Bones Flashcards
5 common osteoporotic #s
hip NOF vertebral body distal radius humeral neck
cells that cause bone resorption
osteoclasts
cells that cause bone formation
osteoblasts
function - bone mineralisation
osteoid
drugs that can enhance osteoporosis progression
steroids aromatase inhibitors (breast cancer Rx)
bone loss usually starts at this age
40yo
DEXA scan measures your __
and so predicts your __ risk independent of other risk factors
bone mineral density #
fracture risk calculator validated in the UK =
refer on for a DEXA if ___
Q fracture
10yr risk for an osteoporotic # is >= 10%
DEXA result if you are osteopenic
> 1 but <2.5SD less than the mean
DEXA result if you are osteoporotic
> =2.5 SD less than mean
severe osteoporosis is defined as BMD ___ and ___
> =2.5SD less than mean
fragility #
Bence Jones proteins are found if you have __
multiple myeloma
Rx for osteoporosis =
Calcium and vitamin D supplements biphosphonates zoledronic acid denosumab strontium ranelate teriparatide
calcium and vitamin D supplements decrease the risk of ___ # if deficiency risk
non-vertebral
dont give Ca2+ supplements within 2hrs of ___
PO biphosphonates
2 examples of biphosphonates
alendronate
risendronate
biphosphonate mechanism of action =
anti resorptive
analogues of pyrophosphate that are absorbed onto bone in matrix > ingested by osteoclasts > cell deth and resorption sites are filled by new bone > BMD increases by 5-8%
long term adverse affects of biphosphonates
jaw osteonecrosis
oesophagus cancer
atypical #s
therefore - consider a bone holiday
zoledronic acid dose route and duration
1/yr IV for 3 yrs
if get acute phase reaction with 1st infusion of zoledronic acid = give ___
paracetamol
side effects of denosumab
hypoCa2+
eczema
cellulitis
Denosumab mechanism of action
monoclonal Ig that binds to RANKL > prevents activation of RANK (its receptor) > inhibits development and activity of osteoclasts, decreases resorption and increases BMD
route of denosumab and how often its given
S/C injection
6 monthly
denosumab is not contra-indicated in ___
severe renal impairment
recombinant PTH that stimulates bone growth =
given in >65yo with t 2#s
or 55-64yo with t 2#s
teriparatide
when to consider antiresorptive treatment in osteoporosis
if t <=-2.5
ongoing steroid Rx >=3months/prevalent vert# and t <=-1.5
how steroids increase osteoporosis progression =
reduce osteoblast activity and lifespan
suppress replication of osteoblast precursors
reduce Ca2+ absorption from gut
indirectly inhibit gonadal and adrenal steroid production
increase Ca2+ renal excretion
increase PTH sensitivity and secretion => increase osteoclast activity
abnormal osteoclast activity => increased osteoblast activity =
Paget’s disease
Paget’s affects these bones
long bones, pelvis, lumbar sppine and skull predominantly
Paget’s can rarely lead on to cause
osteosarcoma
presentation of Paget’s
bone pain, deformity, deafness, compression neuropathies
diagnosis of Pagets (3 Ix)
XR
isotope scan
normal LFTs but raised ALP
treat paget’s with ___ or __ if 1st line doesnt reduce bone pain
analgesics
biphosphonates
osteogenesis imperfecta is caused by mutations of ___
most mode of inheritance =
type 1 collagen genes (COL1A1/2)
auto dom
very sever form of osteogenesis imperfecta =
type 3 and 4
type of osteogenesis imperfecta that is neonatally lethal
2
ass. with blue sclera +/ dentinogenesis imperfecta
osteogenesis imperfecta
Rx for osteogenesis imperfecta
#fixation, Sx for deformities biphosphonates once growth plates have fused
Ca2+ > ___ in PT gland > ___ PTH to skeleton (=>____) and GI tract (=>___)
CaSR
decreased
resorption
absorption
___(sun > cholecaldiferol/D3(___)>25 OH vit D (___) >_____>PTH, skeleton, GI, kidney
dehydro-cholesterol
liver
kidney
1-25OH vit D
acute hypercalcaemia s+s
may =>
thirst dehydration polyuria confusion => nephrogenic DI
chronic hypercalcaemia s+s
myopathy osteopenia #s depression hbp pancreatitis, GI ulcers, renal stones
hypercalcaemia causes albumin and urea levels to be ___ if dehydrated
raised
blood results if primary/tertiary hyperPT
albumin normal/low
PTH normal/raised
PO4 low or normal
raised urine Ca2+
FHH caused urine calcium levels to be ___
low
hypercalcaemia related to bone pathology blood results
albumin normal/low
suppressed PTH
raised PO4
if ALP is raised and suspect bone pathology it could be //_
thyrotoxicosis
bone metastases
sarcoidosis
if ALP is low and suspect bone pathology it could be //__
myeloma
vitamin D excess
mild-alkali syndrome - sarcoid/thyrotoxicosis/increased bicarbonate
causes of hypercalcaemia
primary and tertiary hyperPT malignancy vit D/thiazides granulomatous diseases FHH high bone turnover
FHH stands for ___
familial hypocalciuric hypercalcaemia
diagnosis of primary hyperPT blood results -
increased serum Ca2+ and PTH (or inapp normal)
increased urine calcium excretion
Ix and results for hypercalcaemia of malignancy
increased serum Ca2+ and ALP
XR
isotope bone scan
Rx of acute hypercalcaemia
immediate = fluids (0.9% saline) loop diuretics biphophonates single dose steroids - if sarcoids chemo in malig
imaging used for the PT =
Sestamibi scan
treatment that can be used for tertiary hyperPT/PT carcinoma
cinacalcet
Indications for a parathyroidectomy in primary hyperparathyroidism:
end organ damage
very high Ca2+ (>2.85mmol/l)
<50yo/fit
eGFR <60
___ hyperparathyroidism = PT is overactive
PTH and Ca2+ =
eg. of a cause
primary
both raised
adenoma of PT
2ndry hyperPT =
Ca2+ and PTH =
physiological response to low Ca2+ levels
Ca2+ low and PTH raised
tertiary hyperPT =
Ca2+ and PTH =
PT autonomous after years of 2ndry
both raised
genetic syndromes associated with hypercalcaemia
MEN1/2 (present young)
FHPT
FHH mode of inheritance
mutation =
auto dom
deactivating mutation in CaSR
usually benign/asympt
s+s of hypocalcaemia
paraesthesia muscle cramps/tetany muscle weakness fatigue fits broncho/laryngospasm Chovstek's sign (tap CNVII) Trousseau sign (carpopedal spasm) QT prolonged
emergency Rx for hypocalcaemia
IV Ca2+ gluconate (10ml 10% over 10 mins in 50ml saline/dextrose)
causes of hypoPT
DiGeorge Sx/radio/malig AI hypoMg2+ (PPI/alcoholic) idiopathic
3 options for long term management of hypocalcaemia
> 1-2g Ca2+ supplements od
vit D (1alpha calcidol 0.5-1mcg)
depot injection cholecalciferol 300,000U/6months
in Mg2+ deficiency intracellular Ca2+ is high/low? because ___
high
Ca2+ release from cells is dependent on Mg2+
causes of hypomagnesaemia
alcohol thiazides and PPIs GI illness pancreatitis malabsorption
in hypomagnesaemia ___ is inhibited, skeletal and muscle receptors are less sensitive to ___
PTH release
PTH
if this mineral is also low in hypocalcaemia then it needs supplemented as well
Mg2+
pseudohypoparathyroidism is caused by the genetic defect ____
__Ca2+ and ___ PTH (as there is PTH ___)
GNAS1 gene defect - dysfunction of Gs alpha subunit
low Ca2+ and high PTH - PTH resistance
symptoms and signs of pseudohypoPT
bone abnormalities (Albright's hereditary osteodystrophy) obesity 4th MC brachydactyly S/C calcification IQ low
pseudo-pseudohypoPT = all of pseudo symptoms but __
normal Ca2+
Looser Zones on XR =
Pseudo#s: wide, transverse lucencies traversing part way through a bone, usually at right angles to the involved cortex
sign of osteomalacia/rickets
in osteomalacia Ca2+, PO4-, ALP, vit D, PTH levels
Ca2+, PO4 3- = low
ALP = high
vit D = low
PTH = high
Rx for osteomalacia
D3 tablets (3200U/day for 12 wks then 400-800/day) calcitriol alfacalcidol
X-linked hypophosphataemia aka
vit D resistant rickets
FGF23 regulates ___ levels which is secreted by ___ in response to calcitriol
Phosphate plasma levels
osteocytes
in pagets ++_ are normal but __ is very high
Ca2+, PTH and phosphate
ALP v raised
vertebrae looks fish shaped =
biconcave vertebral #
T score =
BMD compared to young adult population
Z-score =
compares BMD to same sex and age - shows if increased loss for age
anabolic drug used if severe osteoporosis and vertebral # risk
teraparatide
mothy bone (lytic lesions) indicates
metastatic bone disease
5 cancers likely to spread to bone
breast lung bowel renal prostate
coarse trabecullar pattern and cortical thickening
hot and tender =
Paget’s
marker of remission in Paget’s
ALP normalises from being high
PTH effects on bone and kidneys
increase resorption and Ca2+ release
increase reabsorption and excretion of phosphate in urine
active form of vitamin d
1,25 - dihydroxycholecalciferol
stones bones moans and abdominal groans =
hypercalcaemia
facial muscles twitch when tap CN VII
Chvosteks sign (hypoCa2+)
bp cuff inflation causes tetany in hand and wrist
Trousseaus sign (hypocalcaemia)
genetic abnormality that causes PTH resistance
pseudohypoPT
craniotabes=
soft skull bones at birth (sign of rickets)
___ from the hypothalamuc inhibits GH release from ant pit
somatostatin
A SERM - selective oestrogen receptor modulator for postmenopausal women with osteoporosis
raloxifene
