Osteomyelitis, Osteonecrosis, Osteoradionecrosis of the Bones

Question 1

What is osteomyelitis?

Answer 1

Inflammation in the bone marrow

A spectrum of inflammatory and reactive changes in the bone and the periosteum (a thin sheet/membrane that adheres to bone)

An infective disease of bone which results in necrosis of an area of the affected bone

Can be acute or chronic

Can be suppurative or non-suppurative (pus filled or not)

Chronic forms have a primary and secondary phase

Question 2

What is the periosteum?

Answer 2

A thin sheet / membrane that adheres to bone

Question 3

Osteomyelitis can be broken down into the following:

Answer 3

Acute

Chronic

(Suppurative, non-suppurative)

Syphillitic (really rare division of osteomyelitis that can be caused by syphilis)

Tuberculosis (really rare division of osteomyelitis that can be caused by TB)

Question 4

What does chronic osteomyelitis look like?

Answer 4

Primary (no acute episode, sub-clinical infection)

Secondary (prolonged inflammatory process)

Question 5

List the risk factors for osteomyelitis

Answer 5

Odontogenic infection (a dental infection that has not been treated appropriately)

Peri-implantitis (inflammation around dental implants)

Infected cyst

Infected tumour

Surgical wound (wound that doesn’t heal and therefore becomes infected)

Underlying disorders-
Diabetes mellitus
Fibrous dysplasia
Previous exposure of bone secondary to radiation (osteoradionecrosis)
Osteoporosis
Osteopetrosis
Paget’s disease
Bone tumours
Immunocompromise

Secondary osteomyelitis as a result of bacteria travelling from elsewhere via the bloodstream, into the bone.

Question 6

List the underlying disorders that act as risk factors for osteomyelitis

Answer 6

Diabetes mellitus

Fibrous dysplasia

Previous exposure of bone secondary to radiation (osteoradionecrosis)

Osteoporosis

Osteopetrosis

Paget’s disease

Bone tumours

Immunocompromise

Secondary osteomyelitis as a result of bacteria travelling from elsewhere via the bloodstream, into the bone.

Question 7

Describe the pathophysiology of osteomyelitis

Answer 7

2 routes that can lead to necrosis of the bone-

Host defences reduce or become non-existent causing microbial colonisation of the jaw bone (microbes begin to overgrow and become pathological) subsequent infections and death of bone.

OR

Certain microbes are able to get into the bone or marrow space to cause a collapse of the blood system.

These include bacteriodes, Staphylococcus Aureus, anaerobic Streptococcus.

These microbes can also cause venous stasis, potentially increasing the chances of thrombotic events/ischaemia.

So there is a significant reduction in the blood supply in the region (reducing the ability of the body to fight off the infection/microbes or heal the bone) as well as an increase in the intramedullary pressure.

Together the compromised blood supply and increased intramedullary pressure lead to the death of the affected bone

As the bone begins to die, we may observe the following-

Resorption of the bone

Some new bone formation (known as involucrum, visible on radiographs)

Sequestration (where little pieces of bone are slowly exfoliated out of the surgical wound)

Question 8

What is involucrum?

Answer 8

As the bone begins to die, some new bone may form

Question 9

What is sequestration

Answer 9

As the bone begins to die, little pieces of bone are slowly exfoliated out of the surgical wound

Question 10

As bone necrosis begins, what 3 processes may we observe?

Answer 10

Bone resorption

Bone sequestration

Bone formation (involucrum)

Question 11

What microbes can proliferate, enter a wound and infiltrate the bone marrow space to cause infection (osteomyelitis)

Answer 11

Bacteriodes

Staphylococcus Aureus (skin commensal)

Anaerobic Streptococcus (e.g. Streptococcus Viridans)

Strict anaerobes (e.g. Prevotella, Fusobacterium, Peptostreptococcus)

Question 12

Osteomyelitis more commonly affects the mandible more than the maxilla. Why is this?

Answer 12

The mandible is composed of large amounts of cancellous bone which is more likely to become ischaemic

This means the blood supply to the mandible is less well oxygenated

The dense overlying cortical bone of the mandible also prevents penetration of periosteal blood vessels much more than in the maxilla, leading to a poorer blood supply in the mandible

As a result, the mandible is much more susceptible to infection as it has a poorer blood supply that is less oxygenated than the maxilla

Question 13

Describe the features of acute osteomyelitis

Answer 13

Initially-

Localised infection

Deep intense pain

High intermittent fever 38-40 degrees (sometimes swinging fever, where the patient will have a fever, then return to normalcy, then have a fever again)

Clearly identifiable causative tooth

Minimal swelling

No fistulae

+/- malaise, headache, reduced appetite

Will last 1-2 weeks

If left untreated or treatment has failed, the infection can spread to cause systemic toxic symptoms-

Signs of inflammation (rubor, calor, dolor, tumor, functio laesi)

Lymphadenopathy

Evident purulent discharge that erodes the bone

Extensive, firm swelling that is erythematous and warm to touch

Throbbing jaw pain

Severe tenderness

‘Extrusion’ of teeth

+/- Trismus

+/- Paraesthesia (if there is nerve involvement, there may be numbness in the distribution of the ID nerve- lip, chin numbness)

Blood screen would reveal leukocytosis and elevated CRP (inflammatory marker that indicates generalised inflammation)

Question 14

What special investigations should be undertaken for a patient with suspected osteomyelitis

Answer 14

Imaging/radiographs (to observe the appearance of the bone and look for features of osteonecrosis)

Blood screen (to assess for leukocytosis and elevated CRP (inflammatory marker that indicates generalised inflammation))

Question 15

What would a blood screen of a patient with suspected osteomyelitis reveal?

Answer 15

Leukocytosis

Elevated CRP (inflammatory marker that indicates generalised inflammation)

Question 16

Describe the features of chronic osteomyelitis

Answer 16

Osteomyelitis progresses to become chronic

Normothermic (patient often has a normal temperature)

Acute symptoms resolve / disappear

Teeth are locally tender

Sequestra/exfoliation of small pieces of bone through areas of breached mucosa (the mucosa has to be breached for this to occur)

Risk of pathological fracture

Radiographically presents as moth eaten appearance of bone (hazy radiolucency), sequestration of bone, new bone appearance (involucrum, some areas of increased radiodensity surrounding area of radiolucency due to increased bony production), osteosclerosis (hypersensitivity reaction)

Question 17

Describe the radiographic features of chronic osteomyelitis

Answer 17

Moth eaten appearance of bone (hazy, abnormal radiolucency).

Islands of sequestration within bone

New bone production (involucrum, some areas of increased radiodensity surrounding area of radiolucency due to increased bony production)

Osteosclerosis (hypersensitivity reaction)

Question 18

The method of diagnosis for acute and chronic forms of osteomyelitis differ. Describe how

Answer 18

Acute osteomyelitis is determined using clinical signs and symptoms (deep intense pain, paraesthesia, lymphadenopathy) and blood screens (to detect elevated CRP and lekocytosis)

Chronic osteomyelitis is determined using clinical signs (sequestration of bone through breached mucosa, teeth locally tender) and imaging (moth eaten appearance, islands of radiodense bone in area of radiolucent bone, osteosclerosis)

Question 19

Why are plain film radiographs not useful in the acute phase of osteomyelitis?

Answer 19

It takes 1-2 weeks for radiological changes in bone following osteomyelitis to appear. Radiological imaging is therefore not useful to diagnose osteomyelitis in its acute form

Once the osteomyelitis has become established/chronic, characteristic radiographic features start to become apparent

Individuals with suspected osteomyelitis symptoms should still be imaged but if the imaging appears normal, it does not rule out osteomyelitis as the cause and they should still be treated for it.

Question 20

List the imaging techniques that may be used when osteomyelitis is suspected

Answer 20

OPT

CT (sometimes more useful earlier on than OPT)

Less commonly-

MRI (sometimes more useful earlier on than OPT)

Radionucleotide scanning (superior to conventional imaging, Gallium accumulates at inflammation/infective site)

Question 21

List the treatment options for osteomyelitis

Answer 21

Empirical antibiotic treatment

+/- Surgery, to remove the cause/source (sequestra or infected bone) and get a microbe sample for MC+S to determine the causative pathogen and antibiotic sensitivity

Hyperbaric oxygen (patient made to sit in a hyperbaric chamber to increase the oxygen supply to the area of infection.
Helps angiogenesis and osteogenesis, increases leukocyte activity and stimulates growth factors into the area etc.)

Question 22

How is hyperbaric oxygen used to treat osteomyelitis

Answer 22

Patient is made to sit in a hyperbaric oxygen chamber to increase the oxygen supply to the area of infection.

This enables-
An augmentation of angiogenesis

An improvement in osteogenesis

An increase in leukocyte activity

A stimulation growth factors into the area

Question 23

Which antibiotics may be used to treat osteomyelitis? What is the rationale behind these choices?

Answer 23

High dose of broad spectrum Penicillins (as there is a compromised blood supply in osteomyelitis, it is often challenging to get antibiotics to the site of infection).

E.g. Clindamycin is often favoured as it penetrates avascular tissue, proving useful where there is a poor blood supply. One drawback of this antibiotic however is that it can cause a C. difficile superinfection which is quite serious and often can be fatal.

Metronidazole may be added sometimes (to counter the anaerobes).

If the patient is really unwell, they may require hospitalisation and IV administration of the antibiotics

Question 24

How is surgery used to treat osteomyelitis? What are its benefits?

Answer 24

Surgery used to remove the source/cause (sequestra or infected bone)

Known as a sequestrectomy

Once removed, the sequestra/infected bone can provide a microbial sample to be sent to MC+S so that the causative pathogen and its antimicrobial sensitivity can be determined

Surgery allows-
An improvement of blood supply (allowing the aggressive antibiotic to penetrate the infective site adequately to have its beneficial effects)

Maximisation of host defence mechanisms

Self-healing ability

Question 25

What is alveolar osteitis

Answer 25

Dry socket

Question 26

Describe the differences between osteomyelitis and alveolar osteitis

Answer 26

Osteomyelitis spreads through bone whereas alveolar osteitis (dry socket) is localised to only the extraction socket. If osteomyelitis is left untreated, it will progress as it is not a self-limiting condition. If a dry socket is left untreated, it will eventually get better. Osteomyelitis is much more chronic and represents failure of the host's normal defences. However, if a patient returns with a dry socket multiple times despite treatment with alveogyl, we should have a high index of suspicion that something else may be happening in the socket (i.e., osteomyelitis or a malignancy). Ideally, sockets should be healed by 8 weeks.

Question 27

A patient as returned to your clinic multiple times, presenting with a dry socket despite treatment with alveogyl. What should you have a high index of suspicion for?

Answer 27

High index of suspicion that something else may be happening in the socket as ideally it should be healed by 8 weeks. E.g. osteomyelitis or a malignancy

Question 28

What is osteoradionecrosis?

Answer 28

Necrosis of bone in a previously irradiated area (in the absence of tumour persistence/recurrence) Bone exposed in the irradiated area with a diameter of >1cm lasting for at least 6 months without any tendency to heal

Question 29

Describe the pathophysiology of osteoradionecrosis

Answer 29

By irradiating bone, we cause endarteritis obliterans which is where blood vessels are obliterated. This reduces the blood supply to the bone leading to hypovascular and hypoxic bone (lack of blood supply and lack of oxygen to bone) The irradiation of bone also causes osteocytes and fibroblasts to undergo cell damage or death, leading to hypocellular bone (lack of cells within bone) Both processes can cause death of bone cells (loss of vitality), which the bone cannot repair itself from due to a lack of blood supply. If this area of affected bone then undergoes some trauma e.g., XLA or there is an odontogenic infection, the affected bone can become necrotic.

Question 30

Describe the features of osteoradionecrosis

Answer 30

Non-healing exposed bone (often asymptomatic small areas but can also be severely sore and painful) Foul smelling necrosis of the jaw Suppuration Presence of orofacial fistula (chronic communication of oral cavity and bone) Pathological fracture Extra-oral drainage

Question 31

How may we diagnose osteoradionecrosis?

Answer 31

Clinical signs and symptoms (severe pain, non-healing exposed bone within a previously irradiated area, foul smell, extra-oral drainage, suppuration, oroantral fistula) Imaging (plain film- OPT, will reveal reduced bone density and sometimes a pathological fracture, CT)

Question 32

What special investigations can we use to diagnose osteoradionecrosis?

Answer 32

Imaging- OPT CT

Question 33

Other than following XLA, what other situation may result in osteoradionecrosis?

Answer 33

May occur where the mucosa in the irradiated area has become so thin that the underlying bone has perforated through and is unable to heal itself.

Question 34

How do we treat osteoradionecrosis?

Answer 34

Preventive management is the best- Pre-radiotherapy, dentists should ensure the patient is as dentally fit as possible (remove all hopeless prognosis treat prior to radiotherapy, treat any active disease and ensure positive behaviour modification to prevent the need for XLA/dental treatment in the future) Irrigation with saline Analgesia Antibiotics if indicated Debridement

Question 35

How would we manage extractions for a patient who has had radiotherapy?

Answer 35

If an XLA is required following radiotherapy, we should refer the patient back to the team who performed the radiotherapy (MDT with OMFS/oral surgeon/restorative dentist usually) Chlorhexidine mouthwash following XLA post-radiotherapy is suggested by some. Some evidence to support the insertion of PRF (platelet rich fibrin) to encourage healing and prevent osteoradionecrosis) following XLA Review to ensure healing- if in doubt, the patient should be referred

Question 36

What is the mechanism of action of bisphosphonates?

Answer 36

Attach to hydroxyapatite binding sites, particularly on surfaces that are actively resorbing This attachment impairs osteoclastic activity (by hindering their ability to bind to the bony surface). As a result, bone resorption is inhibited Reduce osteoclast activity by promoting osteoclast apoptosis and inhibiting development of new osteoclasts

Question 37

What conditions are bisphosphonates used for?

Answer 37

Paget’s disease Steroid induced osteoporosis (long-term steroid use) Post-menopausal osteoporosis Multiple myeloma (malignancy) Metastasising solid cancers (where cancer has spread to other regions within the body) Hypercalcaemia of malignancy (patients with malignancies often develop high Ca2+ levels)

Question 38

What is MRONJ?

Answer 38

Exposed bone or bone that can be probed (through an intra-oral/extra-oral fistula in the maxillofacial region) which has persisted for more than 8 weeks in patients with a history of treatment with certain medications (bisphosphonates, antiangiogenics, biologics) and where there has been no history of radiotherapy or obvious metastasis to the jaws

Question 39

Describe the pathophysiology of MRONJ

Answer 39

Inhibition of osteoclastic bone resorption and remodelling Inhibition of angiogenesis Presence of inflammation / infection of bone Patients develop exposed bone in the jaw (non-healing socket) following extractions or mucosal trauma Toxicity to soft tissues preventing bone turnover (alternative hypothesis)

Question 40

List the drugs that can cause MRONJ

Answer 40

Bisphosphonates (alendronic acid, zoledronic acid) RANKL inhibitors (denosumab) Anti-angiogenic drugs (sunitinib) (RANKL inhibitors and anti-angiogenic drugs are biologics)

Question 41

What is incidence and onset of MRONJ with oral bisphosphonates?

Answer 41

Low incidence rate (<1%) Incidence is time and dose dependent (the longer the patient is on the drug or the higher its dose, the greater the incidence) Time to onset ranges from 3-10 years following drug use

Question 42

List those situations where the risk of MRONJ is higher

Answer 42

Those who have had MRONJ before Those taking anti-resorptive/anti-angiogenic medications for malignancy/cancer (often IV bisphosphonates, higher risk in prostate cancer/myeloma patients or those cancer patients being treated with combination therapy) Those taking IV bisphosphonates Those taking bisphosphonates for >5 years or those who have taken them in the past for >5 years Immunosuppressed patients (those taking long term steroids, Azathiopine, Methotrexate) Immunocompromised patients (Diabetes Mellitus, HIV etc.)

Question 43

How do we manage patients with a high risk of MRONJ?

Answer 43

Prior to medication use, we should ensure the patient is as dentally fit as possible (preventive therapy, treat aggressively from an OH perspective so that XLA is never required) Advise lifestyle changes (modifiable risk factors such as smoking, alcohol and diet) Avoid extractions where possible (if XLA is one indication, consider whether there are possibilities to simply restore or remove the crown and keep the root as an overdenture etc. instead) Ensure follow up healing at 8 weeks for any XLA's undertaken during medication use ? evidence to support the insertion of PRF (platelet rich fibrin) to encourage healing and prevent MRONJ) following XLA No evidence for antibiotics or Chlorhexidine mouth rinses following XLA.

Question 44

What is the incidence rate of MRONJ with IV bisphosphonates?

Answer 44

Variable Up to 16% according to some studies Mostly in myeloma/breast cancer Risk of MRONJ higher in prostate cancer/myeloma patients Risk of MRONJ higher where patients are undergoing combination therapy