diseases of bone Flashcards
describe the composition of bone
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)
what is the role of the bone forming cells
osteoblasts - create and repair bone
make osteoid - mainly type 1 collagen
what is the role of bone reabsorbing cells
osteoclasts - breakdown old bone - multinuceltaed and large
releases calcium into the blood stream
release TRAP and cathepsin K enzymes to dissolve bone
what is the role of an osteocyte
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
what are the contents of the ECM of bone
organic matriculates mainly collagen type 1m ground substance, inorganic compounds and minerals
what is the word used to describe the type of tissue that bone is
dynamic
describe the bone cycle
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
how doe menopause affect bone
loss of oestrogen causes accelerated loss of bone mass
what happens to bone with age
rate of reabsorption out weighs rate of formation which gradually decreases bone mass
what techniques can be used to investigate bone mass
x ray, MRI CT for fractures
DEXA scan for Ca bone mass
surrogate markers for cells
microscopy
what are two biochemical markers of bone formation
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
what are two biochemical markers of bone reabsorption
collagen cross links (NTX, CTX)
released during bone reabsorption
increased during hyperthyroidism, adolescence and menopause
what is a DEXA image used for in bone
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
what leads to failure of structural integrity of bone
decreased bon mass + deranged bone micro architecture
where are ______ fractures most common in osteoporosis
wedge fractures
wrist
spine
hip
what is increased kyphosis and what syndrome is it associated with
osteoporosis
benign forwards and increased longitudinal curvature - impaired breathing
what are the risk factors of increased kyphosis
smoking, alcohol, menopause, increased age, female or have UC
what is a fragility fracture and where is it common and how is it calculated
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
give examples of secondary causes of osteoporosis
endocrine - hormone ablation for breast, prostate cancer, diabetes GI RA myeloma COPD homocysteinyria drugs
what is used for the main bulk of osteoporosis treatment
antiresorptive treatment - work on osteoclasts
anabolic treatment which works on the osteoblasts building new bones
how do bisphosphonates treat osteoporosis
oral
mimic pyrophosphate structure - taken up by osteoclasts and kills them to stop reabsorption
what are the complications of biphosphonate treatment of osteoporosis
causes atypical femur fractures
flu like symptoms
poor absorption
what are the two types of bone metastases
lytic (lysis of bone) - breast lung kidney and sclerotic - new bone formed -
what are the presenting symptoms of a bone malignancy
pain in bone worse at night
numbness, trouble weeing
hypercalcaemia (abdominal pain, nausea, fatigue, kidney stones)
what are the causes of hypercalcameia in bone metastases
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
what two cells are present in the parathyroid and what is their role
chief cells and oxyphil cells
chief cells secrete PTH - the other have unknown function
what happens in homeostasis of parathyroid if calcium levels are low
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
how does VIT D and Mg affect calcium levels
increase in Vit D = acts on parathyroid gland to increase PTH which increases Ca
decreases in Mg decreases PTH production and hypocalcemia
what is the main receptor involved in Ca homeostasis and what does it do
CaSR - down regulates PTH secretion as calcium elves increase
what is the difference between primary, secondary and tertiary hyperparathyroidism
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
what would suggest primary hyperparathyroidism
elevated PTH in the presence of high calcium
what is used to detect neoplasia on the parathyroid
sestamibi scan
what is the treatment for adenomas of the parathyroid
surgery for symptomatic hypercalcaemia
calcimimetics - cinacalcet - activates CaSR to reduce PTH secretion
what does pagets disease look like
cotton wool appearance in trabecular bone - thickened deformed cortical bone
what is pagets disease and what are the features
high bone turnover - abnormal remodelling - mainly in men over 50
elevated alkaline phosphate due to bone turnover
bone pain and fractures
what is the management of pagets disease
biphosphonates - reduce osteoclast function
what is osteomalacia (adult vs child)
lack of mineralisation in bones - not enough calcium which makes soft bones
adult - widened osteoid seams
child - rickets - widened epiphyses and poor skeletal growth
what causes osteomalacia
insufficient calcium absorption from intestines or excessive renal phosphate excretion due to genetics
what are the clinical features of osteomalacia
diffuse bone pain - muscle weakness - high ALP, high PTH, low Vit D
which population are most at risk to osteomalacia
- hijab asians
what are the levels of ALP, Ca, phosphate and PTH in these diseases hyper PTH osetomalacia osteoporosis pagets bone mets
increased, increased, decreased, increased
increased, maybe decreased, deceased, maybe increased
normal
increased and normal for he rest
increased, maybe increased, normal and maybe deceased
