B103 Osteomyelitis, Pagets disease

Question 1

Osteomyelitis, what is it, what causes it

Answer 1

Infectious inflammation of the bone and/or marrow. Can occur as part of a systemic infeciton, but is more often and isolated focal infection. Can be acute or chronic.

Pyogenic osteomyelitis

• Healthy adults: Staph Aureus
• Sickle cell patients: Salmonella in
• Neonatal: E. coli and Group B streptococci
• Bone Trauma or Injury: Mixed pyogenic bacteria, and Anaerobic bacteria (and S. aureus
• Diabetecs and IV drug users: Pseudomonas
• Dog and Cat bites: Pasteurella
• N. gonorrhea
• In as many as 50% of cases there is no identifiable organism isolated.

Tuberculous osteomyelitis

• Typically of the lumbar vertebrae, called Pott’s disease
• ii. Tuberculosis Osteomyelitis
  1. Mycobacterial infection of bone has long been a problem in developing countries.
  2. With the resurgence of tuberculosis (due to immigration patterns and increasing numbers of immunocompromised hosts) it is becoming an important disease in other countries as well.
  3. Bone infection complicates ~ 1 ‐ 3% of cases of pulmonary tuberculosis.
  4. The organisms usually reach the bone through the bloodstream, although direct spread from a contiguous focus of infection (e.g., from mediastinal nodes to the vertebrae) can also occur.
  5. With hematogenous spread, long bones and vertebrae are favored sites.
  6. The lesions are often solitary but can be multicentric, particularly in patients with an underlying immunodeficiency.
  7. Because the tubercle bacillus is microaerophilic, the synovium, with its higher oxygen pressures, is a common site of initial infection. The infection then spreads to the adjacent epiphysis, where it causes a typical granulomatous inflammation with caseous necrosis and extensive bone destruction.
• 8. Tuberculosis of the lumbar vertebral bodies, or Pott disease, is an important form of osteomyelitis.
     a. Infection at this site causes vertebral deformity and collapse, with
     secondary neurologic deficits.
     b. Extension of the infection to the adjacent soft tissues with the
     development of psoas muscle abscesses is fairly common in Pott disease.

Question 2

Morphology and histology of osteomyelitis

Question 3

What are the main anatomical points of a bone (ie parts ending in ‘physis’)

Where does osteomyelitis typically occur in children vs adults?

Answer 3

Children: Typically in the metaphyseal region, where the blood flow is the greatest. Because osteomyelitis is usually the result of bacteremia and hematogenous spread

Adults: Epiphyseal and subchondral areas, also usually from bacteremia and hematogenous spread, but the metaphysis is far less active/vascularized in adults after growth (epiphyseal) plate closure.

See image for anatomy

Question 4

What is the histology of osteomyelitis

Question 5

Clinical presentation and symptoms of acute osteomyelitis

Answer 5

• Bone pain, Fever, Leukocytosis
• Diagnosis by blood culture, tho these can give false negatives and need diagnosis by biopsy of the lesion.
• Treatment by surgical drainage and antibiotics.

Lytic focus, the Sequestrum, of liquifactive necrosis on X-ray. After about a week, growth of new reactive bone forms the Inovlucrum around the infected site.

Infection can spread under the periosteum, especially in children where it is more loosely attached, and create subperiosteal abscesses.

These periosteal foci can cause periosteum rupture, infecting nearby soft tissue and infecting all the way out to the overlying skin and forming a draining sinus. Bits of the Involucrum can fall off and drain out of the sinus.

Viable infectious organisms can persist for years inside the sequestrum of an osteomyelitis lesion, and 5-25% progress to chronic osteomyelitis

Usually in young children, but also uncommonly in adults, epiphyseal infections can spread into the nearby joint to produce purulent arthritis. This can cause destruction of the articular cartilage leading to permanent damage to the joint.

If the infection is in the vertebrae, it can spread up or down the vertebral chain by the same process.

Question 6

What are the potential risks for chronic osteomyelitis

Answer 6

Potential for ‘flare ups’ into acute osteomyelitis

pathological fractures

secondary amyloidosis (SAA)

endocarditis

sepsis

risk for squamous cell carcinomaalong the sinus tract

increased risk (although rare) for osteosarcoma

Question 7

Describe the pathogenesis and histology of Paget’s disease of bone.

Answer 7

• Also called Osteitis Deformans.
• A solitary/focal or polyostotic/multi-focual disease of the bone not the entire skeleton.
• It appears in late adulthood.
• Unknown cause, possibly viral - chronic paramyxovirus
• Related to increased IL-1, IL-6, and M-CSF levels in the affected bone
• Common in the US, Australia, most of europe. Rare in Scandinavia, China and Japan.
• Involves disregulated osteoclast followed by dysregulated osteoblast activity, and has 3 stages.

Osteolytic stage - excessive osteoclast activity and bone resorption

Mixed osteoclast-ostebolast stage - high levels osteoclast resorption simultaneously with high levels of osteoblast deposition. The osteoclasts ‘burn out’ first, and the stage goes on to pure excessive osteoblast deposition phase. The osteoblasts lay down excessive imporperly organized bone. It also invades and replaces the local marrow with loose connective tissue that generates many new vessels and A-V anastomoses. The new bone has a distinct mosaic pattern of lamellar bone. (buzz)

Osteosclerotic stage - The osteoclasts burn out and stop proliferating, the medullary fibrovascular area recedes and is replaced by normal marrow, and the cortex is now very thick, disorganized, and weakened.

Question 8

What is the clinical presentation of Paget’s disease?

Answer 8

• Bone pain at the affected site
• Increasing hat size
• Headache, Backache
• Hearing loss or Vision loss due to cranial nerve impingment
• Facial changes, Lion faces.
• Spinal nerve root compression and pain.
• Deformation or fracture of vertebrae and leg bones.
• High-output cardiac failure due to the formation of A-V anastomoses.
• 1% may develop into osteosarcoma - not vertebral lesions though.
• Isolated elevation in ALP in serum (elevated from the high expression in osteoblasts as they use this enzyme to lay down lots of bone). Calcium, phosphate,
• About 85% are monostotic (single site) and 15% are polyostotic
• Typically involves the skull, vertebrae, humerus, illeum, femur, or tibia. Rarely the hands, feet or ribs.

Question 9

Treatment and prognosis for Paget’s disease

Answer 9

Treatment:

• Bisphosphonates: osteoclast apoptosis
• Calcitonin: inhibit osteoclast function
• Inhibition of the initial phase generally prevents the mixed phase and precludes the excessive deposition by osteoblasts in response to the initial resorption.

Prognosis:

Paget’s disease itself is highly treatable with these medications and is usually well controlled

The exception is the 1% of cases which develops into osteosarcoma, and these Paget’s originated osteosarcomas have a very poor prognosis.