosis

  • Group of diseases in which bone resorption outpaces bone deposit

  • 1 in 3 women over 50 will have a fracture due to osteoporosis

  • Risk Factors:

<ul><li><p>Group of diseases in which <strong>bone resorption outpaces bone deposit</strong></p></li><li><p><strong>1 in 3 women over 50</strong> will have a fracture due to osteoporosis</p></li><li><p><strong>Risk Factors:</strong></p></li></ul><p></p>
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Osteomalacia

  • Group of diseases in which bones are poorly mineralized

  • Results in weak and soft bones

  • Calcium salts not sufficient

  • Childhood version: Rickets

    • Bowed legs

    • Deformities to the skull, pelvis, and ribs

<ul><li><p>Group of diseases in which <strong>bones are poorly mineralized</strong></p></li><li><p>Results in <strong>weak and soft bones</strong></p></li><li><p><strong>Calcium salts not sufficient</strong></p></li><li><p><strong>Childhood version:</strong> Rickets</p><ul><li><p><strong>Bowed legs</strong></p></li><li><p><strong>Deformities</strong> to the skull, pelvis, and ribs</p></li></ul></li></ul><p></p><p></p>
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Osteitis Deformans

  • Haphazard bone deposit and resorption

  • Abnormally high ratio of spongy bone

  • Commonly affects the: spine, pelvis, femur, skull

  • 3% of elderly North Americans – rare before 40

<ul><li><p><strong>Haphazard bone deposit and resorption</strong></p></li><li><p>Abnormally high ratio of <strong>spongy bone</strong></p></li><li><p>Commonly affects the: <strong>spine, pelvis, femur, skull</strong></p></li><li><p><strong>3% of elderly North Americans</strong> – rare before 40</p></li></ul><p></p>

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