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Year 2 - ENDO > 13 - Endocrine and metabolic bone disorders > Flashcards

13 - Endocrine and metabolic bone disorders Flashcards

1
Q

What is stored in bones?

A

calcium (over 95% of the body’s Ca2+)

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2
Q

What are the roles of osteoclasts and osteoblasts and what impact does this have on the amount of calcium in bone?

A

osteoblasts - synthesise bone (make and mineralise osteoid)
—–> assist with deposition of calcium
osteoclasts - consume bone thought release lysosomal enzymes
—–> liberates calcium from the bone

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3
Q

What are the 2 components of bone?

A
  • osteoid
    this is the organic component of bone - unmineralised bone made up of type 1 collagen
  • calcium hydroxyapatite crystals
    inorganic compound of bone - fills the space between the collagen fibrils
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4
Q

What is the mechanism of action of PTH on the bone?

A

(indirectly activates osteoclasts) works on osteoblasts and inhibits various activities
Stimulates osteoblasts to produce OAF (osteoclast activating factors)

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5
Q

What is the action of OAF (osteoclast activating factors)

A

(produced by osteoblasts) move to osteoclasts and stimulate the breakdown of bone matrix to release Ca2+

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6
Q

Give an example of an OAF

A

RANKL

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7
Q

Describe the process of osteoclast differentiation, by which osteoclasts require the action of ostoblasts

A
  • osteoblasts express RANK
  • osteoclasts have a receptor for RANK
  • on binding, the osteoclasts precursor becomes activated
  • osteoclast formation and activity
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8
Q

What 2 substances regulate the balance between bone formation and resorption
and what are the corresponding receptors for these located?

A

PTH and calcitriol regulate the balance

their receptors are located on osteoblasts

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9
Q

Describe the structure of regular bone

How is the strength maintained?

A
  • hard cortical bone around the outside
  • spongy, trabecular bone on the inside

bone is formed in a lamellar pattern - collagen fibrils are laid down in altering orientations - this gives the maximum mechanical strength

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10
Q

Name and describe the type of bone with much less mechanical strength

A

woven bone

collagen fibrils are organised randomly

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11
Q

What is the effect of vitamin D deficiency on bone?

A

inadequate mineralisation of newly formed bone matrix (osteoid)

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12
Q

Describe the presentation of vitamin D deficiency in children

A

RICKETS

  • affects cartilage of epiphyseal growth plates and bone
  • skeletal abnormalities (tibia bowing) and pain, growth retardation. increased fracture risk (‘bendy bones’)
  • particularly problematic in legs (weight bearing)
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13
Q

Describe the presentation of vitamin D deficiency in adults

A

OSTEOMALACIA
- occurs after epiphyseal closure
- skeletal pain, increased risk fracture, proxoimal myopathy
(- not the same bone deformities that are seen in rickets - epiphyseal growth closure)

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14
Q

What are the effects of vitamin D deficiency on bone?What are the typical fracture sites?

A

stress fractures - due to normal stresses i.e. bearing weight
typical fracture sites are in areas of high bone load
abnormal pelvic fractures - patients walk with a ‘waddling gait’

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15
Q

Describe what happens in primary hyperparathyroidism

A
  • the problem is with one of the parathyroid glands
  • autonomous secretion of PTH (e.g. parathyroid adenoma)
  • patients have high serum calcium and high PTH
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16
Q

Describe what happens in secondary hyperparathyroidism

A
  • normal physiological response to low calcium
  • —-> this is due to either renal failure or Via D deficiency
  • high PTH secondary to low Ca2+
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17
Q

Describe what happens in tertiary hyperparathyroidism

A
  • (seen in chronic renal failure)
  • chronically low calcium because calcitriol cannot be made
  • PTH increases in response to low calcium
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18
Q

What is the treatment for tertiary hyperparathyroidism

A

need to have a parathyroidectomy

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19
Q

What are the 2 main effects of kidney failure on calcium serum levels?

A
  • calcitriol cannot be made, so calcium is not absorbed well from the gut
  • (reduced excretion of phosphate =) increased serum phosphate —–> decreases bioavailable serum calcium (phosphate binds to calcium)

inadequate bone mineralisation and increased PTH release (-> increased bone reabsorption)
leads to osteitis fibrosa cystica (rare)

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20
Q

In what way do patients with chronic kidney failure need to manage their diet?

A

try to reduce serum phosphate

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21
Q

What can result because of high serum phosphate?

A

vascular calcification

22
Q

When is osteitis fibrosa cystica seen?

A

in people with very high PTH e.g. in renal failure

23
Q

What is osteitis fibrosa cystica?

What causes it?

A

hyperparathyroid bone disease

high PTH —> osteoclast stimulation —> increased bone resorption

24
Q

What is the treatment for osteitis fibrosa cystica?

A
  • hyperphosphataemia - low phosphate diet and phosphate binders
  • alfacalcidol - active vitamin D/calcitriol analogues
  • parathryoidectomy (when tertiary hyperparathyroidism)
25
Q

Define osteoporosis.

A

(reduction in bone mass)
Having a bone mineral density (BMD) that is 2.5 standard deviations (SD) or more below the average for young healthy adults

26
Q

Describe the features of bone in someone who has osteoporosis

A

loss of bony trabeculae
weaker bone
predisposed to fracture after minimal trauma

27
Q

Who is most likely to have problems caused by osteoporosis?

A

post-menopausal women

elderly

28
Q

How is bone mineral density measured?

Name the key areas that are looked at during this test

A

using Dual Energy X-ray Absorptiometry (DEXA)
the scan looks at the mineral (calcium) content of the bone

the femoral neck and lumbar spine are scanned

29
Q

What are the similarities between osteomalacia and osteoporosis?

A

both predispose to fractures

30
Q

How can you differentiate between osteomalacia and osteoporosis?

A

BIOCHEMISTRY IS COMPLETELY NORMAL IN OSTEOPOROSIS
osteomalacia - diagnosed using serum biochemistry
osteoporosis - diagnosed using DEXA scan

osteomalacia - caused by Vitamin D deficiency causing inadequately mineralised bones
osteoporosis - when bone reabsorption exceeds formation

31
Q

List predisposing conditions for osteoporosis

A
  • post menopausal oestrogen deficiency
  • age-related deficiency in bone homeostasis
  • hypogonadism
  • endocrine conditions
  • —-> Cushings
  • —-> hyperthyroidism
  • —-> primary hyperparathyroidism
  • iatrogenic
  • —-> prolonged use of glucocorticoids
  • —-> heparin
32
Q

What are the 1st, 2nd and 3rd line treatments for osteoporosis?

A

Bisphosphonates
Denusomab
Teriparatide

NOTE: with oestrogen replacement, there is risk of breast cancer and VTE

33
Q

What are the benefits of oestrogen replacement to prevent osteoporosis in post-menopausal women?

A

It has an anti-resorptive effect in bone and, hence, prevents bone loss

34
Q

What are some cautions and risks of oestrogen replacement?

A

In patients with a uterus (i.e. not had a hysterectomy), you must give additional progestogen to prevent endometrial hyperplasia and reduce the risk of endometrial carcinoma
Risks:
• Breast cancer
• Venous thromboembolism

35
Q

What are the 2 types of SERMs?

Give an example of each

A 
Selective Oestrogen Receptor Modulators
1- Tissue selective ER antagonists/anti-oestrogens
e.g. tamoxifen
2- Tissue selector ER agonists
e.g. raloxifene
36
Q

Describe the effects of tissue selective ER antagonists/anti-oestrogens

A
  • Antagonises ERs in breast but has oestrogenic activity in bone
  • Oestrogenic effects on endometrium limit its use in osteoporosis management
37
Q

Describe the effects of tissue selector ER agonists

A
  • Oestrogenic activity in bone, and anti-oestrogenic at breast and uterus
  • Reduces breast cancer risk (anti-oestrogen) but increases risk of venous thromboembolism
38
Q

What is the action of bisphosphonates in treatment of osteoporosis?

A
  • Bind to hydroxyapatite and ingested by osteoclasts - impair ability of osteoclasts to reabsorb bone
  • Decrease osteoclast progenitor development and recruitment
  • Promote osteoclast apoptosis

Net result = reduced bone turnover

39
Q

What conditions are bisphosphonates used to treat?

A
  • Osteoporosis – first line treatment
  • Malignancy (associated hypercalcaemia, reduce bone pain from metastase)
  • Paget’s disease – reduce bony pain
  • Severe hypercalcaemic emergency – i.v. Initially (+++ re-hydration first)
40
Q

Describe the pharmacokinetics of bisphosphonates

A
  • Orally active but poorly absorbed; take on an empty stomach (food, especially milk, reduces drug absorption generally) - so these tablets are a pain to take
  • Accumulates at site of bone mineralisation and remains part of bone until it is resorbed – months, years
41
Q

Give some of the unwanted actions of bisphosphonates

A

• Oesophagitis (heart burn): may require switch from oral to IV
• 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
—> hence, patients are given a bisphosphonate holiday so bones can recover from treatment

42
Q

What is the action of Denosumab in treatment of osteoporosis?

A

• Human monoclonal antibody
• binds RANKL, inhibiting osteoclast formation and activity
—–> Hence inhibits osteoclast-mediated bone resorption

43
Q

Describe the pharmacokinetics of Denosumab

A

Subcutaneous injection every 6 months

44
Q

What is teriparatide?

What is its action in treatment of osteoporosis?

A

• Recombinant PTH fragment
• Increases bone formation and bone resorption, but formation outweighs resorption
(3rd line treatment for osteoporosis - very expensive)

45
Q

Describe the pharmacokinetics of teriparatide

A

Daily subcutaneous injection

46
Q

What is Paget’s disease?

A

Active/accelerated, localised but disorganised bone metabolism – usually slowly progressive.
There is increased bone breakdown and bone formation.

47
Q

What happens in the bone in Paget’s disease?

A
  • excessive bone resorption (over activity of osteoclasts)
  • followed by compensatory increase in bone formation (osteoblasts)
    BUT the new bone formed is woven bone
48
Q

What is Paget’s disease characterised by histologically?

A

Abnormal, large osteoclasts - that are excessive in number

49
Q

State some clinical features of Paget’s disease

A

(most patients are asymptomatic)

  • Fracture
  • Pain
  • Bone deformity
  • Increased vascularity (warmth over affected bone)
  • Most commonly affected bones are: pelvis, femur, tibia, skull, and spine
  • ^arthritis
  • deafness: cochlear involvement
  • radiculopathy - due to nerve compression
50
Q

Describe how you would diagnose Paget’s disease.

A

Biochemical Findings:
- Plasma calcium = NORMAL
- Plasma ALP (alkaline phosphatase) = HIGH
Radiological findings:
- x-rays:
—–> (early) lytic lesions
—–> (later) thickened, early, deformed bones
- Radioisotope scanning can be performed to indicate areas of involvement

51
Q

What is the treatment for Paget’s?

A
  • bisphosphonates

- simple analgesia

Year 2 - ENDO (20 decks)

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