Bone structure, formation, growth and repair

Question 1

What are the 5 tissue types?

Answer 1

Epithelia, muscle, connective tissue, blood, nervous tissue

Question 2

What are the 5 roles of connective tissue?

Answer 2

• Structural support
• Metabolic support
• Cell adhesion
• Medium of exchange
• Defense, protection and repair

Question 3

What components of bone contribute to its rigidity?

Answer 3

Mineralised ECM - hydroxyapatite (calcium and phosphate crystals)

Question 4

What component of bone contributes to it’s resilience?

Answer 4

Type 1 collagen fibres

Question 5

What are the 5 functions of bone?

Answer 5

• Movement
• Mineral homeostasis
• Support
• Protection
• Site of haematopoiesis

Question 6

What is periosteum? What are its functions?

Answer 6

non-calcified dense irregular connective tissue layer covering bone where tendons and ligaments insert.

• Helps bones grow in thickness (as it contains osteoprogenitor cells and osteoblasts)
• Helps protect the bone
• Assists in fracture repair
• Helps nourish bone tissue

Question 7

Describe the microscopic appearance of woven bone

Answer 7

Woven bone (immature/primary bone) – first bone formed at any site. Collagen fibres arranged randomly. Occurs at sites of fracture healing ​

Question 8

Describe the microscopic appearance of lamellar bone

Answer 8

Lamellar bone (mature bone) – collagen fibres remodelling into orderly arrangement -> STRENGTH​

Question 9

Define lamellae

Answer 9

Lamellae = bony plates made up of collagen fibres arranged in parallel ​

Question 10

Describe osteons/haversian systems

Answer 10

Concentric lamellae around a central canal (Haversian canals)​
Haversian canals contain blood vessels, lymphatic vessels and nerves ​
Volkmann’s canals run transversely or obliquely and allow communication between Haversian canals, the periosteum, the marrow cavity, and each other

Question 11

Describe the stages a cell goes through to mature to an osteocyte

Answer 11

Mesenchymal stem cell –> osteoprogenitor cell –> osteoblast –> osteocyte

Question 12

What do osteoblasts secrete?

Answer 12

Osteoblasts secrete organic bone matrix (osteoid) which is subsequently mineralised

Question 13

What type of bone cell are periosteal cells and what are they important for?

Answer 13

Bone lining cells (periosteal cells) are resting osteoblasts – important role in fracture healing​

Question 14

What does osteoid consist of?

Answer 14

Type 1 collagen, proteoglycans, glycoproteins and other proteins secreted by osteoblasts

Question 15

What are the 3 functions of osteocytes?

Answer 15

• Mechanotransduction
• Matrix maintenance
• Calcium homeostasis

Question 16

What are osteoclasts derived from?

Answer 16

Derived from monocytes-macrophage system (haemopeoitic origin) ​

Question 17

What do osteoclasts look like?

Answer 17

Large multinucleate cells with ruffled border

Question 18

Why is bone remodelling necessary?

Answer 18

Bone remodelling allows:​

• Strength and shape of bone to be adjusted in response to patterns of stress and mechanical forces, or to repair microfractures​
• Replacement of old organic matrix which degenerates and becomes brittle and weak

Question 19

Describe the bone remodelling cycle

Answer 19

Quiescence (nothing happens) -> Resorption (Osteoclast act) -> reversal (OC apoptosis and removal) -> formation (OB matrix synthesis)

Question 20

Describe intramembranous ossification

Answer 20

Direct replacement of mesenchyme by bone tissue
​-Membrane of mesenchyme differentiates directly into osteogenic cells​
-Osteoblasts cluster together and secrete organic bone matrix. This region is known as the primary ossification centre. ​
-The bone matrix becomes calcified ​
-The matrix develops into spongy/trabecular bone around the capillaries​
-The blood vessels eventually condense to form red bone marrow which fills the spaces in the spongy bone ​
-Mesenchyme on outside differentiates into fibrous periosteum and bone cells form cellular layer of periosteum​
-The most superficial layer of spongy/trabecular bone (deep to the periosteum) is transformed into compact bone

Question 21

Where does intramembranous ossification occur?

Answer 21

Flat bones of skull, parts of the clavicle, mandible and scapula

Question 22

Describe endochondral ossification

Answer 22

Bone develops on cartilage model.​
Steps of endochondral ossification:​
-Mesenchyme develops into chondroblasts
-Miniature hyaline cartilage model is formed​
-Cartilage model continues to grow, providing a scaffold for bone development. It is eventually resorbed and replaced by bone​

Question 23

In endochondral ossification, where do primary ossification centres form?

Answer 23

In the diaphysis of long bones - in foetus

Question 24

In endochondral ossification, where do secondary ossification centres form?

Answer 24

Secondary (epiphyseal) ossification centres form in epiphyses of long bones which develop at different times after birth. ​

Question 25

In endochondral ossification, in which direction does primary ossification occur?

Answer 25

Primary ossification proceeds inwards from the external surface to the centre of the bone

Question 26

In endochondral ossification, in which direction does secondary ossification occur?

Answer 26

Secondary ossification starts in the centre and proceeds outwards. his leaves an outer ring of cartilage around the epiphysis which will form the articular cartilage of the joint and the epiphyseal growth plate (between the epiphysis and the diaphysis) ​

Question 27

Describe longitudinal growth

Answer 27

- At the epiphyseal growth plate ​ - Proliferation of cartilage cells followed by endochondral ossification Cartilage proliferation occurs at the epiphyseal aspect ​ Replacement by bone occurs at the diaphyseal aspect ​ Eventually ossification zone overtakes proliferation and rest zones -> epiphyseal growth plate closes ​

Question 28

Describe appositional growth

Answer 28

- Growth in width ​ | - New bone formed under periosteum

Question 29

Describe the 5 different zones of the epiphyseal growth plate

Answer 29

1) Resting zone (quiescent zone/zone of reserve cartilage) – scattered chondrocytes, low rate of proliferation, anchors epiphyseal growth plate to bone of epiphysis 2) Proliferation zone – cartilage cells are proliferating under influence of insulin-like growth factor which is produced by hepatocytes in response to growth hormone. Chondrocytes are stacked in columns like coins. 3) Hypertrophic zone – chondrocytes mature and hypertrophy, and secrete signalling molecules that encourage invasion of blood vessels. Eventually the cells undergo apoptosis and die.​ 4) Calcification zone – Hypertrophied chondrocytes die and cartilage matrix becomes calcified. ​ 5) Ossification zone – Osteoclasts remove calcified cartilage and osteoblasts lay done bone matrix

Question 30

What is the clinical significance of growth plates?

Answer 30

- Relative weak point particularly if subject to shearing forces​ - Fractures involving growth plate (Salter-Harris fractures) can cause deformities in developing bone​ - Disorders affecting bone mineralisation, e.g. rickets, can affect size and shape of growth plate

Question 31

Define fracture

Answer 31

A fracture is a breach in the integrity of part or the whole of a bone

Question 32

What are the 6 stages of fracture healing?

Answer 32

1) Haematoma​ 2) Granulation tissue​ 3) Callus​ 4) Woven bone​ 5) Lamellar bone​ 6) Remodelling

Question 33

What happens in the haematoma stage of fracture healing?

Answer 33

- Necrosis of bone fragments ​ | - Inflammatory response -> phagocytosis

Question 34

What happens in the 'granulation tissue' stage of fracture healing?

Answer 34

- Capillaries and fibroblasts invade blood clot -> forms fibrovascular granulation tissue ​ - Cytokines and growth factors induce cellular proliferation Occurs within the first 2 weeks of fracture

Question 35

What happens in the 'callus' stage of fracture healing?

Answer 35

- Fibrous tissue, inflammatory cells and cartilage form a soft callus (fibrocartilagenous callus)​ - Forms a bridge between bone ends The callus is very soft in the first 4-6 weeks of fracture healing and so the patient will need adequate support and bracing until the callus begins to ossify. ​

Question 36

What happens in the 'woven bone' stage of fracture healing?

Answer 36

- Osteoprogenitor cells proliferate and differentiate into osteoblasts to lay down woven bone​ - Strengthens the callus and gives rigidity (bony callus)​ - When callus is sufficiently firm that movement no longer takes place the fracture site is clinically united ​ ​ Depending on the size of the bone and the fracture it can take up to 3 months for the fibrocartilagenous callus to be transformed into bone.

Question 37

What happens in the 'lamellar bone' stage of fracture healing?

Answer 37

Action of osteoblasts and osteoclasts gradually replaces woven bone with lamellar bone​

Question 38

What happens in the remodelling stage of fracture healing?

Answer 38

- Osteoclasts and osteoblasts remodel lamellar bone in response to stresses ​ - Excessive callus is reabsorbed and medullary cavity re-established Remodelling can take between 1 and 2 years.

Question 39

What 3 factors aid fracture healing?

Answer 39

1) Stability of the fracture​ 2) Apposition of bone ends​ 3) Adequate blood supply

Question 40

What 6 factors delay fracture healing?

Answer 40

1) Excessive movement of bone ends​ 2) Bone loss/soft tissue trauma ​ 3) Poor blood supply​ 4) Infection ​ 5) Foreign bodies​ 6) Poor general health, poor nutrition, certain medications, smoking

Question 41

What is osteoprotegerin (OPG)

Answer 41

A non-signalling decoy of RANKL

Question 42

What activates osteoclasts?

Answer 42

RANKL secreted by osteoblasts