Lecture 51: Pathophysiology of bone and OA

How does the skeleton initially form during development?

As cartilage and fibrous membranes that are gradually replaced by bone through ossification

What are two key properties of skeletal cartilage?

It has no blood supply or nerves and is surrounded by a dense perichondrium

What are the 3 types of skeletal cartilage?

Hyaline, elastic and fibrocartilage

What is hyaline cartilage and where is it found?

The most common cartilage, rich in collagen, providing smooth joint surfaces (e.g., joints)

What is elastic cartilage and where is it found?

Cartilage rich in elastic fibres for flexibility (e.g., external ear)

What is fibrocartilage and where is it found?

Strong cartilage with parallel collagen and chondrocytes that resists compression and tension (e.g., intervertebral discs)

What are the four main functions of bone?

Structural support/movement, mineral storage (calcium and phosphate), lipid storage, and blood cell formation

Where does haematopoiesis occur?

In red bone marrow within marrow cavities of long bones

What are the 4 classifications of bones?

Long bone, short bone, flat bone, irregular bone

What defines a long bone?

Has long shaft and two distinct ends, classification based on shape not size, compact bone on exterior with spongey inner bone marrow (e.g., humerus, femur)

What defines a short bone?

Cube-like structure with thin compact bone surrounding spongy bone mass (e.g., carpal bones)

What defines a flat bone?

Thin, flattened, usually curved, with parallel layers of compact bone with a spongy layer between (e.g., sternum, skull, ribs etc)

What defines irregular bones?

Complex shapes that do not fit into other categories, consist of spongy bone with a thin layer of compact (e.g., vertebrae, hip bones)

What are bones composed of?

70% minerals (mainly calcium and phosphate) in the form of hydroxyapatite

Contains 22% protein, predominantly Type I collagen

8% water

Ca2+ crystals are deposited in/around collagen fibres of extracellular matrix, which are very hard and resist compression

Describe compact bone

Mechanical and protective

Dense outer bone tissue, covered by periosteum (thick fibrous membrane)

Made up of osteons

Contains lamellae

At the centre of each osteon there's the central canal containing blood vessels, nerves and lymphatics

Canaliculi (tiny channels) connect osteons to each other and to the central canal

What are lamellae?

Concentric rights of osteocytes in calcified matrix

Describe spongey bone

Interior of bone tissue, consisting of fibres and lamellae (reticular structure)

Responsible for metabolic Ca2+ regulation and storage

Contains stem cells

Does not contain osteons

Honeycomb of matrix spikes is trabeculae

• Irregularly arranged osteocytes interconnected by canaliculi

• The spaces provide balance to dense, compact, heavy bone

• Often contains red bone marrow - haematopoiesis

Nourished by blood vessels of periosteum penetrating spongy bone

What do red and yellow bone marrow do?

Red - produces RBCs and WBCs

Yellow - stores fat

What are the main structures in long bone gross anatomy?

Diaphysis

Medullary (marrow) cavity

Epiphyses

Metaphysis

Periosteum

Endosteum 

What is diaphysis (the bone shaft)?

Long, hard, middle part, made of compact bone surrounding central medullary (marrow) cavity

What is the medullary (marrow) cavity?

Hollow centre of shaft, interior largely spongy bone and cavity filled with yellow marrow (adipose)

What is the endophyses?

End of bone, filled with spongy bone and contains red marrow (myeloid tissue)

What is the metaphysis?

Transition zone between shaft and end, narrow area containing epiphyseal (growth) plate (in children) → epiphyseal line (in adults)

What is the periosteum?

Outer covering of bone, thick fibrous membrane and attachment for muscle and tendons, contains blood vessels, nerves and lymphatic vessels

What is the endosteum?

A thin membrane of connective tissue lining inner surface of all bony tissue

What are the 4 main bone cell types?

Osteoprogenitors, osteoblasts, osteocytes, osteoclasts

What is the function of osteoprogenitors and osteoblasts?

Osteoprogenitors - develop into osteoblasts found in deep layers of periosteum

Osteoblasts - immature bone cells causing osteogenesis, secrete type I collagen, regulate mineralisation and differentiate into osteocytes

What is the function of osteocytes?

Mature bone cells which are entrapped in the bone matrix, act as sensors for mechanical load etc to determine when osteoblast and osteoclast activity is required

What is the function of osteoclasts?

Derived from stem cells (same as macrophages so not from bone cells), responsible for bone resorption by secreting acid/enzymes to dissolve the matrix

What are the 5 stages of bone remodelling (BMU cycle)?

Initiation, activation, resorption, reversal and formation + mineralisation

What is the entire process of bone remodelling (6 points)?

1. Initiation: osteocytes detect microdamage and signal remodelling

2. Activation: osteoclast precursors are recruited

3. Resorption: osteoclasts mature and digest old/damaged bone, releasing growth factors (e.g., IGF, FGF)

4. Reversal: osteoclasts stop and are replaced by osteoprogenitor cells

5. Formation: osteoprogenitor cells differentiate into osteoblasts and secrete osteoid (collagen) onto the resorbed surface

6. Mineralisation: osteoid hardens to form new mineralised bone

How does an osteoclast break down bone at a cellular level (7 steps)?

1. Osteoclast attaches to bone using integrin αvβ3, creating a sealing zone

2. Inside osteoclast, carbonic anhydrase converts CO2 → H+ and HCO3-

3. H+ ions pumped into sealed zone by vacuolar H+-ATPase proton pump and chloride ions follow through Cl- channels

4. H+ and Cl- combine to form HCl

5. HCl dissolves the mineral (calcium salts) of bone

6. Osteoclast secretes cathepsin K and MMPs to digest collagen

7. Breakdown products are transported through the cell and released into the blood

What are the risk factors of osteoarthritis?

Age (>50), obesity, female, previous joint injuries, occupational/recreational use of affected join and family history

What are the key features seen in osteoarthritis which cause the symptoms observed in patients?

Joint space narrowing, osteophyte formation, and subchondral bone changes

How is osteoporosis diagnosed?

Based on typical clinical symptoms, physical examination findings, and imaging studies, with typical X-ray features including joint space narrowing and osteophytes (bone spurs) - no set diagnostic tool

What physiological process occurs within the marrow cavities of long bones to produce blood cells?

Haematopoiesis

Which specific type of protein constitutes 95% of the organic protein matrix in bone?

Type I collagen

What are the two major functional types of bone tissue?

Compact bone and spongy (cancellous) bone

What is the fundamental structural unit of compact bone?

The osteon

What is the structural unit of spongy bone, described as a honeycomb of matrix spikes?

Trabeculae

What defines the pathophysiology of Osteoarthritis (OA)?

An imbalance between the repair and destruction of joint tissue leading to cartilage breakdown

What are 'osteophytes' in the context of osteoarthritic disease?

Bony spurs or overgrowths that form at the joint margins due to bone overload

Which joint site accounts for approximately 85% of the total disease burden in Osteoarthritis?

The knee

What is the name for the hard bony swellings that occur on the distal interphalangeal (DIP) joints in hand OA?

Heberden's nodes

How are Bouchard’s nodes clinically distinguished from Heberden’s nodes?

Bouchard’s nodes occur on the proximal interphalangeal (PIP) joints rather than the distal joints

What is 'crepitus' in the clinical presentation of knee Osteoarthritis?

A grating or popping noise/sensation heard or felt during joint movement