diseases of bone

Question 1

describe the composition of bone

Answer 1

cortical bone - hard outer layer, 80% bone mass
trabecular / cancellous bone - spongy inner layer 20% bone mass
extracellular - organic matrix - mainly collagen
inorganic components - hydroxyapatite, minerals (calcium / phosphate)

Question 2

what is the role of the bone forming cells

Answer 2

osteoblasts - create and repair bone

make osteoid - mainly type 1 collagen

Question 3

what is the role of bone reabsorbing cells

Answer 3

osteoclasts - breakdown old bone - multinuceltaed and large
releases calcium into the blood stream
release TRAP and cathepsin K enzymes to dissolve bone

Question 4

what is the role of an osteocyte

Answer 4

star shaped - trapped / buried osteoblast (in own osteoid)
communicate via cytoplasmic extensions and gap junctions
corodination regulation of bone turnover - signal osteoclasts whee bone needs to be broke/renewewed

Question 5

what are the contents of the ECM of bone

Answer 5

organic matriculates mainly collagen type 1m ground substance, inorganic compounds and minerals

Question 6

what is the word used to describe the type of tissue that bone is

Answer 6

dynamic

Question 7

describe the bone cycle

Answer 7

resting bones with lining cells (inactive osteoblasts)
signalling from osteocytes - bone needs to be remodelled due to degeneration
osteoclasts reabsorb bone from signalling osteoclasts
osteoblasts omen from osteoid which makes type 1 collagen become mineralised and turn into bone
3 month cycle

Question 8

how doe menopause affect bone

Answer 8

loss of oestrogen causes accelerated loss of bone mass

Question 9

what happens to bone with age

Answer 9

rate of reabsorption out weighs rate of formation which gradually decreases bone mass

Question 10

what techniques can be used to investigate bone mass

Answer 10

x ray, MRI CT for fractures
DEXA scan for Ca bone mass
surrogate markers for cells
microscopy

Question 11

what are two biochemical markers of bone formation

Answer 11

alkaline phosphate - released by osteoblasts as involved in mineralisation of bone
high during fractures or puberty
can also be elevated in liver or bone problems

P1NP - pro collagen type 1N pro peptides - used for bone formation synthesised by osteoporosis blasts as precursor to type 1 collagen

Question 12

what are two biochemical markers of bone reabsorption

Answer 12

collagen cross links (NTX, CTX)
released during bone reabsorption
increased during hyperthyroidism, adolescence and menopause

Question 13

what is a DEXA image used for in bone

Answer 13

measure density of bone - via radiation
T score greater than -1 = bone density normal
-1 - -2.5 = osteopenia (low bone mass)
-2.5 and below = osteoporosis

Question 14

what leads to failure of structural integrity of bone

Answer 14

decreased bon mass + deranged bone micro architecture

Question 15

where are ______ fractures most common in osteoporosis

Answer 15

wedge fractures

wrist
spine
hip

Question 16

what is increased kyphosis and what syndrome is it associated with

Answer 16

osteoporosis

benign forwards and increased longitudinal curvature - impaired breathing

Question 17

what are the risk factors of increased kyphosis

Answer 17

smoking, alcohol, menopause, increased age, female or have UC

Question 18

what is a fragility fracture and where is it common and how is it calculated

Answer 18

fracture that shouldn’t occur - fall from minimal height - low bone mass
lumbar spine, neck of femur, wrist
FRAX calculation tool - risk of fracture over next 10 years

Question 19

give examples of secondary causes of osteoporosis

Answer 19

endocrine - hormone ablation for breast, prostate cancer, diabetes 
GI
RA 
myeloma 
COPD 
homocysteinyria 
drugs

Question 20

what is used for the main bulk of osteoporosis treatment

Answer 20

antiresorptive treatment - work on osteoclasts

anabolic treatment which works on the osteoblasts building new bones

Question 21

how do bisphosphonates treat osteoporosis

Answer 21

oral

mimic pyrophosphate structure - taken up by osteoclasts and kills them to stop reabsorption

Question 22

what are the complications of biphosphonate treatment of osteoporosis

Answer 22

causes atypical femur fractures
flu like symptoms
poor absorption

Question 23

what are the two types of bone metastases

Answer 23

lytic (lysis of bone) - breast lung kidney and sclerotic - new bone formed -

Question 24

what are the presenting symptoms of a bone malignancy

Answer 24

pain in bone worse at night
numbness, trouble weeing
hypercalcaemia (abdominal pain, nausea, fatigue, kidney stones)

Question 25

what are the causes of hypercalcameia in bone metastases

Answer 25

non PTH mediated - malignancy = PTH low - most of cases are this - VIT D intoxicating`tion, hyperthyroidism

PTH mediated - increases blood calcium - primary hyperparathyroidism - familial in MEN1/2a

Question 26

what two cells are present in the parathyroid and what is their role

Answer 26

chief cells and oxyphil cells

chief cells secrete PTH - the other have unknown function

Question 27

what happens in homeostasis of parathyroid if calcium levels are low

Answer 27

detected by receipt which makes more PTH which then acts on bowel to absorb more calcium, kidney to reabsorb more calcium from urine and bone decomposition to increase calcium

Question 28

how does VIT D and Mg affect calcium levels

Answer 28

increase in Vit D = acts on parathyroid gland to increase PTH which increases Ca

decreases in Mg decreases PTH production and hypocalcemia

Question 29

what is the main receptor involved in Ca homeostasis and what does it do

Answer 29

CaSR - down regulates PTH secretion as calcium elves increase

Question 30

what is the difference between primary, secondary and tertiary hyperparathyroidism

Answer 30

1 - parathyroid gland issue - malfunction

2 - PT gland detects low Ca or Vit D due to other causes which increases PTH

3 - chronic effect of 2 HPT

Question 31

what would suggest primary hyperparathyroidism

Answer 31

elevated PTH in the presence of high calcium

Question 32

what is used to detect neoplasia on the parathyroid

Answer 32

sestamibi scan

Question 33

what is the treatment for adenomas of the parathyroid

Answer 33

surgery for symptomatic hypercalcaemia

calcimimetics - cinacalcet - activates CaSR to reduce PTH secretion

Question 34

what does pagets disease look like

Answer 34

cotton wool appearance in trabecular bone - thickened deformed cortical bone

Question 35

what is pagets disease and what are the features

Answer 35

high bone turnover - abnormal remodelling - mainly in men over 50
elevated alkaline phosphate due to bone turnover
bone pain and fractures

Question 36

what is the management of pagets disease

Answer 36

biphosphonates - reduce osteoclast function

Question 37

what is osteomalacia (adult vs child)

Answer 37

lack of mineralisation in bones - not enough calcium which makes soft bones
adult - widened osteoid seams
child - rickets - widened epiphyses and poor skeletal growth

Question 38

what causes osteomalacia

Answer 38

insufficient calcium absorption from intestines or excessive renal phosphate excretion due to genetics

Question 39

what are the clinical features of osteomalacia

Answer 39

diffuse bone pain - muscle weakness - high ALP, high PTH, low Vit D

Question 40

which population are most at risk to osteomalacia

Answer 40

• hijab asians

Question 41

what are the levels of ALP, Ca, phosphate and PTH in these diseases 
hyper PTH 
osetomalacia 
osteoporosis 
pagets 
bone mets

Answer 41

increased, increased, decreased, increased

increased, maybe decreased, deceased, maybe increased

normal

increased and normal for he rest

increased, maybe increased, normal and maybe deceased