Infectious and Inflammatory Bone and Joint Disease

Bone is a _________ tissue that continuously undergoes changes in its structure throughout an animal's life

dynamic

Two processes bone continuously undergoes:

1.) bone modeling

2.) bone remodeling

Bone Modeling

process of shaping and reshaping bone by independent action of osteoclasts and osteoblasts

Bone Modeling is most prominent during...

growth and development

Remodeling

replacement of existing bone through the coordinated, sequential actions of osteoclasts and osteoblasts

What triggers remodeling?

damage or the need to adapt to mechanical stress

Remodeling is most prominent during...

adult phase of life

Three bone cells:

1.) osteoclasts

2.) osteoblasts

3.) osteocytes

osteoclasts

large multinucleated cells that resorb or break down the bone matrix

osteoblasts

bone forming cells that form osteoid

Osteoid

unmineralized organic matrix of bone; undergoes mineralization to form mature bone tissue

Three functions of osteoblasts:

1.) osteoid production

2.) regulation of bone resorption

3.) Ca and P control in and out of bone

osteocytes

mature bone cells that develop when osteoblasts become embedded within the osteoid matrix

osteocytes functions

1.) detect micro damage

2.) respond to strain

RANK-RANKL-OPG Pathway

signaling system that regulates bone remodeling by controlling osteoclast development and activity

RANK

receptor located on the surface of immature osteoclasts

What happens when RANK is activated?

it stimulates immature osteoclasts to develop into mature, bone-resorbing osteoclasts

RANKL

RANK ligand; signaling protein produced by osteoblast lineage cells that binds to RANK on immature osteoclasts to stimulate their maturation

Osteoprotegerin (OPG)

acts as a decoy receptor that binds to RANKL and prevents it from interacting with RANK; limits excessive bone resorption

Steps of the RANK-RANKL-OPG Pathway

1.) when bone damage occurs, osteoblast lineage cells produce RANKL

2.) RANKL binds to RANK on immature osteoclasts

3.) immature osteoclasts mature and activate bone resorption

4.) mature osteoblasts remove damaged bone (resorption)

5.) to prevent excessive resorption, OPG binds to RANKL, preventing it from activating additional osteoclasts

Osteolysis

destruction or resorption of bone tissue by osteoclasts

osteoclasts achieve osteolysis by breaking down both the ________ and _________ components of the bone matrix

mineral; organic

Two molecules released by osteoclasts during osteolysis:

1.) hydrogen ions

2.) Cathepsin K

hydrogen ions

dissolves hydroxyapatite, the primary mineral component of bone

Cathepsin K

proteolytic enzyme that breaks down collagen; degrades the organic component of bone

Wolff's Law

A bone grows or remodels in response to forces or demands placed upon it

When mechanical loading increases, bone adapts by...

increasing its strength to accommodate the greater forces

When mechanical loading decreases, bone adapts by...

increased resorption, resulting in reduced bone strength

Repetitive Cyclic Loading

repeated application and removal of mechanical stress on a bone over time, such as the forces experienced during running or jumping

What does Repetitive Cyclic Loading lead to?

areas of microscopic bone damage that cannot repair themselves quickly enough

Normally, osteoclasts remove damaged bone and osteoblasts replace it.

However, during Repetitive Cyclic Loading...

osteoclasts remove bone more rapidly than osteoblasts can replace it!

During Repetitive Cyclic Loading, bone ________ exceeds bone _________

resorption; formation

Example of animals that undergo Repetitive Cyclic Loading

racehorses

Subchondral bone injury

damage to the bone located directly beneath the articular cartilage of a joint; often caused by repetitive cyclic loading or excessive mechanical stress

Four diagnostic tools used to diagnose subchondral bone injury:

1.) radiographs

2.) nuclear scintigraphy

3.) CT

4.) MRI

radiographs and subchondral bone injury

not always useful in diagnosing subchondral bone injury since injury is microscopic

nuclear scintigraphy and subchondral bone injury

identifies areas of increased bone turnover; useful when lameness has been localized to a limb but cannot be localized to a specific anatomical region

CT and subchondral bone injury

effective for identifying subtle bony abnormalities that may be difficult to detect radiographically

MRI and subchondral bone injury

particularly valuable for evaluating soft tissue structures and identifying abnormalities deep within bone; provides excellent detail of cartilage, ligaments, and other soft tissues

Subchondral bone injury represents an ________ stage of damage associated with repetitive loading

early

Four bone injuries that result with advanced repetitive loading:

1.) osteochondral fragmentation

2.) larger fractures

3.) stress related cortical bone injury

4.) catastrophic fractures

osteochondral fragmentation

occurs with continued exercise on weakened subchondral bone

osteochondral fragment

piece of articular cartilage and underlying bone that separates from the surrounding tissue

osteochondral fragments usually remain ________ to the parent bone

attached (rather than becoming completely free floating)

What can be used to treat osteochondral fragmentation?

Arthroscopic Treatment

Arthroscopic Treatment

small camera (arthroscope) is inserted into joint with surgical instruments and abnormal tissue/fragments are removed

If repeated load continued to occur, osteochondral fragmentation can then develop into...

larger fractures

larger fractures

large bone fractures that develop from osteochondral fragments; require surgical repair

Stress-Related Cortical Bone Injury

repetitive loading causes injury to the cortical bone

Stress-Related Cortical Bone Injury example

stress fractures!

stress fractures

small crack that develops in the bone as a result of repetitive cyclic loading

cortical bone

hard, dense, strong bone that forms the outer layer of bone; aka compact bone

If repetitive loading continues after a stress injury, it can develop into...

a catastrophic fracture

Catastrophic Fractures

complete fracture extending through both cortices of the bone

Osteomyelitis

inflammation of bone caused by infection with a microbial organism

The causative organism of osteomyelitis is often...

bacteria (though sometimes fungal)

Two types of osteomyelitis:

1.) acute osteomyelitis

2.) chronic osteomyelitis

acute osteomyelitis

occurs during the early stages of infection and is generally not yet associated with substantial osteonecrosis

osteonecrosis

death of bone tissue

chronic osteomyelitis

more prolonged infection that is commonly associated with some degree of osteonecrosis

Five factors that can influence the development of osteomyelitis:

1.) virulence of organism

2.) immune status

3.) comorbidities

4.) soft tissue trauma

5.) type of bone affected

How does virulence of organism influence osteomyelitis?

Organisms responsible for osteomyelitis may have characteristics that allow them to survive in bone and resist host defenses, making the infection difficult to eliminate

How does immune status influence osteomyelitis?

Immunocompromised animals may be more susceptible to developing osteomyelitis

How do comorbidities influence osteomyelitis?

Concurrent diseases can affect the patient's ability to respond to infection and may complicate treatment

How does soft tissue trauma influence osteomyelitis?

Damaged soft tissues provide a favorable environment for infection and may compromise local blood supply and tissue defenses

How does type of bone affected influence osteomyelitis?

The anatomical characteristics and type of bone involved may influence the development and progression of infection

Infectious organisms can cause bone destruction through both _______ and ________ mechanisms

direct; indirect

Direct mechanism of bone destruction by infectious organisms:

bacteria can directly contribute to bone matrix degradation by producing enzymes and other factors that damage the extracellular matrix

Indirect mechanism of bone destruction by infectious organisms:

Bacteria stimulate the RANK-RANKL-OPG pathway, increasing osteoclast activity, and leading to excessive bone resorption

The development of osteomyelitis often begins when...

bacteria adhere to components of the bone extracellular matrix

The adherence of bacteria to the bone extracellular matrix is mediated by what molecules?

adhesins present on bacterial surface

Following attachment to the bone extracellular matrix, bacteria can...

produce factors that promote matrix degradation and stimulate inflammatory pathways that contribute to bone destruction

Pathogenesis of osteomyelitis:

1.) bacteria adhere to components of the bone extracellular matrix (fibrinogen, collage, etc)

2.) Hyaluronidases, collagenases, and proteases are produced by microbes leading to break down of bone matrix

3.) bacteria evade host defense mechanisms with biofilm formation

biofilm

structured community of microorganisms attached to a surface and surrounded by a protective extracellular matrix; help bacteria evade host immune defenses

Three major routes through which infection can develop within bone:

1.) Hematogenous Infection

2.) Traumatic Infection

3.) Iatrogenic Infection

Hematogenous Infection

occurs when bacteria spread through the bloodstream from an infection elsewhere in the body

Bacteria from a Hematogenous Infection commonly localize where? (3)

growth plate, epiphysis, or joint

Hematogenous Infection is common in what age?

neonatal foals and calves

Why does Hematogenous Infection commonly occur in neonatal foals and calves?

it is associated with failure of passive transfer (or infection elsewhere in body due to immature immune system)

Clinical presentation of Hematogenous Infections

A foal or calf with a swollen joint (esp w/ history of failure of passive transfer, umbilical infection, pneumonia, or diarrhea)

Traumatic Infection

occurs when an external wound introduces bacteria into bone or adjacent joint structures

Traumatic Infection is common in what age?

adult horses

Iatrogenic Infection

develops secondary to a medical or surgical procedure

example of an Iatrogenic Infection

orthopedic implant following fracture repair

Hematogenous infections in young animals can be classified according to...

the anatomical location of the infection

Four classifications of Hematogenous infections:

1.) S-Type Infection

2.) P-Type Infection

3.) E-Type Infection

4.) T-Type Infection

S-Type Infection

Synovial; involves the synovial membrane and synovial fluid, where bacteria spread through the bloodstream and localize within the synovial membrane of a joint

P-Type Infection

Physeal; bacteria establish infection on the physis, or growth plate, of a long bone

E-Type Infection

Epiphyseal; involves the epiphysis, particularly the bone adjacent to the articular cartilage

epiphysis

the end part of a long bone

An E-Type Infection can spread into...

the joint, producing secondary synovial infection

T-Type Infection

Cuboidal Bone; osteomyelitis involving cuboidal bones of the tarsus/carpus

S-Type Infections will lead to _________ arthrtiis

septic arthritis

septic arthritis in foals

common complication of sepsis in foals, that mandates prolonged treatment with substantial medical expense and is associated with poor prognosis.

Gram negative bacteria that can lead to septic arthritis in foals: (3)

1.) E coli

2.) Actinobacillus sp.

3.) Klebsiella sp

Gram positive bacteria that can lead to septic arthritis in foals: (2)

1.) Staphylococcus sp.

2.) Streptococcus sp

Bacteria that can lead to septic arthritis in calves

Mycoplasma

Clinical signs of septic arthritis in foals

-lameness

-joint effusion/swelling

-fever

-pain on palpation

-multiple joint involvement

Are older or younger foals more likely to have multiple joints affected by septic arthritis?

younger foals

What classifications of hematogenous infections are younger foals more likely to be infected with?

S type and E type

*therefore, these types are more likely to affect multiple joints when septic arthritis develops