metabolic bone disease

Question 1

T score of osteoporosis

Answer 1

T score of -2.5 or worse

-1 to -2.5 for osteopenia

Question 2

second degree causes of osteoperosis

Answer 2

increased PTH
glococorticoid use 
autoimmune 
hypogonadism 
calcium/vitamine D defciency 
renal disease 
aromatase inhibition (breast ca.)
androgen deprivation (prostate ca.)

Question 3

diet and lifestyle appraoches

Answer 3

adequate calcium and protein intake 
safe exposure to sunlight 
healthy weight and BMI 
cessation of smoking 
avoidance of alcohol

Question 4

reducing risk of falls

Answer 4

falls risk assessments and initiate targeted fall-prevention programs in older adults

Question 5

exercise

Answer 5

individuals over 50 years of age without osteoperosis should participate regularly in progressive resistance training and balance training exercise

Question 6

patients who should not be recieving treatemtn

Answer 6

patients at low risk (10 year risk <10%)

Question 7

recommendations for calcium

Answer 7

1300mg from diet and suppliment combined

Question 8

recommendation for vit D

Answer 8

800-200 IU daily for age over 50

Question 9

antiresorbtive drugs

Answer 9

aim to inhibit bone resorbtion by decreasing bone turnover or disrupting osteoclast formation and maturation

Question 10

anabolic agents

Answer 10

aim to inverse the imbalance in bone remodelling by stimulating bone formation, therefore increasing BMD

Question 11

3 antiresorptives

Answer 11

• bisphosphates
• denosumab
• SERMs

Question 12

3 anabolics

Answer 12

PTH (teriparatide)
PTHrP (abaloparatide)
sclerosin (romosozumab)

Question 13

3 bisphosphonates

Answer 13

alendronate
risedronate
zoledronic acid

nitrogen containing R2 side chains

Question 14

structure of bisphosphonates

Answer 14

structurally linked to inorgnic phyrophosphate, a naturally occuring compound consisting of two phosphate groups

Question 15

bisphosphonates have a high affinity for

Answer 15

very high affinity for hydroxyapatite (inorganic phase of bone)

Question 16

action of bisphosphonates

Answer 16

induce osteoclast apoptosis following resorption
inhibition of farnesyl pyrophosphate synthase (FPPS), a key enzyme in the mevalonic acid pathway
interferes with small GTP-binding proteins which play central roles in osteoclast function
collapse and death of osteoclast

Question 17

use of bisphosphonates

Answer 17

prevention of vertebral fracture in women with ostepenia (>10 years postmenopause)
reduce vertebral and non-vertebral fractures in women and men >50yo at high risk
use for 5 years then reassess

Question 18

administration of bisphosphonates

Answer 18

oral or IV

Question 19

side effects of bisphosphonates

Answer 19

oesophageal ulceration (oral)
musculoskeletal pain 
hypocalcaemia 
fever 
osteonecrosis of jaw
atypical femoral fracture (spontaneous)
adynamic bone disease

Question 20

denosumab

Answer 20

inhibitor of rank ligand

is an IgG2 monoclonal antibody that suppresses bone resorption by mimicking the action of OPG in bone microenvironment

Question 21

action of denosumab

Answer 21

anti-resoptive

denosumab ibinds to RANKL preventing its binding to RANK, reducing osteoclast development, survival and bone resorption

Question 22

uses of denosumab

Answer 22

denosumab is recommended for the treatment of osteoperosis in post menopausal women and men at increased risk of minimal trauma fracture
considered alternative for bisphosphonates

Question 23

administration of denosumab

Answer 23

subcutaneously at a dise of 60mg once every six months

Question 24

side effects

Answer 24

denosumab used in the treatment of osteoperosis is generally well-tolerated

• cellullitis (skin infections)
• hypocalcaemia (chronic kidney disease)
• osteonecrosis of jaw (ONJ)
• atypical femoral fracture
• multiple vertebral fractures upon discontinuation (rebound)

Question 25

denosumab vs. biphosphonates

Answer 25

unlike bisphosphonates, denosumab is not characterised by a long biological half life not is it incorporated into the bone antiresorptive effect of denosumab caeses after suspension of treatment concerns about a drug rebound 'vertebral fractures following discontinuation' re-evaluation of risk should be assessed after five years

Question 26

denosumab rebound

Answer 26

denosumab cessation should not be considered without alternative osteoporosis treatment

Question 27

patients discontinuing denosumab

Answer 27

should recieve follow-up treatment with bisphosphonate and be monitored closely

Question 28

1 selective estrogen receptor modulators (SERMs)

Answer 28

raloxifene

Question 29

structure of SERMs

Answer 29

synthetic non-steroidal agents

Question 30

action of SERMs

Answer 30

osterogen agonist and antagonist activities in defferent tissues as well as anti-fracture efficacy oestrogen receptors are found on osteoclasts and osteobalsts and ostrogen depletion leads to bone loss SERMs decrease osteoclast activity leading to educed bone resorption

Question 31

raloxfene use

Answer 31

a treatment opton for postmenopausal wmen with osteoperosis where vertebral fractures are considered to be the major osteoperosis rsk and where other agents are porly tolerated may be particularly useful in younger postmenopausal women at risk of vertebral fracture and who have a prior or family history of breast cancer

Question 32

administration of raloxifene

Answer 32

oral at a dose of 60mg per day

Question 33

side effects of raloxifene

Answer 33

oestrogen replacement - increased risk of invasive breast cancer - increased coronary heart disease - increased risks of thromboembolic events and cerebrovascular accident raloxifene - may increase hot flushes - increased thromboembolic events (2.5x) but not heart disease or overall risk of stroke - has little to no effect on endometrium and may not predispose to uterine cancer

Question 34

teriparatide

Answer 34

part of parathyroid hormone anabolic binds to PTH type 1 receptor, a g-protein coupled receptor, expressed on osteoblasts increased new bone formation by osteoblasts increased the osteoblasts survival by reducing apoptosis and inducing recruitment and formation of new osteoblasts

Question 35

use of teriparatide

Answer 35

increases lumbar spine and femorral neck BMD decreases vertebral and non-vertebral fractures in postmenopausal osteoperosis with prior fracture recommended for postmenopausal women and men over 50 years of age with osteoperosis wh have sustained a sebsequent fracture while on anti-resorbtive therapy

Question 36

PBS qualification for teriparatide

Answer 36

a BMD score of <3 or less had two or more fractures due to minimal trauma experiencced at least one symptomatic new fracture after at lleats 12 months continuous therapy with an antiresorptive agent

Question 37

administration of teriparatide

Answer 37

subcutanous 20 micro gram daily (intermittant stimulation) for 18 months (switch to antiresorbtive)

Question 38

teriparatide side effects

Answer 38

``` dizziness leg cramps nausea headache transient hypercalcaemia mild increases in uric acid without the development of acute gout increased risk of osteogenic sarcoma ```

Question 39

teriparatide is not recommended for patients with

Answer 39

paget disease, prior skeletal irridation, bony metastases or prior skeletal malignancies, and for those with metabolic bone disease (other than osteoperosis) or pre-existing hypercaalcaemia

Question 40

cessation of teriparatide

Answer 40

BMD decreases within 12 hours after cessation, required sequential treatment with antiresobtive drug

Question 41

abaloparatide

Answer 41

is a synthetic human parathyroid hormone related peptide

Question 42

action of abaloparatide

Answer 42

anabolic like teriparatide, acts as an agonist at the PTH1 receptor this results in activation of the cAMP signalling pathway is osteoblasts increase bone formation by osteoblasts anabolic profile similar to teriparatide but has reduced bone resorption by an unknown mechanism

Question 43

uses of abaloparatide

Answer 43

for osteoporosis patients at very high fracture risk or do not respond to other osteoporosis drugs

Question 44

administration of abaloparatide

Answer 44

once-daily 80 micrograms subcutaneous injection | 18 months then switch to antiresorbtive

Question 45

side effects of abaloparatide

Answer 45

similar to teriparatide but show dose dependant increased risk of osteosarcoma in rates same cessation effecs

Question 46

issues with anti-resorbtives

Answer 46

administered late - patients are already osteopenic/osteoporotic poor compliance undesirable effects - atypical subchanteric femoral fractures - osteonecross of the jaw

Question 47

issues with anabolics

Answer 47

- few approved - administeres late - patinets are. already osteoporotic, sustained a fracture - expensive - invasive injection - fracture efficacy limites - antiresoorptive required after cycle - osteosarcoma and cardiovascular risks

Question 48

anti-sclerosin

Answer 48

new therapy sclerosin inhibits canonical Wnt signalling pathways Wnt signally pathway in osteoblasts is responisble for stimulating bone formation in response to mechanical loading by stimulating osteoblast proliferation sclerosin in synthesized by osteocytes when bone is inloaded, inhibiting bone formation

Question 49

1 anti-sclerostin

Answer 49

romosozumab

Question 50

structure of romosozumab

Answer 50

a humanised monoclonal antibody against sclerostin

Question 51

action of romosozumab

Answer 51

anabolic - potent inhibitss sclerostin stimulates canonical WNT signalling in osteoblasts increased bone formation and reduced fracture risk

Question 52

use of romosozumab

Answer 52

for the treatment of osteoporosis in postmenopausal women at high risk for fracture

Question 53

administration of romosozumab

Answer 53

210mg subcutaneous injection once monthly for 12 months

Question 54

side effects of romoszumab

Answer 54

increased cardiovascular/stroke risk?