1. Bone Development & Skeleton Formation
Osteogenesis and ossification:
Synonyms of the process of bone tissue formation.
Before 8 weeks the fetal skeleton is made of:
Fibrous membranes
Hyaline cartilage
Ossification begins at week 8 of fetal development
Bone formation (fetal/embryonic) is followed by:
Bone growth (toward adulthood)
Bone remodeling & repair (throughout life)

2. Bone Development & Skeleton Formation
Fetal skeleton is cartilage & fibrous membranes
There are two processes of bone formation:
Intramembranous ossification:
Development of bones from the fibrous membrane
Resulting bone is called membrane bone
Endochondral ossification:
Formation of bones by replacing hyaline cartilage
Resulting bone is called cartilage or endochondrial bone

3. Intramembranous Ossification
Results in the formation of:
The cranial bones of the skull & the clavicles
Most of the flat bones
Mesenchymal cells:
They form the fibrous connective tissue membranes
Fibrous connective tissue membranes:
Become the supporting structures
Ossification begins on these membranes at 8 wk of development

4. Four Main Stages of Intramembranous Ossification
Step 1:
Clustering of centrally located mesenchymal cells
Differentiation of these cells into osteoblatsts
Formation of ossification center
Figure 6.7.1

5. Stages of Intramembranous Ossification
Step 2:
Secretion of osteoid (organic matrix) by osteoblasts
Mineralization of osteoid (inorganic matrix) within few days
Trapping of osteoblasts turns them into osteocytes
Figure 6.7.2

6. Stages of Intramembranous Ossification
Step 3:
Formation of woven bone:
Accumulating osteoid deposits between embryonic blood vessels randomely
This forms a random network of trabeculae
Vascularized mesenchyme condenses on the external surface of the formed bone & become the periosteum
Figure 6.7.3

7. Stages of Intramembranous Ossification
Step 4:
Thickening of trabeculae next to the periosteum
Formation of bone collar (future lamellar bone)
Spongy bone become distinct internally
vascular tissue of spongy bone becomes red bone marrow
Figure 6.7.4

8. Endochondral Ossification
Most bones are made by endochondral ossification
Begins:
In the second month of development
Uses:
Hyaline cartilage as models for bone construction
Requires:
Breakdown of hyaline cartilage prior to ossification

9. Endochondral Ossification (lnitiation)
Begins in a central region of the hyaline cartilage shaft called:
The primary ossification center
Blood vessel infiltrate the perichondrium of cartilage converting it into:
Vascularized periosteum
Resulting change in nutrition causes:
Underlying mesenchymal cells differentaite into osteoblasts
Initiation of the ossification process

10. Stages of Endochondral Ossification (long bones):
Formation of periosteal bone collar:
Osteoblasts secrete osteoid around cartilage diaphysis
A bony collar forms around the cartilage diaphysis
Hyaline
cartilage
Primary
ossification
center
Bone collar
Formation of
bone collar
around hyaline
cartilage model. 1

11. Stages of Endochondral Ossification
Calcification and cavitation:
Shaft chondrocytes hypertrophy
Send calcification signal to surrounding matrix
Impermeable calcified matrix causes:
Chondrocytes death
Matrix deterioration
Formation of central cavities
Figure 6.8

12. Stages of Endochondral Ossification
Deteriorating
cartilage
matrix
Cavitation of
the hyaline carti-
lage within the
cartilage model. 2
Formation of
bone collar
around hyaline 1
Figure 6.8

13. Stages of Endochondral Ossification (long bones):
Invasion of internal cavities by periosteal bud elements
The periosteal bud contains:
Arteries, veins, & lymphatic vessels
Nerve fibers
Red marrow elements
Osteoblasts
Osteoclasts
Formation of the early version of Spongy bone:
Osteoclasts partially erode calcified matrix
Osteoblasts secrete osteoid around fragmented cartilage
Bone-covered cartilage trabeculae form (early spongy bone)

14. Stages of Endochondral Ossification
Spongy
bone
formation
Blood
vessel of
periosteal
bud
Formation of
bone collar
around hyaline
cartilage model.
Cavitation of
the hyaline carti-
lage within the
Invasion of
internal cavities
by the periosteal
bud and spongy
bone formation. 1 2 3
Figure 6.8

15. Stages of Endochondral Ossification (long bones):
Formation of:
The medullary cavity
Appearance of:
Secondary ossification centers in the epiphysis
Continuation and completion of:
Epiphysis ossification

16. Stages of Endochondral Ossification
Epiphyseal
blood vessel
Secondary
ossificaton
center
Medullary
cavity
Formation of
bone collar
around hyaline
cartilage model.
Cavitation of
the hyaline carti-
lage within the
Invasion of
internal cavities
by the periosteal
bud and spongy
bone formation.
Formation of the
medullary cavity as
ossification continues;
appearance of sec-
ondary ossification
centers in the epiphy-
ses in preparation
for stage 5. 1 2 3 4
Figure 6.8

17. Stages of Endochondral Ossification (long bones):
When secondary ossification is complete hyaline cartilage remains only in two locations:
Epiphyseal plates:
At the epiphysis-diaphysis junction
Articular cartilages:
At the epiphyseal surfaces

18. Stages of Endochondral Ossification
Formation of
bone collar
around hyaline
cartilage model.
Hyaline
cartilage
Cavitation of
the hyaline carti-
lage within the
Invasion of
internal cavities
by the periosteal
bud and spongy
bone formation.
Formation of the
medullary cavity as
ossification continues;
appearance of sec-
ondary ossification
centers in the epiphy-
ses in preparation
for stage 5.
Ossification of the
epiphyses; when
completed, hyaline
cartilage remains only
in the epiphyseal plates
and articular cartilages.
Deteriorating
matrix
Epiphyseal
blood vessel
Spongy
bone
formation
plate
Secondary
ossificaton
center
Blood
vessel of
periosteal
bud
Medullary
cavity
Articular
Primary
ossification
Bone collar 1 2 3 4 5
Figure 6.8

19. Bone Development and Growth (infants & youth)
Most bones stop growing during adolescence
Some bones (facial) continue to grow ex. (nose & lower jaw)
Growth in length is entirely by:
Interstitial (from inside) growth of epiphyseal plates
Growth in thickness (all bones) by:
Appositional (from outside) growth
Thickness of epiphyseal plates is maintained by a balance between :
Cartilage growth at epiphysis side
Bone replacement of cartilage at diaphysis side

20. Bone Development and Growth
Toward puberty the plates become thinner due to:
Less chondroblast division
More bone replacement
Longitudinal growth ends (epiphyseal closure) when:
The bone of the epiphysis and diaphysis fuses
Epiphyseal closures occurs at:
18 yr of age in females
21 yr of age in males

21. Hormonal Regulation of Bone Growth
During infancy and childhood:
Anterior pituitary growth hormone (GH):
Stimulates epiphyseal plate activity
Thyroid hormones:
Modulate GH activity
Maintain bone proportions

22. Hormonal Regulation of Bone Growth
During puberty:
Male & female hormones (testosterone & estrogens):
Are released in increased amounts
Initially, they:
Promote growth spurts (adolescence associated)
Masculinize & feminiz specific skeleton parts
Later, they:
Induce epiphyseal plate closure
End longitudinal bone growth

23. Bone Remodeling: Bone Deposition & Resorption
Occurs in adult skeleton
Involves two processes:
Bone deposition
Bone resorption (removal)
The processes are coupled & coordinated by:
Osteoblasts (deposition)
Osteoclasts (resorption)
Occurs at both:
Periosteum surface
Endosteum surface

24. Bone Resorption Accomplished by osteoclasts Osteoclasts are:
Multinucleated giant cells
Arise from hematopoietic stem cells (same as macrophages)
They move along bone surfaces digging grooves in matrix
Bone resorption by osteoclasts involves secretion of:
Lysosomal enzymes:
Digest organic matrix
Hydrochloric acid:
Converts calcium salts into soluble forms

25. Long Bone Growth and Remodeling
Figure 6.10

26. Break Slide
Biol2401.____
Wed, Feb ___, ’13

27. Importance of Ionic Calcium in the Body
Calcium is necessary for:
Transmission of nerve impulses
Muscle contraction
Blood coagulation
Glands & nerve cells secretion
Cell division

28. Two control loops regulate bone remodeling
Control of Remodeling
Two control loops regulate bone remodeling
Hormonal mechanism:
Maintains calcium homeostasis in the blood
Not to preserve the skeleton strength or well being
Bones serve as a storehouse for ionic calcium
Mechanical and gravitational forces :
Forces acting on the skeleton

29. Hormonal Mechanism: Falling blood Ca2+ levels signal: PTH signals:
The parathyroid glands
Parathyroid releases parathyroid hormone (PTH)
PTH signals:
Osteoclasts
Osteoclasts degrade bone matrix
Ca2+ is releases into the blood

30. Hormonal Mechanism (cont’d):
Rising blood Ca2+ level triggers:
Thyroid parafollicular cells (C cells)
Parafollicular cells release calcitonin
Calcitonin:
Inhibits bone resorption
stimulates calcium salt deposition in bone matrix
Most effective in children

31. Hormonal Control of Blood Ca
PTH;
calcitonin
secreted
Calcitonin
stimulates
calcium salt
deposit
in bone
Thyroid
gland
Rising blood
Ca2+ levels
Imbalance
Calcium homeostasis of blood: 9–11 mg/100 ml
Falling blood
Ca2+ levels
Imbalance
Thyroid
gland
Osteoclasts
degrade bone
matrix and release
Ca2+ into blood
Parathyroid
glands
Parathyroid
glands release
parathyroid
hormone (PTH)
PTH
Figure 6.11

32. Reading Assignment (The folllowing Slides)
Bone fractures
Common types of bone fracture
Homeostatic Imbalances
Osteomalacia (adult)
Rickets
Osteoporosis

33. Bone Fractures Bone fractures are classified by:
The position of the bone ends after fracture:
Nondisplaced:
bone ends retain their normal position
Displaced:
bone ends are out of normal alignment
The completeness of the break
Complete:
bone is broken all the way through
Incomplete:
bone is not broken all the way through

34. Bone Fractures (Breaks)
The orientation of the bone to the long axis
Linear:
the fracture is parallel to the long axis of the bone
Transverse:
the fracture is perpendicular to the long axis of the bone
Whether or not the bones ends penetrate the skin
Compound (open):
bone ends penetrate the skin
Simple (closed):
bone ends do not penetrate the skin

35. Common Types of Fractures
Comminuted:
bone fragments into three or more pieces
common in the elderly
Compression:
bone is crushed
common in porous bones

36. Common Types of Fractures
Table 6.2.1

37. Common Types of Fractures
Spiral:
ragged break when bone is excessively twisted
common sports injury
Epiphyseal:
epiphysis separates from diaphysis along epiphyseal line
occurs where cartilage cells are dying

38. Common Types of Fractures
Table 6.2.2

39. Common Types of Fractures
Depressed:
broken bone portion pressed inward
typical skull fracture
Greenstick:
incomplete fracture (one bone side breaks and the other bends)
common in children

40. Common Types of Fractures
Table 6.2.3

41. Homeostatic Imbalances
Osteomalacia (adult)
Soft and weak bones due to inadequate mineralization
Main symptom is pain when weight is put on the affected bone
Caused by:
Insufficient dietary calcium
Vitamin D deficiency

42. Homeostatic Imbalances
Rickets
Soft and weak bones of children (inadequately mineralized)
Bowed legs and deformed pelvis, skull, and rib cage
Caused by:
Insufficient dietary calcium
Vitamin D deficiency

43. Homeostatic Imbalances
Osteoporosis
Group of diseases
Bone resorption outpaces bone deposit
Matrix composition is normal; bone mass is reduced
Spongy bone of the spine is most vulnerable
Femur neck also susceptible
Most often in postmenopausal women
Bones become so fragile (sneezing or stepping off a curb can cause fractures)