4. Chapter 6 Bones and Skeletal Tissues
Part C
Bone Development and Growth

5. Ossification (Osteogenesis)
Bone Development
Ossification (Osteogenesis)
the process of bone tissue formation
Starts with the formation of the bony skeleton in 8 week old embryos as bone replaces cartilage and membranes

6. Bone Development
Bone grows in length until early adulthood (Bone growth)
Bone is capable of growing in thickness throughout life (by appostional growth)

7. Bone Development
In adults, ossification is mostly for remodeling, and repair
However, some facial bones, such as the nose and lower jaw, may continue to grow throughout life

8. Changes in the Human Skeleton
In embryos, the skeleton is made of fibrous membranes and hyaline cartilage
During development, much of the fibrous or cartilage structures are replaced by bone
Cartilage remains in isolated areas
Bridge of the nose
Parts of ribs
Joints

9. Formation of the Bony Skeleton
Intramembranous ossification – bone develops from a fibrous membrane
The bone called a membrane bone
Endochondral ossification – bone forms by replacing hyaline cartilage
The bone is called a cartilage bone

10. Intramembranous Ossification
Begins at the 8th week of development – All are flat bones
Formation of most of the flat bones of the skull and the clavicles
Fibrous connective tissue membranes are the structures on which ossification begins
Four Stages

11. Stages of Intramembranous Ossification
1. An ossification center appears in the fibrous connective tissue membrane

12. Stages of Intramembranous Ossification
2. Bone matrix (osteoid) is secreted within the fibrous membrane

13. Stages of Intramembranous Ossification
3. Woven bone (with trabeculae) and periosteum form
4. Bone collar of compact bone forms, and red marrow appears

14. Endochondral Ossification
Begins in the second month of development
Uses hyaline cartilage “bones” as models for bone construction
Requires breakdown of hyaline cartilage prior to ossification

15. Stages of Endochondral Ossification
Formation of bone collar
Cavitation of the hyaline cartilage
Invasion of internal cavities by the periosteal bud, and spongy bone forms – happens during the 3rd month

16. Stages of Endochondral Ossification
Formation of the medullary cavity; appearance of secondary ossification centers in the epiphyses
Secondary ossification centers appear right before or right after birth

17. Stages of Endochondral Ossification
Ossification of the epiphyses, with hyaline cartilage remaining only in the epiphyseal plates

18. Stages of Endochondral Ossification
Short bones will usually have just the primary ossification center
Irregular bones have several distinct secondary ossification centers
When complete, hyaline cartilage will remain in the epiphyseal plates and as articular cartilage

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

20. During infancy and youth
Bone Growth
During infancy and youth

21. Bone Growth During infancy and youth
During infancy and youth, long bones lengthen entirely by interstitial growth of the epiphyseal plates
All bones grow in thickness by appositional growth

22. Bone Growth of long bones During infancy and youth
Cells of the epiphyseal plate form three functionally different zones:
Growth zone
Transformation
osteogenic

23. Functional Zones in Long Bone Growth
Growth zone
cartilage cells undergo mitosis, pushing the epiphysis away from the diaphysis

24. Functional Zones in Long Bone Growth
Transformation zone
older cells enlarge, the matrix becomes calcified, cartilage cells die, and the matrix begins to deteriorate

25. Functional Zones in Long Bone Growth
Osteogenic zone
new bone formation occurs

26. Bone Growth
Epiphyseal plates allow for growth of long bone during childhood
New cartilage is continuously formed
Older cartilage becomes ossified
Cartilage is broken down
Bone replaces cartilage

27. Bone Growth Bones are remodeled and lengthened until growth stops
Epiphyseal plate become thinner and thinner until entirely replaced by bone tissue
Called epiphyseal plate closure
Happens about 18 in females and 21 in males

28. Long Bone Formation and Growth
Figure 5.4b
Slide 5.14b
Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings

29. Bone Growth In Adults Bones change shape somewhat
Bones can continue to grow in width by appositional growth
When stressed by excessive muscle activity or body weight

30. Hormonal Regulation of Bone Growth During Youth
During infancy and childhood, epiphyseal plate activity is stimulated by growth hormone

31. Hormonal Regulation of Bone Growth During Youth
During puberty, testosterone and estrogens:
Initially promote adolescent growth spurts
Cause masculinization and feminization of specific parts of the skeleton

32. Hormonal Regulation of Bone Growth During Youth
During puberty, testosterone and estrogens:
Later induce epiphyseal plate closure, ending longitudinal bone growth

33. Hormonal Regulation of Bone Growth During Youth
Excesses or deficits of any of these hormones can result in abnormal skeletal growth
Hypersecretion of growth hormone in children results in excessive height (gigantism)

34. World's Tallest Man 8' 11"

35. Hormonal Regulation of Bone Growth During Youth
Excesses or deficits of any of these hormones can result in abnormal skeletal growth
Deficits of growth hormone or thyroid hormone produce types of dwarfism

36. 23" tall Pituitary Dwarf

37. Quiz Next Time!
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38. Chapter 6 Bones and Skeletal Tissues
Part D
Bone Remodeling and Repair

39. Bones
We may picture bones as lifeless structures – like we see them in movie graveyards or hanging in front of our classroom – But this isn’t at all the truth!
Bones are very active, dynamic tissues!

40. Bone remodeling Changes in bone architecture occur continually
Every week we recycle 5 – 7% of our bone mass
A half a gram of calcium enters or leaves the adult skeleton each day

41. Bone remodeling Spongy bone is replaced every 3 to 4 years
Compact bone is replaced every 10 years

42. Types of Bone Cells Osteocytes Mature bone cells Osteoblasts
Bone-forming cells
Osteoclasts
Bone-destroying cells
Break down bone matrix for remodeling and release of calcium

43. Bone Remodeling
Bone remodeling is a process by both osteoblasts and osteoclasts
Remodeling units – adjacent osteoblasts and osteoclasts deposit and resorb bone at periosteal and endosteal surfaces

44. Bone Resorption Accomplished by osteoclasts
Resorption bays – grooves formed by osteoclasts as they break down bone matrix

45. Bone Resorption Resorption involves osteoclast secretion of:
Lysosomal enzymes that digest organic matrix
Acids that convert calcium salts into soluble forms

46. Bone Resorption
Dissolved matrix is transcytosed across the osteoclast’s cell where it is secreted into the interstitial fluid and then into the blood

47. Bone Deposition
Occurs where bone is injured or added strength is needed
Requires a diet rich in protein, vitamins C, D, and A, calcium, phosphorus, magnesium, and manganese

48. Bone Deposition
Alkaline phosphatase is essential for mineralization of bone
Sites of new matrix deposition are revealed by the:
Osteoid seam – unmineralized band of bone matrix
Calcification front – abrupt transition zone between the osteoid seam and the older mineralized bone

49. Control of Remodeling Two control loops regulate bone remodeling
Hormonal mechanism maintains calcium homeostasis in the blood
Mechanical and gravitational forces acting on the skeleton

50. Importance of Ionic Calcium in the Body
Calcium is necessary for:
Transmission of nerve impulses
Muscle contraction
Blood coagulation
Secretion by glands and nerve cells
Cell division

51. Homeostatic Imbalances of Ionic Calcium in the Body
When blood Ca2 are too low, severe neuromuscular problems may occur -like hyperexcitability

52. Homeostatic Imbalances of Ionic Calcium in the Body
When blood Ca2 are too high (hypercalcemia), nonresponsiveness and inability to function may occur
With hypercalcemia deposits of calcium may occur in blood vessels, kidneys, and other soft organs, which can lead them to stop functioning

53. Hormonal Mechanism
Rising blood Ca2+ levels trigger the thyroid to release calcitonin
Calcitonin stimulates calcium salt deposit in bone
Falling blood Ca2+ levels signal the parathyroid glands to release PTH
PTH signals osteoclasts to degrade bone matrix and release Ca2+ into the blood

54. Response to Mechanical Stress
Wolff’s law –
a bone grows or remodels in response to the forces or demands placed upon it

55. Response to Mechanical Stress
Observations supporting Wolff’s law include
Long bones are thickest midway along the shaft (where bending stress is greatest)
Curved bones are thickest where they are most likely to buckle

56. Response to Mechanical Stress
Trabeculae form along lines of stress
Large, bony projections occur where heavy, active muscles attach

57. Response to Mechanical Stress
Figure 6.13

58. Bone Repair

59. Bone Fractures (Breaks)
Bone fractures are classified by:
The position of the bone ends after fracture
The completeness of the break
The orientation of the break to the long axis of the bone
Whether or not the bones ends penetrate the skin

60. Types of Bone Fractures
Nondisplaced – bone ends retain their normal position
Displaced – bone ends are out of normal alignment

61. Types of Bone Fractures
Complete – bone is broken all the way through
Incomplete – bone is not broken all the way through

63. Types of Bone Fractures
Linear – the fracture is parallel to the long axis of the bone
Transverse – the fracture is perpendicular to the long axis of the bone

64. Types of Bone Fractures
Compound (open) – bone ends penetrate the skin
Simple (closed) – bone ends do not penetrate the skin

65. Common Types of Fractures
Comminuted – bone fragments into three or more pieces; common in the elderly
Spiral – ragged break when bone is excessively twisted; common sports injury

66. Common Types of Fractures
Depressed – broken bone portion pressed inward; typical skull fracture
Compression – bone is crushed; common in porous bones

67. Common Types of Fractures
Epiphyseal – epiphysis separates from diaphysis along epiphyseal line; occurs where cartilage cells are dying
Greenstick – incomplete fracture where one side of the bone breaks and the other side bends; common in children

68. Common Types of Fractures
Table 6.2.1

69. Common Types of Fractures
Table 6.2.2

70. Common Types of Fractures
Table 6.2.3

71. Stages in the Healing of a Bone Fracture
Hematoma formation
Torn blood vessels hemorrhage
A mass of clotted blood (hematoma) forms at the fracture site
Site becomes swollen, painful, and inflamed
Hematoma 1
Hematoma formation
Figure

72. Stages in the Healing of a Bone Fracture
Fibrocartilaginous callus forms
Granulation tissue (soft callus) forms a few days after the fracture
Capillaries grow into the tissue and phagocytic cells begin cleaning debris
External callus
New blood vessels
Internal callus (fibrous tissue and cartilage)
Spongy bone trabeculae 2
Fibrocartilaginous callus formation
Figure

73. Stages in the Healing of a Bone Fracture
The fibrocartilaginous callus forms when:
Osteoblasts and fibroblasts migrate to the fracture and begin reconstructing the bone
Fibroblasts secrete collagen fibers that connect broken bone ends

74. Stages in the Healing of a Bone Fracture
The fibrocartilaginous callus forms when:
Osteoblasts begin forming spongy bone
Osteoblasts furthest from capillaries secrete an externally bulging cartilaginous matrix that later calcifies

75. Stages in the Healing of a Bone Fracture
Bony callus formation
New bone trabeculae appear in the fibrocartilaginous callus
Fibrocartilaginous callus converts into a bony (hard) callus
Bony callus of spongy bone 3
Bony callus formation
Figure

76. Stages in the Healing of a Bone Fracture
Bony callus formation
Bone callus begins 3-4 weeks after injury, and continues until firm union is formed 2-3 months later
Bony callus of spongy bone 3
Bony callus formation
Figure

77. Stages in the Healing of a Bone Fracture
Bone remodeling
Excess material on the bone shaft exterior and in the medullary canal is removed
Compact bone is laid down to reconstruct shaft walls
Healing fracture 4
Bone remodeling
Figure

78. Clinical Advances in Bone Repair
Electrical stimulation of fraction sites
Increases speed of healing
Ultrasound treatments
Daily exposure to ultrasound reduces healing time of broken arms and legs by 35 to 45% by stimulating the production of the callus

79. Clinical Advances in Bone Repair
Bone grafts using the fibula
Grafts from hip bones often fail
Blood vessels are grafted with the fibula, having a better success rate
Bone graphs more successful in adults than children

80. Clinical Advances in Bone Repair
VEGF (vascular endothelial growth factor)
Protein that stimulates growth of blood vessels- speeds
Bone substitutes molded to the shape of desired bone or inserted into existing bone – replacing bone grafts

81. Clinical Advances in Bone Repair
Bone substitutes
May be crushed bone from cadavers
Small risk of hepatitis or HIV, or may be rejected
synthetic bone material
Can be rejected
Heat treated coral (to kill living coral cells) mixed with mineral salts of bone (calcium phosphate ) - new

82. Homeostatic Imbalances of Bone

83. Homeostatic Imbalances
Osteomalacia
Bones are inadequately mineralized causing softened, weakened bones
Main symptom is pain when weight is put on the affected bone
Caused by insufficient calcium in the diet, or by vitamin D deficiency

84. Homeostatic Imbalances
Rickets
Bones of children are inadequately mineralized causing softened, weakened bones
Bowed legs and deformities of the pelvis, skull, and rib cage are common
This is an xray of a child with bowed legs due to rickets (thanks to Dr. Mike Richardson)

85. Homeostatic Imbalances
Rickets
Caused by insufficient calcium in the diet, or by vitamin D deficiency
This is an xray of a child with bowed legs due to rickets (thanks to Dr. Mike Richardson)

86. Homeostatic Imbalances
Osteoporosis
Group of diseases in which bone reabsorption outpaces bone deposit
Spongy bone of the spine is most vulnerable

87. Homeostatic Imbalances
Osteoporosis
Occurs most often in postmenopausal women
Bones become so fragile that sneezing or stepping off a curb can cause fractures

88. Osteoporosis: Treatment
Calcium and vitamin D supplements
Increased weight-bearing exercise
Hormone (estrogen) replacement therapy (HRT) slows bone loss
Natural progesterone cream prompts new bone growth
Statins increase bone mineral density

89. Paget’s Disease
Characterized by excessive bone formation and breakdown
Pagetic bone with an excessively high ratio of woven to compact bone is formed

90. Paget’s Disease
Pagetic bone, along with reduced mineralization, causes spotty weakening of bone
Osteoclast activity wanes, but osteoblast activity continues to work

91. Paget’s Disease
Usually localized in the spine, pelvis, femur, and skull
Unknown cause (possibly viral)
Treatment includes the drugs Didronate and Fosamax

92. Developmental Aspects of Bones
Bones are on a precise schedule from the time they form until a person’s death

93. Developmental Aspects of Bones
Mesoderm gives rise to embryonic mesenchymal cells, which produce membranes and cartilages that form the embryonic skeleton
The embryonic skeleton ossifies in a predictable timetable that allows fetal age to be easily determined from sonograms

94. Developmental Aspects of Bones
At birth, most long bones are well ossified (except for their epiphyses)
Epiphyseal plates persist and provide long-bone growth during childhood
Epiphyseal plates provide the sex-hormone-mediated growth spurt at adolescence

95. Developmental Aspects of Bones
By age 25, nearly all bones are completely ossified and skeletal growth ceases
In children and adolescents, bone formation exceeds bone resorption
In young adults formation and resorption are balanced
In old age, bone resorption predominates

96. Developmental Aspects of Bones
A single gene that codes for vitamin D docking determines both the tendency to accumulate bone mass early in life, and the risk for osteoporosis later in life
In your 40’s bone mass will start decreasing with age, except bones in the skull

97. Developmental Aspects of Bones
In young adults skeletal mass is greater in males than females
With age, the rate of bone loss is faster in females than in males

98. Quiz Next time!
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