Anatomy and Physiology Bones and Bone Tissue

Process of bone formation

Process of bone formation is ossification or osteogenesis; begins in embryonic period; continues through childhood with most bones completing process by age 7: ◦ Can proceed by two different mechanisms; both have similar features:

◦ First bone formed is immature primary (woven) bone; irregularly arranged collagen bundles, osteocytes, and sparse inorganic matrix

◦ Usually primary bone is broken down by osteoclasts and replaced with mature secondary or lamellar bone; more inorganic matrix and increased strength

Intramembranous ossification

Bones formed by intramembranous ossification are built on model (starting material) made of membrane of embryonic connective tissue

Endochondral ossification

Bones formed by endochondral ossification are built on model of hyaline cartilage

Intramembranous ossification

Forms many flat bones, (skull and clavicles) during fetal development

-Larger bones have more than one primary ossification center

-Leads to pieces of bone that must fuse to one another over time

Example of early incomplete ossification

Fontanels (soft spots) in skulls of newborn babies

Endochondral Ossification

-Bone development for all bones below head except clavicles

-Begins in fetal stage of development for most bones; some bones (wrist and ankle) ossify much later

-Many bones complete ossification by age 7

Where does endochondral ossification occurs

Within model of hyaline cartilage; serves as scaffold for developing bone

Cartilage model forms, endochondral ossification occurs in 4 steps

1) The chondroblasts in the perichondrium differentiate into osteoblasts

2a) Osteoblasts build the bone collar on the bone’s external surface as the bone begins to ossify from the outside

2b) Simultaneously, the internal cartilage begins to calcify and the chondrocytes die

3) In the primary ossification center, osteoblasts replace the calcified cartilage with early spongy bone; the secondary ossification centers and medullary cavity develop

4) As the medullary cavity enlarges, the remaining cartilage is replaced by bone; the epiphyses finish ossifying

Where does cartilage remain?

Cartilage only remains in epiphyseal plates and on articular surfaces where bones interact at joint (articular cartilage)

Articular cartilage, epiphyseal plates

Articular cartilage persists into adulthood; epiphyseal plates are eventually replaced with bone, once growth in length ceases

Longitudinal growth

-Long bones lengthen by longitudinal growth; involves division of chondrocytes (not osteocytes or osteoblasts) in epiphyseal plate

-Bone growth takes place at epiphysis on side closest to diaphysis

Why does longitudinal growth continues at epiphyseal plate?

Longitudinal growth continues at epiphyseal plate as long as mitosis continues in zone of proliferation

Appositional growth

Bones grow not only in length but also in width

-Osteoblasts, in between periosteum and bone surface, lay down new bone

-Appositional growth does not result in immediate formation of osteons; instead, new circumferential lamellae are formed. As new lamellae are added, older deeper circumferential lamellae are removed or restructured into osteons

Multiple factors play role in how much cell division occurs in epiphyseal plate and how long process remains active

• One of the main factors affecting bone growth are hormones

• Hormones are secreted by cells of endocrine glands; Cell–Cell Communication Core Principle

Growth hormone

secreted by anterior pituitary gland; enhances protein synthesis and cell division in nearly all tissues, including bone

Growth hormone effects on both longitudinal and appositional growth

• Increases rate of cell division of chondrocytes in epiphyseal plate

• Increases activity of osteogenic cells, including activity in zone of ossification

• Directly stimulates osteoblasts in periosteum; triggers appositional growth

Male sex hormone testosterone has pronounced effect on bone growth

• Increases appositional growth; bones in males become thicker with more calcium salt deposition than females

• Increases rate of mitosis in epiphyseal plate; leads to “growth spurts” in teenage years

• Accelerates closure of epiphyseal plate

Female sex hormone estrogen also plays a role in bone growth

• Increases rate of longitudinal bone growth; inhibits osteoclast activity

• When estrogen levels spike in teen years an accompanying “growth spurt” occurs in females

• Accelerates closure of epiphyseal plate at much faster rate than testosterone; leads to average height differences between genders

Bone remodeling

Continuous process of bone formation and loss after growth in length is finished; new bone formed by bone deposition; old bone removed by bone resorption; cycle occurs for following reasons:

• Maintenance of calcium ion homeostasis

• Replacement of primary bone with secondary bone

• Bone repair

• Replacement of old brittle bone with newer bone

• Adaptation to tension and stress

Process of formation and loss in healthy bone of adults

In healthy bone of adults, process of formation and loss occur simultaneously; bone breakdown by osteoclasts matches bone formation by osteoblasts

Bone deposition

Carried out by osteoblasts

• Found in both periosteum and endosteum; make organic matrix and facilitate formation of inorganic matrix

Bone resorption

Osteoclasts secrete hydrogen ions on bone ECM

• Osteoclasts secrete enzymes

  • Degrade organic matrix, including proteoglycans, glycosaminoglycans, and glycoproteins

Bone remodeling in response to tension and stress

Compression

Tension

Pressure

Braces is due to bone remodeling

Other factors influencing bone remodeling: Hormones

testosterone promotes bone deposition; estrogen inhibits osteoclast activity

Other factors influencing bone remodeling: Age

as individual ages growth hormone and sex hormones decline; decreases protein synthesis in bone

Other factors influencing bone remodeling: Calcium ion intake

(diet) must be adequate to support bone deposition

Other factors influencing bone remodeling: Vitamin D intake

(diet) must be adequate to promote calcium ion absorption from gut and prevent calcium ion loss in urine

Other factors influencing bone remodeling: Vitamin C intake

(diet) must be adequate for synthesis of collagen

Other factors influencing bone remodeling: Vitamin K intake

(diet) must be adequate for synthesis of calcium ion-binding glycoproteins secreted by osteoblasts

Other factors influencing bone remodeling: Protein intake

(diet) must be adequate for osteoblasts to synthesize collagen fibers in organic matrix

Bone remodeling and calcium ion homeostasis

• Bone stores most of calcium ions in body

• Stored calcium ions are not only used for bone deposition and remodeling; used throughout body for several critical processes (muscle contraction)

• Negative feedback loop maintains calcium ion homeostasis in blood; Feedback Loops Core Principle

• Calcium ion levels in blood are closely monitored; both high and low levels can lead to major homeostatic disruptions (even death)

Negative feedback loop: Stimulus and receptor

when calcium ion level drops in blood it is detected by parathyroid cells

Negative feedback loop: Control center and effector

parathyroid cells act as control center; secrete parathyroid hormone (PTH)

Increased blood calcium levels trigger different negative feedback loop

first response is drop in PTH secretion by parathyroid gland

• Calcitonin – secreted by thyroid gland; opposite effects as PTH; leads to bone deposition; from gut

Bones are commonly injured while performing their protective and supportive functions. Most dramatic bone injury is fracture (broken bones)

• Simple fractures – skin and tissue around fracture remain intact

• Compound fractures – skin and tissues around fracture are damaged

Spiral fracture

Fracture resulting from twisting forces applied to the bone

(An illustration and an X ray of a spiral fracture in the upper leg

Comminuted fracture

Fracture in which the bone is shattered into multiple fragments; difficult to repair

(An illustration and an X ray of a comminuted fracture in the lower leg.)

Greenstick Fracture

Fracture in which the bone breaks on one side but only bends on the other side, similar to the break observed when a young (“green”) twig is bent; common in children, whose bones are more flexible

(An illustration and an X ray of a greenstick fracture in the forearm.)

Compression Fracture

Fracture in which the bone is crushed under the weight it is meant to support; common in the elderly and those with reduced bone mass

(An illustration and an X ray of a compression fracture in the spine)

Avulsion Fracture

Fracture in which a tendon or ligament pulls off a fragment of bone; often seen in ankle fractures

(An illustration and an X ray of a avulsion fracture in the ankle.)

Epiphyseal plate fracture

Fracture that involves at least part of the epiphyseal plate; occurs only in children and young adults; may interfere with growth

(An illustration and an X ray of a epiphyseal plate fracture in the wrist.)

General process of fracture healing

• Hematoma (blood clot) fills in gap between bone fragments

  • Mass of blood cells and proteins form due to ruptured blood vessels

  • Bone cells in surrounding area die

• Fibroblasts and chondroblasts (from periosteum) infiltrate hematoma and form soft callus (mixture of hyaline cartilage and collagenous connective tissue); bridges gap between fragments

  • Fibroblasts form dense irregular collagenous connective tissue

  • Osteogenic cells become chondroblasts; secrete hyaline cartilage

• Osteoblasts build bone callus (hard callus); collar of primary bone made by osteoblasts in periosteum; forms bridge between fragments

• Bone callus is remodeled and primary bone is replaced with secondary bone; bone regains previous structure and strength after several months