Bisphosphonates and Bone Flashcards
why and how does bone remodel? how do antiresorptives work? what are the problems? how is this relevant to dentistry?
what is bone composed of
water-10%
collagen-20%
mineral-70%
what minerals are found in bone
hydroxyapatite/Ca5(PO4)3(OH)
what are cortical bones comprised of
a basic unit called an osteon which goes the entire length of the bone
what does the osteon contain
concentric rings of bone tissues
why is the bone tissue strong
because of the arrangement of the collagen fibre and minerals are in different directions which means it can resist stress in different directions
what is contained inside a osteon
lacunae containing osteocytes blood vessels haversian canal lamellae canaliculi
which cells take away bone
osteoCLAST
which cells remake bone
osteoBLAST
how do the osteoblasts and osteoclasts communicate with one another
by negative and positive feedback reactions
which hormones are involved in balancing bone absorption and bone formation
parathyroid hormone
oestrogen
what happens if you have hyperparathyroidism
dissolves bones
what can people with parathyroid tumours have
weak bones and can have high blood calcium levels
what other chemicals are involved in bone homeostasis
cytokines- inflammation
tumour factors- influences bone homeostasis
RANK-L inhibitors are more commonly prescribed and more patients take them
OPG-
what does RANK-L stand for
Receptor activator for nuclear factor kappa B ligand
what is a common drug which is a RANK-L inhibitor
denosumab- for the treatment of osteoporosis treatment-induced bone loss, metastases to bone,and giant cell tumor of bone
what is OPG
OsteoProtegerin
what are the stages of bone homeostasis
- the osteoblasts secrete RANK-L AND OPG
- the osteoclast has a receptor for the OPG molecule and the OPG has a receptor for RANK-L
3.
what happens if rank-l and opg are working well
you get the same amount of bone formation and resorption
what happens if the osteoblast is only secreting RANK-L
we get osteoclast simulation- this is why a rank-l inhibitor may be helpful
what is the issue with bone homeostasis
can go wrong-
usually occurs with age naturally
also can be because of disease process- eg osteoporosis
what is osteoporosis
pores forming in the bone- not as much bone and the remaining bone is not as well calcified meaning it is weak
what is the result of osteoporosis in the long bone
massive pores in the bone- meaning when weight is applied stress is not applied evenly and more concentrated leading to fractured bone
what is a common compression fracture in the spine
a osteoporotic wedge fracture- causes a hunched spine
if you were to break a bone what could happen
calcium released into the blood
travels to the heart
causes heart dysrhythmia
leading to a heart attack
what is a distal radius fracture also known as
Colles fracture
which gender is in much more of a risk of severe osteoporosis
female due to the fact of menopause
who is at risk of osteoporosis
female-post menopause
elderly
long term corticosteroids
give examples of corticosteroids
hydrocortisone
predisolone
why might people take corticosteroids
asthma
RA
what other diseases can we get in bones
bone cancer- eg breast, prostate and lung cancer can spread to the bone and metastasise
hypercalcaemia
pain
pathological fracture
what is myeloma
bone cancer( cancer of the bone marrow)
what can multiple bone metastasis lead to
pathological fracture- which causes pain
what is the symptoms of hypercalcaemia in the GI tract
nausea
vomiting
loss of apatite
constipation
what is the symptoms of hypercalcaemia in the CV system
bradycardia
cardiac arythmias
hypertension
what is the symptoms of hypercalcaemia in the kidneys
kidney stones
nephrogenic diabetes insipidus
kidney failure
what is the symptoms of hypercalcaemia in the brain
fatigue- mild hyperglycaemia
memory loss, depression and anxiety- moderate hypercalcaemia
extreme drowsiness coma death- severe hyperglycaemia
what is Pagets disease
too much bone laid down
What are the symptoms of Paget’s disease
Can get pathological fracture
As the bone is thicker leading to limb deformities
Compression of nerves
Pain
What is osteogenesis imperfects
Weak bones which can break very easily
What is the main take home message for people with osteoporosis
Stay active Sunlight- vitamin D deficiency Drink sensibly and don’t smoke Healthy balanced diet Hormone replacement therapy And bisphosphonates
What are bisphosphonates
Given to people to stabilise bones and minimise effects of osteoporosis
What are two phosphate molecules together called
Pyrophosphate
What do pyrophosphate molecules bind to
Bone-HAP
for how long do people need to take bisphosphonates for osteoporosis
oral or yearly injection
for how long do people need to take bisphosphonates for cancer/myeloma
intravenous- once a week/once a month depending
disadvantages of bisphosphonates
reduced activity of osteoclasts and osteoblasts
reduced healing ability
pain
dead bone
pathological fracture
can also affect other cells, keratinocytes and fibroblasts
what is BRONJ
BISPHOSPHONATE RELATED OSTEONECROSIS OF THE JAW- used to be discussed a lot
what is ARONJ
anti resorptive related necrosis of the jaw such as with denosumab
what is MRONJ
medicated related osteonecrosis of the JAW- can get it with anti angiogenecis such as avastin sutent and zaltrap
what is the half life of bisphosphonates
years- takes a long time to release from the bone
do we advise a patient to stop taking bisphosphonates when a tooth is getting extracted
no as the dosage in the bone takes years to reduce
we might advise a drug holiday- haven’t been on it for long but might stop it for 6 months
when do we review out patient if we have extracted a tooth and they are taking bisphosphonates
in 8 weeks and we check for Exposed bone Pain Infection Radiographic changes Pus discharge
if we find out a patient is taking bisphosphonates in the MH what follow up questions do we ask
Why are you taking it?
What kind of medicine are you taking?
How long have you taken it for?
Other risk factors
what is the risk of MRONJ in osteoporosis
less than 0.15%
what is the risk of MRONJ in cancer
3%
what is the risk of MRONJ in myeloma
7%
does alendronate have a high or low risk of MRONJ
low
does zolendronate have a high or low risk of MRONJ
high
what is the relative efficacy of Etidronate
1
what is the relative efficacy of Clodranate
10
what is the relative efficacy of Pamidronate
100
what is the relative efficacy of Alendronate
500
what is the relative efficacy of Risedronate
2000
what is the relative efficacy of Zolendrote
10000
what are the risks of MRONJ
60% risk after dental extraction Untreated gum disease- we can help this Untreated decay- we can help this Poorly fitting dentures- we can help this Smoking Alcohol Steroids (think about patients if they have rheumatoid arthritis!)
