Bone structure and formation

Question 1

What kind of tissue is bone?

Answer 1

Specialised connective tissue

Question 2

What is bone composed of?

Answer 2

Living cells embedded in a mineralised extracellular matrix

Question 3

Bone types

Answer 3

Trabecular bone
Cortical bone
Woven bone

Question 4

How hard is bone?

Answer 4

One of the hardest CTs
Mineralised
Enamel, dentine, cementum are harder
Bone is 4th hardest

Question 5

Bone constituents

Answer 5

30% organic (majority collagen)

45% inorganic (HA)

Question 6

What is HA?

What does it do?

Answer 6

A hydrated crystalline material of calcium and phosphate

Hydroxyapatite provides strength

Question 7

Bone matrix

Answer 7

Scaffold of interwoven collagen fibres (>95% type I collagen, <5% type V)
Between fibres are small, uniform, plate-like crystal of carbonated HAP
Small amounts of non-collagenous proteins, some which are unique to calcified tissues (e.g. osteocalcin)

Question 8

Formula of carbonated HAP

Answer 8

Ca10(PO4)6(OH)2

Question 9

Bone functions

Answer 9

Supports body and protects internal organs
Allows movement
Metabolic: haemotopoiesis and calcium homeostasis

Question 10

Bone function: support

Answer 10

Mineralised CT when fully developed (45% HAP)
Supports body & protects internal organs
-bones of legs, pelvis, vertebrae support body
-mandible supports teeth
-bones enclose & protect brain, SC, lungs, heart, pelvic viscera, bone marrow
Allows movement
-bones provide attachment for muscles so allowing leverage e.g. leg/arm movements, ventilation of lungs

Question 11

Bone function: metabolic

Answer 11

Haematopoiesis
-bone marrow (red marrow) is major producer of blood cells including cells of immune system
Calcium homeostasis (99% body Ca, 85% PO4)
-serum Ca2+ levels maintained by interplay between intestinal absorption, renal excretion & skeletal mobilisation or uptake

Question 12

Cortical bone

Answer 12

Cortical/ compact/ laminar

• approx 80% of skeleton
• dense
• very strong
• forms outer layer of all bones

Question 13

Trabecular bone

Answer 13

Trabecular/ cancellous

• porous meshwork of bone
• makes up ~20% of skeleton, mainly in axial skeleton
• bone strength also determined by trabecular microstructure - can change in disease e.g. osteoporosis

Question 14

Woven bone

Answer 14

Forms quickly during periods of repair or rapid growth and is remodelled into lamellar bone

Question 15

Periosteum

Answer 15

Lines outer surface of cortical bone

Question 16

Bone is living dynamic tissue

Answer 16

Constructed to ensure maximum strength for minimum weight

Changes all the time to meet stress loads and to release Ca2+ and phosphate if required

Question 17

Cell types in bone

Answer 17

Osteoclast: large multinucleated bone resorbing cells
Osteoblast: bone forming cells
Osteocyte: originate from Ob which have become embedded in bone matrix, involved in sensing mechanical loads and Ca homeostasis
Bone lining cells: originate from Ob, line quiescent periosteal and endosteal surfaces of bone
Osteoprogenitor cells (stromal cells): precurosors of osteoblastic lineage

Question 18

Bone structure: osteocytes

Answer 18

Osteocytes have spider like appearance

-cell processes lie in cannaliculi and link to each other and BVs for passage of nutrients

Question 19

Is bone tissue static?

Answer 19

No, it is continuously remodelling

Question 20

Bone remodelling

Answer 20

Remodelling occurs at ~1-2 million microscopic sites/ skeleton at a time
Bone remodelling follows ordered sequence of events
Occurs to:
-release calcium or
-alter architecture of cancellous bone to meet new stresses

Question 21

Remodelling requires cells to:

Answer 21

Make new bone (osteoblasts)
-cuboid cells arranged in rows on bone surface because bone can only grow by appositional growth
Break down existing bone (osteoclasts)

Question 22

Phases of bone remodelling

Answer 22

Starts with resorption phase: bone ECM destroyed and removed
-takes ~3 weeks/ site
Bone formation phase follows: new ECM formed and mineralised
-takes ~3-4 months/ site

Question 23

Mechanism of bone remodelling

Answer 23

1. Resorption initiated by recruitment of osteoclast precursors to remodelling site
2. Oc precursors mature into Oc
3. Bone lining cells erode a little ECM and leave remodelling site
4. Oc bind to ECM exposed by bone lining cells and digest bone matrix with enzymes to form resorption pit
5. Oc stop digesting matrix & die by apoptosis
6. Ob precursors recruited to remodelling site
7. Ob precursors develop into mature Ob
8. Ob make new ECM to fill resorption pit made by osteoclasts
9. When synthesis of matrix is complete, new bone surface becomes covered in bone lining cells
   - osteoblasts trapped within ECM become osteocytes

Question 24

Bone formation

Answer 24

Required to produce new bone
-during formation of skeleton
-during fracture repair
-during tooth socket healing after extraction
First type of bone laid down is woven bone
-trabeculae are disorganised and cannot bear weight until remodelling occurs

Question 25

2 types of bone formation in skeleton

Answer 25

1. Bone formed directly from condensed mesenchyme or ectomesenchyme = intramembranous ossification (IMO) 2. Cartilagenous precursor of bone is formed and replaced by bone as it grows = endochondral ossification (ECO) - ECO more common: all bones outside skull formed this way except clavicle - IMO only occurs in neurocranium and viscerocranium of skull & clavicle - Basicranium formed by ECO

Question 26

Intramembranous ossification

Answer 26

Mesenchymal stem cells condense, differentiate into Obs and secrete ECM (osteoid) in long strands Obs lay down bone mienral on strands of osteoid COnsecutive growth rings of osteoid (lamella) added on to trabecula to > thickness Further bone growth by cycles of osteoid secretion and mineralisation (appositional growth) Multiple trabecula within developing bone contact one another to form lattice structure Areas of bones may completely fill-in with mineralised osteoid (compact bone) Bones containing lattice structures called primary cancellous bones Most bones are mixtures with compact outer surface & cancellous interior

Question 27

Intramembranous ossification (Obs and Ocs)

Answer 27

1. Mesenchymal cells condense and differentiate into osteoblasts 2. Osteoblasts lay down osteoid 3. Some cells remain in bone (osteocytes) and others on the surface as osteoblasts

Question 28

An osteon

Answer 28

Haversian system

Question 29

Defects in intramembranous ossification

Answer 29

Cleidocranial dystosis: rare genetic disorder that interferes with IO (skeletal dysplasia) ~1/ 1 million affected -autosomal dominant (defect in RUNX2 gene) -neurocranium underdeveloped -viscerocranium underdeveloped with severe dental maocclusion, delayed formation -large head and frontal bossing -clavicles reduced or absent: characteristic feature

Question 30

Endochondral ossification

Answer 30

1) Miniature cartilage replica of bone is formed by differentiation of mesenchymal or ectomesenchymal cells into chondroblasts which mature into chondrocytes 2) Cartilage grows in specific direction - by interstitial and appositional growth 3) Cartilage converted into bone

Question 31

Epiphysial growth plate

Answer 31

``` Proliferation zone -parallel columns of dividing cells -formation of ECM Hypertrophic zone -significant increase in cellular size (5 fold) -matrix reduced to thin struts -down regulation of ECM -production of factors to stimulate blood vessel ingrowth Cartilage/ bone interface -cartilage matrix mineralisation -chondrocyte apoptosis (cell death) -ingrowth of BVs -production of new bone on mineralised cartilage -matrix ```

Question 32

Bone formation routes in fracture healing

Answer 32

``` Impact Induction Inflammation Soft callus Ossification Remodelling ```

Question 33

Achondroplasia

Answer 33

Recessive genetic condition that affects bone formation via ECO -autosomal dominant -incidence 1/ 20,000 -most common form of dwarfism All bones formed by ECO reduced in length -trunk and limbs short (drawfism) -basicranium short: middle 1/3 face sunken producing 'dish-face' profile with Class III malocclusion

Question 34

Achondroplasia genetic defect

Answer 34

In gene for FGFR-3, a membrane receptor that is important in response of chondrocytes to growth factor during development of cartilage 'template'

Question 35

LOOK AT PICTURES ON SLIDES

Answer 35

LOOK AT PICTURES ON SLIDES