Calcium, bone and osteoporosis Flashcards
(167 cards)
1
Q
what do osteoclasts do
A
dissolve the bone and release IGF1 and TGFβ (transforming growth factor)
2
Q
what recruits osteoclasts to bone
A
cytokines (ILs) and parathyroid hormone
3
Q
what do osteoblasts do
A
lay down new oesteoid which will then become the new bone matrix
4
Q
what are osteocytes
A
bone cells which are osteoblasts that became embedded in the matrix
5
Q
at what age does bone loss start occuring
A
age 35-40
6
Q
what % rate bone loss happens per year in both sexes
A
0.5-1%
7
Q
why does bone decrease by 0.5-1% per year in both sexes
A
due to decrease in osteoblast numbers
8
Q
what is the rate of loss increase during menopause in women
A
10X increase
9
Q
why does bone decrease by 10X during menopause in women
A
due to increase in osteoclast activities
10
Q
what % of the body calcium is contained in bone
A
98%
11
Q
what % of the body phosphates is contained in bone
A
85%
12
Q
how is calcium phosphate stores as in bone (name and formula)
A
hydroxyapatite, Ca10(PO4)6(OH)2
13
Q
what is the formula for hydroxyapatite
A
Ca10(PO4)6(OH)2
14
Q
what are the 3 major hormones involved in bone metabolism and remodeling
A
parathyroid hormone, vitamind D, calcitonin
15
Q
what does high plasma [Ca++] do to PTH release
A
decreases PTH release
16
Q
what does low plasma [Ca++] do to PTH release
A
increases PTH release
17
Q
what G proteins are coupled to Ca++ sensing receptors
A
Gq Gi
18
Q
what does high [PO4-] do to PTH secretion and how
A
indirectly increases
-forms complex with Ca++, so less Ca++ in plasma
19
Q
what does low [PO4-] do to PTH secretion and how
A
indirectly decreases
-forms complex with Ca++, so more Ca++ in plasma
20
Q
what does calcitriol do to PTH release and why
A
makes less, suppresses PTH gene expression
21
Q
what is calcitriol
A
a vitamin D metabolite
22
Q
what does high intracellular Ca++ do to PTH secretion
A
inhibit
because that means Gq was activated by Ca++ in plasma and high plasma Ca++ means low PTH
23
Q
what does low intracellular cAMP do to PTH secretion
A
inhibit
because that means Gi was activated by Ca++ in plasma and high plasma Ca++ means low PTH
24
Q
what does PTH do to the bone
A
induce osteoblasts to express and secrete a protein RANKL (RANK ligand)
25
what are PTH receptors coupled to
adenylate cyclase
26
what does RANKL do
activate RANK receptors on osteoclast precursors to cause differentiation and activation of osteoclasts
27
what does RANK receptor activation on osteoclasts do
cause differentiation and activation of osteoclasts
28
what bone cell has RANK receptors
osteoclasts
29
which bone cell releases RANKL
osteoblasts
30
what does an increase in bone resorption lead to
bone formation
31
what does intermittent exposure to PTH promote
bone formation
32
what does chronic high level exposure to PTH promote
bone resorption
33
what does PTH do to GI tract
increase in Ca++ and phosphate absorption via an increase in synthesis of calcitrol in the kidney
34
what does PTH do to Ca++ absorption
increase
35
what does PTH do to phosphate absorption
increase
36
what does PTH do to calcitriol synthesis (where does this occur)
increase, in the kidney
37
where does calcitriol synthesis occur
in the kidney
38
what does PTH do to kidney
- increase calcitrol synthesis
- increase Ca++ reabsorption
- increase PO4- excretion
39
what do kidneys do to Ca++ reabsorption (with PTH)
increase
40
```
what do kidneys do to phosphate excretion
and how (with PTH)
```
increase excretion by decreasing reabsorption in proximal tubules
41
what does PTH do to plasma calcium
elevates
42
what does PTH do to plasma po4-
decrease
43
what is a synthetic PTH used for in osteoporosis
PTH 1-34
44
what are the 2 major sources of vitamin D called
ergocalciferol (D2)
| cholecalciferol (D3)
45
where does ergocalciferol (D2) come from
plants
46
where does cholecalciferol (D3) come from
in the skin, generated by UV light
47
is D2 or D3 more strong in humans
same potency
48
what is vitamin D tho and what does it do
a prohormone that is converted into a number of biologically active metabolites
49
what enzyme converts calfidediol into calcitriol
25(OH)D1αhydroxylase
50
where is calcifediol produced
in the liver
51
where is calcitriol produced
in the kidney
52
what does calcitrol do to PTH production
inhibit
53
what does high calcitrol do to PTH production
inhibit
54
what does low calcitrol do to PTH production
enhance
55
what does calcitrol do to calcitrol production
inhibit
56
what is calceifediol
the main storage form of vitamin D
57
what does calcifediol do to Ca++ (renal)
stimulates renal reabsorption
58
what does calcifediol do to PO4-
stimulates renal reabsorption
59
what does calcifediol do to Ca++ (muscle)
regulates Ca++ inlfux and contractility
60
where is excessive vitamine D stored
in body fat
61
what does vitamin D binding protein have high affinity to
calcifediol
62
what does vitamin D binding protein have low affinity to
calcitriol
63
what is the most potent vitamin D metabolite
calcitriol
64
what is the vitamin D metabolite with the longer plasma half life
calcifediol (23 days) vs calcitriol (hours)
65
what is calcitriols affinity to vitamin D binding protein
low
66
what is calcifediol affinity to vitamin D binding protein
high
67
what does calcitriol do to osteoblasts and what does this cause
induces RANKL secretion from osteoblasts so more recruitment of osteoclast precursor cells and maturation of osteoclasts
this causes production of osteocalcin
68
what does calcitriol do to bone (major effect)
bone resorption
69
what is osteocalcin
Ca++ binding protein in bOne maTriX
70
what secretes osteocalcin
osteoblasts
71
why do osteoblasts secrete osteocalcin
to regulate bone mineralization
72
what does calcitriol do to GI tract
increased Ca++ and PO4- absorption
73
what does calcitriol do to Ca++ reabsorption
increase absorption
74
what does calcitriol do to PO4- absorption
increase absorption
75
how does calcitriol increase Ca++ absorption in GI (3)
by increasing Ca++ binding proteins. TPV6 Ca++ channels and Ca++ flux across basal lateral membranes
76
what does calcitriol do to plasma Ca++
increase
77
what does calcitriol do to plasma PO4-
increase
78
what does calcitriol do to kidney
decrease ca po4 excretion
79
what does calcitriol do to ca in kidney
decrease excretion
80
what does calcitriol do to po4 in kidney
decrease excretion
81
what does calcitriol do to parathyroid glands
decrease PTH secretion
82
what does calcitriol do to PTH secretion
decrease
83
what does calcitriol do to other tissues
cell maturation and differentiation
84
what are 4 common therapeutic uses for vitamin D
- hypocalcemia
- rickets
- osteomalacia
- osteoporosis
85
what is hypocalcemia
failure to mineralize newly formed bone in children, resulting in bone softening and skeletal deformities
86
what is osteomalacia
accumulation of undermineralized bone matrix in adults, associated with bone pain and tenderness
87
what are 5 possible causes of hypocalcemia
```
hypoparathyroidism
vitamin D deficiency
chronic kidney disease
malabsorption (GI disease)
liver disease
```
88
why would chronic kidney disease cause hypocalcemia
decrease in calcitriol synthesis
89
why would liver disease cause hypocalcemia
decrease in calcifediol formation
90
what are 4 manifestations of hypocalcemia
tetany (tremor/spasms), paresthesia, muscle cramps, seizures
91
what is the main treatment for hypocalcemia
Ca++ supplement in conjunction with calcitriol
92
why is Ca++ supplement given in conjunction with calcitriol
cause calcitriol helps it absorb in the GI
93
what can cause rickets and osteomalacia (4)
nutritional
hypophosphatemic vitamin D resistant
type 1 vitamin D dependent (pseudovitamin D deficiency)
type 2 vitamin D dependent (hereditary vitamine D resistant)
94
how can you fix nutritional causing rickets and osteomalacia
cod liver oil or vit D supplement
95
what is hypophosphatemic vitamin D resistant
genetic disorder resulting in reduction in renal PO4- reabsorption and decrease calcitriol production
96
what is phosphate critical for with bones
BONE mineralization
97
how do you treat hypophosphatemic vitamin D resistant
calcitriol and phosphate supplement
98
what causes type 1 vitamin D dependent (pseudovitamin D deficiency)
mutation in 25(OH)D 1 hydroxylase
99
what are you deficient in with type 1 vitamin D dependent (pseudovitamin D
calcitriol production
100
how do you treat type 1 vitamin D dependent (pseudovitamin D
calcitriol
101
what causes type 2 vitamin D dependent (hereditary vitamin D resistant)
mutations in the gene for vitamin D receptors
102
what is serum cortisol levels in type 2 vitamin D dependent (hereditary vitamin D resistant)
actually high (but low tissue response)
103
how do you treat type 2 vitamin D dependent (hereditary vitamin D resistant)
high dose of calcitriol
104
kind of cell releases calcitonin
parafollicular C cell in thyroid gland
105
what triggers calcitonin release from parafollicular C cell in thyroid gland
high Ca++ in plasma
106
which G receptors is calcitonin coupled to
Gs
107
what does calcitonin do to bone
less osteoclast activities
| less bone resorption
108
how do the bone effects of vitamin D and calcitonin compare
they are opposite
109
what does calcitonin do to GI
increase Na+ K+ Cl- H2O secretion
| less gastrin and gastric acid secretion
110
what does calcitonin do to kidney
less Ca++ and PO4- reabsorption
| and other ions (Na+ K+Mg++)
111
what does calcitonin do to plasma Ca++ levels
lower
112
what does calcitonin do to plasma PO4- levels
lower
113
is calcitonin used for osteoporosis and why
no cause it gave tumors
114
what does hypercalcemia manefest as
CNS depression
coma
fatigue
muscle weakness
115
what can cause hypercalcemia
cancer that stimulates bone resoprtion, hyperparathyroidism
116
what is pagets disease
abnormality in bone remodelling: uncontrolled osteoclastic bone resorption, secondary increases in poorly organized bone formation
117
what causes pagets disease
unknown, maybe virus
118
how can you treat pagets disease
calcitonin
119
how can calcitonin help pagets disease
lowers pain and compilation
120
what is osteoperosi (simple)
increase in bone resorption relative to bone formation
121
what are 2 common causes of osteoporosis
low sex hormone production
| low vitamin D level and GI Ca++ absorption
122
what are 4 less common causes of osteoporosis
glucocorticoids
thyrotoxicosis (thyroid hormone stimulates osteoclasts)
hyperparathyroidism
alcohol abuse (decrease vit D uptake)
123
what are 6 treatments for osteoporosis
```
teriparatide (fragment of PTH)
vit D supplement
Ca++ supplement
biphosphonate
estrogen replacement therapy/ receptor modulators
denosumab
```
124
how many generations of biphosphonates have there been
3
125
how do 1st gen biphosphonates work
metabolize into a nonhydrolyzable ATP analog that accumulates within osteoclasts and induce apoptosis
126
what happens if given a 1st gen biphosphonate at continuously at high doses
osteomalacia (bone minerilzation, softening)
127
are 1st gen biphosphonates given as a first line of treatment
no
128
how do 2nd gen biphosphonates work
inhibit farnesyl pyrophosphate synthesis, an enzyme that is important for osteoclast function and survival
129
how must 2nd gen biphosphonates be administered
first thing in the morning on an empty stomach
130
how much more potent are 2nd gen biphosphonates than 1st gen
10-100
131
how do 3rd gen biphosphonates work
inhibit farnesyl pyrophosphate synthesis, an enzyme that is important for osteoclast function and survival
132
how much more potent are 3rd gen biphosphonates than 1st gen
10 000
133
how can you administer 3rd gen biphosphonates
once a year IV
134
what do biphosphonates do to bone remodeling and how
decrease by decreasing osteoclast activity
135
what do biphosphonates do to osteoclast activity
reduce
136
where is the action of biphosphonates concentrated
at the site of active bone remodeling
137
what do biphosphonates do to hydroxyapatite
reduce formation and dissolution of hydroxyapatite
138
what are 4 therapeutic uses of biphosphonates
pagets disease
prophylaxis + treatment of osteoperosis
hypercalcemia
prevent fracture in patients with bone metastases
139
what is a complication with using biphosphonates
osteonecrosis of jaw (more with 3rd gen due to limit of blood supply)
140
what happens to calcium levels in blood when on biphosphonates and why
lowers because they inhibit bone resorption
141
how is estrogen good for osteoperosis
it opposes the action of PTH on bone resorption
142
how does estrogen oppose the action of PTH on bone resorption
there are estrogen receptors on bone
143
is estrogen used in postmenopausal women for osteoporosis and why
no because there is an increase risk in breast cancer with long-term use
144
what do SERMs stand for
selective estrogen receptor modulators
145
what do SERMs do to bone
agonist effects on bone - behaves like estrogen
146
what do SERMs do to lipid metabolism
agonist effects on lipid metabolism - behaves like estrogen
147
what do SERMs do to breast tissue
antagonist effects on breast cancer - so wont cause cancer
148
what do SERMs do to uterus
its inactive
149
when are SERMs used
alternative to estrogen replacement therapy
150
what do SERMs do to thromboembolic events
increased risk
151
what are the agonist effects of SERMs
on bone and lipid metabolism
152
what are the antagonist effects of SERMs
on breast tissue
153
what is denosumab
a human monoclonal antibody
154
what does denosumab do/cause
reduces the stimulatory action of RANKL on osteoclasts formation and activation
155
what is the mechanism of denosumab
binds to RANKL to prevent it from binding to RANL receptors on osteoclast precursor cells (so it wont become an osteoclast)
156
which drug can be used for postmenopausal osteoporosis
denosumab
157
can denosumab be used for postmenopausal osteoporosis
yes
158
what do glucocorticoids do to bone (2)
decrease bone formation
| decrease activities of osteoblasts
159
what do glucocorticoids do to bone formation
decrease
160
what do glucocorticoids do to osteoblasts
decrease activity
161
what do glucocorticoids do to GI tract
decrease Ca++ and PO4- absorption
162
what do glucocorticoids do to Ca++ absorption
decrease
163
what do glucocorticoids do to PO4- absorption
decrease
164
what do glucocorticoids do to kidneys
increase Ca++ excretion
165
what do glucocorticoids do to Ca++ excretion
increase
166
what are 3 things that glucocorticoids in treatment of hypercalcemia are good for / associated with
- vitamin D intoxication
- sarcoidosis
- cancers that stimulate osteoclastic bone resorption
167
what is sarcoidosis
lung granuloma that causes unregulated ectopic production of vitamin D
