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MMB > (038) BONE DISEASE > Flashcards

(038) BONE DISEASE Flashcards

1
Q

Three general components of Bone matrix ?

A

1) colagen (structural protein)

2) non-structural proteins

3) Hydroxyapatite

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2
Q

Precentage composition of bone matrix ?

A
  • 90% type I collagen
  • 10% non-structural proteins
  • traces of Hydroxyapatite
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3
Q

non-structural proteins present in bone matrix ?

A

• Phosphoproteins

• Sialoprotein

• Osteonectin

• Osteocalcin

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4
Q

A non-structural protein of bone matrix : that it’s blood level indicates bone turnover

A

Osteocalcin

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5
Q

What’s Hydroxyapatite ?

A

Mineral crystals which enclose the collagen microfibrils to form a composite material with the required properties of stiffness, flexibility and strength.

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6
Q

Role of Hydroxyapatite in the bone matrix ?

A

Mineral crystals which enclose the collagen microfibrils to form a composite material with the required properties of stiffness, flexibility and strength.

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7
Q

This figure illustrated the three cell types in bone , name them and mention their roles

A
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8
Q

Define the hidden and explain the role of these cells of bone

A
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9
Q

secretions of Osteoblasts ? (Bone forming cells)

A

-Osteoid

-Alkaline phosphatase (ALP)

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10
Q

What’s osteoid

A

new, unmineralized bone matrix secreted by osteoblasts

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11
Q

Role of Alkaline phosphatase (ALP) ; secreted by osteoblasts

A

an enzyme involved in the mineralization process by liberating inorganic phosphate.

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12
Q

…..is a useful circulating marker for bone cell activity.

A

Alkaline phosphatase (ALP)

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13
Q

Osteoblasts express receptors for many hormones, eg:

A

• PTH

• 1,25(OH)2-vitamin D

• sex steroids

• adrenal steroids

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14
Q

OB are also responsive to (and may produce):

A

• growth factors

• cytokines

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15
Q

Role of Osteocytes ?

A

Osteocytes mediate adaptive bone remodeling by responding to mechanical deformation

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16
Q

How are Osteocytes formed ?

A

• Some Osteoblasts become incorporated in the matrix & differentiate into osteocytes

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17
Q

…. Is a chemical produced by Osteocytes

A

sclerostin – FGF 23

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18
Q

What are Osteoclasts ?

A

Osteoclasts (OC) are multinucleate cells which resorb all the components of skeletal and dental hard tissues, unaided.

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19
Q

What’s Howship’s lacunae ?

A

resorption pits occupied by Osteoclasts in the mineralized bone surfaces.

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20
Q

sealing zone of Bone resorption ?

A

OC form a tight annular sealing zone with the bone, which encloses a clear zone (resorption lacuna).

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21
Q

Osteoclasts express large amounts of the enzyme….

A

tartrate-resistant acid phosphatase (TRAP).

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22
Q

Explain Bone remodeling

A

Throughout life, the skeleton undergoes a continual process of repair and renewal. Bone remodeling is a surface phenomenon.

Mineralized bone matrix is resorbed by OC and replaced in lamellae, by OB.

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23
Q

Bone remodeling takes place in response to :

A

altered mechanical loading

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24
Q

Figure illustrated the process of bone remodeling , define the hidden

A
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25
Q

The age of remodeling activity ?

A

In young adults (20-45 years)

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26
Q

Characteristics of bone remodeling In young adults (20-45 years) ?

A

keeps bone mass relatively constant:

bone may be removed from one site & deposited at another in order to achieve shape changes, whilst keeping overall bone mass constant.

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27
Q

If the balance of the turnover process is altered,

and resorption begins to outstrip formation, this leads to…. (Disease)

A

Osteoporosis

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28
Q

General mechanism of osteoporosis ?

A

enhanced OC resorption or declining OB function

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29
Q

…. (Site) are particularly susceptible to remodeling imbalances, as a result of the relatively high turnover rate (~25% / year).

A

Trabecular bone sites (e.g. in vertebral bodies)

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30
Q

How is Bone growth and remodeling regulated ?

A

Bone growth and remodeling is influenced by many factors. These include:

  1. Calcium regulating hormones
  2. Cell signals:
  3. Inorganic agents
  4. Intracellular factors
  5. Other molecules
  6. Mechanical effects
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31
Q

Major general Functions of Calcium ?

A

• Ca 2+ is used as a vital second messenger within cells

• Ca 2+ is necessary for normal blood coagulation, muscle contraction and nerve function

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32
Q

(>99%) of the Ca 2+ in the body exists as :

A

mineral deposits in the skeleton and teeth.

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33
Q

…….is the key PO4 3- lowering factor.

A

Fibroblast growth factor (FGF 23)

34
Q

PO4 3- retention is toxic and implicated in…

A

accelerated ageing.

35
Q

Mention the major Calcium Regulating Hormones

A

• Parathyroid hormone (PTH)

• 1,25(OH)2-vitamin D (calcitriol)

• Calcitonin

36
Q

Effect of Parathyroid hormone (PTH) on bone regulation ?

A

↑ OC formation, activity
↑ OB proliferation, activity → ↑ bone turnover

37
Q

Effect of continuous high-dose PTH on bone regulation (in vivo) ?

A

↑ bone resorption → bone loss.

38
Q

Mechanism of calcitriol’s effect on bone regulation ?

A

↑ plasma Ca2+ ; ↑ gut Ca 2+ uptake,

↑ OB differentiation ; required for normal matrix mineralization;

39
Q

Effect of Calcitonin on bone regulation ?

A

↓ plasma Ca 2+ by depositing Ca 2+ in bone
↓ OC formation, activity

40
Q

Effect of excess Glucocorticoids on bone ?

A

bone loss / osteoporosis

41
Q

…..&…. exert critical long term (i.e. slow acting) beneficial effects to bone

A

• Sex steroids (estrogens & androgens)

42
Q

Effect of deficient Sex steroids on bone ?

A

↑ bone turnover, osteoporosis

43
Q

Bone Growth factors are sectreted by…

A

Osteoblasts and deposited in bone matrix

44
Q

Growth factors include:

A

Mitogens e.g.:

-transforming growth factor ß (TGF ß )

-bone morphogenetic proteins (BMP)

-insulin-like growth factors I &II (IGF)

-platelet-derived growth factor (PDGF)

-fibroblast growth factors (FGF)

45
Q

……are signaling molecules that ↑ OB differentiation ,, and blocked by sclerostin.

A

Wnt proteins

46
Q

….. is a Bone-specific protein which acts as a natural brake on bone formation, and is secreted by Osteocytes

A

Sclerostin

47
Q

Cytokines that ↑ OC formation and activity ? (Resorbtion)

A

• Interleukins (IL) – 1, 6

• tumor necrosis factor (TNF) -α

• RANK ligand

• macrophage colony-stimulating factor (M-CSF)

48
Q

Explain the role of RANK ligand in bone resorption

A

the major factor required for OC formation :

49
Q

Cytokines that ↓ OC formation and activity ? (↑ Bone formation)

A

• Interleukins (IL) 4

• Interferon (IFN)-γ

• granulocyte macrophage colony-stimulating factor (G-CSF)

50
Q

Intracellular factors affecting bone regulation ?

A

-Wnt mediator: Wingless-related integration site

-Nuclear factor of activated T-cells 1 (NFATc1)

51
Q

WHO definition of Osteoporosis ?

A

bone mass < 2.5 SDs

52
Q

WHO definition of Osteopenia ?

A

bone mass < 1 SD

53
Q

Figure illustrates a condition associated with osteoporosis , what’s the condition ?

A

vertebral crush fractures, leading to loss of height, with the typical “Dowager’s hump” (hunchback) appearance.

54
Q

Why is osteoporosis 10 times more common in women than men ?

A

abrupt decline in circulating estrogens at menopause

(Androgens decline more gradually with age)

55
Q

Figure illustrates a condition associated with osteoporosis :
- name the condition
- it’s common age group
- gender prevealance

A

Femoral neck (“hip”) fractures:

-associated with 20% mortality rates

-occur in patients over age of 70

-2:1 prevalence in favor of females

56
Q

Osteoporosis is much less common in….(race)

A

Afro-Caribbeans

57
Q

main risk factors for osteoporosis :

A
58
Q

Preventive medicine of osteoporosis ?

A

Hormone replacement therapy with low level estrogens in postmenopausal women effectively prevents osteoporosis

59
Q

Risk of preventive osteoporosis treatment for woman Through : Hormone replacement therapy ?

A

associated slight increased risks of breast and endometrial cancer

60
Q

Role of Intermittent PTH injections in osteoporosis treatment ?

A

can help restore lost bone by stimulating OB

61
Q

Drugs that block OC action ?

A

1) bisphosphonates (mostly cheap, orally-active)

2) A synthetic antibody that binds RANK ligand

62
Q

The key difference between osteomalacia and osteoporosis ?

A

-Osteomalacia: the proportion of mineralized bone matrix is reduced

-Osteoporosis: there is loss of bone but no impairment of mineralization

63
Q

Give diagnosis and explain

A

-Paget’s disease ; It affects one or several bones throughout the skeleton

It is characterized by focal areas of increased bone turnover:
-greatly accelerated bone resorption at certain focal sites

-bone formation by OB is increased&raquo_space; The new bone formed is disorganized

64
Q

Potential triggers of Paget’s disease ?

A

• paramyxovirus infection

• deficiency of dietary calcium

• repetitive mechanical loading of the skeleton

65
Q

Symptoms of Paget’s disease ?

A

• bone pain (hot to the touch)

• bone deformity

• osteoarthritis

• pathological fracture

• deafness

• nerve compression syndromes

66
Q

Medical management of Paget’s disease ?

A

Inhibitors of osteoclastic bone resorption are given :

Bisphosphonate is primarily indicated for patients who have bone pain

67
Q

Name the condition and explain it

A

Sclerostosis ;

an autosomal recessive disorder characterized by bone overgrowth Excessive bone formation especially in the skull, mandible and tubular bones.

68
Q

A severe complication of Sclerostosis ?

A

Increased intracranial pressure can cause sudden death in patients.

69
Q

Osteopetrosis ?

A

• “Stone bone”, or marble bone disease, is a rare inherited disorder

• Bones harden, becoming too thick and heavy

• The cause is understood to be malfunctioning osteoclasts leading to impaired modelling & remodeling of bone

70
Q

Osteosarcoma ?

A

An osteoblast tumor - frequently aggressive – most common in younger individuals

71
Q

Osteoclastoma ?

A

An osteoclast tumor which does not metastasize – not life threatening – can result in rapid local destruction of bone

72
Q

….(bone tumor) is most common in younger individuals

A

Osteosarcoma

73
Q

Cancers that metastasize to bone ?

A

• Breast

• Lung

• Kidney

• Prostate

• Multiple myeloma

74
Q

Metabolic Acidosis ?

A

• Results from net addition of H + to blood  HCO 3 - ↓ and pH↓

• Chronic MA is usually the result of kidney disease

75
Q

Effect of Diseased kidneys on bone resorption ?

A
  1. Diseased kidneys lose the ability to form 1,25 (OH) 𝟐 vit D

> > ↓ Ca 2+ uptake from gut &raquo_space; ↓ plasma Ca 2+ &raquo_space; ↑ PTH secretion

> > ↑ osteoclast formation and activity

76
Q

Effect of Metabolic Acidosis on bone resorption ?

A

Osteoclasts are directly responsive to extracellular H+

low pH&raquo_space; ↑ resorption pit formation&raquo_space; release of alkaline bone mineral (hydroxyl apatite)

77
Q

name the condition and the nerve injury causing it

A

Scapular winging (long thoracic nerve palsy)

78
Q

This is knee MRI ; point to lesion and diagnose

A

Torn anterior cruciate ligament

79
Q
A
80
Q

Figure illustrates an imaging of rotator cuff ; name the imaging method and diagnose

A

Rotator cuff tear

MMB (72 decks)

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