Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Y2 LCRS1 Endocrinology > Endocrine and Metabolic Bone Disorders > Flashcards

Endocrine and Metabolic Bone Disorders Flashcards

1
Q

What percentage of the body’s calcium is stored in the bone?

A

>95% of body’s Ca2+

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are the two main components of bone and what proportion of its mass is made up by these?

A

Organic component/osteoid(unmineralised bone) - makes up 35% bone mass; mostly made of type 1 collagen fibres (95%)

Inorganic mineral component - makes up 65% of bone mass; calcium hydroxyapatite crystals fill the space between collagen fibrils

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are the two main cells involved in bone remodelling? Describe their functions.

A

Osteoblasts - synthesise osteoid and participate in mineralisation/calcification of osteoid (bone formation)

Osteoclasts - release lysosomal enzymes whihc break down bone (bone resporption)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is required for the formation of an osteoclast?

A

RANKL found on onsteoblasts

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Describe the process of osteoclast differentiation.

A

RANKL expressed on osteoblast surface

RANKL binds to RANK-R (on the osteoclast precursor) to stimulate osteoclast formation and activity

Activated osteoclast is invovled in bone resorption

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

How do osteoblasts help regulate bone formation and resorption?

A

Osteoblasts express receptors for PTH & calcitriol (1,25 (OH)2 vit D) – regulate balance between bone formation & resorption

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is the RANK ligand?

A
  • An osteoclast-activating factor – it increases the activation of osteoclasts
  • It stimulates the maturation of osteoclasts from osteoclast precursors
  • If there are more mature osteoclasts, you get more bone resorption
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What are the two types of bone? What are the two ways in which collagen fibrils are laid down?

A

Cortical - hard bone

Trabecular - spongy bone

Both formed in lamellar pattern = collagen fibrils laid down in alternating orientations, mechanically strong.

Woven bone =disorganised collagen fibrils, wekaer.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What are the effects of Vit D deficiency on bone, in adults and children?

A

Inadequate mineralisation of newly formed bone matrix/osteoid:

Children –> rickets

  • Epiphyseal growth plates + bone affected
  • Skeletal abnormalities, pain
  • Growth retardation and increased fractures

Adults –> osteomalacia

  • After epiphyseal closure but affects bone
  • Skeletal pain
  • Increased fracture risk
  • Proximal myopathy
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What are the zones where insufficiency fractures are common?

A

Looser zones

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What type of gait is typical in a pelvic fracture caused by Vit D deficiency?

A

Waddling gait

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Summarise the three types of hyperparathyroidism.

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Name a hyperparathyroid bone disease.

A

Osteitis fibrosa cystica

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

How can renal disease cause osteitif fibrosa cystica? Name another consequence.

A

Vascular calcification

NB: in patients with renal failure you need to monitor clacium deficiency and monitor the parathyroid and ensure that they do not develop tertiary hyperparathyroidism.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is the cellular cause of osteoitis fibrosa cystica?

A

Excess osteoclastic bone resorption secondary to high PTH

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What are Brown tumours?

A

Radiolucent bone lesions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What is the treatment of hyperparathyroid bone disease?

A
  1. Low phosphate diet + Phosphate binders (reduce GI phosphate absorption) - to treat the hyperphosphataemia
  2. Alphacalcidol – ie calcitriol analogues
  3. Parathyroidectomy in 3o hyperparathyroidism - Indicated for hypercalcaemia &/or hyperparathyroid bone disease
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What are the bone features in osteoporosis?

A
  • Fewer trabeculae
  • Reduced bone mass
  • Bone mineral density >2.5 SDs below the average value for young healthy adults (a T score of -2.5 or lower)

–> weaker bone predisposed to fractures after minimal trauma

19
Q

What is measured to predict future fracture risk in osteoporosis? How?

A

Bone mineral density

DEXA - Dual Energy X-ray Absorptiometry of femoral neck and lumbar spine

Ca content of bone is measured - the more mineral the greater the bone density.

20
Q

Compare and contrast osteomalacia and osteoporosis.

A
  • Osteomalacia is Vid D deficiency –> inadequately mineralised bone. In osteoporosis the cause is bone reabsorption exceeding formation.
  • In osteomalacia the serum biochemistry is ABNORMAL (low 25(OH)D, low Ca and high PTH i.e. secondary hyperparathyroidism) whereas in osteoporosis the serum biochemistry in normal.

BOTH predispose to fracture.

21
Q

What are the predisposing factors for osteoporosis?

A
  • Postmenopausal oestrogen deficiency –> loss of bone matrix + risk of fracture
  • Age-related deficiency in bone homeostasis (men and women) eg osteoblast senescence
  • Hypogonadism in young women and in men
  • Endocrine conditions e.g. Cushing’s syndrome, Hyperthyroidism, Primary hyperparathyroidism
  • Iatrogenic - Prolonged use of glucocorticoids, Heparin
22
Q

How debilitating are hip fractures one year later?

A
  • 20% die within a year
  • 80% are unable to carry out at least one independent activity of daily living
23
Q

List the treatment options for osteoporosis.

A

Oestrogen

Bisphosphonates

Denosumab

Teriparatide

24
Q

When would you treat osteoporosis with HRT?

A

Post-menopausal women - osteorgen is given to have anti-resoprtive effects on the skeleton and to prevent bone loss.

Additional progestogen needed if INTACT uterus to prevent endometrial hyperplasia/cancer.

25
Q

Describe the mechanism of action of bisphosphonates.

A
  • Bind avidly to hydroxyapatite and ingested by osteoclasts – impair ability of osteoclasts to reabsorb bone
  • Decrease osteoclast progenitor development and recruitment
  • Promote osteoclast apoptosis (programmed cell death)
  • Net result = reduced bone turnover.
26
Q

Lsit 4 uses of bisphosphonates.

A
  1. Osteoporosis – first line treatment
  2. Malignancy - if associated hypercalcaemia or to reduce bone pain from metastases
  3. Paget’s disease – reduce bony pain
  4. Severe hypercalcaemic emergency – i.v. initially (+++ re-hydration first)
27
Q

Descirbe the pharmacokinetics of bisphosphonates. Why are they not used much in younger people?

A

Orally active but poorly absorbed; take on an empty stomach (food, especially milk, reduces drug absorption generally)

Accumulates at site of bone mineralisation and remains part of bone until it is resorbed - months, years (unsure about long term effects so not used as much in younger people)

28
Q

List and explain the unwanted actions of bisphosphonates.

A
  • Oesophagitis - may require switch from oral to iv preparation
  • Osteonecrosis of the jaw - greatest risk in cancer patients receiving iv bisphosphonates
  • Atypical fractures - may reflect over-suppression of bone remodelling in prolonged bisphosphonate use
29
Q

What is the mechanism of action of Denosumab?

A
  • Human monoclonal antibody
  • Binds RANKL, inhibiting osteoclast formation and activity
  • Hence inhibits osteoclast-mediated bone resorption
30
Q

Describe the administration of denosumab.

A
  • SC injection 6/12ly
  • 2nd line to bisphosphonates
31
Q

What type drug is teripartide? How does it act?

A
  • Recombinant PTH fragment - amino-terminal 34 aa’s of native PTH
  • Increases bone formation and bone resorption, but formation outweighs resorption
  • 3rd line for osteoporosis
32
Q

How is teripartide administered?

A

SC injection

DAILY

33
Q

Describe Paget’s Disease.

A

Accelerated, localised but disorganised bone remodelling.

  1. Excessivee resorption (by osteoclastic overactivity)
  2. Then compensatory increase in bone formation (by osteoblasts)
  3. New bone = WOVEN so structurally disorganised and mechanically wekaer than adult lamellar bone
  4. Causes bone frailty, hypertrophy and deformity.
34
Q

Describe the prevalence of Paget’s Disease of bone.

A
  • Highest in UK, N America, Australia and NZ
  • Lowest in Asian and Scandinavia
  • Men and women equally
  • Disease not apparent under 50 - most asymptomatic
35
Q

What is a characteristic cellular feature of Paget’s?

A

Abnormal, large osteoclasts – excessive in number

36
Q

Why would you feel warmth over bone in Paget’s ?

A

Increased vascularity

37
Q

What bones are most commonly affected in Paget’s?

A

Skull, thoracolumbar spine, pelvis, femur and tibia

38
Q

What are the clinical features of Paget’s?

A
  • Arthritis
  • Fracture
  • Pain
  • Bone deformity
  • Increased vascularity (warmth over affected bone)
  • Deafness – cochlear involvement
  • Radiculopathy – due to nerve compression
39
Q

How is Paget’s Disease diagnosed?

A

Blood test:

  • Plasma Ca normal
  • But plasma ALKALINE PHOSPHATASE increased

Plain X ray:

  • Lytic lesions (early), thickened, enlarged, deformed bones (later)

Radionucleotide bone scan

  • Shows extent of skeletal involvement
40
Q

What are the treatment options for Paget’s disease?

A
  • Bisphosphonates – very helpful for reducing bony pain and disease activity
  • Simple analgesia
41
Q

What are the possible causes of Paget’s?

A
  • Could be genetic (often positive family history)
  • Viral origin - measles ?
42
Q

Vitamin D deficiency:
- is relatively common in the elderly
- can be associated with renal failure
- is called rickets in children
- is usually confirmed by the presence of a low
circulating 1,25(OH)2D level
- can be a cause of proximal myopathy

A

True
True
True
False
True

43
Q

Paget’s disease:

  • is defined as demineralisation of bone
  • is caused by inadequate levels of calcitriol
  • may be associated with a localized vasodilatation
  • is often asymptomatic
  • may be treated with bisphosphonates
A

False
False
True
False
True

Response Feedback:
Inadequate levels of calcitriol cause rickets in children or osteomalacia in adult, not Paget’s disease of bone

Can be asymptomatic, but often presents with bone pain

44
Q

Parathyroid hormone:

  • is low in hypercalcaemia of malignancy
  • inhibits synthesis of calcitriol
  • stimulates renal excretion of phosphate
  • is usually low in renal failure
  • stimulates bone resorption
A

True
False
True
False
True

Y2 LCRS1 Endocrinology (18 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions