Skeletal System:

Bones and Bone Tissue

 Skeletal System Functions
• Support - provides hard framework for soft tissue

• Protection of underlying organs

– Brain, Eyes, Inner ear structures, heart & lungs, kidneys

• Movement - skeletal muscles use bones as levers

• Storage.
– Calcium and Phosphorous
• Stored then released as needed.
– Fat stored in marrow cavities

• Blood cell production (Hematopoiesis). Bone marrow that gives

rise to blood cells and platelets
Bone Shapes
• Long
– Ex. Upper and lower
limbs
• Short
– Ex. Carpals and
tarsals
• Flat
– Ex. Ribs, sternum,
skull, scapulae
• Irregular
– Ex. Vertebrae, facial
 Long Bone Structure
• Diaphysis : Shaft
– Compact bone
• Epiphysis
– End of the bone
– Aka Cancellous bone
– Epiphyseal plate - responsible for growth in length of bone
• Composed of hyaline cartilage
• present until growth stops
• Medullary cavity - centra, hollow cavity
– filled with yellow marrow
• Membranes
– Periosteum - surrounds diaphysis
– Sharpey’s fibers
– Endosteum - lines medullary cavity
 Long Bone Structure
• Periosteum - membrane surrounding diaphysis
– Composed of 2 layers
• Outer fibrous layer of collage fibers
• Inner osteogenic (bone forming) layer
– A single layer of bone cells including osteoblasts, osteoclasts and
osteochondral progenitor cells
– Fibers of tendon that bind muscle to bone become continuous with
fibers of periosteum.
– Sharpey’s fibers - periosteal fibers that penetrate into the bone
matrix.
– Strengthen attachment of tendon to bone.
• Endosteum. Similar to inner layer of periosteum. Lines all
internal spaces including spaces in cancellous bone.
Structure of a Long Bone

Figure 6.3a-c
 Compact Bone
• Osteon - basic function unit of compact bone
– Central canal - run parallel to surface of bone
• contains blood vessels
– Concentric lamellae - cylinders of bone
– Lacunae - house osteocytes
– Canaliculi - minute passageways that lacunae
• Processes of osteocytes extend into canaliculi
– Perforating or Volkmann’s canal -
• run perpendicular to long axis.
• contain blood vessels that then branch to enter central canal
Microscopic Structure of
Compact Bones

Figure 6.6
Flat, Short, Irregular Bones
• Flat Bones
– No diaphyses or
epiphyses
– A sandwich of
cancellous (spongy)
bone between compact
bone
• Cancellous bone
(Spongy bone)
– Composed of bony
plates known as
trabeculae
 Cancellous (Spongy) Bone

• Trabeculae: interconnecting rods or plates of bone.

Like scaffolding.
– Spaces filled with marrow.
– Covered with endosteum.
– Oriented along stress lines
 Bone Histology
• Recall that bone is a connective tissue that
consists of a matrix, cells, and fibers
• Bone matrix
– Resembles reinforced concrete. Rebar is collagen
fibers, cement is hydroxyapetite
– Organic components (35%)
• Composed of cells, fibers and organic substances
(osteoid)
• Collagen is most abundant organic substance
– Inorganic mineral salts (65%):
• Primarily calcium phosphate (hydroxyapatites)
• Gives bone its hardness; resists compression
 Bone Matrix

• If mineral removed, bone is too bendable

• If collagen removed, bone is too brittle
 Bone Cells
• Bone cells (see following slides for
particulars)
– Osteoblasts
– Osteocytes
– Osteoclasts
– Stem cells or osteochondral progenitor cells
 • Osteoblasts
Bone Cells – Active in bone formation, a
process known as ossification or
osteogenesis.
– Collagen produced by E.R. and
golgi. Released by exocytosis
– Precursors of hydroxyapetite
stored in vesicles, then released
by exocytosis.
• Osteocytes
– Essentially osteoblasts that have been
trapped in the matrix
– Mature bone cells commonly found in
Iacunae
– Carry out the normal metabolic
processes of bone
– Found in compact and spongy bone
 Osteoclasts and Stem Cells
• Osteoclasts.
– Cells used to breakdown bone (bone resorption)
– Ruffled border: where cell membrane borders bone and
resorption is taking place.
– H+ ions pumped across membrane, acid forms, breaks down
mineral salts (demineralization)
– Release enzymes that digest the organic proteins of matrix
– Derived from monocytes (which are formed from stem cells in
red bone marrow)
– Multinucleated and probably arise from fusion of a number of
cells
• Stem Cells. Mesenchyme (Osteochondral
Progenitor Cells) become chondroblasts or
osteoblasts.
 Osteoclast – A Bone-
Degrading Cell
• A giant cell with many nuclei
• Crawls along bone surfaces
• Breaks down bone tissue
– Secretes
concentrated
hydrochloric acid
– Lysosomal
enzymes are
released
Figure 6.13a
 Bone Development
Osteogenesis
• Bone formation occurs in 2 different ways
– Intramembranous ossification
• Occurs in connective tissue membrane
– Endochondral ossification
• Occurs in cartilage
• Both methods of ossification
– Produce woven bone that is then remodeled
Intramembranous Ossification
• Takes place in connective tissue membrane
formed from embryonic mesenchyme
• Forms many flat skull bones, part of
mandible, diaphyses of clavicles
• When remodeled, indistinguishable from
endochondral bone.
 Endochondral Ossification
• All bones except some bones of the
skull and clavicles
• Bones are modeled in hyaline cartilage
• Begins forming late in 2nd month of
human development
• Continues forming until early adulthood
Stages in Endochondral
Ossification

Figure 6.10
 Anatomy of Epiphyseal
Growth Areas
• In epiphyseal plates of growing bones
– Cartilage is organized for quick, efficient growth
– Cartilage cells form tall stacks
• Chondroblasts at the top of stacks divide
quickly
– Pushes the epiphysis away from the diaphysis
– Lengthens entire long bone
 Anatomy of Epiphyseal
Growth Areas
• Older chondrocytes signal surrounding matrix
to calcify
• Older chondrocytes then die and disintegrate
– Leaves long trabeculae (spicules) of calcified
cartilage on diaphysis side
– Trabeculae are partly eroded by osteoclasts
– Osteoblasts then cover trabeculae with bone
tissue
– Trabeculae finally eaten away from their tips by
osteoclasts
Zones of the Epiphyseal Plate
Growth in Bone Length
 Postnatal Growth of
Endochondral Bones
• During childhood and adolescence
– Bones lengthen entirely by growth of the
epiphyseal plates
– Cartilage is replaced with bone tissue as
quickly as it grows
– Epiphyseal plate maintains constant
thickness
– Whole bone lengthens
 Postnatal Growth of
Endochondral Bones
• As adolescence draws to an end
– Chondroblasts divide less often
– Epiphyseal plates become thinner
• Cartilage stops growing
• Replaced by bone tissue
– Long bones stop lengthening when
diaphysis and epiphysis fuse
 Postnatal Growth of
Endochondral Bones
• Growing bones widen as they lengthen
– Osteoblasts – add bone tissue to the
external surface of the diaphysis
– Osteoclasts – remove bone from the
internal surface of the diaphysis
• Appositional growth – growth of a bone
by addition of bone tissue to its surface
 Bone Remodeling
• Bone deposit and removal
– Occurs at periosteal and endosteal
surfaces
• Bone remodeling
– Bone deposition – accomplished by
osteoblasts
– Bone reabsorption – accomplished by
osteoclasts
Remodeling, Spongy Bone
 Fracture Repair

1. Hematoma formation - blood clot formation.

2. Callus formation - mass of tissue that forms at a fracture site and connects the broken ends of the bone Macrophages
clean up debris, osteoclasts break down dead tissue, fibroblasts produce collagen and granulation
tissue.
– Chondroblasts from osteochondral progenitor cells of periosteum and endosteum produce cartilage within the
collagen.
– Osteoblasts invade. New bone is formed.
– External callus - collar around opposing ends. Periosteal osteochondral progenitor cells 
osteoblasts and chondroblasts. Bone/cartilage collar stabilizes two pieces.
3. Callus ossification. Callus replaced by woven, cancellous bone
4. Bone remodeling - Replacement of cancellous bone and damaged material by compact bone. Sculpting of site by
osteoclasts
 Factors Affecting Bone Growth
• Size and shape of a bone determined genetically but can be modified
and influenced by nutrition and hormones
• Nutrition
– Lack of calcium, protein and other nutrients during growth and development
can cause bones to be small
– Vitamin D
• Necessary for absorption of calcium from intestines
• Can be eaten or manufactured in the body
• Rickets: lack of vitamin D during childhood
• Osteomalacia: lack of vitamin D during adulthood leading to softening
of bones
– Vitamin C
• Necessary for collagen synthesis by osteoblasts
• Scurvy: due to deficiency of vitamin C
• Lack of vitamin C also causes wounds not to heal, teeth to fall out
Dwarfism
• Achondroplastic
– 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
 Factors Affecting Bone
Growth, cont.
• Hormones
– Growth hormone from anterior pituitary. Stimulates interstitial
cartilage growth and appositional bone growth
– Thyroid hormone required for growth of all tissues
– Sex hormones such as estrogen and testosterone
• Cause growth at puberty, but also cause closure of the
epiphyseal plates and the cessation of growth
 Calcium Homeostasis
• Bone is major storage site for calcium
• The level of calcium in the blood depends
upon movement of calcium into or out of bone.
– Calcium enters bone when osteoblasts create new
bone
– Calcium leaves bone when osteoclasts break down
bone
– Two hormones control blood calcium levels-
parathyroid hormone increases it and calcitonin
lowers it.
 Ion Imbalances

• Changes in blood calcium levels can be serious

– plasma concentration is ~ 10 mg/dL
– Hypocalcemia - low blood blood calcium
• causes excitability of nervous system if too low
– muscle spasms, tremors or tetany ~6 mg/dL
– laryngospasm and suffocation ~4 mg/dL
– Hypercalcemia -excess of blood calcium
• muscle weakness and sluggish reflexes, cardiac arrest at
~12 mg/dL
 Control of Hypocalcemia by
Parathormone
• Secreted by parathyroid glands on posterior surface of thyroid
• Released in response to low calcium blood levels (hypocalcemia)
• Function = raises calcium blood level
– causes osteoblasts to release osteoclast-stimulating factor
(RANKL) increasing osteoclast population
• Osteoclast in turn increase bone resorption and add Ca to blood
– promotes calcium resorption by the kidneys
– promotes calcitriol (Vit D) synthesis in the kidneys
• Calcitriol then increases calcium absorption by intestines
– inhibits collagen synthesis and bone deposition by osteoblasts
• Sporatic injection of low levels of PTH causes bone deposition
 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
Bone & calcium disorders
 PTH-Ca2+ feedback loop
Parathyroid -
glands

PTH PTH
-
GI Tract
1,25 D

Ca 2+ Ca2+
Ca2+

ECF Ca2+ -
 Vitamin D

7-dehydrocholesterol Cholecalciferol

25-OH vitamin D

PTH

Calcitriol 24,25(OH)2 - D

Intestinal
PTH Multiple effects Effects
Ca & PO4
secretion in bone in muscle
absorption
Calcium Homeostasis
Correction for Hypercalcemia
 Bone • Open (compound)- bone break with
open wound. Bone may be sticking
out of wound.
Fractures • Closed (simple)- Skin not perforated.
• Incomplete- doesn’t extend across
the bone. Complete- does
• Greenstick: incomplete fracture that
occurs on the convex side of the
curve of a bone
• Hairline: incomplete where two
sections of bone do not separate.
Common in skull fractures
• Comminuted fractures: complete
with break into more than two pieces
Bone Fractures, cont.
• Impacted fractures: one
fragment is driven into the
cancellous portion of the other
fragment.
• Classified on basis of direction
of fracture
• Linear
• Transverse
• Spiral
• Oblique
• Dentate: rough, toothed,
broken ends
• Stellate radiating out from a
central point.
 Osteoporosis
• 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 (> 50) at greatest risk
– by age 70, average loss is 30% of bone mass
– black women rarely suffer symptoms
• Risk factors include
– Smoking - lowers blood estrogen levels
– Body wt - thin, anorexic, heavy exercisers (runners, ballet dancers) - less
adipose available to make estrogen
– Body build - short females have less total bone mass
– Calcium deficiency
– Vitamin D deficiency
– Certain drugs - alcohol, cortisone, tetracycline promote bone loss
– Family history
– Females with eating disorders including junk food diets
 Osteoporosis
• Estrogen maintains density in both sexes (inhibits
resorption)
– testes and adrenals produce estrogen in men
– rapid loss in females 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
Spinal Osteoporosis
 Other Pathologies of Bone
• Osteomyelitis - all infectious diseases of bone
– Organisms spread via the blood from wounds, boils, TB
– Pott’s disease = tuberculosis of the spine (Hunchback)
• Osteosarcoma - malignant tumors of bone
– Capable of metastasizing to other tissues/organs
• Paget’s disease
– Characterized by excessive bone formation and breakdown
– In males more than females
– In skull (hat size changes), pelvis, extremities
• Myeloma - cancer of bone marrow
• Osteogenesis imperfecta
– Familial in nature
– Very fragile bones; may break while turning in bed
– Due to an inborn error of metabolism - aminoaciduria
 Effects of Aging on Skeletal System
• Bone matrix decreases.
– More brittle due to lack of collagen; but also less
hydroxyapetite.
• Bone mass decreases.
– Highest around 30.
– Male bone mass denser due to testosterone and greater
weight.
– African Americans and Hispanics have higher bone
masses than Caucasians and Asians.
– Rate of bone loss increases 10 fold after menopause.
• Cancellous bone lost first, then compact.
• Increased bone fractures
• Bone loss causes deformity, loss of height, pain, stiffness
– Stooped posture
– Loss of teeth