Metabolic Bone Disease: Histopathology Flashcards
what are the main functions of bone?
o Mechanical – support and muscle attachment.
o Protective – vital organs and bone marrow.
o Metabolic – calcium reserve.
what is the inorganic composition of bone?
65%
calcium hydroxyapatite-99% of body calcium
85% of phosphorus
65% of Na, Mg
what is the organic composition of bone?
35%
bone cells and protein matrix
what are the two functional classifications of bone?
cortical: long bones
cancellous: vertebrae/pelvis
what are the anatomical types of bone?
- flat e.g. skull
- long e.g. femur
- short/cuboid e.g. carpals
- irregular e.g. vertebrae
- sesamoid e.g. patella
how calcified is cortical bone?
what function does it serve?
80-90%
mainly protective/mechanical
how calcified is cancellous bone?
what function does it serve?
15-25%
mainly metabolic, with large surface
what are the main distinguishing features of cortical bone?
- osteons containing Haversian canals
- Volkmann’s canals (horizontal)
- Howship’s lacunae (lacunae left by osteoclasts)
- canaliculi
- concentric layers of lamellae
what are the main features of cancellous bone?
trabecular bone (avascular- lack blood vessels) no osteons
what separates the diaphysis and epiphysis?
metaphysis
what part of the skeleton is cortical bone? how much of the skeleton?
80% of the skeleton making the appendicular skeleton
what part of the skeleton is cancellous bone? how much of the skeleton?
20% of the skeleton making the axial skeleton
what is the diameter of an osteon?
0.2mm
when must a bone biopsy be done?
o Evaluate bone pain. o Investigate x-ray abnormalities – e.g. brown lesions. o Bone tumour diagnosis. o Cause of unexplained infection. o Evaluate medical therapy.
what are the two types of bone biopsy?
closed: (Jamshidi needle) into the core of the bone
open: for sclerotic or inaccessible lesions
what is the role of osteoblasts?
build bone by laying osteoid
surface osteoblasts become osteocytes
what is the role of osteoclasts?
resorb bone (crush) multinucleate cell removes bone
what is the role of osteocytes?
osteoblast-like cells that sit-in lacunae. 90% of all bone cells works as the mechanosensory network
where is RANK found?
on the osteoclast precursors in response to stimulation via M-CSF
what is competitive inhibitor of RANK?
OPG (osteoprotegrin) inhibits RANK and RANKL binding therefore inhibiting osteoclastogenesis
how does mature bone compare to woven bone in organisation?
more well organised
what type of ossification occurs in flat bones?
intramembranous
what type of ossification occurs in long bones?
endochondral except clavicle
what are the two architectural classifications of bone?
woven (immature)
lamellar (mature)
where is woven bone found?
at the base of teeth
only physiological in fracture healing
what is metabolic bone disorder?
disorder of bone turnover due to imbalance of chemicals in bone
overall effect: reduced bone mass (osteopenia) leadings to pathological features
what are stains that can be used in bone biopsy?
H&E stain
Masson-Goldner trichrome
tetracycline/calcein binding
what are the 3 main categories of MBD?
- endocrine abnormalities e.g. Vit D, PTH
- non-endocrine e.g. age-related osteoporosis
- disuse osteopenia e.g. astronauts
when is the Masson-Goldner trichrome stain appropriate?
to see calcification levels in samples i.e. non mineralised vs mineralised bone
result:
mineralised –>green
non-mineralised–> orange
when is the tetracycline/calcein binding stain appropriate?
see the rate of bone formation and bone turnover
fast or slow
produces fluorescent lines upon IV injections over bone and a later second injection reveals the time it to to lay new bone by looking at the distance between the lines
what are the two types of osteoporosis aetiology?
primary and secondary causes
1) primary- age, post-menopause (physiological)
2) secondary- drugs, systemic disease (pathological)
what is osteomalacia?
defective bone mineralisation of normally synthesised bone
what is osteoporosis?
reduced bone density
T score < or = -2.5 SD
what is high bone turnover?
increased bone formation and resorption but resorption is greater than formation
what is low bone turnover?
decreased bone formation and resorption but a greater reduction in formation
what are the two types of osteomalacia causes?
deficiency of Vit D
deficiency in phosphate
what does the bone anatomy of osteoporosis look like?
large areas of trabecular bone is thinner and goes missing
they are less well connected leading to the thinning of cortical bone
what is the role of vit D in osteomalacia?
role in PTH secretion
- a deficiency in Vit D leads to increased PTH secretion and therefore bone resorption (calcium is taken from bone)
- Vit D def is the most common cause of hypocalcaemia
results in proximal myopathy aswell
how does low level of calcium manifest itself?
muscle spasms, twitches and tingling and numbness
High Na+ influx
what is osteomalacia in children?
how does it present?
rickets
widening of growth plates and leg bowing to spread the weight
what are the features of osteomalacia?
o Sequelae.
o Bone pain/tenderness.
o Fractures – e.g. horizontal fractures in Looser’s zone
o Proximal myopathy.
o Bone deformity – e.g. bowing in rickets.
what are Looser’s Zones?
perpendicular fractures to cortex in areas of high tensile stress
what stain can be used in examining osteomalacia?
MG trichrome to see the mineralisation level of the bone
how is hyperparathyroidism defined?
excess PTH
what are the features resulting from excess PTH?
o Increased Ca2+ and PO42- excretion in the urine.
o Hypercalcaemia due to increased calcium resorption
o Hypophosphatemia due to increased phosphate excretion
o Osteitis fibrosa cystica – skeletal changes including brown tumours and kidney stones.
what is the role of vitamin D in calcium metabolism?
The major function of vitamin D is to optimize intestinal calcium and phosphorus absorption for proper formation of the bone mineral matrix.
Channels are dependent on vitamin D e.g. TRPV6
what are the four organs involved with PTH?
Parathyroid glands
bones
kidneys
proximal small intestine
what are the two forms of hyperparathyroidism?
primary- due to PT adenoma (85-90%) resulting in chief cell hyperplasia
secondary- accompanying a primary disease like chronic renal def resulting Vit D def
what are the symptoms of hyperparathyroidism (and hypercalcaemia)?
1) stones (CA oxalate renal stones)
2) bones (osteitis fibrosa cystica)
3) abdominal groans (acute pancreatitis)
4) psychic moans (psychosis & depression)
what is renal osteodystrophy?
comprises of all the skeletal changes of chronic renal disease
failure to excrete phosphate
what are the skeletal changes that occur in chronic renal disease?
o Increased bone reabsorption (osteitis fibrosa cystica) – shows multiple lytic lesions on x-ray. o Osteomalacia. o Osteosclerosis. o Growth retardation. o Osteoporosis.
what are the biochemical markers of renal osteodystrophy?
o PO4 retention/hyperphosphataemia.
o Hypocalcaemia – because of low vitamin D.
o Secondary hyperparathyroidism – low calcium due to low vitamin D so reflex hyperparathyroidism.
o Metabolic acidosis.
o Aluminium deposition.
why does PTH remain high in hypercalcaemia of hyperparathyroidism?
negative feedback has been switched off
what are the x-ray findings in hyperparathyroidism?
periosteal bone erosion
channel resorption in the trabecular (middle parts missing)
what is Paget’s disease?
disorder of bone turnover
bone resorption followed by compensatory bone formation
what are the 3 stages of Paget’s?
o Osteolytic stage – rapid breakdown of bone.
o Osteolytic-osteosclerotic – bone formation.
o Quiescent osteosclerotic – quiescent stage.
what does formation breakdown in paget’s affect the bone?
produces a mosaic effect in the bone
what is the epidemiology of Paget’s?
o Onset >40yo (but only 3% greater than 55yo).
o Equally affects males and females.
o Rare in Asians and Africans.
o Only affects one bone in 15% (most are poly-ostotic
what is the aetiology of paget’s ?
o Mainly unknown.
o Familial cases – autosomal – mutation 5q35-qter – sequestosome 1 gene.
o Parvomyxovirus found in Pagetic bone.
what are the clinical symptoms of Paget’s?
o Pain.
o Micro fractures and bowing of tibia.
o Nerve compression.
o Skull changes may put the medulla at risk.
o Deafness.
o Haemodynamic changes and possible cardiac failure.
o Hypercalcaemia.
o Development of sarcoma (in area of involvement).
