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Year 2 - Endocrinology > Endocrine and Metabolic Bone Disorders > Flashcards

Endocrine and Metabolic Bone Disorders Flashcards

1
Q

What does bone store?

A

Stores >95% of body’s Ca2+

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2
Q

What makes up bone?

A
  1. Organic components - OSTEOID (unmineralised bone)

o 35% bone mass
o Type 1 collagen fibres (95%)

  1. Inorganic mineral component

o 65% bone mass
o Calcium hydroxyapatite crystals - fill space betw. collagen fibres

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3
Q

Main 2 types of bone cells?

A

o Osteoblasts - bone FORMATION

o Osteoclasts - bone RESORPTION

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4
Q

How do osteoblasts work?

A

Bone FORMATION

Synthesise OSTEOID
Participate in mineralisation/calcification of osteoid

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5
Q

How od osteoclasts work?

A

Bone RESORPTION

Release lysosomal enzymes - breaks down bone

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6
Q

How do osteoclasts differentiate?

A

From OSTEOBLASTS!

  1. RANKL expressed on osteoblast membrane
  2. RANK-R binds to RANKL
  3. Stimulates osteoblast formation & activity
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7
Q

How is bone remodelling controlled?

A

Osteoblasts!

Express receptors for:
o PTH
o calcitriol

SO regulate balance between bone formation & resoprtion

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8
Q

Describe brief structure of bone

A

Cortical bone - HARD
Trabecular bone - SPONGY

Both formed in a lamellar pattern
o collagen fibrils laid in alternating
o mechanically strong

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9
Q

Woven bone?

A

DISORGANISED collagen fibrils

WEAKER!!

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10
Q

Definition of VitD deficiency?

A

Inadequate mineralisation of newly formed bone matrix (osteoid)

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11
Q

Affect of VitD deficiency on children?

A

RICKETS!

affects cartilage of epiphysial growth plates & bone (still growing!)

o skeletal abnormalities and pain
o growth retardation
o increased fracture risk

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12
Q

Affect of VitD deficiency on adults?

A

OSTEOMALACIA!

AFTER epiphyseal closure so just affects bone

o skeletal pain
o increased fracture risk
o proximal myopathy

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13
Q

2 things typical to bone when VitD deficient?

A
  1. Looser zones - normal stresses on abnormal bone cause insufficiency fractures
  2. Waddling gait
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14
Q

Explain renal failure and bone disease

A

Normally 3o hyperparathyroidism!
o PTH is HIGH
o Ca2+ is also HIGH
o Parathyroid becomes autonomous

Leads to DECREASED calcitriol
 o so LESS PO4 excreted
 o leads to higher serum PO4
 o PO4 hence binds to Ca2+ in the blood
 o leads to extra-skeletal deposits 
= VASCULAR CALCIFICATION

Also due to the HYPOcalcaemic nature
o leads to DECREASED bone mineralisation
= OSTEITIS FIBROSA CYSTICA

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15
Q

Osteitis fibrosa cystica?

A

Hyperparathyroid bone disease - RARE

o XS osteoCLASTIC bone resorption
o 2o to high PTH
o ‘Brown tumours’ - radiolucent bone lesion

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16
Q

Treatment of osteitis fibrosa cystica?

A
  1. Hyperphosphataemia
    o low PO4 diet
    o phosphate binders - reduce GI phosphate absorption
  2. Alphacalidol
    o calcitriol analogue
  3. Parathyroidectomy (in 3o hyperparathyroi)
    o indicated for hypercalacaemia
    AND/OR
    o hyperparathyroid bone disease
17
Q

Define osteoporosis

A

Loss of bony TRABECULAE
Reduced BONE MASS
WEAKER bone

All of this predisposes to fracture after minimal trauma

18
Q

When do you diagnose osteoporosis?

A

BMD <2.5 SDs BELOW average value for young healthy adults

19
Q

How can osteoporosis be measured?

A

DEXA - dual energy X-ray Absorpitometry
o femoral neck
o lumbar spine

Mineral (Ca2+) content of bone measured
o the more mineral = grater bone density (BM)

20
Q

Difference between Osteoporsis vs. Osteomalacia?

A

BOTH predispose to fracture!

Osteomalacia
o VitD DEFICIENCY (adults) = inadequate mineralisation of bone

o Serum biochemistry = ABNORMAL

  • LOW calciferol
  • LOW/N Ca2+
  • HIGH PTH (2o hyperparathyroid)

Osteoporosis
o Bone RESORPTION&raquo_space; bone formation
o DECREASED bone mass
o Diagnosis via. DEXA Scan

o Serum biochemistry = NORMAL

21
Q

Pre-disposing conditions for osteoporosis?

A
  1. Postmenopausal oestrogen deficiency
    o leads to loss of bone matrix
    o subsequent increased risk of fracture
  2. Age-related deficiency in bone homeostasis
    o e.g. osteoblast senescence
  3. Hypogonadism in young people
  4. Endocrine conditions
    o Cushing’s
    o Hyperthyroidism
    o 1o hyperparathyroidism
  5. Iatrogenic
    o prolonged use of glucocotricoids
    o Heparin
22
Q

4 treatment options for osteoporosis?

A
  1. Oestrogen/SERMs
  2. Bisphosphonates
  3. Denosumab
  4. Teriparatide
23
Q

Evaluate use of Oestrogen (HRT) for treatment in Osteoporosis

A

Anti-resorptive effects on the skeleton = prevents bone loss

Women w intact uterus need PG - to prevent endometrial hyperplasia/cancer

Use limited largely due to concerns of:
o increased breast Ca risk
o VTE

24
Q

Evaluate use of SERMs (HRT) for treatment in Osteoporosis

A

Tissue-selective ER antagonist
e.g. Tamoxifen

o antagonises ER in breast
BUT
o oestrogenic activity in bone
o oestrogenic effects on endometrium persist

Tissue-selective ER agonist
e.g. Raloxifene

o oestrogenic activity in bone
o anti-oestrogenic activity on breast & uterus
BUT
o still have VTE and stroke risks

25
Q

Explain the MOA of bisphosphonates in oesteoporosis

A
  1. Bind to hydroxyapatite
  2. Ingested by osteoclasts
  3. Impair osteoclast ability to reabsorb bone

i.e. DECREASES osteoclast progenitor development & recruitment
PROMOTES osteoclast apoptosis

Net Result = REDUCED one turnover

26
Q

Uses of bisphosphonates?

A
  1. Osteoporosis = 1st line treatment!
  2. Malignancy
    o associated hypercalacaemia
    o reduce bone pain from metastases
  3. Paget’s Disease
    o reduce bony pain
  4. Sever hypercalcaemic emergency
    o i.v. initially (re-hydration FIRST)
27
Q

Pharmokinetics of bisphosphonates

A

Orally active BUT poorly abosrbed
(need to eat on empty stomach)

Accumulates at site of bone mineralisation
AND
remains part of bone UNTIL it is resorbed - month/years

28
Q

What are some unwanted effects of bisphosphonates?

A
  1. Oesophagitis
    - may require switching from oral to iv preparation
  2. Osteonecrosis of the jaw
    - greatest risk in cancer patients receiving iv bisphosphonates
    - necrosis may occur as switch OFF bone remodelling
  3. Atypical fractures
    - could show OVER-suppression of bone remodelling
29
Q

Evaluate use of Denosumab for treatment in Osteoporosis

A

Human monoclonal antibody!

  1. Binds to RANKL
  2. Inhibits osteoblast formation & activity
  3. Hence inhibits osteoclast-mediated bone resorption

SC injection 6/12 yearly
2ND-LINE to bisphosphonates

30
Q

Evaluate use of Teriparatide for treatment in Osteoporosis

A

Recombinant PTH fragment!
(amino-terminal 34aa of native PTH)

o Increased BOTH bone formation & resorption
BUT
Formation&raquo_space;> resorption

3RD-LINE for osteoporosis
Daily SC injection
£££

31
Q

Define Paget’s Disease of Bone

A

Accelerated, localised BUT disorganised bone remodelling

o XS bone resorption (osteoclastic overactivity)
FOLLOWED BY
o compensatory INCREASE in bone formation (osteoblasts)

New bone formed = WOVEN BONE

  • structually disorganised
  • mechanically weaker than normal adult lamellar bone

o BONE FRAILTY
o BONE HYPERTROPHY & DEFORMITY

32
Q

Features of people with Paget’s Disease?

A 
o ?Genetic
o ? viral origin e.g. measles
o prevalent more in 1st world countries
o men &amp; women affected equally
o disease not apparent <50years
o most patients are asymptomatic

Characterised by:
ABNROMAL, LARGE osteoclasts - XS in number

33
Q

Clinical features of Paget’s Disease?

A

MAIN:
o skull, thoracolumbar spine, pelvis, femus and tibia MOST commonly affected

o arthritis
o fracture
o pain
o bone deformity
o increase vascularity (warmth over affected bone)
o deafness - cochlear invovlement
o radiculopathy - due to nerve compression

34
Q

How do you diagnose Paget’s?

A

o Ca2+ is NORMAL

o Plasma [alkaline phosphatase] normally INCREASED
(due to over activity of bones secreting ALP)

Plain X-rays
o lytic lesions (early)
o thickened, enlarged, deformed bones (later)

Radionuclide bone scan
o shows extent of skeletal involvement

35
Q

Treatment for Paget’s Disease?

A

Bisphosphonates!
o helpful for reducing bony pain
o and reducing disease activity

OR simple analgesia

Year 2 - Endocrinology (19 decks)

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