1 Metabolic Bone Disease: Histopathology Flashcards
What are the 4 functions of bone?
- 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
Describe the composition of bone
organic = \_\_\_% inorganic = \_\_\_%
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
what is the difference between cortical + cancellous bone?
- 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
When would you perform bone biopsy?
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
What are the 2 types of bone biopsy?
- closed (needle)
- open
- -> for sclerotic/inaccessible lesions
- -> under general anesthesia
- -> removal of chunk of bone
What are the 3 different types of bone cells?
- osteoblasts
- osteoclasts
- osteocytes
what do the osteoblasts do?
builds bones by laying down osteoid
what do the osteoclasts do?
multinucleate cell of macrophage family that resorbs/ removes bone
what do the osteocytes do?
- osteoblast like cells
- sits in bone lacunae
what happens when RANK binds to RANKL?
- it causes osteoclast precursor cells to differentiate –> and increase bone resorption
What does OPG do?
OPG = osteoprotegerin
- outcompetes with RANK for RANKL
- inhibits RANK-RANKL binding
- -> inhibiting osteoclastogenesis
what is meant by metabolic bone disease?
- 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
define osteopaenia
- reduced bone mass
What are the 3 main categories of metabolic bone disease?
- Endocrine abnormality (Vit D deficiency, PTH-excess)
- Non-endocrine (e.g. age-related osteoporosis)
- Disuse osteopenia (when don’t use legs so much, bones weaker)
What is the difference between primary and secondary osteoporosis?
1º - age, post-menopause
2º - drugs, systemic disease
define osteomalacia
defective bone mineralization of normally synthesized bone matrix
what are the 2 types of osteomalacia?
- Deficiency of vitamin D
2 Deficiency of PO4
What complications can occur due to osteomalacia?
i.e describe the sequelae of osteomalacia
Sequelae of osteomalacia =
- bone pain/tenderness
- fracture
- proximal weakness
- bone deformity
describe biochemical changes in hyperparathyroidism
increase/decrease
PTH =
Ca2+ excretion =
PO4 excretion =
PTH = excess
Ca2+ excretion = increased
PO4 excretion = increased
hyperparathyroidism leads to :
- hypercalcaemia
- hypophosphataemia
- increased excretion of phosphate + calcium
- osteitis fibrosa cystica
what are the 4 organs indirectly/directly affected by PTH?
- Parathyroid glands
- Bones
- Kidneys
- Proximal small intestine
What is the difference between causes of primary and secondary hyperparathyroidism?
Primary causes:
- adenoma (majority)
- chief cell hyperplasia
Secondary causes:
- chronic renal deficiency
- Vit D deficiency (mainly)
what are symptoms of hyperparathyroidism?
- Stones
(Calcium oxalate renal stones) - Bones
(osteitis fibrosa cystica, bone resorption) - Abdominal groans
(acute pancreatitis) - Psychic moans
(psychosis & depression)
Brown cell tumours = seen in hyper/hypoparathyroidism, formed by osteoclast/blast cell groups
Brown cell tumours = seen in hyperparathyroidism, formed by osteoclast cell groups
what is renal osteodystrophy?
- all skeletal changes of chronic renal disease:
- Increased bone resorption (osteitis fibrosa cystica)
- Osteomalacia
- Osteosclerosis
- Growth retardation
- Osteoporosis
What are comorbidities associated with renal osteodystrophy ?
- hyperphosphataemia
- Hypocalcaemia
(as a result of ↓vit D) - Secondary hyperparathyroidism
- Metabolic acidosis
- Aluminium deposition
What are the 3 stages of Paget’s disease?
- Osteolytic
- Osteolytic-osteosclerotic (mixed phase)
- Quiescent osteosclerotic
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)
-
Paget’s disease =
Common/ Rare in fingers or toes,
usually _/_vertebrae (most common), skull, pelvis, lower limbs e.g. tibia
Rare in fingers or toes,
usually T/L vertebrae (most common), skull, pelvis, lower limbs e.g. tibia
What are clinical symptoms of Paget’s disease?
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%)
describe + Identify bone geography
- epiphysis
- diaphysis
- periosteum
- cortex
- medulla
- metaphysics
- epiphyseal line
- subchondral bone
-
note: to show up on X-ray bones need to be 50% mineralized
-
5 diff types of anatomical bones
- flat
- long (e.g tibia)
- short/cuboid (carpals)
- irregular bones (e.g pelvis/ vertebrae)
- sesamoid (patellar –> has protective functions)
what is the 2 diff macroscopic classification of bone
- trabecular/ cancellous/ spongy
- cortical / compact
what is the 2 diff microscopic classification of bone
- woven bone (weaker) - immature
- lamellar bone - mature
identify different parts of the cortical bone micro anatomy
-
note: immature woven bone = disorganized
mature bone = striae is visible
refer to slides for microscopic diagrams of bone parts
describe the bone remodeling cycle
- 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
typical site for bone biopsy =
transiliac bone biopsy
what are the 3 different histological stains for the bone biopsy ?
what are they used for?
- 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)
define osteoporosis
bone mineral density T score <2.5
high turnover osteoporosis
vs
low turnover osteoporosis
high turnover osteoporosis
**
low turnover osteoporosis
decrease in bone formation greater than decreased bone resorption
what might you see in a microscopic biopsy of osteoporosis?
thinner trabeculae
thinning of cortical bone
what bone change might you observe in hyperparathyroidism ?
- subperiosteal bone erosions
- tunnelling erosion
- brown cell tumors
Note = paget’s disease:
early stages= high turnover
later = goes on to form disorganized bone
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