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 Bone composed of numerous tissue types:
– cartilage
– dense connective tissue
– epithelium
– blood-forming, adipose, & nervous tissues
 Each individual bone is an organ
 Bone, along with cartilage, makes up skeletal system
 Dynamic tissue: ever-changing throughout life
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 Support
 Protection of soft tissues
 Movement
 Mineral homeostasis
 Blood cell production in red bone marrow
 Energy (TG) storage in yellow bone marrow
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Anatomy of Long Bone
 Diaphysis = shaft
 Epiphysis = distal & proximal ends
 Metaphyses = where epiphysis & diaphysis meet
– epiphyseal plate in growing bone
 layer of hyaline cartilage
 Articular cartilage over joint surfaces ↓ friction & shock
 Medullary cavity = marrow cavity w/in diaphysis
 Periosteum = tough membrane covering bone
– enables widthwise growth
– assists in fracture repair
– nourishes bone
– attachmt point for tendons/ligaments
 Endosteum = lining of marrow cavity
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 Inorganic salts & minerals within matrix
– Hydroxyapatite & calcium carbonate
– Mg +2 , K + , SO
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-2 , F -
 Salts deposited in a framework of collagen fibers during calcification ( mineralization)
– Occurs only in the presence of collagen fibers
– Mineral salts give hardness to bone
– Collagen fibers give tensile strength
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1.
Osteogenic cells
• undergo cell division
• develop into osteoblasts
2.
Osteoblasts = bone-building cells
3.
Osteocytes
• mature bone cells
• principal cells of bone tissue
4.
Osteoclasts
• derived from monocytes
• break down bone tissue (resorption)
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 Inorganic mineral salts provide hardness
– hydroxyapatite (CaPO
4
+ Ca(OH)
2
) & CaCO
3
 Collagen fibers provide flexibility
– their tensile strength resists being stretched or torn
 Bone is not completely solid  has small spaces for vessels & red bone marrow
– spongy bone has many such spaces
– compact bone has very few such spaces
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 Arranged in units called osteons or Haversian systems
 Osteons contain:
– blood & lymphatic vessels
– nerves
– osteocytes
– calcified matrix
 Osteons aligned in same direction along stress lines
– lines can slowly change as the stresses on bone change
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 Looks like solid, hard layer of bone
 Shaft of long bones & external layer of all bones
 Resists stresses produced by weight & movement
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Histology of Compact Bone
 Osteon = concentric rings (lamellae) of calcified matrix surrounding vertically oriented blood vessel
 Osteocytes found in lacunae
 Osteocytes communicate through canaliculi filled with ECF
– Canaliculi connect cells
 Interstitial lamellae represent older osteons that were partially removed during bone remodeling
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 Does not contain osteons
 Consists of trabeculae surrounding many red marrow-filled spaces (Figure 6.3b)
 Most of structure of short, flat, & irregular bones
 Epiphyses of long bones
 Lightweight
 Supports & protects red bone marrow
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 Oriented along lines of stress & where stress applied from many directions, but not in areas of high stress
 Spaces between trabeculae are filled with red marrow where blood cells develop
 Lacunae contain osteocytes
– Directly nourished by blood in medullary cavities
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 Highly vascularized & innervated
 Periosteal arteries enter diaphysis thru Volkmans canal
– supply periosteum
 Nutrient arteries
– enter thru nutrient foramen in center of diaphysis
– supply compact bone of diaph., spongy bone,
& red marrow up to epiphys. plates
 Metaphys & epiphyseal arteries
– enter thru meta-/epiphysis
– supply red marrow & bone tissue of meta-
/epiphyses 13

 Veins carry blood away from long bones
– Nutrient veins accompany nutr. artery in diaphy.
– Numerous epiphyseal/metaphyseal veins
 exit thru epiphyses
– Periosteal arteries exit thru perisoteum
 Nerves accompany blood vessels
– Sensory nerves in periosteum
 REMEMBER: Arteries carry oxygenated blood FROM the heart to the tissues (bone)
& veins carry deoxygenated blood from the tissues TO the heart.
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 Osteogenesis or ossification
 Begins when mesenchymal cells provide template for subsequent ossification
 Two types of ossification:
– Intramembranous ossification = formation of bone directly within mesenchyme
 arranged in sheetlike layers
 resemble membranes
– Endochondral ossification = formation of bone from hyaline cartilage that develops from mesenchyme
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 Forms flat bones of skull and mandible
1) Formation of ossification center
• mesenchymal cells differentiate into osteogenic cells
& then into osteoblasts
• osteoblasts secrete XC matrix until surrounded by it
2) Calcification
• matrix secretion stops
 osteoblast becomes osteocyte
• Ca & other minerals deposited  calcification
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3) Trabeculae formation
• XC matrix centers join to form bridges of trabeculae that constitute spongy bone
• blood vessels fill spaces btwn trabeculae
• CT develops into red bone marrow
4) Formation of periosteum
• mesenchyme condenses at outer edge & becomes periosteum
• thin layer of compact bone covers spongy bone center
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 Replacement of cartilage by bone
 Forms most bones of the body
1) Formation of cartilage model
• Mesenchymal cells cluster in shape of future bone & develop into chondroblasts
• Chondroblasts secrete cartilage ECM  form cartilage model
• Perichondrium formation
2) Growth of cartilage model
• Chondrocytes continually divide  growth in length
(interstitial)
• Addition of ECM from chondroblasts in perichond.
 growth in thickness (appositional)
• Chondrocytes in mid-region hyptertrophy & calcify
• Other chondrocytes die  form lacunae 18

3) Development of Primary Ossification Center
– proceeds inward from external surface of bone
– nutrient artery stimulates differentiation of osteogenic cells in perichondrium into osteoblasts
 penetrates perichondrium thru ctr of cartilage model
– perichondrium becomes periosteum
– @ ctr of model, periosteal capillaries grow & stimulate growth of prim. ossific. ctr
 where bone will replace most of cartilage
– osteoblasts deposit bone matrix over calcified cartilage
 form spongy bone trabeculae
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4) Development of medullary cavity
• Osteoclasts break down some of newly formed spongy bone trabeculae
• Resultant cavity in diaphysis becomes medullary (marrow) cavity
• Wall of diaphysis eventually replaced by compact bone
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5) Development of secondary ossification center
– Formed @ birth when epiphyseal artery enters epiphyses
– Spongy bone remains @ center of epiphyses
 No formation of medullary cavity (as in 1 ° ossification)
– Proceeds outward from center of epiphysis to outer surface
6) Formation of articular cartilage & growth plates
– Hyaline cartilage covering epiphyses becomes articular cartilage
– Epiphyseal plates responsible for lengthwise growth of long bones
 When growth plates “close,” growth stops
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 Radioactive tracer is given intravenously
 Amount of uptake is related to amount of blood flow to the bone
 “Hot spots” are areas of increased metabolic activity that may indicate cancer, abnormal healing or growth
 “Cold spots” indicate decreased metabolism of decalcified bone, fracture or bone infection
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 Two types
– Appositional (↑ in thickness)
 All bones
– Lengthwise
 Long bones
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 Epiphyseal plate consists of four zones:
1) Zone of resting cartilage
• Nearest epiphysis
• Scattered chondrocytes
 Do not function in bone growth
 Anchor epiphyseal plate to epiphysis
2) Zone of proliferation cartilage
• Chondrocytes divide  replace dying chondrocytes
3) Zone of hypertrophic cartilage  large chondrocytes
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4) Zone of calcified cartilage
• Dead chondrocytes  ECM has calcified
• Osteoclasts dissolve calcified cartilage
• Osteoblasts lay down bone ECM
 Replace calcified cartilage  become “new diaphysis”
 Activity of epiphyseal plate = only means by which diaphysis can increase in length
– New chondrocytes formed on epiphys side of plate
– Old chondrocytes on diaphys side replaced by bone
– Thickness remains constant, growth in length occurs
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 Closure of epiphyseal plate = completion of growth in length
– Epiphyseal line forms
– Damage to epiphyseal plate accelerates closure
 Between ages 18 & 25, epiphyseal plates close
– Females: about age 18
– Males: about age 21
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 Appositional growth
 Four steps in this process:
1) Periosteal cells differentiate into osteoblasts
 secrete collagen fibers & other substances
 osteoblasts become surrounded by ECM  osteocytes
2) Ridges fuse to form canal for blood vessels
 periosteum becomes endosteum
3) New concentric lamellae formed when osteoblasts in endosteum deposit bone ECM  inward
4) As new osteon forms, osteoblasts under periosteum form new outer lamellae
 Repetition of step 2  growth continues
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 Ongoing replacement of old bone tissue w/ new bone tissue
– Resorption: osteoclasts destroy old bone
– Deposition: osteoblasts construct new bone
– @ any given time, 5% of total bone mass remodeled
 Renewal varies w/ bone type & location within body
 Removes injured bone
 Triggered by a number of factors
– Bone strength related to degree by which it is stressed
 Lifting weights strengthens bone  thickens it
 Controlled by hormones, vitamins & minerals
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 Resorption
– Osteoclasts attach to endosteum/periosteum & form leak-proof seal around cell edges
– Secrete lysosomal enzymes & acids
 enzymes digest collagen
 acids dissolve bone minerals
– Degraded proteins, Ca & P released into interstitial fluid  diffuse into capillaries
 Deposition
– Osteoclasts depart site of remodeling
– Osteoblasts begin new bone deposition
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 Nutrition
– Minerals
 primarily Ca and P for bone growth
 also F, Mg, Fe & Mn in lesser quantities
– Vitamins
 vitamin C for collagen formation
 vitamins K and B
12 for protein synthesis
 vitamin A activates osteoblasts
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 Sufficient hormones
– During childhood
 insulinlike growth factor (IGF) most important
– promotes cell division at epiphyseal plate
– enhance protein synthesis
– stimulated by human growth hormone (hGH)
– Thyroid hormones (T
3
– Estrogens & androgens
&T
4
)
 @ puberty: stimulate sudden growth
– ↑ osteoblast activity & synthesis of bone ECM 
“growth spurt”
– modifications of skeleton characteristic of male/female forms
 adulthood: contribute to remodeling
– Vitamin D, parathyroid hormone (PTH) & calcitonin
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 A fracture = any break in bone
 4 steps to fracture repair (Figure 6.10)
1) Formation of fracture hematoma
• Blood leaks from vessels crossing fracture line  clot forms
• Nearby bone cells die  swelling & inflammation occur
• Phagocytes & osteoclasts remove damaged bone tissue
• May last up to several weeks
2) Fibrocartilaginous callus formation
• Mass of repair tissue consisting of collagen fibers & cartilage
 Bridges broken ends of bone
 Secreted by blast cells in periosteum
• Takes about 3 weeks
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3) Bony callus formation
• Osteogenic cells differentiate into osteoblasts
 Well-vascularized tissue
 Form spongy bone trabeculae
• Trabeculae join living & dead parts of bone
• Fibrocartilage converted into spongy bone  bony callus
• 3-4 months
4) Bone remodeling
• Osteoclasts gradually resorb dead portions of fragments
• Compact bone replaces spongy bone @ periphery of fracture
• Usually a thickened area remains on bone surface  evidence of break
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 Named for shape or position of fracture line
 Common types of fracture
– greenstick -- partial fracture
– impacted -- one side of fracture driven into the interior of other side
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 Named for shape or position of fracture line
 Common types of fracture
– closed -- no break in skin
– open fracture --skin broken
– comminuted -- broken ends of bones are fragmented
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 Named for shape or position of fracture line
 Common types of fracture
– Pott’s -- distal fibular fracture
– Colles’s -- distal radial fracture
– stress fracture -- microscopic fissures from 36 repeated strenuous activities

 99% of total body calcium found in bone
 Ca +2 ions required by several body systems
– nerve & muscle cell function
– blood clotting
– enzyme function in many biochemical reactions
 Plasma level maintained @ 9-11mg/100mL
– Bone helps maintain plasma [Ca +2]
 balance rates of deposition & resorption
– Small changes in blood levels of Ca +2 can be deadly
 cardiac arrest if too high
 respiratory arrest if too low 37

 Parathyroid hormone (PTH) is secreted if Ca +2 levels falls
– PTH gene turned on  more
PTH secreted from gland
– osteoclast activity increased
– kidney retains Ca +2
– stimulates calcitriol production
 Calcitonin secreted from parafollicular cells in thyroid if
Ca +2 blood levels get too high
– inhibits osteoclast activity
– increases bone formation by osteoblasts
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 Parathyroid hormone acts to RAISE blood
Ca +2 levels
 Calcitonin works to DECREASE blood Ca +2 levels
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 Ability to alter its strength in response to mechanical stress
– increased deposition of mineral salts & production of collagen fibers
– removal of mechanical stress leads to weakening of bone through demineralization
(loss of bone minerals) and collagen reduction.
 reduced activity while in a cast
 astronauts in weightless environment
 bedridden person
– Weight-bearing activities help build & retain bone mass 40

 loss of calcium and other minerals from bone matrix (demineralization)
– may result in osteoporosis
– very rapid in women 40-45 as estrogens levels decrease
– in males, begins after age 60
 decreased rate of protein synthesis
– decrease in collagen production which gives bone its tensile strength
– decrease in growth hormone
– bone becomes brittle & susceptible to fracture
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 Decreased bone mass resulting in porous bones
 Those at risk
– white, thin menopausal, smoking, drinking female with family history
– athletes who are not menstruating due to decreased body fat & decreased estrogen levels
– people allergic to milk or with eating disorders whose intake of calcium is too low
 Prevention or decrease in severity
– adequate diet, weight-bearing exercise, & estrogen replacement therapy (for menopausal women)
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– behavior when young may be most important factor

 Rickets
 calcium salts are not deposited properly
 bones of growing children are soft
 bowed legs, skull, rib cage, and pelvic deformities result
 Osteomalacia
 new adult bone produced during remodeling fails to ossify
 hip fractures are common
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