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Bone Homesostasis Flashcards

1
Q

Calcium has this effect on blood coagulation

A

Promotes it

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2
Q

3 organ systems involved in calcium balance

A

Bone, kidney, intestine

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3
Q

3 hormones involved in calcium balance

A

PTH, Vitamin D, Calcitonin

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4
Q

This is the primary mineral form in bone

A

Hydroxyapatite (Ca10(PO4)6(OH)2)

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5
Q

Osteoid is the protein matrix of bone, and the majority of it is made up of this

A

Type I collagen oriented in a tight triple helical structure

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6
Q

This provides site of nucleation of hydroxyapatite crystals with alignment along collagen fibers for tensile strength

A

Type 1 collagen oriented in tight triple helical structure in osteoid (bone matrix)

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7
Q

Type 1 collagen oriented in a tight triple helical structure within osteoid provides site of nucleation of this, with alignment along collagen fibers for tensile strength

A

Hydroxyapatite crystals

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8
Q

Cells the promote bone formation

A

Osteoblasts

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9
Q

Cells that promote bone resoprtion

A

Osteoclasts

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10
Q

Osteoblasts that localize to the bone during during mineralization and remain there

A

Osteocytes

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11
Q

Cells that sense mechanical stress on bone and secrete factors to stimulate osteoblasts

A

Osteocytes

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12
Q

Osteocytes are this type of cell that localize to the bone matrix during mineralization and remain there

A

Osteoblasts

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13
Q

Flat quinescent cells with barrier function

A

Bone lining cells

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14
Q

Mononuclear cells that seem to prepare areas for new bone deposition

A

“Reversal” cells

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15
Q

Osteoprogenitor cells arise from this

A

Mesenchymal stem cells

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16
Q

When these cells are stimulated by growth factors, daughter cells differentiate into osteoblasts

A

Osteoprogenitor cells

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17
Q

When osteoprogenitor cells are stimulated by growth factors, daughter cells differentiate into these

A

Osteoblasts

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18
Q

Osteoblasts are activated by this signaling

A

Wnt/beta-catenin

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19
Q

The Wnt/beta-catenin signaling pathway governs this

A

Differentiation of osteoprogenitor cells into osteoblasts

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20
Q

Cells that produce and deposit organic components to form matrix, and initiate the mineralization process

A

Osteoblasts

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21
Q

Osteoblasts remaining on bone surface transforming to these

A

Bone lining cells

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22
Q

Osteoblasts surrounded by new matrix differentiate to these

A

Osteocytes

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23
Q

Osteocytes communicate via this

A

Canaliculi

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24
Q

Regulators of bone remodeling that communicate via canaliculi

A

Osteocytes

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25
Q

Osteocytes secrete this which decreases bone formation

A

Wnt inhibitor sclerostin

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26
Q

What is sclerostin?

A

Wnt inhibitor secreted by osteocytes that decreases bone formation

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27
Q

Cells that secrete Wnt inhibitor sclerostin that decreases bone formation

A

Osteocytes

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28
Q

Mechanical forces induce signaling of these cells, leading to expression of growth factors that stimulate osteoblasts and bone formation

A

Osteocytes

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29
Q

What effect does osteocyte death have on bone?

A

Triggers remodeling
(apoptosis recruits osteoclasts, initiates resorption; lack of mechanical stimulation increases apoptosis, also aging and glucocorticoids)

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30
Q

What effect does mechanical force/stimulation have on bone?

A

Induces osteocyte signaling, leading to formation of growth factors that stimulate osteoblasts and bone formation
Lack of mechanical stimulation increases osteocyte apoptosis, triggering remodeling

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31
Q

Osteoclasts originate from these

A

Myeloid precursors that arise from hematopoietic stem cells

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32
Q

Macrophage colony stimulating factor (M-CSF/CSF1), IL-2, and TNF regulate these cells

A

Osteoclasts

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33
Q

Osteoclasts are regulated by cytokines and growth factors, including these 3

A

Macrophage colony stimulating factor (M-CSF/CSF1), IL-2, and TNF

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34
Q

Cells that originate from myeloid precursors that arise from hematopoietic stem cells

A

Osteoclast

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35
Q

Mature multinucleated osteoclasts (a fusion of 6-12 precursors) survive about this long

A

2 weeks

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36
Q

Cells that promote bone resorption

A

Osteoclasts

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37
Q

Osteoclasts promote this

A

Bone resorption

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38
Q

Cells that bind tightly to bone surface via integrins attachment to vitronectin

A

Osteoclasts

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39
Q

Osteoclasts bind tightly to bone surface via this attachment

A

Integrins attachment to vitronectin

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40
Q

Osteoclasts bind tightly to bone surface via integrins attachment to this

A

Vitronectin

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41
Q

Cells that dissolve minerals by acid (uses proton pump system) and organic elements by proteases

A

Osteoclasts

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42
Q

Osteoclasts dissolve minerals by this

A

Acid (proton pump system)

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43
Q

Osteoclasts dissolve organic elements by this

A

Proteases

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44
Q

Cells that when mature, are multinucleated due to fusion of 6-12 precursors

A

Osteoclasts

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45
Q

Paracrine factor expressed by osteoblasts that induces osteoclast precursor differentiation

A

CSF1

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46
Q

CSF1 induces differentiation of this

A

Osteoclast precursors

47
Q

Paracrine factor expressed by osteoblasts that promotes differentiation of preosteoclasts to osteoclasts

48
Q

RANKL promotes differentiation of this

A

Preosteoclasts to osteoclasts

49
Q

Paracrine factor expressed by osteoblasts that inhibits differentiation of osteoclast precursors by competing with RANKL for receptor binding (a decoy)

A

Osteoprotegrin (OPG)

50
Q

Osteoprotegerin (OPG) inhibits differentiation of this

A

Osteoclast precursors
(competes with RANKL for receptor binding)

51
Q

What effect does RANKL have on bone?

A

Promotes osteoclasts, which promote bone resorption

52
Q

What effect does Osteoprotegerin (OPG) have on bone?

A

Inhibits differentiation of osteoclast precursors, preventing bone resorption

53
Q

Cells that express CSF1, osteoprotegerin (OPG), and RANKL to control osteoclast differentiation

A

Osteoblasts

54
Q

Osteoblasts express CSF1, osteoprotegerin (OPG) and RANKL to control differentiation of this cell type

A

Osteoclast

55
Q

Osteoblasts secrete these 3 paracrine factors to control osteoclast differentiation

A

CSF1, osteoprotegerin (OPG), RANKL

56
Q

Osteoclasts express this to induce osteoblast maturation

57
Q

Cells that express ephrinB4 to induce osteoblast maturation

A

Osteoclasts

58
Q

Osteoclasts express ephrinB4 to induce maturation of this cell type

A

Osteoblast

59
Q

What is ephrinB4?

A

Factor expressed by osteoclasts that induces osteoblast maturation

60
Q

What effect do glucocorticoids have on bone?

A

Promote osteoblast cell death

61
Q

PTH have this effect on calcium balance in the kidney

A

Promotes Ca reabsorption

62
Q

PTH has this effect on phosphate balance in the kidney

A

Inhibits tubular phosphate reabsorption

63
Q

Hormone that stimulates conversion of Vitamin D to 1,25-dihydroxyvitamin D (calcitriol) in the kidney

A

Parathyroid hormone

64
Q

PTH in the kidney stimulates conversion of vitamin D to this

A

1,25-dihydroxyvitamin D (calcitriol)

65
Q

Hormone that promotes calcium reabsorption in the kidney

66
Q

Hormone that inhibits tubular phosphate reabsorption in the kidney

67
Q

Hormone that stimulates conversion of Vitamin D to 1,25-dihydroxyvitamin D (calcitriol) in the kidney

68
Q

Hormone that promotes bone homeostasis in the physiologic state

69
Q

What effect does PTH have in bone in the physiologic state?

A

Promotes bone homeostasis

70
Q

Hormone that stimulates bone resorption by osteoclasts during pathologic state

71
Q

What effect does PTH have on bone in a pathologic state?

A

Stimulates bone resorption by osteoclasts

72
Q

In the pathologic state, PTH inhibits synthesis of this by osteoblasts

73
Q

Hormone that stimulates calcium absorption by inducing expression of key proteins (calcium channels) and may also enhance diffusion by increasing overall permeability in the small intestine

74
Q

Hormone that stimulates phosphate absorption by increasing transporter protein levels in the small intestine

75
Q

What effect does Vitamin D have on phosphate balance in the small intestine?

A

Stimulates phosphate absorption by increasing transporter protein levels

76
Q

Hormone that acts synergistically with parathyroid hormone to enhance calcium reabsorption in the kidney

77
Q

Vitamin D acts synergistically with this hormone to enhance calcium reabsorption in the kidney

78
Q

What effect does Vitamin D have on calcium balance in the kidney?

A

Acts synergistically with parathyroid hormone to enhance calcium reabsorption

79
Q

Hormone that directly mobilizes calcium out of bone

80
Q

Hormone that inhibits resorption activity when it binds to osteoclasts receptor to induce retraction

A

Calcitonin

81
Q

What effect does calcitonin have on bone?

A

Binding inhibits resorptive activity of osteoclasts

82
Q

In the kidney, this hormone promotes diuresis and excretion of phosphate, sodium and calcium in urine

A

Calcitonin

83
Q

Does calcitonin secretion increase when calcium is high or low?

A

High
to inhibit osteoclast bone resorption and activate osteoblast bone formation

84
Q

Does PTH secretion increase when calcium is high or low?

A

Low
to enhance Ca reabsorption in the kidney, stimulate conversion of vit D to calcitriol, and inhibit tubular reabsorption of P

85
Q

Testosterone and estradiol have this effect on bone

A

Promote bone deposition
favors balance of bone formation over resorption

86
Q

These enhance bone resorption by altering gene expression and cell survival

A

Glucocorticoids
promote death of osteoblasts and osteocytes

87
Q

What effect do glucocorticoids have on bone?

A

Enhance bone resorption

88
Q

Pyrophosphate analogs that chelate calcium, have strong affinity for bone and inhibit bone resorption

A

Bisphophonates

89
Q

Bisphophonates are analogs of this

A

Pyrophosphate

90
Q

Bisphophonates chelate this

91
Q

Bisphophonates have this effect on bone

A

Inhibit bone resorption

92
Q

Which are more potent: nitrogenous bisphophonates or non-nitrogenous?

A

Nitrogenous

93
Q

Heartburn and esophageal irritation are adverse effects of these

A

Bisphophonates

94
Q

Very potent bisphophonate that may induce hypocalcemia and reduced renal function

A

Zoledronate

95
Q

Zoledronate is this type of drug

A

Bisphophonate

96
Q

Alendronate is this type of drug

A

Bisphophonates

97
Q

Zoledronate is a Bisphophonate that may induce this

A

Hypocalcemia and reduced renal function

98
Q

2 common adverse effects of Bisphophonates

A

Heartburn
Esophageal irritation

99
Q

Monoclonal antibody targeting sclerostin

A

Romosozumab

100
Q

Romosozumab targets this

A

Sclerostin

101
Q

Anabolic drug with black box warning of increased risk of cardiovascular events

A

Romosozumab

102
Q

Romosozumab have this black box warning

A

Increased risk of cardiovascular events

103
Q

Anabolic drug that is a terminal fragment of PTH

A

Teriparatide

104
Q

Anabolic drug that needs intermittent administration

A

Teriparatide

105
Q

Anabolic drug with a black box warning of increased risk of osteosarcoma

A

Teriparatide

106
Q

Teriparatide has a black box warning of this

A

Increased risk of osteosarcoma

107
Q

Bisphophonate alternative that inhibits osteoclast formation by depleting RANKL, and can lead to bone gain

108
Q

Bisphophonate alternative with a black box of severe hypocalcemia in patients with advanced kidney disease

109
Q

Denosumab inhibits formation of these cells by depleting RANKL

A

Osteoclasts

110
Q

Denosumab inhibits formation of these cells

A

Osteoclasts

111
Q

Denosumab inhibits formation of osteoclasts by depleting this

112
Q

Denosumab has a black box of this in patients with advanced kidney disease

A

Severe hypocalcemia

113
Q

What are SERMs?

A

Selective estrogen receptor modulators
Used as a Bisphophonate alternative
Ex: Raloxifene

Skin & MSK (20 decks)

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