Bone Pathology

Question 1

What is osteopetrosis?

Answer 1

• Marble bone disease; defective remodelling.
• Failure of osteoclasts.

Question 2

What is osteogenesis imperfecta?

Answer 2

• Multiple genetic syndromes.
• Causes brittle bones.

Question 3

What are the stages of fracture healing?

Answer 3

• Injury and resultant necrosis
• Inflammation
• Repair - callus formation
• Mineralisation
• Remodelling

Question 4

Describe Paget’s Disease (epidemiology, affected sites, pathology).

Answer 4

• Familial or sporadic.
• Commoner in Northern Europeans - up to 4% of the elderly.
• Can either affect a single bone or be more diffuse.
• Possible viral trigger.
• Remodelling gone wrong.
• Can cause bone pain which otherwise might be difficult to diagnose.

Question 5

What are the most common causative organisms of osteomyelitis?

Answer 5

• S. aureus
• TB

Question 6

What are the risks for osteomyelitis?

Answer 6

• The risks are 3fold:
  
  • Septicaemia – source of inflammation. Abscess within the circulation which can discharge pus and infective material into the circulation.
  • Development of amyloidosis (deposition of an abnormally processed protein in tissues, effectively starving them by preventing oxygen and nutrients from reaching the tissues).
  • Fracture.

Question 7

Describe the progression of osteomyelitis.

Answer 7

• Starts with nidus of infection in the bone (might be due to haematogenous spread if previous septicaemia, or occasionally can occur post-fracture) with local inflammation; local osteoblastic and osteoclastic response, formation of new bone and inflammation. But, if you don’t remove the inflammation and infection you can develop abscess and infection can spread within the bone, rupture through the bone and may even drain through to the skin.
• The importance of this is that much like with fracture healing, there will be typical inflammation and granulation tissue, but also cartilage and bone coming in. So, chronic osteomyelitis locally can lead to gross distortion of the bone. Once this infection has set up, it can be extremely difficult to treat because while there is a blood supply, it may be compromised or not rich. Makes it difficult to get ABx to the site of infection. May resort to surgical drainage or resection of bone.
• Easy to miss and can have significant long-term sequalae.

Question 8

Describe osteoporosis (include basic pathology).

Answer 8

• Bone becomes thinner.
• Loss of bone mass - calcium and osteoid.
• Loss of mineralised bone makes it thinner and easier to break.
• Major cause of morbidity in the elderly.
• They are often not diagnosed but some are becuase they present with fracture / pain / nerve trapping.
• Can be type 1 or type 2 osteoporosis.
  
  • The change, whether environmental, genetic or endocrine leads to a change in resorption of bone - resorption is increased and the result is less bone mass.

Question 9

Describe osteomalacia.

Answer 9

• Inadequate mineralisation.
• Caused by:
  
  • Rickets in children
  • Lack of sunlight
  • Inadequate diet
  • Malabsorption
  • Renal failure
• Symptoms:
  
  • Lethargy
  • Non-specific muscle pain
  • Can be asypmtomatic
• Trabecula may be normal size or even enlarged. There is increased deposition of osteoid but no mineralisation of this osteoid. Instead of having calcified bone, you end up with non-calcified matrix which is far less strong and makes the bone less resilient.

Question 10

What are the causes of hyperparathyroidism and how can this affect bone?

Answer 10

• Causes:
  
  • Parathyroid adenoma
  • Parathyroid hyperplasia
  • Secondary hyperparathyroidism can occur in renal failure
• Can cause increased resorption of bone because it promotes the action of osteoclasts.
• Can result in loss of bone tissue which would present in osteoporotic fashion.
• In the acute setting, it more typically presents with hypercalcaemia because more Ca²⁺ is released.

Question 11

What is osteoarthrosis?

Describe its treatment.

Answer 11

• Primary and secondary types.
• Affects:
  
  • Small joints
  • Neck and vertebral column
  • Hips
  • Knees
• Degenerative ‘wear and tear’ but may be more complex.
• Symptomatic treatment including joint replacement.
  
  • We only ever give symptomatic treatment.
  • ​NSAIDS, weight loss, arthroplasty.
  • We do not treat the underlying condition or pathogenesis.
• Common. Often not debilitating.

Question 12

Describe the pathology of osteoarthrosis.

Answer 12

• First thing that happens is the death of chondrocytes. They are important because they replace the wear and tear of articular cartilage.
• So, if these are damaged there will be cracking of the articular cartilage and synovial fluid will leak into the crack (this can be pro-inflammatory and cause further degradation of the cartilage).
• In time this can promote inflammation which can cause new blood vessels to form.
• Osteoclasts come in. Cartilage cannot grow back across. Difficult to repair; all you can do is slow progression.

Question 13

Describe rheumatoid arthritis.

Answer 13

• Systemic disease. Not just joints affected. Probably not a single disease.
• Tends to be symmetrical.
• Affects ages 30-70.
• Vague symptoms including joint pain which is worse after lack of movement.
• Pannus formation - inflammation leads to osteoclast activation.
• Progressive deformation.
• 1/2 progress; 1/4 relatively mild; 1/4 may recover.

Question 14

Can rheumatoid arthritis be triggered?

Answer 14

Yes. Can be triggered by infection.

Question 15

What is pannus formation?

Answer 15

• Pannus = inflammatory slough lying in the synovium affecting the articular cartilage leading to osteoclast activation in the adjacent periosteum therefore causing bone resorption.
• The persistence of this inflammatory pannus in the synovium causes progressive deformation. Damage to bone, damage to cartilage, remodelling and the cycle continues. This gives the classic chronic appearance of rheumatoid arthritis.

Question 16

What is the effect os rheumatoid factor?

Answer 16

• Rheumatoid factor = autoantibody.
• Causes a chronic inflammatory reaction (shown in picture).
• Growth factors cause the synovial cells to proliferate; not only is there inflammation and fibrin, there are more synovial cells, hyperplasia (eventually these cells are thrown into folds), there are lymphoid follicles present and plasma cells contributing lots of antibodies and all of this happens adjacent to the bone which causes secondary changes.
  • Inflammatory setting – swelling, redness, pain, restricted movement.

Question 17

Describe the treatment for rheumatoid arthritis.

Answer 17

• NSAIDs - but cause GI haemorrhage.
• Steroids still have a place in very acute disease but cause osteoporosis.
• DMARDs such as anti-TNF used increasingly.
  
  • They have many SEs.
• Physiotherapy is important.

Question 18

Who is commonly affected by avascular necrosis of the femoral head?

How is it treated and what are the consequences?

Answer 18

• Affects elderly. Female > Male.
• Often post-fall.
• Made worse by osteoporosis.
• The only treatment for this is replacement of the entire femoral head.
• Avascular necrosis in an elderly person resulting in a fractured NOF is significant - some no longer cope at home ad some die within 18 months.

Question 19

Describe the pathology of gout.

Answer 19

• Problem of uric acid metabolism.
  
  • Increased intake
  • Decreased removal
  • Increased cell turnover or death

Question 20

Which populations are affected by gout?

Describe the symptoms.

Answer 20

• Male > Female 20:1
• Age 40-50
• Family history common
• Symptoms are variable:
  
  • Inflammation and pain
  • Renal stones

Question 21

Describe the treatment of gout.

Answer 21

• Treatment is diet control and use of inhibitors of the enzymes involved in processing the hypoxanthine through to uric acid (allopurinol).

Question 22

Describe neoplasia in bone.

Answer 22

• Commonest tumours in bone are secondary metastatic.
  
  • Breast, kidney, lung, prostate. Less commonly colon and thyroid.
• Lung cancer and prostate cancer patients in particular can present for the first time with bone pain or a pathological fracture as the presenting feature of the disease.
• Benign – omas.
• Malignant tumours are sarcomas.
• When it is not strictly within the bone – myeloma. Myeloma = malignant proliferation of plasma cells typically present in the marrow.