endocrine and metabolic bone disorders Flashcards
what bone stores and components of it
stores 95% of Ca2+, has osteoids (unmineralised bone made from type 1 collagen) and inorganic mineral component (calcium hydroxyapatite crystals- mostly this)
cells of bone
osteoblasts (produces osteoid and helps mineralise it) and osteoclasts (releases enzymes to break down/RESORB bone)
osteoclast differentiation DIAGRAM
RANK receptor of osteoclast precursors bind to RANKL receptor on osteblasts to become activated- thus needs osteoblasts
receptors that osteoblasts express
those for PTH and calcitriol- hence osteoblasts regulates balance between bone formation and resorption
how bone looks like
cortical (HARD) bone on outside, with trabecular (spongy) bone inside- they are formed in a LAMELLAR pattern (way collagen laid down to make it strong)
effect of vit D deficiency on bone in children and adults
not enough mineralisation of bone (osteoids)- can lead to LOOSER ZONES (easily have stress fractures- can’t hold body weight) and WADDLING GAIT (way of walking) rickets- growth plates affected= skeletal abnormalities, pain, growth issues and increased fracture risk osteomalacia- growth plates close so growth not affected, but pain, myopathy and increased fracture risk occurs
what is tertiary hyperparathyroidism
often occurs in chronic kidney disease- chronic low Ca2+ (as kidney can’t produce calcitriiol), hence gland becomes bigger and bigger, so PTH rises and is AUTONOMOUS, increasing Ca2+
renal failure and bone disease DIAGRAM
less calcitriol and PO4 excretion, and PO4 binds to calcium, so these 2 things= hypocalcaemia this leads to high PTH= high bone resorption, as well as less bone mineralisation (as not enough calcium), which gobbles up bone and calcifies BLOOD VESSELS; this can lead to brown tumours ie gobbled up bone (osteitis fibrosa cystica)
treatment of osteitis fibrosa cystica (hyperparathyroid bone disease)
low phosphate diet and phosphate binders to prevent XS phosphate alphacalcidol (active D3) parathyroidectomy for tertiary hyperparathyroidism
what is osteoporosis and effect on men/women
loss of trabeculae, lower mass of bone and increased RISK OF FRACTURE bone mass goes down for both women and men, but goes down a lot POSTMENOPAUSE
define osteoporosis and score threshold
bone mineral density ie bone MASS greater than 2.5 SD’S BELOW average value of young healthy adults (T score of -2.5 or lower)
how to measure BMD
using DEXA scan of lumbar spine and neck- measures mineral content ie bone mass
osteoporosis vs osteomalacia
although both cause increased fracture risk, malacia is due to vit D deficiency causing less MINERALISATION, whereas osteoporosis is where resorption exceeds formation= less bone MASS also, serum levels normal is osteoporosis, so diagnosis via DEXA scan , but serum levels in malacia bad (low Ca, high PTH), so diagnosis via blood test
predisposing conditions for osteoporosis
postmenopausal oestrogen deficiency (leads to loss of bone) age related lack of osteoblasts (occurs as u age) hypogonadism (low LH/FSH= low oestrogen) endocrine problems like cushings, hyperthyroidism and primary hyperpara. drugs eg glucocorticoids/heparin
consequences of hip fracture
20% with the fracture dead within a year, 80% cannot independently do one activity in daily life
treatment of osteoporsis
oestrogen, bisphosphonates, denosumab, teriparatide
oestrogen- what it does, problem
treats post menopausal women to prevent bone loss however, its a short term solution- can lead to breast cancer, and must be taken with progestogen to prevent endometrial hyperplasia/cancer
bisphosphonates- mechanism
binds to hydroxyapatite crystals- osteoclasts ingest this and become paralysed, then death= less gobbling up of bone= less bone turnover
uses of bisphosphones
FIRST LINE treatment for osteoporosis also for hypercalcaemia of malignancy- reduces bone pain and reduces hypercalcaemia (as osteoclasts die) paget’s disease- reduces pain severe hypercalcaemic emergency (rehydration first)
pharmocokinetics of bisphosphonates
given as tablet but poorly absorbed- MUST take on empty stomach can paralyse osteoclasts for years
side effects of bisphosphonates
oesophagitis- can irritate oesophagus when taken orally osteonecrosis of jaw (breaking down)- cancer patients most at risk atypical factures- because bone remodelling has become ADYNAMIC (no longer dynamic as osteoclasts not working), can lead to fractures
denosumab DIAGRAM
binds to RANKL on ostebblasts, preventing osteoclasts precursor from binding and differentiating 2nd line- taken every 6 months unlike bisphosphonates
teriparatide
recombinant PTH- increases both formation and resorption/reabsorption, but formation MORE 3rd line treatment as EXPENSIVE
what is paget’s disease and how it occurs
excessive bone resorption by ABNORMAL osteoclasts- compensate by laying down lots of bone, but in an unorganised way (WOVEN rather than laminar)- thus weaker= hypertrophy and frailty
