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MSK EXAM I > Bone homeostasis > Flashcards

Bone homeostasis Flashcards

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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
Symptoms of scurvy
small hemorrhages caused by fragile blood vessels, tooth loss, poor wound healing and the reopening of old wounds, bone pain and heart failure
26
What are the byproducts of collagen degradation and how are they used clinically?
pyridinoline, deoxypiridinoline, N telopeptides and C telopeptides. measured in serum and urine to measure collagen breakdown
27
What is in inorganic bone matrix
Ca and phosphate ions that make hydroxyapatite crystals
28
Components of bone
Osteon, lacunae, lamellar bone, canaliculi | osteoid
29
Are bone resorption and formation coupled during bone modeling during puberty
no uncoupled-- net bone formation
30
Is bone remodeling coupled or uncoupled
coupled so that there is no net formation of bone
31
Osteoblasts are derived from what cell lineage
mesenchymal stem cells
32
What is the job of osteoblasts
lay down collagen and noncollagen proteins BEFORE mineralization
33
Why is mineralization delayed for several days
so collagen can cross link
34
What happens to the osteoblasts that become trapped in the cellular matrix
become osteocytes and cellular processes that lie in canaliculi to connect osteocytes to osteoblasts
35
What conneciton allows for the communication of mechanical stress in bone to be heard on surface
the canaliculi and osteocytes
36
What are the markers for bone formation
alkaline phosphatase and osteocalcin
37
How are osteoblasts and osteoclast so connected
osteoblasts signal for osteoclast activation
38
Osteoclasts are derived form what cell lineage
hematopoietic stem cells
39
What hormone inhibits osteoclasts
Calcitonin
40
When osteoblasts are stimulated by PTH what do they secrete
M-CSF RANK Ligand osteoptrotegerin
41
What responds to RANK Ligand
osteoclasts. stimulates them. have RANK receptor
42
What is the role of osteoprotegerin
soluble Receptor for RANKL- inhibits its binding to osteoclasts
43
Diseases of hyperactive and chaotic bone deposition result in stronger or weaker bones
weaker
44
4 steps of bone remodeling
activation, resorption, reversal and formation
45
Why do bones get more frail as we age
uncoupled bone resorption and formation. usually net bone resorption
46
How is PTH used therapeutically
used intermittently to activate osteoblasts without then activating osteoclasts
47
What systemic hormones have a positive influence on bone formation
growth hormone, thyroid hormone, insulin, and gonadal hormones
48
What effect do gluccocorticoids have on bone formation
suppress bone formation. suppress intestinal Ca absorption and induce osteoclastogenesis also deplete osteoblasts through suppression of differentiation factors and induction of apoptosis
49
What gonadal hormones influence bone homeostasis
estrogen and androgens
50
Estrogen is needed for what specific event in bone growth
closure of epiphyseal plates
51
estrogen deficiency results in
loss of bone mass
52
Local regulators of bone homeostasis
Cytokines IL1 TNFa TNFb and IL6 increased bone resorption | prostaglandins stimulate bone resorption
53
What growth factors have effects on bone
FGF, PDGF, Insulin-like GF and bone morphogenetic proteins
54
DEXA SCAN is used to measure what, what is the criteria
bone density T > -1 is normal T under -2.5 osteoporosis
55
What is measured in serum to measure bone formation
alkaline phosphatase osteocalcin PINP and PICP peptides
56
What is the role of osteocalcin
osteoblasts release osteocalcin
57
What is measured to measure bone resorption
urinary hydroxyproline | NTx and CTX telopeptides
58
Most common metabolic bone disease
osteoporosis
59
nonmodifiable risk factors for osteoporosis
Age, race, gender, menopause, build and family Hx
60
modifiable risk factors for osteoporosis
Ca intake, Vit D intake, Estrogen supp, sedentary lifestyle, smoking, alcohol excess, caffeine excess and medications
61
Post menopausal women have primary or secondary osteoporosis
primary
62
2 examples of secondary osteoporosis
gluccocorticoid excess and hypogonadism
63
What pharmacological agents are used to treat osteoporosis
antiresorptive (bisphosphonates) and anabolic intermittent injections of PTH
64
Rickets and osteomalacia are characterized by what type of disorder
mineralization of organic matrix. usually Vit D deficient also hypophosphatemia and alkaline phosphatase deficient
65
Classification levels for Vit D deficiency
severe 0-10 moderate 10-20 mild 20-30 greater than 30 is normal (ng/ml)
66
What disease is characterized by excessive osteoblastic activity and hyperactive bone remodeling
Paget's disease
67
Symptoms of Pagets
usually none. can have bone pain, deformity, fracture, and arthritis
68
Tx of Pagets
bisphosphanates
69
3 phases of Pagets
1) osteolytic- excessive osteoclastic activity 2) mixed phase osteoclast and osteoblast activity 3) osteosclerotic phase- predominance of osteoblast activity and sclerosis
70
The third phase of pagets is diagnosed based on what
extremely elevated alkaline phosphatase levels
71
What is the brittle bone disease
osteogenesis imperfecta, mutations in collagen
72
Most common type of Osteogenesis Imperfecta
type I- most common 80% cases. autosomal dominant one allele of alpha1 pro collagen gene is missing decreased collagen formation but normal structure
73
symptoms of OI type I
bone fragility, short stature, blue sclerae, joint laxity and hearing loss
74
What type of OI is characterized by osteopenia of long bones and wormian bones of skull
type I
75
OI type II
severe. point mutation of COL1A1 | extreme bone fragility usually death intrauterine
76
OI type III
like type II but less severe. skeletal deformities
77
OI type IV
milder phenotype similar to type I
78
Osteopetrosis
marble bone disease, genetic mutations
79
What is defective in ostepetrosis
osteoclastic bone resorption resulting in disorganized bone structure
80
Mech of bisphosphonates
selectively taken up by the bone and inhibit osteoclast activation, inhibiting bone resorption
81
mechanism of prolia
monoclonal ab against RANK Ligand. inhibits bone resorption

MSK EXAM I (9 decks)

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