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NUTR 4320 > Calcium and Bone Health > Flashcards

Calcium and Bone Health Flashcards

1
Q

What is osteoporosis

A

A skeletal disorder characterized by compromised bone strength that predisposes a person to an increased risk of fracture

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2
Q

Osteoporosis is characterized by

A

→ Reduction in bone mineral density (↓ in bone
quantity)
→ Changes in bone structure (↓ in bone quality)

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3
Q

Osteoporosis results in

A

Increased risk of fractures - often leads to permanent and severe disability

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4
Q

True or false: in elderly populations there is a strong correlation between
hip fractures and congestive heart failure

A

True

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5
Q

What is the most important determinant of bone strength and BMD (also used to diagnose osteoporosis)

A

Dual X-ray absorptiometry (DXA/DEXA)

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6
Q

Osteopenia

A

reduced bone mass and mineral density, less severe compared to osteoporosis)

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7
Q

How do YOU know if you have osteopenia

A

No symptoms - you dont know until you fall

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8
Q

Are male or female at higher risk of osteoporosis

A

Female

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9
Q

Where is calcium stored in the body

A

-99% stored in bone (& teeth)
-Remaining 1% in extracellular fluid
and soft tissues

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10
Q

Calcium concentration in
extracellular fluid is very tightly regulated through

A

Hormones

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11
Q

What is the homeostatic set point of calcium we must maintain in the blood

A

[Ca+2] = 9-10.5 mg/dL

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12
Q

Calcium absorption

A

Occurs in the small intestine. Acts to increase dietary calcium uptake.

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13
Q

Calcium reabsorption (kidney)

A

Calcium can be excreted in the urine (when blood calcium levels are HIGH) OR reabsorbed back into the blood (when blood calcium levels are LOW)

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14
Q

Calcium reabsorption (bone)

A

Resorption involves dissolving bone structure to release calcium (stored in the bone) into the bloodstream.

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15
Q

1st response to low blood calcium

A

Parathyroid hormone (PTH)
–> secreted by parathyroid gland

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16
Q

2nd response to low blood calcium

A

Calcitriol
–> active metabolite of vitamin D made in the kidney

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17
Q

Response to high blood calcium

A

Calcitonin
–> secreted by thyroid parafollicular cells

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18
Q

How does PTH increase blood calcium

A
  • Stimulates production of calcitriol in kidney (activates 1α-hydroxylase enzyme)
  • Stimulates resorption of bone (breakdown of bone to release Ca+2) → blood
  • Maximizes tubular reabsorption of calcium in kidney → blood
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19
Q

How does calcitriol increase blood calcium

A
  • Stimulates resorption of bone (immediate response)
  • Facilitates absorption of calcium from the small intestine (short term response)
  • Maximizes tubular reabsorption of calcium in kidney (short term response)
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20
Q

How does calcitonin decrease blood calcium

A
  • Suppresses tubular reabsorption of calcium in kidney
  • Inhibits bone resorption and facilitates remineralization
  • This is a longer term response which improves bone density
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21
Q

What does calcitriol do that can influence many disease processes

A

Decreases adaptive immune system activation

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22
Q

5 ways calcitriol decreases adaptive immune system activation

A

– ↓ B cell and T cell proliferation
– ↓ Antigen presenting cell maturation (cannot present antigen)
– ↓ Inflammatory cytokine production (IL-6, TNFα, IFNγ, IL-12)
– Inhibits Th17 cell activation and IL-17 secretion
– Stimulates antimicrobial protein secretion (e.g cathelocidin, beta-defensins)

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23
Q

Calbindin

A

transports Ca+2 to and
from intracellular stores in the mitochondria and ER to help maintain both intestinal Ca+2 levels
(needed by the epithelial cell) and contribute to blood Ca+2 levels

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24
Q

Basolateral calcium transport

A

A) Sodium Calcium Exchanger
(3 Na+ in / 1 Ca+2 out)
B) Calcium pump (Ca+2 out, H+ in)

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25
Calcium transport: uptake from intestinal lumen (across apical border)
#1. Passive Diffusion (paracellular transport) active when consuming a high Ca+2 diet to allow for maximal uptake of dietary Ca+2...this mechanism ↓ as the lumen [Ca+2] #2. Calcium Channel (TRPV6, apical border)
26
Calcitriol stimulates gene expression and protein synthesis of (3)
ALL Ca+2 apical and basolateral transporters AND Calbindin
27
What does PTH do to raise blood calcium
Inhibits bone forming reactions: – Type 1 collagen formation – Osteocalcin production in osteoblasts -Stimulates the activity of 1-α-hydroxylase in the kidney -Decreases renal excretion of Ca+2
28
How do we get rapid PTH response when blood calcium is low
pre-formed PTH is stored in vesicles so that release of active PTH can happen very quickly
29
How does PTH release get stopped
Ca+2 binds to the CaSR (calcium sensing receptor)..activates a signaling pathway to STOP PTH RELEASE
30
Are FHH Mutations in the CaSR responsive to Ca+2 levels
not responsive to changes in blood Ca+2 levels (body perceives a lack of Ca+2 levels and sustains secretion of PTH
31
Hypercalcemia
→ high or increased blood Ca+2 levels → sustained by bone resorption → over time this increases the risk of osteoporosis and fractures
32
Hypocalciuric
→ low levels of Ca+2 in the urine → instead develop kidney stones because Ca+2 stays trapped in the kidney and is neither lost in urine OR reabsorbed back into the blood Homeostatic blood Ca+2 range
33
Two types of bones
-corticol/compact bone -trabecular bone
34
Cortical/compact bone makes up what % of total bone mass and what is it composed of
80% -dense tissue composed of bone minerals and ECM proteins
35
Trabecular bone makes up what % of total bone mouse, and is composed of
20% -composed of thin spicules of bone that extend from cortex to medullary cavity
36
Which type of bone is the outer layer (cortex) of all bones and forms the bulk of the interior of the long bones
Cortical bone
37
Which type of bone is found in the interior of bones and is especially prominent within vertebral bodies
Trabecular bone
38
The lacework of bone spicules on WHAT TYPE OF BONE is lined by areas of osteoblasts and osteoclasts
Trabecular bone
39
What type of bone provides much of the strength for weight bearing by the long bones
Cortical
40
What type of bone undergoes constant turnover (is synthesized and reabsorbed) at much higher rates
Trabecular bone
41
Why do trabecular bones undergo constant turnover at a much higher rate?
42
Types of bone cells
-Osteoblasts -Osteoclasts -Osteocytes
43
Osteoblasts
Bone forming cells – through the process of ossification (bone deposition) * Secrete organic matrix (largely composed of collagen) + other proteins
44
Osteoclasts
Bone resorbing cells (breakdown), found on the growth surfaces of bone
45
Osteocytes
* Old osteoblasts that are embedded in bone matrix (after they’ve secreted it in the process of forming new bone) * Sense mechanical stress on bone and secrete growth factors that stimulate new osteroblasts and bone formation
46
How are mature osteoblasts formed (basic explanation, not the in-depth process)
- Old osteoblasts embedded in the bone matrix - Sense mechanical stress on the bone - Secrete growth factors to simulate new osteoblast activity and new bone formation
47
how mature osteoblasts are formed from stem cell
Mesenchymal steam cells --> Pre-osteoblasts --> (Runx2) --> Mature osteoblasts
48
How mature osteoclasts are formed from sytem cell
Hematopoietic stem cells --> M-CSF(stimulates RANK expression_ --> Pre-osteoclasts --> (RANK-L binds to RANK) --> Mature osteoclast
49
What type of stem cell turns into osteoblasts
Mesenchymal
50
What type of stem cells turn into osteoclasts
Hematopoietic
51
Bone remodelling cycle (4 stages)
1. Osteoclast reabsorption 2.Osteoblast activity matrix formation (osteoid) - (no minerals added yet) 3. Mineralization 4. Resting phase SEE DIAGRAM
52
Bone is composed of a touch ___________ that is greatly strengthened by _______
Organic matrix, deposits of calcium salts
53
Majority of organ matrix is ___________, and what does that do
Type 1 collagen fibers - gives bone its tensile strength and stability
54
Ground sybstance (organic matrix make up)
largely made of chondroitin sulfate and hyaluronic acid
55
Bone salts
Crystalline salts deposited within the organic matrix composed principally of calcium and phosphate
56
Deposition of proteins by osteoblasts form
the organic matrix (osteoid)
57
Type I collagen is hardened by
Deposits of hydroxyapatite
58
Other proteins secreted by osteoblasts (OC and ON) lead to
cross-linking of bone structures
59
What does osteocalcin bind
Strongly binds Ca2+ and hydroxyapatite
60
What does osteonectin bind and facilitate
* Binds to hydroxyapatite AND collagen fibers → forms a lattice work holding the organic matrix and bone salts together * Facilitate the mineralization of collagen fibers
61
Other proteins secreted by osteoblasts regulate
The activation of osteoclasts
62
How does RANK-L causes cells to mature into a functional osteoclast that can break down bone
Binds to RANK (a receptor) on surface of osteoclast progenitor cells (also called a pre-osteoclast), which stimulates the cell to MATURE into a functional osteoclast capable of breaking down bone
63
Where is RANK-L expressed and/or secreted
Can be expressed on the osteoblast surface (for a cell-contact dependent mechanism) OR secreted as a free protein (for a cell-contact independent mechanism)
64
RANK-L secretion/expression is stimulated by
– Calcitriol – PTH – Inflammatory cytokines (TNFa, IL-6) – Prostaglandin E2 (PGE2) inflammatory eicosanoid derived from n-6 PUFA arachidonic acid (AA)
65
What does osteoprotegerin (OPG) do
* RANK-L antagonist – secreted and binds to RANK-L forming a complex that cannot bind to the RANK receptor (INHIBITS OSTEOCLAST MATURATION)
66
How is osteoprotegerin secretion stimulated
Stimulated by estrogen and IL-4 (amongst other)
67
How is RANK-L expressed or secreted
PTH (and other stimuli) will stimulate the osteoblast to express (on the cell surface) or secrete RANK-L
68
OC expression of RANK is stimulated by
M-CSF (macrophage colony stimulating factor)
69
What happens when there is no M-CSF expression
no RANK expression and no osteoclast maturation and activity
70
Osteoclast surface receptors
- RANK - Cytokine receptors e.g IL 6R, TNFR (stimulate activation of OC) - Calcitonin Receptor → signals to reduce OC activity and reduce bone resorption
71

NUTR 4320 (8 decks)

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