SA Musculoskeletal Conditions - Bone Disease and Bisphosphonates.

Question 1

Common sites of osteosarcoma?

Answer 1

Distal radius.
Proximal humerus.
Proximal tibia.
Distal femur.
(distal tibia and proximal femur).
Generally in the metaphyseal area of the long bone.
Patients may present with pathological fractures due to weakening of the bone.

Question 2

1. Osteosarcoma signalment.
2. Osteosarcoma clinical signs.

Answer 2

1. Middle aged.
   Large/giant breeds (occasionally in smaller breeds).
   Can be seen in younger dogs
   - tends to be more aggressive.
2. Lame (can be acute).
   Hx.
   Swelling/pain.
   Pathological fractures.

Question 3

Tx options for osteosarcoma?

Answer 3

*By time apparent in the bone, may have already metastasised elsewhere.
Euthanasia - reasonable option.
Medical / symptomatic - limited pain relief.
Bisphosphonates - delays mets and analgesic.
Radiation - no effect on mets, but analgesic w/ 4-6mths survival.
Amputation - no effect on mets, but analgesic w/ 4-5mths survival.
Amputation and chemo - delays growth of mets w/ 8-12mths survival (Cisplatin/Carboplatin).
Limb sparing and chemo - delays growth of mets w. 8-10mths survival (Cisplatin/Carboplatin).

Question 4

1. Panosteitis aetiology.
2. Panosteitis pathogenesis.
3. Panosteitis signalment.
4. Clinical signs of panosteitis.

Answer 4

1. Unknown (viral, excess nutrition, hereditary).
2. Degeneration of intramedullary adipocytes.
   Intramedullary ossification.
3. 5-18mths, large breed male dogs, GSD.
4. Lame, NWB, shifting, migratory.
   Dull, anorexia, pyrexia, painful bone on palpation.

Question 5

Dx of panosteitis.

Answer 5

Radiography/CT.
Patchy increased density of medulla of bone.
- distal humerus.
- proximal ulna.
‘Thumbprints’.
Near nutrient foramen.
Worth taking radiographs of several limbs as lameness may occur w/o lesion in limb.

Question 6

Tx and Px of panosteitis.

Answer 6

Symptomatic treatment of pain w/ good prognosis as condition will resolve w/ age.

Question 7

1. Metaphyseal osteopathy aetiology?
2. Metaphyseal osteopathy signalment?
3. Metaphyseal osteopathy clinical signs?

Answer 7

1. Infection, hereditary, nutrition.
2. Large and giant breed dogs aged 2-8mths.
3. Inappetance, reluctance to stand, lameness.
   Bilaterally symmetrical changes.
   Swollen painful and hot metaphyseal areas of lower limb bones.
   Pyrexia.

Question 8

Dx of metaphyseal osteopathy.

Answer 8

Radiographs.
Distal tibia and antebrachium.
Sclerotic line immediately adjacent to normal physis.
Radiolucent zone adjacent to sclerotic line.
ST swelling.
Periosteal new bone formation.

Question 9

Tx of metaphyseal osteopathy?

Answer 9

Balanced diet / no supplements.
Analgesia - NSAIDs/opiates.
Rest.
ABX / steroids.

Question 10

Px of metaphyseal osteopathy.

Answer 10

Good/guarded.
May have residual bone deformity which may cause problems.
Prolonged course/recurrences.

Question 11

1. What is physitis?
2. Aetiopathogenesis of physitis?
3. Clinical signs of physitis?

Answer 11

1. Enlargement of physeal region of long bones in growing horses.
2. Unclear - rapid growth.
3. Variable lameness/stiffness.
   Widening of the bone at level of physis.
   Especially distal radius, tibia and metacarpus/metatarsus.
   May be seen w/ other developmental orthopaedic diseases e.g. angular limb deformities, osteochondrosis, flexural deformities, wobbler syndrome.

Question 12

1. Dx of physitis.
2. Tx of physitis.

Answer 12

1. Radiography.
   Flaring of the metaphysis and epiphysis adjacent to physis.
   Irregularity of physis and sclerosis.
2. Reduction of energy content of ration to slow down growth, ensure correct mineral balance in ration.
   Rest.
   NSAIDs.

Question 13

1. Nutritional secondary hyperparathyroidism aetiology?
2. Nutritional secondary hyperparathyroidism.

Answer 13

1. Diet high in phosphorus / low in calcium e.g. all meat diet.
2. If Ca in blood low, stimulates release of parathormone to return levels to normal.
   Calcium reabsorbed from bone.
   Osteopenia / osteoporosis cause pathological fractures.
   Normal bone still produced and normal growth plates.

Question 14

Nutritional secondary hyperparathyroidism clinical signs.

Answer 14

Puppies and kittens post-weaning.
Lameness, pathological fractures, lax ligaments, neuro deficits.
Growth and teeth deformity.

Question 15

Dx of nutritional secondary hyperparathyroidism.

Answer 15

Imaging.
- cortices thin – little differentiation between cortex and medulla.
- normal growth plates.
Bloods:
- low / normal calcium and phosphorus.
- high parathormone.

Question 16

Tx and px of nutritional secondary hyperparathyroidism?

Answer 16

Tx:
- balanced diet.
- NSAIDs.
- cage rest.
- avoid open reduction and internal fixation – bone such poor density that does not hold implants well.
– most fractures will heal but malunions likely.
Px:
- guarded for full recovery.
- depends on initial injuries and severity.

Question 17

Rickets.

Answer 17

VERY RARE.
Diet deficient in Ca, P and vit D.
Dx:
- imaging – widened cup shaped growth plates due to accumulation of unmineralized osteoid.
Tx:
- correct diet.

Question 18

1. Synonyms of hypertrophic osteopathy.
2. Aetiopathogenesis of hypertrophic osteopathy.
3. Clinical signs of hypertrophic osteopathy.

Answer 18

1. Maries, hypertrophic pulmonary osteoarthropathy.
2. Secondary manifestation of thoracic (abdominal) disease.
   Pulmonary neoplasia in 90% of cases.
   Various theories to pathogenesis.
   - e.g. NV?
3. Usually older dogs (and cats).
   Firm, warm, non oedematous swelling on all limbs,
   Lame, stiff, dyspnoea, cough.
   Respiratory signs prior to lameness in only 30% of cases.

Question 19

Dx of hypertrophic osteopathy?

Answer 19

Radiography.
- ST swelling.
- periosteal new bone on MT/MC.
- long bones affected in severe cases.
- thoracic (or abdominal mass).

Question 20

Tx and px of hypertrophic osteopathy.

Answer 20

Tx - pulmonary mass removal?
Px - guarded as often malignant neoplasia.
May get regression of bony changes after mass removal.

Question 21

1. What do bisphosphonates do?
2. What are they used for?

Answer 21

1. Reduce bone resorption.
   Inhibit osteoclasts (cells that resorb bone).
2. Bone tumours.
   Hypercalcaemia to reduce calcium levels.
   IMHA.
   Malignant histiocytosis.

Question 22

2 types of bisphosphonates.

Answer 22

Non amino bisphosphonate.
- disrupt metabolism of osteoclast leading to apoptosis of osteoclast.
Amino bisphosphonate.
- newer.
- better antiresorptive properties.
- disrupts intracellular signalling leading to apoptosis of osteoclast.

Question 23

In vivo potency of Zolendronate (Zometa) in comparison to Etidronate (Didronel)?

Answer 23

10,000x.

Question 24

Actions of bisphosphonates?

Answer 24

Inhibit osteoclasts.
Inhibit neoplastic cell proliferation.
Induce apoptosis (cell death).
Inhibit angiogenesis.
Inhibit matrix metalloproteinase, affect cytokines and growth factors.
Immunomodulatory.
Deplete phagocytic cells.

Question 25

Bisphosphonates uses.

Answer 25

Inhibit bone mets.
Reduce bone pain.
Therapy for hypercalcaemia.
Malignant histiocytosis.
IMHA.

Question 26

Bisphosphonates use in bone tumours.

Answer 26

Decrease bine resorption.
Decrease tumour pain.
Decrease mets.
May be used in dogs that are not good candidates for amputation.

Question 27

1. Causes of hypercalcaemia?
2. How does bisphosphonate work in hypercalcaemia?

Answer 27

1. Renal failure.
   Malignancy.
   Hyperparathyroidism.
   Toxicity.
   Idiopathic.
2. Decreased bone resorption decreases calcium levels.
   (not a commonly used tx in hypercalcaemia).

Question 28

Use of bisphosphonate in malignant histiocytosis?

Answer 28

Limited clinical use.
Liposome encapsulated clodronate.
Tumour regression in 2/5 dogs.
Combining bisphosphonates w/ chemotherapeutic agents shows promise.
- bisphosphonates increase susceptibility of the tumour cells to the chemotherapeutic agents.

Question 29

Use of bisphosphonate in IMHA.

Answer 29

Liposome encapsulated clodronate may have a role in treating IMHA.
Interferes w/ macrophages which stops erythrocyte death.
Gains time for slower onset drugs to start working.

Question 30

Administration of bisphosphonates.

Answer 30

Orally or IV.
Orally - poor absorption.
- Usually administer daily or every other day.
IV - rapidly cleared from plasma (1-2hrs).
- Half-life in bone (alendronate 300d).
- Administer every 3-4wks.

Question 31

Bisphosphonate side effects.

Answer 31

Oesophagitis, gastritis.
Delayed bone healing - ‘frozen bone’.
- Increased bone fragility.
Nephrotoxicity.
Allergic reactions.
*not a widely accepted tx - owners should be warned of potential side effects!