week 26 - fractures and osteosarcoma

Question 1

what are your differentials for bone pain

Answer 1

hyperparathyroidism
osteogenesis imperfecta
paget’s disease
leukaemia

Question 2

what are your differentials for bone fractures

Answer 2

osteoporosis 
malignancy - primary or secondary 
gaucher disease
beta thalassemia 
hyperthyroidism

Question 3

differentials for bone pain and fractures

Answer 3

cushing’s
osteomalacia/rickets
multiple myeloma

Question 4

what in a history would lead you to think of bone tumours

Answer 4

persisent pain, swelling, tenderness +/- decrease ROM
pathological fracture
bony enlargement, deformity, radiodensity or radiolucency
histological evidence of bone neoplasm

Question 5

what are the main bone cells

Answer 5

osteoprogenitor– cells - stem cells - produce osteoblasts

Oestrocytes - resting mature osteoblasts, maintain matrix

Osteoblasts - secrete organic components of matrix (lays down matrix)

Osteoclast - multinucleated cells that secretes acids and enzymes to dissolve bone matrix -> release ca2+ and PO43-

Osteon - fundamental functional unit of bone

bone matrix - type 1 collagen, non collagenous proteins (ground substance, proteoglycans), minerals, Ca3(PO4)2 interacts with Ca(OH)2 to make hydroxyapatite crystals

Question 6

what is the function of osteocytes

Answer 6

terminally differentiates osteoblasts and function within syncytial networks to support bone structure and metabolism within the lacunae
extensive filipodial processes that lie within the canaliculi in mineralised bone which maintain connection with each other and the bone surface
transduce stress signals

Question 7

what is the function of osteoblasts

Answer 7

synthesize bone matrix
osteoprogenitor cells (of mesenchymal origin) 
synthesize bone matrix have large nuclei, enlarge golgi structures and extensive endoplasmic reticulum. these osteoblasts secrete collagen type I and other matrix proteins

Question 8

what is the function of osteoclasts

Answer 8

breakdown and remodelling
derived from monoculear precursor cells of the monocyte macrophage lineage, activated multinucleated osteoclasts are the only cells known capable of resorption of bone
RANKL and macrophage-CSF, cytokines produced by marrow stromal cells are two cytokines critical for osteoclast formaton
OPG
secrete - H+ ions and cathepsin K enzyme

Question 9

what are the hormones involved in bone remodelling

Answer 9

RANK-L - stimulate osteoclast differentiation and activity
OPG - inhibits osteoclast activity by binding RANK-L and blocking it
IGF-1 - stimulate osteoblasts
IL-6
oestrogen -

Question 10

what are the stages of bone repair

Answer 10

• haematoma formation
• acute inflammation
• organisation
• cartilage formation (provisional callus)
• replacement of cartilage by bone
• bone remodelling

Question 11

what are the steps of bone remodelling

Answer 11

ACTIVATION

• recruitment and activation of mononuclear monocyte macrophage osteoblast precurors from circulation
• bind to bone matrix via integrin R in their own cell membranes and peptides in bone mtrix proteins –> forming annular sealing zones around bone resorbing compartments beneath multinucleated osteoclasts

RESORPTION
- regulated by ratio of RANKL:OPG, IL-1, IL6, CSF, PTH, Vit D, calcitonin
- secrete H+ via H+ATPase proton pumps and Cl- channels
0 enzymes

REVERSAL

• resorption cavities contain a variety of mononuclear cells invluding monocytes
• osteocytes released
• preosteoblasts recruited

FORMATION

• osteoblasts synthesize new collagenous organic matrix and regulate mineralisation of the matrix by releasing small, membrane bound matrix vesicles that concentrate calcium and phosphate
• osteoblasts surround by and buried within matrix become osteocytes with an extensive canalicular network connecting them to bone surface lining cells, osteoblast and other osteocytes, maintained by gap junctions (forming functional syncytium)
• completion 50% osteoblasts apoptosis 50% osteocytes

Question 12

define a fracture

Answer 12

injury of soft tissue
vascular injury to bone
break in calcium

Question 13

types of fractures

Answer 13

traumatic
pathologic
stress
insufficiency

Question 14

healing of fractures

Answer 14

HAEMATOMA (immediate) - rupture of blood vessels –> filling of fracture gaps surrounds with blood

• clotting - fibrin mesh - seal off fracture site and provide framework for inflammatory cells
• influx of inflam cells and fibroblasts –> release PDGF, TGF-beta, FGF, ILs –> activation of osteoprogenitor cells in periostum
• angiogenesis

SOFT CALLUS (end of first week) - haematoma and surrounding tissue are organising

• monocytes –> osteoclasts –> remove dead bone
• callus - cellular mass with islands of immature bone

HARD CALLUS (2-3 weeks) - activated oestoprogenitor cells deposite subperiosteal trabeculae of woven bone

• newly formed cartilage along fracture line undergoes endochondrial ossification –> lamellar bone
• strength increases to point of controlled wt bearing

REMODELLING - portions not physically stressed are resorbed –> callus decrease in size

Question 15

how to describe a fracture

Answer 15

complete vs incomplete
compound vs simple
stable/nondisplaced vs unstable/displaced
nature - spiral, transverse, oblique, greenstick, fissure, impacted, avulsion, displaced, ephyseal, compression, communicated
displaced
angulation

Question 16

investigations for fracture

Answer 16

xray, fluoroscopy, us, ct, bone scan, mri

Question 17

how do you interpret/assess an xray

Answer 17

radiolucent lines
sclerotic lines
change in aligment
avulised fragment of apophysis
joint effusion
soft tissue swelling

Question 18

what is the management of fractures

Answer 18

first aid - DRSABC - immobilisation
assessment - systematic, primary survey, secondary survey, definitive care
compression
immobilisation - decrease pain, improve circulation, decrease pressure