Physiology of bone repair

Question 1

Describe the balance in healthy bone physiology

Answer 1

Balance between one resorption and bone formation

Question 2

What does an imbalance in bone resorption lead to?

Answer 2

Osteoporosis
Osteopenia
Rickets

Question 3

What does imbalance in bone formation lead to?

Answer 3

Osteopetrosis

Question 4

Describe the classifications of bone structure

Answer 4

Long bone
Flat bone
Macroscopic - cortical bone, cancellous sponge
Microscopic - Lamellar (osteons) and woven (immature and disorganised)

Question 5

Name the 3 types of cells in bone

Answer 5

Osteoclasts
Osteoblasts
Osteocytes

Question 6

What is between the cells in bone?

Answer 6

Extracellular matrix

Question 7

Where are osteoblasts found?

Answer 7

On surface bone

Question 8

What do osteoblasts do?

Answer 8

produce protein component acellular matrix – regulate bone growth and degradation

Question 9

Where are osteocytes found?

Answer 9

Embedded in bone matrix

Question 10

What do osteocytes do?

Answer 10

Maintain bone.

Question 11

What are osteoclasts responsible for?

Answer 11

Responsible for bone degradation and remodelling

Question 12

What is meant by organic?

Answer 12

Cells and proteins

Question 13

What is meant by inorganic?

Answer 13

Minerals, eg Ca2+ & PO4- (hydroxyapatite)

Question 14

What is bone dominated by?

Answer 14

Extracellular matrix

Question 15

What is the Harversian system in lamellar bone?

Answer 15

Osteons - structural unit which allows for cells of the bone to receive nutrients from central canal
Communication system between cells immobilised in bone matrix
HS runs Parallel to bone and along long axis of bone
Canaliculi allows communication
Haversian canal - allows main flow of nutrients

Question 16

Where do osteocytes arise?

Answer 16

From osteoblasts from mesenchyme

From precursor cells in bone marrow stroma

Question 17

Describe osteoblasts

Answer 17

Osteoblasts are post-mitotic
Most osteoblasts will undergo apoptosis
Number of osteoblasts decrease with age

Question 18

What will happen to a small percentage of osteoblasts

Answer 18

A low % of osteoblasts will become osteocytes locked in lacuna

Question 19

What is the function of osteoclasts?

Answer 19

Resorption

Question 20

Describe the structure of osteoclasts

Answer 20

Multinucleate
40 micrometer in diameter.
15-20 closely packed oval-shaped nuclei.
Can proliferate

Question 21

Give the function of osteoclasts

Answer 21

Phagocytose (bone matrix & crystals)
Secrete Acids - easier to manipulate the bone as acid causes re-solubilization of calcium
Secrete proteolytic enzymes from lysosomes

Question 22

Where does bone resorption occur?

Answer 22

Ruffled border

Question 23

What percentage of extracellular matrix is minerals

Answer 23

70%

Question 24

Describe compressive and tensile strength of bone

Answer 24

High

Question 25

List the acellular components of bone

Answer 25

collagen fibres – protein, flexible but strong hydroxyapatite – mineral, provides rigidity calcium/phosphate crystals > 50 %

Question 26

What are Glycosaminoglycans?

Answer 26

``` long polysaccharides Highly negative Attract Water Repel each other Resists compression ``` Abundant in Cartilage

Question 27

Where are growth factors found in bone?

Answer 27

In the ECM

Question 28

What is the function of growth factors in bone?

Answer 28

They are revealed by osteoclast action Which leads to proliferation & mineralisation bone remodelling = bone turnover = the activation-resorption-formation sequence

Question 29

How does bone form?

Answer 29

bone forms either as compact or cancellous and by either intramembranous or endochondral bone formation

Question 30

What 2 factors remodel bone?

Answer 30

Recurrent mechanical stress calcium homeostasis Plasma calcium is essential in maintaining structural integrity of skeleton

Question 31

Describe the effect of mechanical stress on bone

Answer 31

inhibits bone resorption promotes deposition Surface osteoblasts & osteocyte network detect stresses skeleton reflects forces acting on it

Question 32

What happens to bone when there is not any mechanical stress?

Answer 32

Bone weakens

Question 33

Give two examples of where there is no mechanical stress to bone

Answer 33

Bed rest Lack of gravity

Question 34

What are bisphosphonates used for?

Answer 34

For osteoporosis

Question 35

Name a drug used for osteoporosis

Answer 35

Alendronate

Question 36

Describe the function of bisphosphonates

Answer 36

inhibit osteoclast-mediated bone-resorption related to inorganic pyrophosphate the endogenous regulator of bone turnover Accumulate on bone & ingested by osteoclasts Interfere with osteoclasts metabolism

Question 37

What other drugs are used for osteoporosis

Answer 37

Encourage osteoblast formation of bone Teriparatide portion of human parathyroid hormone (PTH) Intermittent application activates osteoblasts more than osteoclasts Prevent osteoclast maturation Denosumab Monoclonal Antibody that targets RANKL

Question 38

What is bone composed of?

Answer 38

Living cells and acellular matrix

Question 39

Describe the mechanism o osteopetrosis

Answer 39

Osteoclasts cannot remodel bone Defective Vacuolar proton pump or Defective Chloride channel

Question 40

What does osteopetrosis lead to?

Answer 40

Excess bone growth Bone growths at foramina press on nerves Brittle (dense) bones Blindness Deafness Severe anaemia

Question 41

How long do fractures to bones in the upper body take to heal?

Answer 41

2-3 weeks

Question 42

How long do fractures to bones in the lower body take to heal?

Answer 42

> 4 weeks

Question 43

How does parathyroid hormone regulate calcium?

Answer 43

Parathyroid chief cells | Increases plasma Ca2+

Question 44

How does vitamin D regulate calcium?

Answer 44

1,25-di-OH cholecalciferol (calcitriol) Made in stages: Skin - Liver - Kidney Increases plasma Ca2+

Question 45

How does calcitonin regulate calcium?

Answer 45

Made by thyroid C cells “tones down” blood calcium Calcium goes into bone Used as a treatment for osteoporosis

Question 46

How does PTH stimulate resorption via osteoblasts?

Answer 46

When PTH is high, Binds on osteoblast cell which presents RANK ligand Precursor on osteoclast binds and differentiates to fuse and form an activated osteoclast - leads to bone resorption

Question 47

List some causes of low plasma concentration

Answer 47

Loss - Pregnancy, Lactation, Kidney dysfunction Low Intake - Insufficient ingestion of Calcium, Rickets (low vit D) Parathyroid dysfunction

Question 48

How is vitamin D produced and activated?

Answer 48

Cholecalciferol (Vitamin D3) - 25OH cholecalciferol - 1,25 OH cholecalciferol (calcitriol) - calbindin in gut enterocytes - increase intestinal absorption of calcium and increase calcium resoption by kidney - increase plasma calcium

Question 49

What does chronic hypocalcemia result in?

Answer 49

Skeletal deformities Increased tendency toward bone fractures Impaired growth Short stature (adults less than 5 feet tall) Dental deformities

Question 50

What does acute hypocalcemia cause?

Answer 50

C - Convulsions A – Arrhythmias T – Tetany

Question 51

List some signs of acute hypocalcemia

Answer 51

Chvostek's sign | Trousseau's sign

Question 52

Name a syndrome where there is hypocalcemia?

Answer 52

DiGeorge syndrome

Question 53

Describe how low calcium leads to excitability

Answer 53

Effect seems paradoxical i.e. counter-intuitive Hypocalcaemia makes membranes “more excitable” and “less stable” Sodium is more able to leak through it Explains latent tetany and its signs Hypercalcaemia paradoxically reduces excitability By making membranes more stable

Question 54

List some signs and symptoms of hypercalcemia

Answer 54

Can be asymptomatic Reduced excitability - Esp. Constipation - Depression + other psychiatric Abnormal heart rhythms Severe hypercalcemia - Coma - Cardiac arrest

Question 55

How does hypercalcemia do to excitability?

Answer 55

Less excitability

Question 56

Describe intramembranous ossification

Answer 56

Direct mineralisation of connective tissue (mesenchyme) Cells divide and condense around capillary network Starting point is called primary ossification center Grows radially, finally fusing together replacing the connective tissue Connective tissue that remains penetrated by blood cells and undifferentiated mesenchyme gives rise to bone marrow. Examples include the skull, mandible and clavicle

Question 57

Describe endochondral ossification

Answer 57

Cartilaginous template made from the mesenchyme Template is replace by bone- osteogenesis Different ossification centres emerge, a primary one in the diaphysis and secondary ones in the epiphysis Initially a bone collar is produced and from here the primary centre develops The epiphyseal plate (Growth Plate) exists between the diaphysis and the epiphysis