Bone physiology

Question 1

Bone classifications

Answer 1

Long bone or flat bone

• Long= longer than it is wide
• Flat= thin, often curved

Cortical or cancellous (macroscopic)

• Cortical= thick bone, organised in osteons. 80% of skeleton
• Cancellous= spongy bone

Lamellar vs woven bone (microscopic)

• Lamellar= secondary to woven bone. Stronger and more flexible
• Woven= Less organised and stress oriented

Question 2

Cancellous bone

Answer 2

Spongy bone
- Open porous network (bony struts) with blood/ marrow in-between

Less dense than cortical bone

Weaker but more flexible than cortical bone

High turnover to remodel when bone is under stress

Question 3

Cortical bone

Answer 3

Thick bone, organised in osteons
- 80% of skeleton

Slow turnover rate

Question 4

Composition of bone

Answer 4

Cells

• Osteoclasts
• Osteocytes
• Osteoblasts

Extracellular matrix= osteoid.

Question 5

Osteoclasts

Answer 5

Multinucelate bone cell

• In Howship’s lacunae
• Can proliferate
• Same precursor as monocytes

Function–> creates ruffled borders during bone reabsorption

• Phagocytose bone matrix and crystals (bone degradation)
• Secretes acids [for hydroxyapatite
• Secretion of proteolytic enzymes from lysosomes [to digest matrix proteins]

Question 6

Osteocytes

Answer 6

Quiescent bone cells in bone matrix
- Derived from osteoblasts

Functions
- Maintain bone and detects environmental stress

Question 7

Osteoblasts

Answer 7

Mononucleate bone cell located on developing bone surfaces
- Most mitotic, gives rise to osteocytes

Function

• Formation of new bone
• Release of signalling substances
• Produces protein components of acellular matrix

Question 8

Extracellular matrix

Answer 8

Hardened material surrounded cells.

Contains few cells:

• Inorganic material: minerals, hydroxyapatite
• Connective tissue sometimes
• Osteoid (unmineralised bone )
• Ground substance (organic, acellular)
• Growth factors

Question 9

Haversian system

Answer 9

Communication system between cells in bone matrix

Osteon
- Functional unit containing everything

Haversian canal

• Runs parallel to bone and on long axis
• Lined by lamellae
• Contains one or two capillaries and nerve fibres

Osteocyte
- Contains radiating processes into canaliculi

Canaliculi
- Canals between lacunae of ossified bone

Question 10

Acellular components of bone

Answer 10

Collagen fibres
- Give flexibility and strength

Hydroxyapatitre

• Provides rigidity
• Mainly calcium/phosphate crystals

Question 11

Ground substance in bone

Answer 11

Things in ECM that is not inorganic and not collagen

Includes

• Proteoglycans
• Glyosaminoglycans
• Matrix proteins
• Water

Question 12

Glycosaminoglycans

Answer 12

Component of ECM (Ground substance)
- Abundant in cartilage

Structure

• Long polysaccharide
• Highly negative–> attracts water, repels each other
• Resists compression

Question 13

Activation-resorption-remineralisation sequence

Answer 13

Controlled by osteoblasts

1. Osteoblast detects mechanical stresses/ hormonal factors/ cytokines on the bone–> releases IL-6 and other cytokines
2. IL-6 and other cytokines active osteoclast to begin bone reabsorption
   - Forms ruffled border as it absorbs bone
3. Reabsorbed bone releases growth factors bound to matrix which activates osteoprogenitor cells into active osteoblasts.

Question 14

Endochondral ossification

Answer 14

Bone is formed on a cartilaginous template.

Chondrocytes proliferate and secrete ECM and proteoglycans.

Osteoblasts then lays down osteoid and begin mineralisation

Question 15

Intramembranous ossification

Answer 15

No cartilage template

Osteoblast lays down osteoid and being mineralisation without cartilage
- Forms tiny bony spicules

Forms woven bone when nearby spicules join into trabeculae.

Question 16

Factors that govern remodelling of bone

Answer 16

Recurrent mechanical stress

Calcium homeostasis

Question 17

Mechanical stress on bone

Answer 17

Strengthens bone

Surface osteoblasts and osteocytes detect stresses

• Stimulates more deposition of bone minerals, inhibits bone resorption
• Bone trabeculae become more dense

Without weight bearing (i.e bed rest and lack of gravity) = loss in bone density

Question 18

Osteopenia

Answer 18

Low bone density

- Considered to be precursor to osteoporosis sometimes

Question 19

Bisphosphonates

• Mechanism
• Example
• Indication

Answer 19

Inhibits osteoclast from bone -resorption
- Related to inorganic pyrophosphate= interfere with osteoclast metabolism

Alendronate

For osteoporosis

Question 20

Teriparatide

• Mechanism
• Indication

Answer 20

Encourage osteoblast formation of bone (PTH portion)

Indication
- Osteoporosis

Question 21

Denosumab

• Mechanism
• Indication

Answer 21

Prevents osteoclast maturation

- Monoclinary antibody that targets RANK-ligand

Question 22

Osteopetrosis

• Genetics
• Mechanism
• Symptoms

Answer 22

Autosomal recessive condition

Mechanism

• Osteoclast cannot remodel bone= excess bone growth
• Defective vacuolar proton pump/ chloride channels [cannot secrete acid]

Symptoms–> Excess bone presses on skull foramina

• Brittle bones
• Blindness
• Deafness
• Severe anaemia

Fatal within 10 year

Question 23

Phases of fracture healing 1

Answer 23

Reactive phase- takes a week

• Haematoma forms
• Inflammation occurs= granulation tissue

Bone precursor cells from periosteum arrive

Question 24

Phase 2 of fracture healing

Answer 24

Soft callus formation [week 2-3]

Woven bone/ hyaline cartilage is formed to join pieces

Question 25

Phase 3 of fracture healing

Answer 25

Hard callus formation [week 4-16] - Woven bone/ hyaline cartilage is replaced by lamellar bone - Lamellar bone turned into tribecular bone

Question 26

Phase 4 of fracture healing

Answer 26

Remodelling - Osteoclast remodel trabecular bone to original bone shape - Trabecular bone is replaced with compact bone where appropriate.

Question 27

PTH and Ca2+

Answer 27

Release from chief cells - Increase plasma calcium Mechanism - Stimulates osteoblast to activate osteoclast precursor via RANKL

Question 28

Vit.D and Ca2+

Answer 28

1,25-OH Vit D increases plasma Calcium | - Stimulates more absorption in gut and kidney

Question 29

Calcitonin

Answer 29

Made by thyroid C cells - Decreases calcium levels--> stimulates entry into bones Can be used as treatment for osteoporosis

Question 30

OPG

Answer 30

Secreted by osteoblast--> signals reduced bone formation - Binds to block RANKL Stimulated by oestrogen in vivo Stimulated by strontium renovate

Question 31

Calbindin

Answer 31

Increase stimulated by calcitriol | - Increases intestinal and kidney absorption of calcium

Question 32

Causes of low plasma calcium

Answer 32

Due to loss - Pregnancy - Lactation - Kidney dysfunction Low intact - Insufficient ingestion - Rickets due to low vit.D Parathyroid dysfunction

Question 33

Consequences of chronic hypocalcaemia

Answer 33

Skeletal deformities [i.e rickets] Increased tendency for fractures Impaired growth Short stature Dental deformities

Question 34

Acute hypocalcaemia

Answer 34

Causes excitability - Neurone become much more permeable to Na+ Symptoms = CAT - Convulsions - Arrhythmias - Tetany Signs - Chvostek's sign - Trousseaus's sign -

Question 35

Effects of hypercalcaemia

Answer 35

Reduces excitability of neurones - Makes neurones more stable - High calcium inactivates channels= less ions conducted

Question 36

hypercalcaemia symptoms

Answer 36

Constipation Depression + other psychiatric problems Abnormal heart rhythm If severe - Coma - cardiac arrest