bone mineral homeostasis MT1 Flashcards

1
Q

this is the site of new bone growth

A

epiphyseal plate

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2
Q

this type of cell “B”uilds bone

A

osteo”B”lasts

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3
Q

this type of cell breaks down bone

A

osteoclasts

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4
Q

how is plasma Ca2+ maintained?

A

plasma Ca2+ is maintained from diet and bone “recycling”

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5
Q

what are some key roles of Ca2+

A
  • muscle contraction (including the heart)
  • cell signalling
  • bone support
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6
Q

true/false: 99% of calcium in the body is in the bone

A

true

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7
Q

the body will resorb Ca2+ from the bone if there is not enough in the plasma. what effect will this have on the bones?

A

will cause them to become weaker

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8
Q

this vitamin is necessary for calcium absorption

A

vitamin D

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9
Q

this form of vitamin D is from ergosterol in plants which is aka dietary vitamin D

A

vitamin D2 (ergocalciferol)

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10
Q

this form of vitamin D is generated in skin using UV light which is aka sunlight vitamin D

A

vitamin D3 (cholecalciferol)

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11
Q

cholecalciferol is converted to calcifediol in the ______

A

liver

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12
Q

calcifediol is converted to calcitrol (1,25-dihydroxyvitamin D3) in the ______ with the help of PTH

A

kidneys

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13
Q

what are the three mechanisms which vitamin D increases plasma Ca2+?

A
  1. mobilizes ca2+ from the bone (aka resorbing calcium from the bone to put it into the blood)
  2. promoting reabsorption by the kidneys (less Ca2+ lost in urine)
  3. promoting absorption from the intestine (through dietary/supplements)
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14
Q

this hormone increases plasma Ca2+ by mobilizing Ca2+ from bone, promoting reabsorption by the kidney and stimulating synthesis of calcitriol

A

parathyroid hormone (PTH)

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15
Q

does the effects of vitamin D on PTH represent a positive feedback loop or a negative feedback loop

A

negative feedback loop - helps prevent too much Ca2+ in blood and too little in bone (maintains homeostasis)

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16
Q

where is calcitonin released?

A

released from the C cells of the thyroid

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17
Q

this hormone does the opposite of PTH
- decreases plasma Ca2+, inhibits mobilization of calcium from bone and decreases reabsorption in the kidney

A

Calcitonin

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18
Q

this is a disease of bone growth and calcium metabolism; bone resorption exceeds deposition.
- osteoclasts break down bone in order to mobilize calcium to plasma
- leads to low bone mineral density and an increased fracture risk

A

osteoporosis

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19
Q

what are some risk factors of osteoporosis

A
  • increased age
  • inadequate calcium intake
  • genetics
  • smoking
  • hormones
20
Q

this hormone has a protective effect on bone

A

estrogen

21
Q

this is a disease caused by deficient bone mineralization due to vitamin D deficiency (affects growing bone in children)

A

rickets

22
Q

this is a disease due to vitamin D deficiency which causes softening of existing bones in adults.
- decrease in absorption of calcium and increased PTH release = increased bone resorption

A

osteomalacia

23
Q

this is a disease which is due to localized increases in bone turnover rate and causes bone to grow large with low density
- exact cause is unknown. could be combination of environmental factors and genetics

A

pagets disease

24
Q

this disease LEADS to hypocalcemia and hypercalcemia, respectively

A

hypoparathyroidism (decreased PTH) and hyperparathyroidism (increased PTH)

25
Q

this medication/hormone can impact bone homeostasis. it causes weaker bones by an over arching effect
- decreased Ca2+ absorption leading to increased PTH
- decreased Ca2+ reabsorption in kidney (thus more excreted in urine)
- decreased osteoblast activity
- increased osteoclast activity

A

glucocorticosteroids (e.g. prednisone)

26
Q

this hormone causes stronger bones by an over arching effect.
- decreases osteoclast activity
- increases osteoclast apoptosis
- decreases osteoblast apoptosis

A

gonadal steroids (e.g. testosterone)

27
Q

this supplement is used to treat osteoporosis, hypoparathyroidism and electrolyte imbalances. side effects include: GI disturbance, kidney stones

A

calcium supplements
e.g. calcium gluconate (IV), calcium carbonate (most common - PO) and calcium citrate (less constipating - PO)

28
Q

what is the MOA of calcium supplements

A

essential for bone mineralization, density and strength

29
Q

what is the maximum amount of elemental calcium that can absorbed PO as a single dose

A

500mg ELEMENTAL

30
Q

this supplement is used to treat osteoporosis, hypoparathyroidism and rickets/osteomalacia. there are usually no side effects, may cause hypercalcemia in renal impaired pts

A

vitamin D supplements

31
Q

what is the MOA of vitamin D supplementation

A

increases intestinal calcium absorption

32
Q

this vitamin D supplement is usually reserved fir people with poor kidney function

A

Calcitrol

33
Q

this is the main drug class of osteoporosis. side effects include: N/V/D, esophageal erosion, atypical femur fracture and osteonecrosis of the jaw

A

bisphosphonates
e.g. alendronate, risedronate and zoledronic acid

34
Q

what is the MOA for bisphosphonates

A

inhibit the mevalonate pathway which leads to osteoclast apoptosis which prevents destruction of bone

35
Q

this is a drug used for osteoporosis in female patients only. side effects include increased incidence of breast cancer, increased CV risk, breast tenderness, uterine bleeding and VTE

A

hormone replacement therapy (HRT)
e.g. estrogen + progesterone

36
Q

what is the MOA for hormone replacement therapy

A

increases osteoclast apoptosis (decreases destruction of bone) and increases osteoblast lifespan (which helps build bone)

37
Q

this is a drug used for osteoporosis in female patients only. side effects include hot flashes and VTE

A

selective estrogen receptor modulators (SERMs)
e.g. raloxifene

38
Q

what is the MOA for SERMs

A

it is an estrogen receptor partial agonist/antagonist
it is an agonist in bone and CV tissue
it is an antagonist in mammary and uterine tissue (thus often used to treat breast cancer)

leads to increased osteoblast activity and decreased osteoclast activity

39
Q

this drug is an injectable medication used for osteoporosis. side effects include musculoskeletal pain, hypocalcemia and skin reactions

A

Denusomab (Prolia, Xgeva)

40
Q

what is the MOA for Denusomab?

A

it is a monoclonal Ab that binds to RANKL. this prevents osteoclast development and reduces their function/survival

41
Q

this drug is a once daily SC injection for osteoporosis. it is a recombinant human PTH analog. side effects include hypotension, hypercalcemia and MK pain

A

teriparatide

42
Q

what is the MOA of teriparatide

A

it promotes bone anabolism (aka building of bone) by decreasing osteoclast activity and increasing osteoblast activity

43
Q

recall, high continuous exposure of PTH favours bone catabolism (breakdown). so how come teriparatide causes bone anabolism and bone catabolsim?

A

with teriparatide, there is intermittent exposure to PTH which activates osteoblasts more than osteoclasts. thus, OD injections have a net effect of stimulating bone formation leading to increasing BMD

44
Q

this drug is generally given IM or SC for osteoporosis, pagers disease and hypercalcemia. side effects include facial flushing and N/V/D

A

calcitonin

45
Q

what is the MOA of calcitonin

A

decreases osteoclast resorptive activity (aka decreases breakdown of bone to recycle Ca2+ to blood) thus decreases plasma Ca2+
- binds to G-protein-coupled receptors on osteoclasts