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Dentistry Module 5 > Bone Biology > Flashcards

Bone Biology Flashcards

1
Q

What is the principle hormone for regulation of plasma, sodium and potassium ion concentrations?

A

Aldosterone

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2
Q

What are the three hormones involved in regulating plasma calcium ion concentration and plasma phosphate levels?

A
  1. Parathyroid hormone (PTH)
  2. Calcitonin
  3. 1,25-dihydroxyvitamin D
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3
Q

What type of calcium ions are biologically active and subject to regulation?

A

Free calcium ions (not plasma bound calcium ions)

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4
Q

What form is calcium found in within the bone?

A

Precipitated calcium phosphate

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5
Q

Give an example of an enzyme that is regulated in response to intra-cellular calcium concentration.

A

Calmodulin-dependant kinase II (CaMK-II)

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6
Q

Give 10 roles that free calcium ions play in essential activities around the body.

A
  1. Bone and teeth rigidity
  2. Muscle contraction
  3. Maintenance of membrane potential stability
  4. Neurotransmitter release
  5. Secretory processes
  6. Blood clotting
  7. Intracellular 2nd messenger
  8. Enzyme regulation
  9. Membrane stability
  10. Excitation-contraction coupling of cardiac and smooth muscle cells
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7
Q

What causes hypocalcaemia?

A

When levels of calcium in your blood are too low

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8
Q

What serious side effect of severe hypocalcaemia can lead to asphyxiation?

A

Over-excitability/contraction of skeletal muscles

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9
Q

Define asphyxiation

A

The state or process of being deprived of oxygen

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10
Q

In skeletal muscles, what initiates contraction?

A

Calcium ions released from intra-cellular stores in response to an action potential

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11
Q

In muscles, what happens when there is an increase in systolic calcium ions?

A

Contraction

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12
Q

In muscles, what happens when there is an increase in free extra-cellular fluid calcium ions?

A

Decreases neuromuscular excitably and therefore likelihood of contraction

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13
Q

Where is calcium ion concentration higher, outside or inside the cell?

A

Outside

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14
Q

What controls the intestinal absorption of calcium?

A

Hormones

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15
Q

What are the functions of kinases?

A
  1. add phosphate groups to specific amino acid residues on target proteins , that in turn alter the functional activity of that target protein.
  2. They play an important role in intra-cellular signalling.
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16
Q

What is the function of phosphotases?

A

Remove phosphate from residues on target proteins

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17
Q

What is the careful regulated range of calcium concentration in plasma?

A

2.2-2.6mmol/L

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18
Q

What is the careful regulated intracellular range of calcium concentration?

A

Approx 0.1micro moles/L

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19
Q

Unlike calcium, why is the plasma phosphate concentration not strictly regulated?

A

Because phosphate levels tend to fluctuate throughout the day, especially after meals.

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20
Q

In what two ways are calcium and phosphate balance linked?

A
  1. both are the principal components of hydroxyapatite crystals in bone
  2. Both are regulated by the same three hormones
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21
Q

What three bodily systems do the hormones PTH, 1,25-dihydroxyvitamin D, and calcitonin act on?

A
  1. Bone
  2. Kidneys
  3. GI tract
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22
Q

How many parathyroid glands do humans have?

A

4

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23
Q

Where are the 4 parathyroid glands situated?

A

2 are located on the posterior surface of the left lobe of the thyroid gland, and 2 on the right.

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24
Q

What cells compose the parathyroid glands?

A

Chief cells

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25
Q

What do chief cells synthesis and secrete?

A

PTH

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26
Q

What is the main regulator of PTH?

A

Plasma calcium ions

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27
Q

In regards to PTH secretion, what does a decrease in plasma calcium ion concentration (hypocalcaemia) stimulate?

A

PTH secretion

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28
Q

What type of hormone is PTH?

A

A peptide hormone

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29
Q

What are the net effects of PTH on kidney and bone?

A

To increase plasma calcium ion concentration and to lower plasma phosphate concentration

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30
Q

How does PTH reduce the amount of calcium ions secreted in the urine?

A

By stimulating renal reabsorption of calcium ions in the distal nephron

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31
Q

In the kidneys, where are PTH receptors located?

A

On the lateral membranes of tubular epithelial cells

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32
Q

What two events occur due to PTH modifying transepithelial transport?

A
  1. Stimulates renal calcium ion reabsorption
  2. Inhibits renal phosphate reabsorption
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33
Q

What is the outcome of PTH inhibiting renal phosphate reabsorption?

A

Increased excretion of phosphate in the urine, helping to avoid any precipitation of free calcium ions. (This would be counter-productive if an increase in free calcium ions was necessary)

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34
Q

Where does stimulation of 1,25-dihydroxyvitamin D occur?

A

In the mitochondria of cells in the proximal convolluted tubule

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35
Q

What are the 3 actions of 1,25-dihydroxyvitamin D?

A
  1. Enhance renal calcium ion reabsorption
  2. Enhance calcium ion absorption by the small intestine
  3. Modulate movement of calcium ions and phosphate in and out of bone
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36
Q

What is the function of osteoblasts?

A

Build bone cells and play a role in deposition of bone

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37
Q

What is the function of osteoclasts?

A

Release enzymes to resorb bone, through this process calcium and phosphate ions are released.

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38
Q

What effect does a persistent increase in PTH concentration have on osteoclast number and activity?

A

Increases them

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39
Q

What effect does an intermittent increase in PTH concentration have on osteoblasts?

A

Promotes osteoblasts differentiation and inhibition of osteoblast apoptosis

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40
Q

What two forms does vitamin D exist in the body?

A
  1. Vitamin D3
  2. Vitamin D2
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41
Q

How is vitamin D3 synthesised?

A

From skin if sufficient UV light is absorbed

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42
Q

How do you obtain vitamin D2?

A

Only from the diet (vegetables)

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43
Q

In their chemical structure, what is the only difference between vitamin D3 and D2?

A

Differ in the side chains of ring D. (The side chain of D3 is characteristic of cholesterol, whereas the side chain of D2 is characteristic of plant steroids)

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44
Q

What is the action of 1,25-dihydroxyvitamin D?

A

It acts on the small intestine and kidney to raise plasma calcium ion concentration

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45
Q

What are the two roles of the small intestine (duodenum) in regards to calcium and phosphate?

A
  1. Up-regulates trans cellular reabsorption of calcium ions by increasing expression for epithelial calcium ion channels, pumps and binding proteins
  2. Stimulates the syneresis of a NaPi co-transporter to increase phosphate absorption
46
Q

What are the two roles of the kidneys in regards to calcium and phosphate?

A
  1. Acts synergistically with PTH to enhance calcium ion reabsorption in the distal tubule
  2. promotes phosphate reabsorption
47
Q

What activated vitamin D?

A

Addition of two hydroxyl groups

48
Q

Two hydroxyl groups activate vitamin D. Where is the first hydroxyl group added?

A

In the liver

49
Q

Two hydroxyl groups activate vitamin D. Where is the second hydroxyl group added?

A

In the renal proximal tubule under regulation by PTH

50
Q

What is the consequence of vitamin D deficiency?

A

Impaired intestinal absorption of calcium ions , resulting in hypocalcaemia, which then leads to an increase in PTH secretion, which increases bone resorption- softening and deforming bones. (Rickets or osteomalacia)

51
Q

What is the consequence of vitamin D deficiency?

A

Impaired intestinal absorption of calcium ions , resulting in hypocalcaemia, which then leads to an increase in PTH secretion, which increases bone resorption- softening and deforming bones. (Rickets or osteomalacia)

52
Q

In children, what disease occurs as a consequence of vitamin D deficiency, and how does it present?

A

Rickets, it has a characteristic bow leg appearance

53
Q

In adults, what disease occurs as a consequence of vitamin D deficiency, and what does this mean for the patient?

A

Osteomalacia, means that the patient is much more prone to developing fractures

54
Q

What cells synthesise calcitonin?

A

C cells (clear or parafollicular cells) of the thyroid gland

55
Q

What triggers the release of calcitonin?

A

An increase in extracellular calcium ion concentration above normal (hypercalcaemia)

56
Q

What is the action of calcitonin?

A

To lower plasma calcium ion concentration

57
Q

What cells express calcitonin receptors?

A

Osteoclasts

58
Q

What effect does calcitonin have on osteoclasts?

A

Inhibits the resorptive activity of osteoclasts, slowing the rate of bone turnover

59
Q

What are the 4 skeletal functions of bone?

A
  • protects organs
  • provides rigidity
  • allows attachment of muscles and teeth
  • movements
60
Q

What is the composition of bone?

A
  • 60% mineral (largely hydroxyapatite)
  • 25% organic (90% type 1 collagen, 10% non-fibrous extracellular matrix)
  • 15% water
61
Q

What is the purpose of alveolar bone?

A

To support the tooth

62
Q

What is the purpose of the basal bone?

A

Forms the structure of jaw bone (mandible or maxilla)

63
Q

What type of bone disappears gradually after extraction of a tooth?

A

Alveolar bone

64
Q

What is the bone called that surrounds the tooth socket?

A

Cortical bone

65
Q

The alveolar bone structure consists of two types of bone, what are they?

A
  1. Cortical
  2. Trabecular
66
Q

What bone, within alveolar bone, is loose, spongy and cancellous?

A

Trabecular bone

67
Q

When using intraligamentary anaesthetic, how does the LA reach the apex of the tooth?

A

When injecting under pressure into the PDL, the LA diffuses through the porous lining of the socket, through the trabecular bone and reaches the apex.

68
Q

When looking at microscopic lamellar bone structure, what three types of lamellae bone can be visualised?

A
  1. Circumferential
  2. Concentric
  3. Interstitial
69
Q

What type of ossification forms cartilage?

A

Endochondral ossification

70
Q

What bone cells are mesenchymal/ectomesenchymal derived, live on bone surfaces and produce osteonecrosis matrix?

A

Osteoblasts

71
Q

What bone cells are essentially trapped osteoblasts in the bone?

A

Osteocytes

72
Q

What bone cells are derived from haemopoietic sources (macrophage/mopnocyte line) and dissolve hydroxyapatite out of bone in the process of bone turnover?

A

Osteoclasts

73
Q

In the body, how often is bone completely replaced?

A

Every 10 years

74
Q

What are the benefits of complete bone turnover in the body?

A
  • keeps skeleton effectively engineered for its use
  • helps maintain plasma calcium ion levels
75
Q

What cells lay down new bone?

A

Osteoblasts

76
Q

What is tetany?

A

“ a symptom that involves involuntary muscle contractions and overly stimulated peripheral nerves”

77
Q

What causes tetany?

A

Low calcium ion levels resulting in spontaneous action potentials

78
Q

What cells does fast Ca2+ efflux (due to PTH) in bone involve?

A

Osteocytes

79
Q

What cells does slow Ca2+ efflux (due to PTH) in bone involve?

A

Osteoclasts

80
Q

What are the three actions of calcitonin on bone cells?

A
  1. Reduce osteocyte activity
  2. Reduce osteoblast activity
  3. Reduce osteoclast numbers
81
Q

What is the main action of vitamin D in regards to calcium levels?

A

Increases calcium ion absorption in the intestine

82
Q

What are the 5 phases in bone remodelling?

A
  1. Activation
  2. Osteoclast recruitment and resorption
  3. Reversal
  4. Osteoblast recruitment and bone formation
  5. Termination- quiescence
83
Q

Give two examples of genetic abnormalities of bone?

A
  • osteogenesis imperfecta
  • osteoperosis
84
Q

What is osteogenesis Imperfecta?

A

Is a defect in collagen formation, resulting in fragile bones that break easily

85
Q

What is osteoperosis?

A

A condition characterised by reduction of overall bone density

86
Q

What medication, when used in long-term, is well known for inducing osteoperosis?

A

Glucocorticoids

87
Q

What is hyperparathyroidism?

A

A condition where excess PTH is synthesised due to over activity of the parathyroid glands.

88
Q

Name two metabolic bone diseases

A
  1. Paget’s disease
  2. Fibrous Dysplasia
89
Q

What is Paget’s disease?

A

A disease that involves disruption of the normal cycle of bone renewal and repair, which causes bones to be weakened and become deformed.

90
Q

What is fibrous dysplasia?

A

A condition where scar-like tissue develops in place of normal bone.

91
Q

What is meant by a sequestrum?

A

A piece of necrotic bone detached from the healthy tissue, usually secondary to trauma

92
Q

What is the clinical relevance of bone remodelling and what further treatments could be effected by this process post extraction?

A
  • provision and design of bridges
  • the need for immediate dentures
  • the timing of dental implant placement
93
Q

What 4 drugs affect bone remodelling?

A
  1. Bisphosphonates
  2. Denosumab and anti-angiogenic drugs
  3. Steroids
  4. NSAID’s
94
Q

Define, non-metabolised analogues of pyrophosphate that are capable of localising to bone and inhibiting osteoclastic function.

A

Bisphosphonates

95
Q

What is the half life of bisphosphonates and what does this mean?

A

Half life is approx 10 years, therefore high concentrations are maintained within bone for long periods of time.

96
Q

What other characteristic do Bisphosphonates have that helps to inhibit bone remodelling?

A

Anti-angiogenic

97
Q

What are the two classes of Bisphosphonates? Give examples.

A
  1. Non-nitrogen containing bisphosphonate (e.g. clodronate)
  2. Nitrogen containing bisphosphonates (e.g. alendronate)
98
Q

What class of bisphosphonates is more common?

A

Nitrogen containing Bisphosphonates (e.g. alendronate)

99
Q

Why is it necessary to swallow bisphosphonate tablets sitting upright?

A

Because they are acidic, so you don’t want them getting stuck in the oesophagus as they may burn the mucosa

100
Q

What are the conditions normally treated with bisphosphonates?

A
  • multiple myeloma (44%)
  • breast cancer (32%)
  • osteoperosis (13%)
  • prostate cancer (5%)
101
Q

Why is it important to distinguish whether a patient takes oral bisphosphonates or IV bisphosphonates?

A

Oral intake puts patient at low risk complications, whereas IV intake puts patient at high risk of complications.

102
Q

According to the SDCEP guidlines 2011 and 2017, what patients are categorised as low risk for complications?

A
  • patients not yet started taking bisphosphonates
  • patients taking bisphosphonates for the prevention of osteoporosis
103
Q

According to the SDCEP guidlines 2011 and 2017, give examples of patients that are categorised as high risk for complications?

A
  • previous diagnosis of MRONJ
  • taking bisphosphonates as part pf cancer treatment
  • if they have another non-malignant condition of the bone (e.g. Paget’s disease)
  • concurrent use of systemic corticosteroids or other immunosuppressants
  • radiotherapy treatment
    Etc.
104
Q

Why would someone treated with radiotherapy be at higher risk for MRONJ?

A

This procedure damages the vasculature to the bones and compromises their ability to heal, making them more likely to get necrosis.

105
Q

Why is the mandible more predisposed to MRONJ/necrosis than the maxilla?

A

Because the maxilla has a better vascular supply

106
Q

What is denosumab?

A

A human mono-clonal antibody that inhibits osteoclast function, by inhibiting the receptor activator of nuclear factor kappa B ligand (RANKL).

107
Q

What is the function of RANKL?

A

Acts as the primary signal for bone removal

108
Q

Name three newer drugs that have been developed to treat MRONJ.

A
  1. Everolimus
  2. Raloxifene
  3. Teriparatide
109
Q

Give two reasons as to why corticosteroids delay healing?

A
  1. Due to anti-inflammatory action
  2. Due to Inhibiting action on fibroblastic proliferation, collagen synthesis and epithelialization
110
Q

What group of medication should be avoided following bone augmentation surgery for dental implants and why?

A

NSAID’s, as they have been found to interfere with production of prostaglandins.

Dentistry Module 5 (9 decks)

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