Cellular structure of bone (MS system)

Question 1

Bone types and classifications

Answer 1

Anatomical bones:
- flat, long, short/cuboid, irregular, sesamoid

Macroscopic structure:

• trabecular / cancellous / spongy
• cortical / compact

Microscopic structure:

• woven bone (immature)
• lamellar bone (mature)

Question 2

Cortical vs Trabecular

Answer 2

Cortical:

• long bones
• 80% of skeleton
• appendicular
• 80-90% calcified
• mainly structural, mechanical and protective

Trabecular:

• vertebrae and pelvis
• 20% of skeleton
• axial
• 15-25% calcified
• mainly metabolic
• large surface area

Question 3

Bone development

Answer 3

Bones develop throughout growth and into adulthood:

• growth plate fusion and ossification completes development
• clavicles growth plates fuse at around 20 years

Intramembranous ossification:

• direct differentiation of osteoblasts from connective tissue
• flat bones

Endochondral ossification:

• bones form form a cartilage model
• long bones
• growth plate allows rapid growth

Question 4

Specialised bone cells

Answer 4

• the skeleton is not a fixed or stagnant organ
• it is dynamically regulated to maintain health
• small portions of bone are constantly being removed and replaced
• your whole skeleton has been replaced after 7 years
• this is done by the specialised bone cells via the bone remodelling cycle

Types of cells:
Osteocytes - mechanosensory network embedded in mature bone
Osteoclasts - multinuclear cells that reabsorb and remove bone
Osteoblasts - produce osteoid to form new bone

Question 5

Osteoclasts

Answer 5

• giant multinuclear cells formed from the fusion of macrophages
• seal off a portion of bone beneath them
• they secrete acids and enzymes to resorb and sealed off bone

Question 6

Osteoblasts

Answer 6

• form new bone
• secretes osteoid (organic compound of new bone)
• osteoid is mineralised over time to become mature bone
• some are embedded in new bone and differentiate into osteocytes

Question 7

Control of bone remodelling

Answer 7

Endocrine:

• oestrogen
• thyroid hormone
• PTH

Paracrine:

• RANKL
• Wnt signalling

Question 8

Osteoclast differentiation and RANKL

Answer 8

• RANK receptor - activation required for osteoclast differentiation and survival
• RANK ligand - produced by osteocytes and osteoblasts
• OPG (osteoprotegerin) - decoy receptor for RANKL also produced by osteocytes and osteblasts

Question 9

Wnt signalling and bone formation

Answer 9

• highly complex pathway involved in many different organ systems
• stimulates osteoblast differentiation
• inhibited by Sclerostin and Dkk-1

Question 10

Bone disorder - Osteopetrosis

Answer 10

• LRP5 activating mutations
• van Buchem’s and SOST
• defined as having a bone mass greater than 2.5 SD below average peak bone mass
• estimated that it will effect 1:2 women and 1:5 men
• causes 500,000 low impact bone fractures every year in UK
• can be primary (menopause, ageing) or secondary (drugs, disease, lifestyle)