Metabolic Bone Disease: Histopathology

Question 1

what are the main functions of bone?

Answer 1

o Mechanical – support and muscle attachment.
o Protective – vital organs and bone marrow.
o Metabolic – calcium reserve.

Question 2

what is the inorganic composition of bone?

Answer 2

65%

calcium hydroxyapatite-99% of body calcium
85% of phosphorus
65% of Na, Mg

Question 3

what is the organic composition of bone?

Answer 3

35%

bone cells and protein matrix

Question 4

what are the two functional classifications of bone?

Answer 4

cortical: long bones
cancellous: vertebrae/pelvis

Question 5

what are the anatomical types of bone?

Answer 5

• flat e.g. skull
• long e.g. femur
• short/cuboid e.g. carpals
• irregular e.g. vertebrae
• sesamoid e.g. patella

Question 6

how calcified is cortical bone?

what function does it serve?

Answer 6

80-90%

mainly protective/mechanical

Question 7

how calcified is cancellous bone?

what function does it serve?

Answer 7

15-25%

mainly metabolic, with large surface

Question 8

what are the main distinguishing features of cortical bone?

Answer 8

• osteons containing Haversian canals
• Volkmann’s canals (horizontal)
• Howship’s lacunae (lacunae left by osteoclasts)
• canaliculi
• concentric layers of lamellae

Question 9

what are the main features of cancellous bone?

Answer 9

trabecular bone (avascular- lack blood vessels) 
no osteons

Question 10

what separates the diaphysis and epiphysis?

Answer 10

metaphysis

Question 11

what part of the skeleton is cortical bone? how much of the skeleton?

Answer 11

80% of the skeleton making the appendicular skeleton

Question 12

what part of the skeleton is cancellous bone? how much of the skeleton?

Answer 12

20% of the skeleton making the axial skeleton

Question 13

what is the diameter of an osteon?

Answer 13

0.2mm

Question 14

when must a bone biopsy be done?

Answer 14

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.

Question 15

what are the two types of bone biopsy?

Answer 15

closed: (Jamshidi needle) into the core of the bone
open: for sclerotic or inaccessible lesions

Question 16

what is the role of osteoblasts?

Answer 16

build bone by laying osteoid

surface osteoblasts become osteocytes

Question 17

what is the role of osteoclasts?

Answer 17

resorb bone (crush) 
multinucleate cell removes bone

Question 18

what is the role of osteocytes?

Answer 18

osteoblast-like cells that sit-in lacunae. 90% of all bone cells works as the mechanosensory network

Question 19

where is RANK found?

Answer 19

on the osteoclast precursors in response to stimulation via M-CSF

Question 20

what is competitive inhibitor of RANK?

Answer 20

OPG (osteoprotegrin) inhibits RANK and RANKL binding therefore inhibiting osteoclastogenesis

Question 21

how does mature bone compare to woven bone in organisation?

Answer 21

more well organised

Question 22

what type of ossification occurs in flat bones?

Answer 22

intramembranous

Question 23

what type of ossification occurs in long bones?

Answer 23

endochondral except clavicle

Question 24

what are the two architectural classifications of bone?

Answer 24

woven (immature)

lamellar (mature)

Question 25

where is woven bone found?

Answer 25

at the base of teeth | only physiological in fracture healing

Question 26

what is metabolic bone disorder?

Answer 26

disorder of bone turnover due to imbalance of chemicals in bone overall effect: reduced bone mass (osteopenia) leadings to pathological features

Question 27

what are stains that can be used in bone biopsy?

Answer 27

H&E stain Masson-Goldner trichrome tetracycline/calcein binding

Question 28

what are the 3 main categories of MBD?

Answer 28

- endocrine abnormalities e.g. Vit D, PTH - non-endocrine e.g. age-related osteoporosis - disuse osteopenia e.g. astronauts

Question 29

when is the Masson-Goldner trichrome stain appropriate?

Answer 29

to see calcification levels in samples i.e. non mineralised vs mineralised bone result: mineralised -->green non-mineralised--> orange

Question 30

when is the tetracycline/calcein binding stain appropriate?

Answer 30

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

Question 31

what are the two types of osteoporosis aetiology? | primary and secondary causes

Answer 31

1) primary- age, post-menopause (physiological) | 2) secondary- drugs, systemic disease (pathological)

Question 32

what is osteomalacia?

Answer 32

defective bone mineralisation of normally synthesised bone

Question 33

what is osteoporosis?

Answer 33

reduced bone density | T score < or = -2.5 SD

Question 34

what is high bone turnover?

Answer 34

increased bone formation and resorption but resorption is greater than formation

Question 35

what is low bone turnover?

Answer 35

decreased bone formation and resorption but a greater reduction in formation

Question 36

what are the two types of osteomalacia causes?

Answer 36

deficiency of Vit D | deficiency in phosphate

Question 37

what does the bone anatomy of osteoporosis look like?

Answer 37

large areas of trabecular bone is thinner and goes missing | they are less well connected leading to the thinning of cortical bone

Question 38

what is the role of vit D in osteomalacia?

Answer 38

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

Question 39

how does low level of calcium manifest itself?

Answer 39

muscle spasms, twitches and tingling and numbness | High Na+ influx

Question 40

what is osteomalacia in children? how does it present?

Answer 40

rickets | widening of growth plates and leg bowing to spread the weight

Question 41

what are the features of osteomalacia?

Answer 41

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.

Question 42

what are Looser's Zones?

Answer 42

perpendicular fractures to cortex in areas of high tensile stress

Question 43

what stain can be used in examining osteomalacia?

Answer 43

MG trichrome to see the mineralisation level of the bone

Question 44

how is hyperparathyroidism defined?

Answer 44

excess PTH

Question 45

what are the features resulting from excess PTH?

Answer 45

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.

Question 46

what is the role of vitamin D in calcium metabolism?

Answer 46

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

Question 47

what are the four organs involved with PTH?

Answer 47

Parathyroid glands bones kidneys proximal small intestine

Question 48

what are the two forms of hyperparathyroidism?

Answer 48

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

Question 49

what are the symptoms of hyperparathyroidism (and hypercalcaemia)?

Answer 49

1) stones (CA oxalate renal stones) 2) bones (osteitis fibrosa cystica) 3) abdominal groans (acute pancreatitis) 4) psychic moans (psychosis & depression)

Question 50

what is renal osteodystrophy?

Answer 50

comprises of all the skeletal changes of chronic renal disease failure to excrete phosphate

Question 51

what are the skeletal changes that occur in chronic renal disease?

Answer 51

``` o Increased bone reabsorption (osteitis fibrosa cystica) – shows multiple lytic lesions on x-ray. o Osteomalacia. o Osteosclerosis. o Growth retardation. o Osteoporosis. ```

Question 52

what are the biochemical markers of renal osteodystrophy?

Answer 52

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.

Question 53

why does PTH remain high in hypercalcaemia of hyperparathyroidism?

Answer 53

negative feedback has been switched off

Question 54

what are the x-ray findings in hyperparathyroidism?

Answer 54

periosteal bone erosion | channel resorption in the trabecular (middle parts missing)

Question 55

what is Paget's disease?

Answer 55

disorder of bone turnover bone resorption followed by compensatory bone formation

Question 56

what are the 3 stages of Paget's?

Answer 56

o Osteolytic stage – rapid breakdown of bone. o Osteolytic-osteosclerotic – bone formation. o Quiescent osteosclerotic – quiescent stage.

Question 57

what does formation breakdown in paget's affect the bone?

Answer 57

produces a mosaic effect in the bone

Question 58

what is the epidemiology of Paget's?

Answer 58

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

Question 59

what is the aetiology of paget's ?

Answer 59

o Mainly unknown. o Familial cases – autosomal – mutation 5q35-qter – sequestosome 1 gene. o Parvomyxovirus found in Pagetic bone.

Question 60

what are the clinical symptoms of Paget's?

Answer 60

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).