1. Bones and Skeletal Tissues6
P A R T B
Bones and Skeletal Tissues

2. Bone Growth & Development
Figure 6.15

3. 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
At birth, most long bones are well ossified (except for their epiphyses)

4. Developmental Aspects of Bones
By age 25, nearly all bones are completely ossified
In old age, bone resorption predominates
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

5. Bone Development
Osteogenesis (aka ossification) – the process of bone tissue formation, which leads to:
The formation of the bony skeleton in embryos
Bone growth until early adulthood
Bone thickness, remodeling, and repair

6. Formation of the Bony Skeleton
Begins at week 8 of embryo development – two different types of bone formation:
Intramembranous ossification – bone develops from inside a fibrous membrane – occurs in flat and irregular bones
Endochondral ossification – bone forms by replacing hyaline cartilage – occurs in long and short bones

7. Intramembranous Ossification
Formation of most of the flat bones of the skull and the clavicles
Fibrous connective tissue membranes are formed by mesenchymal cells

8. Stages of Intramembranous Ossification
An ossification center appears in the fibrous connective tissue membrane
Bone matrix is secreted within the fibrous membrane
Woven bone (precursor to spongy bone) and periosteum form
Bone collar of compact bone forms, and red marrow appears

9. Stages of Intramembranous Ossification
Figure 6.7.1

10. Stages of Intramembranous Ossification
Figure 6.7.2

11. Stages of Intramembranous Ossification
Figure 6.7.3

12. Stages of Intramembranous Ossification
Figure 6.7.4

13. Endochondral Ossification
Begins in the second month of development
Uses patterns made of hyaline cartilage as models for bone construction
Most bones are formed by this process
Requires breakdown of hyaline cartilage prior to ossification, so more complex than intramembranous ossification

14. 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

15. Summary of Endochondral Ossification
1. Hyaline cartilage model
2. Compact bone from periosteum surrounds diaphysis in a bone collar
3. Primary Ossification Center in diaphysis converts cartilage into spongy bone
4. Core of P.O.C. eroded to make medullary cavity
5. Secondary Ossification Centers in epiphyses convert cartilage into spongy bone
6. Location where P.O.C meets S.O.C is the epiphyseal plate: cartilage remains here to allow the bones to continue growing with age

16. Stages of Endochondral Ossification I
1. Perichondrium converted to periosteum by increased nutrition from blood vessels
2. Formation of bone collar: osteoblasts in periosteum secrete osteoid, which surrrounds diaphysis in a collar of compact bone
3. Cavitation of the hyaline cartilage: Chondrocytes in the center of the diaphysis die, opening up cavities in the developing bone – this will become the Primary Ossification Center. Meanwhile, cartilage keeps growing at the epiphyses of the bone, increasing its length

17. Stages of Endochondral Ossification II
4. Periosteal bud invades the internal cavities, bringing arteries, veins, nerves, osteoblasts, and osteoclasts. This converts the cartilage and its cavities into spongy bone.
5. Formation of the medullary cavity by osteoclasts, which break down the spongy bone from the inside out.
6. Appearance of secondary ossification centers in the epiphyses: cartilage cavitated and replaced with spongy bone by periosteal bud (this occurs around birth)
7. Ossification of the epiphyses, with hyaline cartilage remaining only in the epiphyseal plates and on the articular surface of the epiphyses

18. Stages of Endochondral Ossification
Hyaline
cartilage
Primary
ossification
center
Bone collar
Formation of
bone collar
around hyaline
cartilage model. 1
Figure 6.8

19. 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

20. 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

21. 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

22. Stages of Endochondral Ossification
Epiphyseal
plate
cartilage
Articular
Spongy
bone
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.
Ossification of the
epiphyses; when
completed, hyaline
cartilage remains only
in the epiphyseal plates
and articular cartilages. 1 2 3 4 5
Figure 6.8

23. 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

24. Growth in length of long bones
Postnatal Bone Growth
Growth in length of long bones
Cartilage on the side of the epiphyseal plate closest to the epiphysis is relatively inactive
Cartilage on the diaphysis side of the epiphyseal plate organizes into a pattern that allows fast, efficient growth
Cells of the epiphyseal plate form zones: resting, growth, transformation, and osteogenic

25. Functional Zones in Long Bone Growth
Figure 6.9

26. Functional Zones in Long Bone Growth
Growth zone or proliferation zone – cartilage cells undergo mitosis, pushing the epiphysis away from the diaphysis
Transformation zone includes 2 sub regions – first, in the hypertrophic zone, older cartilage cells enlarge, second, in the calcification zone, the matrix becomes calcified, cartilage cells die, and the cartilage matrix begins to deteriorate
Osteogenic zone or ossification zone – new bone formation occurs as osteoblasts deposit bone matrix

27. Long Bone Growth
Growth in length – cartilage continually grows and is replaced by bone at the epiphyseal plates
Growth in width – intramembranous ossification occurs under the periosteum
Bone growth ends around age 18 in females and age 21 in males. The cartilage in the epiphyseal plates is completely replaced with bone, leaving an epiphyseal line. This event is known as epiphyseal plate closure.

28. Hormonal Regulation of Bone Growth During Youth
During infancy and childhood, epiphyseal plate activity is stimulated by HGH (Human Growth Hormone)
During puberty, testosterone and estrogens:
Initially promote adolescent growth spurts
Cause masculinization and feminization of specific parts of the skeleton
Later induce epiphyseal plate closure, ending longitudinal bone growth

29. Bone Remodeling
Remodeling (changing the bone shape) – old bone is resorbed by osteoclasts and new bone is added by osteoblasts – constant balance between resorption vs. deposition of bone matrix.
Remodeling units – adjacent osteoblasts and osteoclasts deposit and resorb bone at periosteal and endosteal surfaces

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

31. Long Bone Growth vs. Remodeling
Figure 6.10

32. 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
An enzyme called alkaline phosphatase is essential for mineralization of bone

33. Sites of new matrix deposition are revealed by the:
Bone Deposition
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

34. Bone Resorption Accomplished by osteoclasts
Resorption bays – grooves formed by osteoclasts as they break down bone matrix
Resorption involves osteoclast secretion of:
1. Lysosomal enzymes that digest organic matrix
2. Acids that convert calcium salts into soluble forms
Dissolved matrix is transcytosed across the osteoclast’s cell where it is secreted into the interstitial fluid and then into the blood

35. Calcium Balance

36. Roles of Calcium in the Body
Along with bone formation, Calcium is necessary for:
Transmission of nerve impulses
Muscle contraction
Blood coagulation/ clotting
Secretion by glands and nerve cells
Cell division

37. Hormonal Mechanism of Calcium Balance
PTH (parathyroid hormone) is the main hormone responsible for Ca2+ homeostasis – Calcitonin also contributes, but most in children
Falling blood Ca2+ levels signal the parathyroid glands to release PTH (parathyroid hormone)
PTH signals osteoclasts to degrade bone matrix and release Ca2+ into the blood
Rising blood Ca2+ levels slow PTH release and trigger the thyroid to release calcitonin
Calcitonin stimulates calcium salt deposition in bone (osteoblasts are activated)

38. Hormonal Mechanism
Thyroid
Parathyroid

39. Hormonal Control of Blood Ca
PTH drops;
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

40. Hormonal Control of Blood Ca
Rising blood
Ca2+ levels
Imbalance
Calcium homeostasis of blood: 9–11 mg/100 ml
Imbalance
Figure 6.11

41. Hormonal Control of Blood Ca
Thyroid
gland
Rising blood
Ca2+ levels
Imbalance
Calcium homeostasis of blood: 9–11 mg/100 ml
Imbalance
Figure 6.11

42. Hormonal Control of Blood Ca
PTH;
calcitonin
secreted
PTH drops;
Thyroid
gland
Rising blood
Ca2+ levels
Imbalance
Calcium homeostasis of blood: 9–11 mg/100 ml
Imbalance
Figure 6.11

43. Hormonal Control of Blood Ca
PTH;
calcitonin
secreted
PTH drops;
PTH;
calcitonin
secreted
Calcitonin
stimulates
calcium salt
deposit
in bone
Thyroid
gland
Rising blood
Ca2+ levels
Calcium homeostasis of blood: 9–11 mg/100 ml
Figure 6.11

44. Hormonal Control of Blood Ca
Imbalance
Calcium homeostasis of blood: 9–11 mg/100 ml
Falling blood
Ca2+ levels
Imbalance
Figure 6.11

45. Hormonal Control of Blood Ca
Imbalance
Calcium homeostasis of blood: 9–11 mg/100 ml
Falling blood
Ca2+ levels
Imbalance
Thyroid
gland
Parathyroid
glands
Parathyroid
glands release
parathyroid
hormone (PTH)
Figure 6.11

46. Hormonal Control of Blood Ca
Imbalance
Calcium homeostasis of blood: 9–11 mg/100 ml
Falling blood
Ca2+ levels
Imbalance
Thyroid
gland
Parathyroid
glands
Parathyroid
glands release
parathyroid
hormone (PTH)
PTH
Figure 6.11

47. Hormonal Control of Blood Ca
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

48. Hormonal Control of Blood Ca
Calcium homeostasis of blood: 9–11 mg/100 ml
Falling blood
Ca2+ levels
Thyroid
gland
Osteoclasts
degrade bone
matrix and release
Ca2+ into blood
Parathyroid
glands
Parathyroid
glands release
parathyroid
hormone (PTH)
PTH
Figure 6.11

49. Hormonal Control of Blood Ca
PTH drops;
calcitonin
secreted
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

50. Bone Injuries and Diseases

51. Response to Mechanical Stress
Wolff’s law – a bone grows or remodels in response to the forces or demands placed upon it
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
Trabeculae form along lines of stress
Large, bony projections occur where heavy, active muscles attach

52. Response to Mechanical Stress
Figure 6.12

53. 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 fracture to the long axis
Whether or not the bone’s ends penetrate the skin
Some breaks are considered specialty fractures

54. Position of bone ends:
Nondisplaced – bone ends retain their normal position
Displaced – bone ends are out of normal alignment

55. Completeness of Fracture
Complete – bone is broken all the way through
Incomplete – bone is not broken all the way through

56. Orientation of Fracture
Linear – the fracture is parallel to the long axis of the bone
Transverse – the fracture is perpendicular to the long axis of the bone

57. Skin Penetration
Compound (open) – bone ends penetrate the skin
Simple (closed) – bone ends do not penetrate the skin

58. Specialty Fractures I
Comminuted – bone fragments into three or more pieces; common in the elderly
Spiral – ragged break when bone is excessively twisted; common sports injury
Depressed – broken bone portion pressed inward; typical skull fracture

59. Specialty Fractures II
Compression – bone is crushed; common in porous bones
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

60. Common Types of Fractures
Table 6.2.1

61. Common Types of Fractures
Table 6.2.2

62. Common Types of Fractures
Table 6.2.3

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

64. Stages in the Healing of a Bone Fracture
2. 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
Figure

65. Stages in the Healing of a Bone Fracture
2. (Continued)
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
Osteoblasts begin forming spongy bone
Osteoblasts furthest from capillaries secrete an externally bulging cartilaginous matrix that later calcifies

66. Stages in the Healing of a Bone Fracture
3. Bony callus formation
New bone trabeculae appear in the fibrocartilaginous callus
Fibrocartilaginous callus converts into a bony (hard) callus
Bone callus begins 3-4 weeks after injury, and continues until firm union is formed 2-3 months later
Figure

67. Stages in the Healing of a Bone Fracture
4. 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
Figure

68. 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

69. 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
Caused by insufficient calcium in the diet, or by vitamin D deficiency

70. Isolated Cases of Rickets
Rickets has been essentially eliminated in the US
Only isolated cases appear
Example: Infants of breastfeeding mothers deficient in Vitamin D will also be Vitamin D deficient and develop rickets

71. Homeostatic Imbalances
Osteoporosis
Group of diseases in which bone reabsorption outpaces bone deposit
Spongy bone of the spine is most vulnerable
Occurs most often in postmenopausal women
Bones become so fragile that sneezing or stepping off a curb can cause fractures

72. 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

73. Paget’s Disease
Characterized by excessive bone formation and breakdown
Pagetic bone with an excessively high ratio of woven to compact bone is formed
Pagetic bone, along with reduced mineralization, causes spotty weakening of bone
Osteoclast activity wanes, but osteoblast activity continues to work

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