1 Metabolic Bone Disease: Histopathology

Question 1

What are the 4 functions of bone?

Answer 1

• structural function = gives structure + shape to body
• mechanical function = acts as site for muscle attachment
• Protects vital organs + bone marrow
• Metabolic function = acts as a reserve for calcium and other minerals

Question 2

Describe the composition of bone

organic = \_\_\_% 
inorganic = \_\_\_%

Answer 2

organic = 35 %
- contains bone cells + protein matrix

inorganic = 65 %

• contains calcium hydroxyapatite crystals
• stores 99% of calcium in body
• stores P (85%), Na (65%), Mg

Question 3

what is the difference between cortical + cancellous bone?

Answer 3

• Cortical:
• Long bones
• 80% of skeleton
• Appendicular
• 80-90% calcified
• Mainly mechanical + protective
• Cancellous (trabecular):
• in BM
• Vertebrae + pelvis
• 20% of skeleton
• Axial skeleton
• 15-25% calcified
• Mainly metabolic –> high turnover (can quickly release mineral)
• Large SA

Question 4

When would you perform bone biopsy?

Answer 4

Indications/uses:
- To confirm diagnosis of bone disorder

• to find cause of bone pain/ tenderness
• to Investigate abnormality seen on X-ray
• For bone tumour diagnosis (benign or malignant)
• To Determine cause of unexplained infection
• To Evaluate therapy performance

Question 5

What are the 2 types of bone biopsy?

Answer 5

1. closed (needle)
2. open
   - -> for sclerotic/inaccessible lesions
   - -> under general anesthesia
   - -> removal of chunk of bone

Question 6

What are the 3 different types of bone cells?

Answer 6

1. osteoblasts
2. osteoclasts
3. osteocytes

Question 7

what do the osteoblasts do?

Answer 7

builds bones by laying down osteoid

Question 8

what do the osteoclasts do?

Answer 8

multinucleate cell of macrophage family that resorbs/ removes bone

Question 9

what do the osteocytes do?

Answer 9

• osteoblast like cells

- sits in bone lacunae

Question 10

what happens when RANK binds to RANKL?

Answer 10

• it causes osteoclast precursor cells to differentiate –> and increase bone resorption

Question 11

What does OPG do?

Answer 11

OPG = osteoprotegerin

• outcompetes with RANK for RANKL
• inhibits RANK-RANKL binding
• -> inhibiting osteoclastogenesis

Question 12

what is meant by metabolic bone disease?

Answer 12

• disordered bone turnover due to an imbalance of various chemicals in the body
  e. g vitamins, hormones, minerals

–> causes altered bone cell activity / rate of mineralization / change in bone structure

• overall effect = osteopaenia
• -> often leads to fracture with little/no trauma

Question 13

define osteopaenia

Answer 13

• reduced bone mass

Question 14

What are the 3 main categories of metabolic bone disease?

Answer 14

1. Endocrine abnormality (Vit D deficiency, PTH-excess)
2. Non-endocrine (e.g. age-related osteoporosis)
3. Disuse osteopenia (when don’t use legs so much, bones weaker)

Question 15

What is the difference between primary and secondary osteoporosis?

Answer 15

1º - age, post-menopause

2º - drugs, systemic disease

Question 16

define osteomalacia

Answer 16

defective bone mineralization of normally synthesized bone matrix

Question 17

what are the 2 types of osteomalacia?

Answer 17

1. Deficiency of vitamin D

2 Deficiency of PO4

Question 18

What complications can occur due to osteomalacia?

i.e describe the sequelae of osteomalacia

Answer 18

Sequelae of osteomalacia =

• bone pain/tenderness
• fracture
• proximal weakness
• bone deformity

Question 19

describe biochemical changes in hyperparathyroidism

increase/decrease
PTH =
Ca2+ excretion =
PO4 excretion =

Answer 19

PTH = excess
Ca2+ excretion = increased
PO4 excretion = increased

Question 20

hyperparathyroidism leads to :

Answer 20

• hypercalcaemia
• hypophosphataemia
• increased excretion of phosphate + calcium
• osteitis fibrosa cystica

Question 21

what are the 4 organs indirectly/directly affected by PTH?

Answer 21

• Parathyroid glands
• Bones
• Kidneys
• Proximal small intestine

Question 22

What is the difference between causes of primary and secondary hyperparathyroidism?

Answer 22

Primary causes:

• adenoma (majority)
• chief cell hyperplasia

Secondary causes:

• chronic renal deficiency
• Vit D deficiency (mainly)

Question 23

what are symptoms of hyperparathyroidism?

Answer 23

• Stones
  (Calcium oxalate renal stones)
• Bones
  (osteitis fibrosa cystica, bone resorption)
• Abdominal groans
  (acute pancreatitis)
• Psychic moans
  (psychosis & depression)

Question 24

Brown cell tumours = seen in hyper/hypoparathyroidism, formed by osteoclast/blast cell groups

Answer 24

Brown cell tumours = seen in hyperparathyroidism, formed by osteoclast cell groups

Question 25

what is renal osteodystrophy?

Answer 25

- all skeletal changes of chronic renal disease: 1. Increased bone resorption (osteitis fibrosa cystica) 2. Osteomalacia 3. Osteosclerosis 4. Growth retardation 5. Osteoporosis

Question 26

What are comorbidities associated with renal osteodystrophy ?

Answer 26

- hyperphosphataemia - Hypocalcaemia (as a result of ↓vit D) - Secondary hyperparathyroidism - Metabolic acidosis - Aluminium deposition

Question 27

What are the 3 stages of Paget's disease?

Answer 27

1. Osteolytic 2. Osteolytic-osteosclerotic (mixed phase) 3. Quiescent osteosclerotic

Question 28

Paget's Disease Notes: - More common in whites (rare in Asians/Africans) - develops over 40, - same freq. in M + F, - mostly asymptomatic o 85% polyostotic (multiple bones affeceted) , 15% mono-ostotic (1 bone affected)

Answer 28

-

Question 29

Paget's disease = Common/ Rare in fingers or toes, usually _/_vertebrae (most common), skull, pelvis, lower limbs e.g. tibia

Answer 29

Rare in fingers or toes, usually T/L vertebrae (most common), skull, pelvis, lower limbs e.g. tibia

Question 30

What are clinical symptoms of Paget's disease?

Answer 30

o Pain o Microfractures (spontaneous) + deformity o Nerve compression due to new bone formation, spinal stenosis o Skull changes may put medulla at risk o Deafness o Possible haemodynamic changes, cardiac failure o Hypercalcaemia o Osteogenic sarcoma in area of involvement (1%)

Question 31

describe + Identify bone geography - epiphysis - diaphysis - periosteum - cortex - medulla - metaphysics - epiphyseal line - subchondral bone

Answer 31

-

Question 32

note: to show up on X-ray bones need to be 50% mineralized

Answer 32

-

Question 33

5 diff types of anatomical bones

Answer 33

- flat - long (e.g tibia) - short/cuboid (carpals) - irregular bones (e.g pelvis/ vertebrae) - sesamoid (patellar --> has protective functions)

Question 34

what is the 2 diff macroscopic classification of bone

Answer 34

- trabecular/ cancellous/ spongy | - cortical / compact

Question 35

what is the 2 diff microscopic classification of bone

Answer 35

- woven bone (weaker) - immature | - lamellar bone - mature

Question 36

identify different parts of the cortical bone micro anatomy

Answer 36

-

Question 37

note: immature woven bone = disorganized | mature bone = striae is visible

Answer 37

refer to slides for microscopic diagrams of bone parts

Question 38

describe the bone remodeling cycle

Answer 38

- osteocytes - forms when they are signaled by apoptosis of osteocytes which forms RANKL - which is stimulated to form mature osteoclasts that differentiate into reversal cells

Question 39

typical site for bone biopsy =

Answer 39

transiliac bone biopsy

Question 40

what are the 3 different histological stains for the bone biopsy ? what are they used for?

Answer 40

- H&E stains - Masson Goldner trichrome stain = labels unmineralized (orange) + mineralized (green) bone - tetracycline / calcein labelling = looks at bone turnover (difference btw 2 lines --> shows difference in bone formation)

Question 41

define osteoporosis

Answer 41

bone mineral density T score <2.5

Question 42

high turnover osteoporosis vs low turnover osteoporosis ****

Answer 42

high turnover osteoporosis **** low turnover osteoporosis decrease in bone formation greater than decreased bone resorption

Question 43

what might you see in a microscopic biopsy of osteoporosis?

Answer 43

thinner trabeculae | thinning of cortical bone

Question 44

what bone change might you observe in hyperparathyroidism ?

Answer 44

- subperiosteal bone erosions - tunnelling erosion - brown cell tumors

Question 45

Note = paget's disease: early stages= high turnover later = goes on to form disorganized bone

Answer 45

-