bone mineral homeostasis MT1

Question 1

this is the site of new bone growth

Answer 1

epiphyseal plate

Question 2

this type of cell “B”uilds bone

Answer 2

osteo”B”lasts

Question 3

this type of cell breaks down bone

Answer 3

osteoclasts

Question 4

how is plasma Ca2+ maintained?

Answer 4

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

Question 5

what are some key roles of Ca2+

Answer 5

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

Question 6

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

Answer 6

true

Question 7

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

Answer 7

will cause them to become weaker

Question 8

this vitamin is necessary for calcium absorption

Answer 8

vitamin D

Question 9

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

Answer 9

vitamin D2 (ergocalciferol)

Question 10

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

Answer 10

vitamin D3 (cholecalciferol)

Question 11

cholecalciferol is converted to calcifediol in the ______

Answer 11

liver

Question 12

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

Answer 12

kidneys

Question 13

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

Answer 13

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)

Question 14

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

Answer 14

parathyroid hormone (PTH)

Question 15

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

Answer 15

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

Question 16

where is calcitonin released?

Answer 16

released from the C cells of the thyroid

Question 17

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

Answer 17

Calcitonin

Question 18

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

Answer 18

osteoporosis

Question 19

what are some risk factors of osteoporosis

Answer 19

• increased age
• inadequate calcium intake
• genetics
• smoking
• hormones

Question 20

this hormone has a protective effect on bone

Answer 20

estrogen

Question 21

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

Answer 21

rickets

Question 22

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

Answer 22

osteomalacia

Question 23

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

Answer 23

pagets disease

Question 24

this disease LEADS to hypocalcemia and hypercalcemia, respectively

Answer 24

hypoparathyroidism (decreased PTH) and hyperparathyroidism (increased PTH)

Question 25

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

Answer 25

glucocorticosteroids (e.g. prednisone)

Question 26

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

Answer 26

gonadal steroids (e.g. testosterone)

Question 27

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

Answer 27

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

Question 28

what is the MOA of calcium supplements

Answer 28

essential for bone mineralization, density and strength

Question 29

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

Answer 29

500mg ELEMENTAL

Question 30

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

Answer 30

vitamin D supplements

Question 31

what is the MOA of vitamin D supplementation

Answer 31

increases intestinal calcium absorption

Question 32

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

Answer 32

Calcitrol

Question 33

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

Answer 33

bisphosphonates e.g. alendronate, risedronate and zoledronic acid

Question 34

what is the MOA for bisphosphonates

Answer 34

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

Question 35

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

Answer 35

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

Question 36

what is the MOA for hormone replacement therapy

Answer 36

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

Question 37

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

Answer 37

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

Question 38

what is the MOA for SERMs

Answer 38

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

Question 39

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

Answer 39

Denusomab (Prolia, Xgeva)

Question 40

what is the MOA for Denusomab?

Answer 40

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

Question 41

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

Answer 41

teriparatide

Question 42

what is the MOA of teriparatide

Answer 42

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

Question 43

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

Answer 43

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

Question 44

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

Answer 44

calcitonin

Question 45

what is the MOA of calcitonin

Answer 45

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