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PHA332 > Osteoporosis > Flashcards

Osteoporosis Flashcards

1
Q

What is osteoporosis?

A

This is the loss of bone mass due to the reduction in organic bone matrix and mineral content.
-decreased mechanical strength of the bones
-increased incidences of fractures
-more common in females as oestrogen controls the balance between osteoblast and clasts.

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2
Q

What do osteoclasts and osteoblasts do?

A

Osteoclast- degrade bone
Osteoblast- formation of bone

There is a balance of these. A balance is required.

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3
Q

Why are women at a higher risk of osteoporosis?

A

This is due to the loss of oestrogen levels this helps to maintain the balance of osteoblast and osteoclasts.

RANKL is not suppressed when a women is oestrogen deficient

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4
Q

What is rank L ?

A

Receptor activated NFkb ligand- this is a osteoclast activator.

It’s main role is to activate osteoclasts

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5
Q

What is OPG and what is the job?

A

Osteoprotegerin- this inhibits bone resorption (breakdown of bone)

Binds to rankL to stop the formation of osteoclasts.
Increased bone formation via the osteoblasts.

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6
Q

What pharmacological treatments are available for osteoporosis?

A

BISPHOSPHONATES: ANTI RESORPTIVE THERAPIES
-ORAL(Alendronic acid and risedronate)
-parental( zoledronic acid)
-RALOXIFENE AND OESTROGEN
-Denosumab ( sub injection)

Less commonly used:
-HRT ( early menopause)

BONE FORMING ANABOLIC THERAPIES:
-Calcitonin
-teriparatide

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7
Q

What is primary osteoporosis?

A

Menopause - increased bone reabsorption
Age associated - decrease in bone formation

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8
Q

What is secondary osteoporosis?

A

-Drug or disease induced.
-Malnutrition (anorexia)
-Lack of vitamin D
-Hyperparathyroidism
-Cancer

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9
Q

What is RANK?

A

Rank is the receptor activated NFkB, this is found on the surface of pre osteoclasts.

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10
Q

What can cause the bone to release RANK L?

A

Parathyroid hormone
If there is a stimulation of PTH then more RANK L to be released.

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11
Q

Why is oestrogen important for bone?

A

Oestrogen promotes the formation of osteoblasts.
Oestrogen will inhibit the T cell formation/activation thus inhibits the release of RANK L.

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12
Q

WHAT HAPPENS IF THERE IS AN ABSENCE OF OESTROGEN FOR BONE ?

A

Increased activation of T cells which can go onto promote the release of RANK L to form osteoclasts that can again promote bone reabsorption.

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13
Q

What does calcified bone contain?

A

-25% organic matrix
-5% water
-70% hydroxyapatite (holds the bone together)

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14
Q

Why can’t we give pyrophosphate and what would we give instead?

A

This is because it is hydrolysed when taken orally by the GI tract, into two phosphate groups, thus we would use a biphosphonate, e.g. alendronic acid

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15
Q

How does the pyrophosphate and bisphosphatonates differ in structure?

A

The bisphosphonate replaces the oxygen of the pyrophosphate with a carbon with two functional groups. Therefore they cannot be hydrolysed.

They bind and stabilise calcium phosphate in the bone.

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16
Q

What is the job of bisphosphonates?

A

They work like pyrophosphate, like a glue to hold the bones together.
-inhibit osteoclast proliferation
-inhibit osteoclast activity
-inhibit the malaveonate pathway of osteoclasts

THEY ALLOW OSTEOBLASTS TO FUNCTION.

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17
Q

Why is it effective to have a hydroxyl group as R1 functional groups in bisphosphonates?

A

This is because it maximises the effects to bind to hydroxyapatite and increases the calcium affinity.

18
Q

What happens if we add an amino acid residue on functional group R2 in bisphosphonates?

A

This will increase the potency (concentration)

19
Q

Bisphosphonates and the pharmacology?

A

-absorption is poor due to being polar
-50% incorporated into bone the rest is excreted via the kidneys
-serum half life is 4-6 hr the tissue half life is 10 years

20
Q

What is 1st line treatment for osteoporosis and what is the drugs job?

A

ALENDRONIC ACID (second generation)
- it strengthens the bone lattice
-decreases osteoclast formation
-impacts the malaveonate pathway.
-reduces fracture risks by 50%

21
Q

What is the second line drug used in osteoporosis?

A

Risedronate

22
Q

What is the bisphosphonate that requires to be adminstrated via IV route?

A

Zolendronic acid and it is given every 12 months or annually.
-it is give if oral route are not tolerated.

23
Q

What does the renal function of a patient require to be if they take Alendronic acid and risedronate?

A

Alendronic acid = <35ml/min

Risedronate= <30ml/min

24
Q

What do we need to look out for when a patient is on an osteoporosis medication?

A

Hypocalcaemia= this is when the calcium levels are too low in the body.

Dysphagia= patient unable to swallow properly

25
Q

Why is a patient advised to take bisphosphonates on an empty stomach?

A

To avoid binding by calcium in the food.

26
Q

What adverse effects are experienced with bisphosphonates?

A

-GI disturbances
-nausea
-abdominal pain
-diarrhoea
-constipation.
-headaches
-dizziness
-vertigo
-musculoskeletal pain
-oesophagitis
-I.V can cause osteonecrosis of the jaw.

27
Q

What is denosumab and how does it work?

A

Denosumab is a monoclonal antibody that mimics OPG, it is seen as a synthetic version.
-thus it binds to RANK L to prevent osteoclast activation.

28
Q

How often is denosumab injected?

A

6 monthly injections

29
Q

What are selective estrogen receptor modulators and give examples?

A

Raloxifene
This is seen as an antagonist in breast tissue, thus stops the formation of breast cancer
In osteoclasts it is an ER agonist, thus it will switch on the estrogen receptors in bones and switches off the estrogen in the breast tissue.
-reduces the osteoclast activity

30
Q

What are the disadvantages to taking SERMS?

A

-It doesnt prevent:
Hot flushes
And other symptoms of menopause

31
Q

What is the job of raloxifene?

A

-it decreases fracture risk
-promotes bone formation
-excreted in bile
-stimulates estrogen receptor and reduces osteoclast activity.

32
Q

Why is HRT less favoured in the treatment of osteoporosis?

A

This is because there is an increased risk of breast cancer and thrombosis.

33
Q

How does raloxifene differ depending on where it is in the body?

A

In breast tissue= antagonist thus switches the genes off here.

Bones/osteoclasts=agonist

34
Q

HOW IS RALOXIFENE EXCRETED?

A

VIA BILE

35
Q

What are the 2nd generation SERMS and grove an example?

A

Lasofoxifene
-prevents bone loss
-impoirves bone density by 3%

36
Q

What is a SERM?

A

A serm stands for a selective estrogen receptor modulator

37
Q

What causes the SERM effect?

A

Raloxifene binds to the estrogen receptor, moves into the nucleus of the bone environment, and then binds to raloxifene response element that is only found in bone, and not in the breast.

Helper proteins in the bone environment will help and aid the binding into the receptors, this isn’t present in the breast environment thus activating the genes.

38
Q

What is teriparatide and what is its job in the treatment of osteoporosis?

A

This is an anabolic treatment, it stimulates osteoblasts
-it is a synthetic version of the PTH hormone, which means that continuous use of it will promote bone formation.
-activates osteoblasts and OPG stimulation
-decreases osteoclasts

NEEDS TO BE INJECTED DAILY

39
Q

What does the parathyroid hormone do?

A

It indirectly stimulates intestinal absorption of calcium and promotes bone reabsorption, it does this by:

-osteoprogenitor cells becoming osteoclasts in the presence of PTH.

-PTH promotes the deep osteocytes to mobilise calcium

-surface osteocytes are stimulated by PTH to increase the flow of calcium out of the bone.

-PTH decreases renal excretion of calcium

40
Q

What function does PTH obtain in bones?

A

PTH effects bones as it can:

1.promote bone reabsorption, it does this by increasing osteoclast activity, through the up regulation of RANK L and down regulation of OPG secretion by osteoblasts.

2.promotes bone formation, it does this by autocrine and paracrine pathways through release of growth factors .
THIS OCCURS ONLY IF PTH IS GIVEN EVERYDAY.

41
Q

What are the risk factors of osteoporosis?

A

-post menopausal women
-being a women
-old age
-repeated steroid use
-excessive alcohol consumption
-underweight
-eating disorders
-smoking
-early menopause

PHA332 (25 decks)

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