1. Bone Tissue Chapter 7 By Abdul Fellah, Ph.D.
Copyright (c) The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

2. Bone Tissue Tissues and organs of the skeletal system
Histology of osseous tissue
Bone development
Physiology of osseous tissue
Bone disorders

3. Bone as a Tissue
Connective tissue with a matrix hardened by minerals (calcium phosphate)
Individual bones consist of bone tissue, marrow, blood, cartilage and periosteum
Continually remodels itself
Functions of the skeletal system
support, protection, movement, electrolyte balances, acid-base balance and blood formation

4. Shapes of Bones Long bones – levers acted upon by muscles
Short bones – glide across one another in multiple directions
Flat bones – protect soft organs
Irregular bones

5. General Features of Bones
Shaft (diaphysis) = cylinder of compact bone
marrow cavity (medullary cavity) lined with endosteum (osteogenic cells and reticular connective tissue)
Enlarged ends (epiphyses)
spongy bone covered by compact bone
enlarged to strengthen joint and attach ligaments
Joint surface covered with articular cartilage
Shaft covered with periosteum
outer fibrous layer of collagen
inner osteogenic layer of bone forming cells
Epiphyseal plate (growth plate)

6. Structure of a Long Bone
Compact and spongy bone
Marrow cavity
Articular cartilage
Periosteum

7. Structure of a Flat Bone
External and internal surfaces composed of compact bone
Middle layer is spongy bone and bone marrow
Skull fracture may leave inner layer of compact bone unharmed

8. Cells of Osseous Tissue (1)
Osteogenic cells in endosteum, periosteum or central canals give rise to new osteoblasts
arise from embryonic fibroblasts
multiply continuously
Osteoblasts mineralize organic matter of matrix
Osteocytes are osteoblasts trapped in the matrix they formed
cells in lacunae connected by gap junctions inside canaliculi

9. Cells of Osseous Tissue (2)
Osteoclasts develop in bone marrow by fusion of 3-50 stem cells
Reside in pits that they ate into the bone

10. Matrix of Osseous Tissue
Dry weight = 1/3 organic and 2/3 inorganic matter
Organic matter
collagen, glycosaminoglycans, proteoglycans and glycoproteins
Inorganic matter
85% hydroxyapatite
10% calcium carbonate
other minerals (fluoride, potassium, magnesium)
Combination provides for strength and resilience
minerals resist compression; collagen resists tension
bone adapts by varying proportions

11. Histology of Compact Bone

12. Compact Bone Osteon = basic structural unit
cylinders formed from layers (lamellae) of matrix around central canal (osteonic canal)
collagen fibers alternate between right- and left-handed helices from lamella to lamella
osteocytes connected to each other and their blood supply by tiny cell processes in canaliculi
Perforating canals or Volkmann canals
vascular canals perpendicularly joining central canals

13. Blood Vessels of Bone

14. Spongy Bone
Spongelike appearance formed by plates of bone called trabeculae
spaces filled with red bone marrow
Trabeculae have few osteons or central canals
no osteocyte is far from blood of bone marrow
Provides strength with little weight
trabeculae develop along bone’s lines of stress

15. Spongy Bone Structure and Stress

16. Bone Marrow
In medullary cavity (long bone) and among trabeculae (spongy bone)
Red marrow like thick blood
reticular fibers and immature cells
Hemopoietic (produces blood cells)
in vertebrae, ribs, sternum, pelvic girdle and proximal heads of femur and humerus in adults
Yellow marrow
fatty marrow of long bones in adults
Gelatinous marrow of old age
yellow marrow replaced with reddish jelly

17. Intramembranous Ossification
Condensation of mesenchyme into trabeculae
Osteoblasts on trabeculae lay down osteoid tissue (uncalcified bone)
Calcium phosphate is deposited in the matrix forming bony trabeculae of spongy bone
Osteoclasts create marrow cavity
Osteoblasts form compact bone at surface
Surface mesenchyme produces periosteum

18. Intramembranous Ossification 1
Produces flat bones of skull and clavicle.

19. Intramembranous Ossification 2
Note the periosteum and osteoblasts.

20. Stages of Endochondral Ossification

21. Endochondral Ossification 1
Bone develops from pre-existing model
perichondrium and hyaline cartilage
Most bones develop this process
Formation of primary ossification center and marrow cavity in shaft of model
bony collar developed by osteoblasts
chondrocytes swell and die
stem cells give rise to osteoblasts and clasts
bone laid down and marrow cavity created

22. Primary Ossification Center and Primary Marrow Cavity

23. Endochondral Ossification 2
Secondary ossification centers and marrow cavities form in ends of bone
same process
Cartilage remains as articular cartilage and epiphyseal (growth) plates
growth plates provide for increase in length of bone during childhood and adolescence
by early twenties, growth plates are gone and primary and secondary marrow cavities united

24. Secondary Ossification Centers and Secondary Marrow Cavities

25. Fetal Skeleton at 12 Weeks

26. The Metaphysis Zone of reserve cartilage = hyaline cartilage
Zone of proliferation
chondrocytes multiply forming columns of flat lacunae
Zone of hypertrophy = cell enlargement
Zone of calcification
mineralization of matrix
Zone of bone deposition
chondrocytes die and columns fill with osteoblasts
osteons formed and spongy bone is created

27. Reserve Cart.
Endrochondral Ossification: TRANSITIONAL ZONE

28. Bone Growth and Remodeling
Bones increase in length
interstitial growth of epiphyseal plate
epiphyseal line is left behind when cartilage gone
Bones increase in width = appositional growth
osteoblasts lay down matrix in layers on outer surface and osteoclasts dissolve bone on inner surface
Bones remodeled throughout life
Wolff’s law of bone = architecture of bone determined by mechanical stresses
action of osteoblasts and osteoclasts
greater density and mass of bone in athletes or manual worker is an adaptation to stress

29. Bone Growth: in Length (childhood)
Zone of ‘Resting’ Cartilage (i.e., not functioning in bone growth, but mitotic)
Nearest epiphysis
Small, scattered chondrocytes doing normal work; anchor E. plate to bone
Zone of Proliferating Cartilage:
Slightly larger chondrocytes arranged in columns
Chondrocytes mitose to replace cells dying at diaphyseal side
Zone of Hypertrophic Cartilage:
Chondrocytes hypertrophy (grow in size), accumulate glycogen (carbohydrate),
Matrix between cells narrows (lacunae getting larger, walls thinner forming hollow columns)

30. Bone Growth: in Length (childhood)
Zone of Calcified Cartilage:
Dead chondrocytes (matrix has calcified; can’t get food/oxygen)
Zone of Bone Deposition
Bone/marrow invades spaces
Chondroclasts invade, disolve calcified cartilage
Osteoblasts lay down osteoid to replace cartilage
Bone eventually is remodeled (layers deposted toward center, so old lamellae are on periphery of osteon)
Epiphyseal plates close (~ years old); process stops; plate  line

32. Dwarfism Achondroplastic Pituitary
long bones stop growing in childhood
normal torso, short limbs
spontaneous mutation during DNA replication
failure of cartilage growth
Pituitary
lack of growth hormone
normal proportions with short stature

33. Bone Growth: in Width - Appositional Growth (forever)
Only way mature bones can grow
Process ~ to intramembranous ossification
Osteogenic cells in periosteum differentiate into osteoblasts which
Secrete osteoid which
Calcifies (osteoblasts become osteocytes)
Ridges form around BV
Ridges fold together & fuse; groove becomes a tunnel that encloses the BV

34. Bone Growth: in Width - Appositional Growth (forever)
Periosteum now is endosteum (note: this is a similar process to forming neural tube in early embryonic development)
Osteoblasts form lamellae (process moves inward)
Results in creation of new osteon
Osteoblasts deep to periosteum simultaneously form circumferential lamellae, so more thickness
Process is dependent on presence of Ca, P, other ions, Vit C (synthesis of collagen etc.), Vit. K, B12 (needed for protein synthesis), Vit A (stimulates osteoblasts)

35. Mineral Deposition Mineralization is crystallization process
osteoblasts produce collagen fibers spiraled the length of the osteon
minerals cover the fibers and harden the matrix
ions (calcium and phosphate and from blood plasma) are deposited along the fibers
ion concentration must reach the solubility product for crystal formation to occur
Abnormal calcification (ectopic)
may occur in lungs, brain, eyes, muscles, tendons or arteries (arteriosclerosis)

36. Mineral Resorption from Bone
Bone dissolved and minerals released into blood
performed by osteoclasts “ruffled border”
hydrogen pumps in membrane secrete hydrogen into space between the osteoclast and bone surface
chloride ions follow by electrical attraction
hydrochloric acid (pH 4) dissolves bone minerals
enzyme (acid phosphatase) digests the collagen
Dental braces reposition teeth and remodel bone
create more pressure on one side of the tooth
stimulates osteoclasts to remove bone
decreased pressure stimulates osteoblasts

37. Calcium and Phosphate
Phosphate is component of DNA, RNA, ATP, phospholipids, and pH buffers
~750 g in adult skeleton
plasma concentration is ~ 4.0 mg/dL
2 plasma forms: HPO4 -2 and H2PO4-
Calcium needed in neurons, muscle contraction, blood clotting and exocytosis
~1100g in adult skeleton
plasma concentration is ~ 10 mg/dL

38. Ion Imbalances Changes in phosphate levels = little effect
Changes in calcium can be serious
hypocalcemia is deficiency of blood calcium
causes excitability of nervous system if too low
muscle spasms, tremors or tetany ~6 mg/dL
laryngospasm and suffocation ~4 mg/dL
with less calcium, sodium channels open more easily, sodium enters cell and excites neuron
hypercalcemia is excess of blood calcium
binding to cell surface makes sodium channels less likely to open, depressing nervous system
muscle weakness and sluggish reflexes, cardiac arrest ~12 mg/dL
Calcium phosphate homeostasis depends on calcitriol, calcitonin and PTH hormone regulation

39. Carpopedal Spasm
Hypocalcemia demonstrated by muscle spasm of hands and feet.

40. Hormonal Control of Calcium Balance
Calcitriol, PTH and calcitonin maintain normal blood calcium concentration.

41. Calcitriol (Activated Vitamin D)
Produced by the following process
UV radiation and epidermal keratinocytes convert steroid derivative to cholecalciferol - D3
liver converts it to calcidiol
kidney converts that to calcitriol (vitamin D)
Calcitriol behaves as a hormone that raises blood calcium concentration
increases intestinal absorption and absorption from the skeleton
increases stem cell differentiation into osteoclasts
promotes urinary reabsorption of calcium ions
Abnormal softness (rickets) in children and (osteomalacia) in adults without vitamin D

42. Calcitriol Synthesis and Action

43. Calcitonin
Secreted (C cells of thyroid gland) when calcium concentration rises too high
Functions
reduces osteoclast activity as much as 70%
increases the number and activity of osteoblasts
Important in children, little effect in adults
osteoclasts more active in children
deficiency does not cause disease in adults
Reduces bone loss in osteoporosis

44. Correction for Hypercalcemia

45. Parathyroid Hormone Glands on posterior surface of thyroid
Released with low calcium blood levels
Function = raise calcium blood level
causes osteoblasts to release osteoclast-stimulating factor (RANKL) increasing osteoclast population
promotes calcium resorption by the kidneys
promotes calcitriol synthesis in the kidneys
inhibits collagen synthesis and bone deposition by osteoblasts
Sporatic injection of low levels of PTH causes bone deposition

46. Correction for Hypocalcemia

47. Other Factors Affecting Bone
Hormones, vitamins and growth factors
Growth rapid at puberty
hormones stimulate osteogenic cells, chondrocytes and matrix deposition in growth plate
girls grow faster than boys and reach full height earlier (estrogen stronger effect)
males grow for a longer time and taller
Growth stops (epiphyseal plate “closes”)
teenage use of anabolic steroids = premature closure of growth plate and short adult stature

48. Fractures and Their Repair
Stress fracture caused by trauma
car accident, fall, athletics, etc
Pathological fracture in bone weakened by disease
bone cancer or osteoporosis
Fractures classified by structural characteristics
break in the skin
multiple pieces

49. Types of Bone Fractures

50. Healing of Fractures 1 Normally 8 - 12 weeks (longer in elderly)
Stages of healing
fracture hematoma (1) - clot forms, then osteogenic cells form granulation tissue
soft callus (2)
fibroblasts produce fibers and fibrocartilage
hard callus (3)
osteoblasts produce a bony collar in 6 weeks
remodeling (4) in 3 to 4 months
spongy bone replaced by compact bone

51. Healing of Fractures 2

52. Treatment of Fractures
Closed reduction
fragments are aligned with manipulation and casted
Open reduction
surgical exposure and repair with plates and screws
Traction risks long-term confinement to bed
Electrical stimulation used on fractures
if 2 months necessary for healing
Orthopedics = prevention and correction of injuries and disorders of the bones, joints and muscles

53. Fractures and Their Repairs

54. Osteoporosis 1
Bones lose mass and become brittle (loss of organic matrix and minerals)
risk of fracture of hip, wrist and vertebral column
complications (pneumonia and blood clotting)
Postmenopausal white women at greatest risk
by age 70, average loss is 30% of bone mass
black women rarely suffer symptoms

55. Osteoporosis 2
Estrogen maintains density in both sexes (inhibits resorption)
testes and adrenals produce estrogen in men
rapid loss after menopause, if body fat too low or with disuse during immobilizaton
Treatment
ERT slows bone resorption, but increases risk breast cancer, stroke and heart disease
PTH slows bone loss if given daily injection
Forteo increases density by 10% in 1 year
may promote bone cancer
best treatment is prevention -- exercise and calcium intake (1000 mg/day) between ages 25 and 40

56. Spinal Osteoporosis