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Limbs And Back - Week 1 > Biochemistry Of Bone Remodelling And Osteoperosis > Flashcards

Biochemistry Of Bone Remodelling And Osteoperosis Flashcards

1
Q

List the 4 main types of bone cells.

A

Osteogenic cells, osteoblasts, osteoclasts and osteocytes.

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2
Q

Describe osteoblasts and their function.

A
  • mononucleated, basophilic and cuboidal in shape.
  • Osteoblasts make bone.
  • They synthesise uncalcified/unmineralised ECM called osteoid. This later becomes calcified/mineralised to form bone.
  • become osteocytes when trapped in ECM
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3
Q

Describe osteocytes and their function.

A
  • mononucleated, few organelles, ellipsoid cell body
  • dendritic projections which can form gap junctions for communication
  • maintain daily metabolism of bone including exchange of nutrients and waste with blood
  • regulate function of osteoblasts and osteoclasts in response to mechanical and hormonal signalling
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4
Q

Describe osteoclasts and their function.

A
  • edge of cell closest to bone has a ruffled border
  • large and multinucleated
  • powerful lysosomal enzymes and acids released to digest ECM
  • removal/resorption of bone during normal development, maintenance and repair
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5
Q

Where are osteogenic cells usually found?

A

Alongside the membranes that surround the bones and the blood vessels in bone canals.

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6
Q

Where are osteoblasts derived from and where are they usually found?

A
  • derived from osteogenic cells

- usually found in regions of bone formation (normal development or remodelling)

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7
Q

Where are osteocytes derived from and where are they usually found?

A
  • when osteoblasts get trapped in ECM they become osteocytes

- found within matrix of bone

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8
Q

Where are osteoclasts derived from and where are they usually found?

A
  • derived from fusion of monocytes present within bone marrow or other blood producing tissue
  • lie in close contact with bone surface in resorption bays known as Howship’s lacunae
  • mainly concentrated within layer of connective tissue found on inside of bone
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9
Q

What are Howship’s lacunae?

A

Resorption bays in close contact with the bone surface in which osteoclasts are usually found.

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10
Q

List some factors/molecules involved in osteoblast proliferation and differentiation.

A
  • PTH (parathyroid hormone)
  • glucocorticoids
  • Wnt
  • TGF-b
  • hedgehog
  • BMPs
  • FGF
  • IGF
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11
Q

What is sclerostin?

A

A negative regulatory protein produced only by mature osteocytes. It inhibits bone formation by osteoblasts and enhances apoptosis of osteoblasts.

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12
Q

What is osteoprotegerin?

A

A RANKL binding decoy cytokine that modulates RANK/RANKL interaction.

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13
Q

What is MCSF?

A
  • Macrophage colony stimulating factor

- a survival factor for cells of monocyte/macrophage/osteoclast lineage

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14
Q

List some factors which regulate osteoclasts formation and activity.

A
  • E2
  • glucocorticoids
  • PTH (parathyroid hormone)
  • vitamin D3
  • IL-1
  • TNFa
  • IFNy
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15
Q

What is RANKL?

A
  • The receptor activator of NF-kB ligand
  • member of TNF ligand family
  • attaches to RANK to stimulate proliferation and differentiation of osteoclasts and inhibit their apoptosis
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16
Q

What is RANK?

A
  • A receptor on the surface of osteoclasts and osteoclast precursors
  • when RANKL binds to RANK, osteoclast proliferation and differentiation is stimulated and apoptosis inhibited
17
Q

What is CBFA1?

A
  • core binding factor alpha 1

- essential in osteoblast differentiation and bone formation

18
Q

List some factors which can stimulate osteoblast expression of RANKL.

A
  • TNF-a
  • PTHrP (parathyroid hormone related peptide)
  • IL-1
  • IL-11
  • Vitamin D
  • glucocorticoids
  • PTH
  • PGE2 (prostaglandin E2)
19
Q

Describe the bone remodelling cycle.

A

Quiescence > osteoclast recruitment, differentiation, activation > resorption > osteoclast apoptosis, removal > reversal > osteoblast recruitment, differentiation, activation > matrix synthesis > formation > mineralisation > quiescence

20
Q

Does OPG stimulate or inhibit osteoclast formation?

A

Inhibits by binding to RANK so that RANKL cannot.

21
Q

How are Wnt proteins involved in bone formation and resorption?

A
  • act on osteoblast precursor cells and promote differentiation into mature osteoblasts
  • suppress bone resorption by regulating RANKL/OPG ratio
22
Q

How do osteoclasts bind to bone matrix?

A

Via integrins

23
Q

What do osteoclasts secrete do resorb bone?

A

Acid and cathepsin K

24
Q

When does primary mineralisation occur?

A

Within the first 100 days following remodelling.

25
Q

When does secondary mineralisation occur?

A

From approx day 101 to 3 years

26
Q

List 5 systemic hormones which stimulate bone remodelling.

A
  • parathyroid hormone
  • 1,25 dihydroxyvitamin D
  • parathyroid hormone related protein
  • growth hormone
  • thyroid hormone
27
Q

List 7 locally acting factors which stimulate bone remodelling.

A
  • interleukin-1
  • tumour necrosis factor (TNF)
  • insulin like growth factor
  • interleukin-6
  • RANKL
  • prostaglandins
  • M-CSF
28
Q

List 4 systemic hormones which inhibit bone remodelling.

A
  • oestrogens
  • androgens
  • progesterone
  • calcitonin
29
Q

List 5 locally acting factors which inhibit bone remodelling.

A
  • OPG
  • mechanical loading
  • interferon gamma
  • IL-4, -10, -13 -18
  • transforming growth factor beta
30
Q

During puberty, which sex typically acquires more bone mineral density first?

A

Females

31
Q

What are some determinants of peak bone mass?

A

Lifestyle, genetics, hormones and nutrition

32
Q

How does spinal bone change in adolescents?

A

Increases in size and trabecular thickness

33
Q

How do long bones change in adolescents?

A

Increase in length and diameter

34
Q

What are the three phases of age related changes in bone mass?

A
  1. Attainment of peak bone mass (from birth until late 20s/30)
  2. Consolidation (from late 20s - early 40s)
  3. Age related bone loss (from 40s until death)
35
Q

Why are women more like to cross the fracture threshold during age related bone loss?

A

They have a lower peak bone density than men do plus after menopause the decrease in oestrogen makes them more susceptible.

36
Q

List some biochemical markers of bone formation.

A
  • bone specific alkaline phosphatase
  • type 1 collagen pro-peptides (carboxyterminal and amino terminal)
  • serum osteocalcin
37
Q

State a biochemical marker of bone resorption.

A

Serum or urine levels of N terminal and C terminal cross linked telopeptides. These can be used to assess fracture risk.

Limbs And Back - Week 1 (7 decks)

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