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MSK EXAM I > Bone homeostasis > Flashcards

Bone homeostasis Flashcards

1
Q

What are the 2 main mineral components of bone

A

Calcium and phosphorus

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2
Q

What is the biologically active form of Ca

A

the ionized calcium

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3
Q

What is the chemical gradient for Ca

A

10,000:1

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4
Q

Symptoms of hypocalcemia

A

nervous system is more excitable. hyper excitability because threshold for Na channels drops
tetany

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5
Q

Symptoms of hypercalcemia

A

decreased QT interval of the heart, lack of appetite and constipation. reflex responses are slowed

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6
Q

What is the range for Ca

A

8.5-10.5 mg/dL

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7
Q

What triggers release of PTH

A

low levels of serum Ca

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8
Q

What are the 4 functions of PTH

A

1) PTH R on osteoblasts trigger initiation of bone resoprtion leading to release of Ca into serum
2-3) regulates Ca retention and phosphate excretion in kidney
4) increase 1,25(OH)2D3 synthesis–> increase Ca absorption from GI

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9
Q

Unregulated release of PTH leads to what and why

A

hypercalcemia because PTH increases Ca absorption in gut and resorption via osteoblasts/clasts

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10
Q

What cells produce calcitonin and in what response

A

C cell sin thyroid gland produce calcitonin when there is an increase of serum Ca

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11
Q

How do calcitonin levels change in individuals with medullary thyroid cancer

A

increase calcitonin levels

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12
Q

When is calcitonin used therapeutically

A

bone disorders characterized by excessive bone resorption

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13
Q

Where in the body is Vit D converted to its active form

A

in the kidney

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14
Q

What is Calcitriol (1,25 (OH2)D3) necessary for

A

absorption of Ca from GI, bone formation and promotes Ca and Pi resorption from kidney

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15
Q

What happens in a Vit D deficiency

A

impaired Ca absorption and poor mineralization of bone

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16
Q

What mineral does FGF23 regulate

A

phosphate

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17
Q

FGF23 knockout mice presented how

A

hyperphosphatemia and hypercalcemia due to increased levels of calcitriol

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18
Q

What percent of bone is minerals

A

70%

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19
Q

Majority of organic bone matrix is what

A

collagen type I

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20
Q

4 amino acids to make up collagen type I matrix

A

glycine, alanine, proline and 4-hydroxyproline

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21
Q

collagen structure

A

Right handed helix of three left handed helices

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22
Q

What is the most necessary aa in collagen

A

glycine because it is so small and links everything

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23
Q

Cleavage for collagen FORMATION creates what byproducts- used how clinically?

A

PINP and PICP peptides

used as a marker for collagen formation

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24
Q

What cross links the tropocollagen in bone, and what co-component is needed

A

pyridinoline molecules

needs Asorbic Acid(Vit C)

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25
Q

Symptoms of scurvy

A

small hemorrhages caused by fragile blood vessels, tooth loss, poor wound healing and the reopening of old wounds, bone pain and heart failure

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26
Q

What are the byproducts of collagen degradation and how are they used clinically?

A

pyridinoline, deoxypiridinoline, N telopeptides and C telopeptides.
measured in serum and urine to measure collagen breakdown

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27
Q

What is in inorganic bone matrix

A

Ca and phosphate ions that make hydroxyapatite crystals

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28
Q

Components of bone

A

Osteon, lacunae, lamellar bone, canaliculi

osteoid

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29
Q

Are bone resorption and formation coupled during bone modeling during puberty

A

no uncoupled– net bone formation

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30
Q

Is bone remodeling coupled or uncoupled

A

coupled so that there is no net formation of bone

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31
Q

Osteoblasts are derived from what cell lineage

A

mesenchymal stem cells

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32
Q

What is the job of osteoblasts

A

lay down collagen and noncollagen proteins BEFORE mineralization

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33
Q

Why is mineralization delayed for several days

A

so collagen can cross link

34
Q

What happens to the osteoblasts that become trapped in the cellular matrix

A

become osteocytes and cellular processes that lie in canaliculi to connect osteocytes to osteoblasts

35
Q

What conneciton allows for the communication of mechanical stress in bone to be heard on surface

A

the canaliculi and osteocytes

36
Q

What are the markers for bone formation

A

alkaline phosphatase and osteocalcin

37
Q

How are osteoblasts and osteoclast so connected

A

osteoblasts signal for osteoclast activation

38
Q

Osteoclasts are derived form what cell lineage

A

hematopoietic stem cells

39
Q

What hormone inhibits osteoclasts

A

Calcitonin

40
Q

When osteoblasts are stimulated by PTH what do they secrete

A

M-CSF
RANK Ligand
osteoptrotegerin

41
Q

What responds to RANK Ligand

A

osteoclasts. stimulates them. have RANK receptor

42
Q

What is the role of osteoprotegerin

A

soluble Receptor for RANKL- inhibits its binding to osteoclasts

43
Q

Diseases of hyperactive and chaotic bone deposition result in stronger or weaker bones

A

weaker

44
Q

4 steps of bone remodeling

A

activation, resorption, reversal and formation

45
Q

Why do bones get more frail as we age

A

uncoupled bone resorption and formation. usually net bone resorption

46
Q

How is PTH used therapeutically

A

used intermittently to activate osteoblasts without then activating osteoclasts

47
Q

What systemic hormones have a positive influence on bone formation

A

growth hormone, thyroid hormone, insulin, and gonadal hormones

48
Q

What effect do gluccocorticoids have on bone formation

A

suppress bone formation. suppress intestinal Ca absorption and induce osteoclastogenesis
also deplete osteoblasts through suppression of differentiation factors and induction of apoptosis

49
Q

What gonadal hormones influence bone homeostasis

A

estrogen and androgens

50
Q

Estrogen is needed for what specific event in bone growth

A

closure of epiphyseal plates

51
Q

estrogen deficiency results in

A

loss of bone mass

52
Q

Local regulators of bone homeostasis

A

Cytokines IL1 TNFa TNFb and IL6 increased bone resorption

prostaglandins stimulate bone resorption

53
Q

What growth factors have effects on bone

A

FGF, PDGF, Insulin-like GF and bone morphogenetic proteins

54
Q

DEXA SCAN is used to measure what, what is the criteria

A

bone density
T > -1 is normal
T under -2.5 osteoporosis

55
Q

What is measured in serum to measure bone formation

A

alkaline phosphatase
osteocalcin
PINP and PICP peptides

56
Q

What is the role of osteocalcin

A

osteoblasts release osteocalcin

57
Q

What is measured to measure bone resorption

A

urinary hydroxyproline

NTx and CTX telopeptides

58
Q

Most common metabolic bone disease

A

osteoporosis

59
Q

nonmodifiable risk factors for osteoporosis

A

Age, race, gender, menopause, build and family Hx

60
Q

modifiable risk factors for osteoporosis

A

Ca intake, Vit D intake, Estrogen supp, sedentary lifestyle, smoking, alcohol excess, caffeine excess and medications

61
Q

Post menopausal women have primary or secondary osteoporosis

A

primary

62
Q

2 examples of secondary osteoporosis

A

gluccocorticoid excess and hypogonadism

63
Q

What pharmacological agents are used to treat osteoporosis

A

antiresorptive (bisphosphonates) and anabolic intermittent injections of PTH

64
Q

Rickets and osteomalacia are characterized by what type of disorder

A

mineralization of organic matrix.
usually Vit D deficient
also hypophosphatemia and alkaline phosphatase deficient

65
Q

Classification levels for Vit D deficiency

A

severe 0-10
moderate 10-20
mild 20-30
greater than 30 is normal (ng/ml)

66
Q

What disease is characterized by excessive osteoblastic activity and hyperactive bone remodeling

A

Paget’s disease

67
Q

Symptoms of Pagets

A

usually none. can have bone pain, deformity, fracture, and arthritis

68
Q

Tx of Pagets

A

bisphosphanates

69
Q

3 phases of Pagets

A

1) osteolytic- excessive osteoclastic activity
2) mixed phase osteoclast and osteoblast activity
3) osteosclerotic phase- predominance of osteoblast activity and sclerosis

70
Q

The third phase of pagets is diagnosed based on what

A

extremely elevated alkaline phosphatase levels

71
Q

What is the brittle bone disease

A

osteogenesis imperfecta, mutations in collagen

72
Q

Most common type of Osteogenesis Imperfecta

A

type I- most common 80% cases.
autosomal dominant
one allele of alpha1 pro collagen gene is missing
decreased collagen formation but normal structure

73
Q

symptoms of OI type I

A

bone fragility, short stature, blue sclerae, joint laxity and hearing loss

74
Q

What type of OI is characterized by osteopenia of long bones and wormian bones of skull

A

type I

75
Q

OI type II

A

severe. point mutation of COL1A1

extreme bone fragility usually death intrauterine

76
Q

OI type III

A

like type II but less severe. skeletal deformities

77
Q

OI type IV

A

milder phenotype similar to type I

78
Q

Osteopetrosis

A

marble bone disease, genetic mutations

79
Q

What is defective in ostepetrosis

A

osteoclastic bone resorption resulting in disorganized bone structure

80
Q

Mech of bisphosphonates

A

selectively taken up by the bone and inhibit osteoclast activation, inhibiting bone resorption

81
Q

mechanism of prolia

A

monoclonal ab against RANK Ligand. inhibits bone resorption

MSK EXAM I (9 decks)

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