Approach to Bone Pain

Question 1

Common causes of bone pain?

Answer 1

Trauma, Tumour, Infection

Question 2

What are insufficiency/fragility fractures?

Answer 2

Fractures by normal physiological stress applied on abnormal (weakened) bones
@spine, tib/fib, pelvis
predisposing factors: osteoporosis, corticosteroid therapy, post-irradiation

Question 3

What is stress fracture?

Answer 3

Fracture resulting from abnormal stress on normal bone

Question 4

What are the imaging findings on a stress fracture?

Answer 4

Linear sclerosis on radiograph
Focal periosteal reaction (new bone formation)

Question 5

Types of fractures

Answer 5

1. Hairline
2. Linear
3. Oblique Non-displaced
4. Oblique Displaced
5. Spiral
6. Comminuted (broken at 3 or more sites)
7. Segmental

Question 6

Stages of Fracture Healing

Answer 6

1. Hematoma forms between 2 ends of bone, creating fibrin mesh, which seals fracture site. Periosteum is stripped from bone surface.
2. Traumatic inflammation: Migration of inflammatory cells and macrophages
3. Demolition: Macrophage invades and phagocytose the hematoma and tissue debris
4. Granulation tissue: neovascularization and fibroblasts from surrounding cells
5. Callus formation (soft bone) occurs over weeks: Periosteal reaction - haphazard osteoid formation producing a woven bone
   -> external callus: bridges fracture site outside bone
   -> internal callus: bridges fracture in medullary cavity
   => callus is well established (by 3rd week) but still woven bone (mechanically weak)
6. Remodelling occurs over months: Organised osteoclastic and osteoblastic activity replacing woven bone with compact lamellar bone

Question 7

Principles of NORMAL fracture healing

Answer 7

• Close apposition of fractured bone ends
• Immobilisation
• Adequate healing capacity

Question 8

Causes of delayed and impaired fracture healing

Answer 8

1. Poor apposition of fractured bone ends
2. Poor blood supply
3. Poor general nutritional status
4. Foreign bodies or non-viable tissue
5. Infection
6. Conditions that suppress healing: Corticosteroids, immunosuppression, immunodeficiency

Question 9

Complications of fracture

Answer 9

1. Problems related to union of bones:
   - delayed union
   - mal-union (union with angulation)
   - fibrous union (fibrous scar -> false joint)
   - non-union
2. Infection (osteomyelitis, septic arthritis)
3. Thrombosis and embolism
4. Soft tissue injury

Question 10

What is osteoporosis?

Answer 10

A condition where the bones are weakened to a point that they can break easily.

Question 11

Treatment for osteoporosis

Answer 11

1. Lifestyle and diet
   - exercise
   - calcium
   - vitamin D
2. Antiresorptive Agents
   - Bisphosphonates
   - Denosumab
   - Oestrogens
   - Calcitonin
3. Anabolic Agents
   - Romosozumab
   - Parathyroid hormone therapies

Question 12

How do bisphosphonates work?

Answer 12

Slow bone loss by increasing osteoclast cell death
- [ORAL] Risedronate, Alendronate (take on empty stomach with 240ml plain water, wait 30 mins before taking food)
- [IV] Zoledronic acid

Question 13

Significant adverse effects of bisphosphonates & contraindications

Answer 13

Atypical femoral fractures
Hypocalcaemia
Severe bone, joint, muscle pain
Osteonecrosis of jaw

contraindications: pts with hypocalcaemia, pregnant

Question 14

How does denosumab work?

Answer 14

Human monoclonal antibody against RANKL
Prevents development of osteoclasts
- subcutaneous injection every 6 months
- co-administer with calcium and vitamin D

Question 15

Adverse effects of denosumab & contraindications

Answer 15

Bone, joint, muscle pain
GI effects
(atypical femur fractures, osteonecrosis of jaw uncommon)

Do NOT discontinue as may cause increased risk of spinal column fractures when discontinued

contraindications: pts with hypocalcaemia, pregnant

Question 16

How does oestrogen work?

Answer 16

Oestrogen can help maintain bone density
- oestrogen therapy used for bone health in younger women or women whose other menopausal symptoms also requires treatment
- Raloxifene:
– selective oestrogen receptor modulator
– mixed oestrogen receptor agonism and antagonism
– mimics effects of oestrogen on bone density in postmenopausal women
– reduces risk of breast cancer
– increases risk of blood clots and hot flashes

Question 17

Adverse effects of oestrogen therapy

Answer 17

increases risk of breast cancer and blood clots which can cause stroke

Question 18

How does calcitonin work?

Answer 18

Calcitonin is a peptide hormone secreted by parafollicular cells of the thyroid gland

Calcitonin reduces blood calcium levels, opposing effects of parathyroid hormone

Inhibits osteoclastic bone resorption

IV, SC, IM injection or nasal spray

Question 19

Adverse effects and contraindications of calcitonin

Answer 19

Red streaks on skin
Injection site reaction (redness, warmth)

contraindications: hypocalcaemia, hypersensitivity

Question 20

How does Romosozumab work?

Answer 20

Humanised mouse monoclonal antibody against sclerostin
Removes sclerostin inhibition of the canonical Wnt signalling pathway that regulates bone growth
-> increases bone formation and decreases bone resorption

• SC injection once monthly for 12 months

Question 21

Adverse effects and contraindications of romosozumab

Answer 21

MI, increased risk of CV death, stroke

contraindications: hypersensitivity, hypocalcaemia, history of MI or stroke

Question 22

How do parathyroid hormone therapies work?

Answer 22

Teriparatide
Stimulates new bone formation and increase bone strength
- once daily SC injection (max treatment 24 months)

Question 23

Adverse effects and contraindications of parathyroid hormone therapies

Answer 23

Calciphylaxis, hypercalcaemia

contraindication: hypersensitivity, pre-existing hypercalcaemia, renal impairment, pregnancy

Question 24

Primary vs Secondary bone tumours

Answer 24

Primary bone tumours
- uncommon
Metastasis
- common

Question 25

What are some Benign Primary Tumours?

Answer 25

1. Exostosis/Osteochondroma 2. Enchondroma 3. Simple Bone Cyst 4. Osteoid osteoma

Question 26

What is osteochondroma/exostosis?

Answer 26

- most common benign bone tumour that arises near end of long bone - benign cartilage-capped tumour that is attached to the underlying skeleton by a bony stalk - usually solitary

Question 27

What is enchondroma?

Answer 27

- benign cartilaginous tumour that arises from diaphyseal medullary cavity - painless swelling - usually occurs at small bones eg phalanges of hands imaging features: - stippled, flocculent calcifications - bulbous expansion histological features: - mature hyaline cartilage - no cytological atypia - no permeation of bone trabeculae or marrow invasion - no invasion of soft tissue

Question 28

What is simple bone cyst?

Answer 28

- occurs in metaphysis - occurs in young child - benign, fluid containing lesion - cyst-like structure with fibrous wall - amorphous pink material with a cementum-like appearance

Question 29

What is osteoid osteoma/osteoblastoma?

Answer 29

- benign bone forming tumour characterised by extensive reaction and pain disproportionate to size - more common in young males radiographic appearance: - oval lytic lesion located within cortical bone - sclerosis may obscure underlying lytic nidus on radiograph - +/- central sclerotic focus within nidus CT imaging: - calcified nidus - reactive periosteal/cortical thickening histological appearance: - anastomosing woven bone trabeculae rimmed by abundant osteoblasts - loose and vascular intratrabecular spaces - no malignant features (ie. atypia, malignant osteoid, invasion)

Question 30

What are some of the malignant primary bone tumours?

Answer 30

1. Ewing's sarcoma (occurs in very young pts in the paediatrics age group) 2. Osteosarcoma (occurs in teenagers to young adults) 3. Chondrosarcoma (occurs in elderly patients) Look at patient's age!

Question 31

What are the features of osteosarcoma?

Answer 31

KEY features: - BONE FORMING tumour - Malignant histological features: -> malignant tumour cells (ie. pleomorphic, cytological atypia, hyperchromatic nuclei) -> malignant lace-like pattern of osteoid -> invasive growth pattern -> tumour necrosis - Metastasise to lungs other features: - occurs in teenagers to young adults - can be a sclerotic lesion - classic sunburst periosteal reaction (seen in radiograph) - occurs at metaphysis of long bones - arises from the medullary cavity and extends to cortex - fleshy appearance with necrosis and haemorrhage

Question 32

What are the features of chondrosarcoma?

Answer 32

- malignant bone tumour that produces cartilaginous matrix - cytological atypia - permeation of bone trabeculae - locally aggressive tumour that invades surrounding bone and soft tissue - large lobulated tumour, pearly white or light blue, with focal calcification

Question 33

Difference between enchondroma and chondrosarcoma

Answer 33

Enchondroma: - mature hyaline cartilage - no cytological atypia - no permeation of bone trabeculae - no soft tissue or marrow invasion Chondrosarcoma: - malignant tumour that produces cartilaginous matrix - cytological atypia - permeation of trabeculae - soft tissue and marrow invasion

Question 34

What are the features of Ewing's Sarcoma?

Answer 34

- permeative destruction - saucerisation defect - onion skin periosteal reaction due to translocation t(11,22)(q24;q12)

Question 35

What modalities can be used in secondary bone tumour/metastasis?

Answer 35

- MRI - Bone scan - Plain film

Question 36

What is Osteomyelitis?

Answer 36

Infection of bone that involves bone cortex, medulla and periosteum - main causative agents: staph aureus e. coli streptococci h. influenzae salmonella mycobacterial tuberculosis - infection through: 1. direct implantation (open wound) 2. bloodborne spread (lung TB to bone) 3. weakened immunity or vascular insufficiency 4. extension from contiguous site

Question 37

likely location of osteomyelitis with age?

Answer 37

children: long bone (upper and lower limbs) adult: feet, vertebral spine, femur

Question 38

what is the progression of osteomyelitis?

Answer 38

1. Bacterial infects and proliferates producing bone microabscesses 2. Infection and inflammation spread within shaft of bone, Haversian system and periosteum 3. If infection extends to joint or synovium -> septic arthritis 4. Inflammation impairs blood supply to bone causing bone ischaemia and necrosis 5. Inflammatory exudate lifts periosteum away from the bone cortex 6. Rupture of the periosteum leads to an abscess in the surrounding soft tissue and the eventual formation of a draining sinus in chronic osteomyelitis 7. The lifting of the periosteum by inflammatory exudate forms a layer of woven bone called involucrum 8. The involucrum often surrounds the underlying dead infected bone

Question 39

What is chronic osteomyelitis?

Answer 39

- acute osteomyelitis may persist and progress to chronic osteomyelitis - due to weakened immunity - potential complications of chronic OM: pathological fracture and deformity secondary amyloidosis sepsis or distant sites of infection malignant transformation

Question 40

What is tuberculous osteomyelitis?

Answer 40

- type of chronic osteomyelitis caused by mycobacterium - spread to bone from lung via blood borne route or lymphatic drainage KEY histological features: - chronic inflammation with epithelioid granulomas and necrosis

Question 41

What is spinal tuberculous osteomyelitis?

Answer 41

- affects vertebral spine - can cause: compression fractures severe deformities neurological deficits due to cord and nerve compression

Question 42

What is spondylodiscitis?

Answer 42

- infection of intervertebral disc and adjacent vertebrae