Calcium (Hockerman)

Question 1

what is the term fr moving both phosphorus and Ca2+ in and out of bone?

Answer 1

continuous balance

Question 2

what ARE OSTEOBLASTS?

Answer 2

bone forming cells

Question 3

what are osteoclasts?

Answer 3

bone reabsorption cells

Question 4

what inc. BMD?

Answer 4

1. osteonectin
2. nitric oxide
3. denin matrix protein 1

Question 5

what dec. BMD?

Answer 5

1. sclerostin
2. DKK-1
3. RANKL

Question 6

what does a deletion of aa in the PTH do?

Answer 6

deletion aa 1&2 eliminates activity

Question 7

what does PTH do?

Answer 7

1. increase calcium in extracellular fluid
2. inc. Ca2+ reabsorption from ECaC1 7 TrpV5
3. inc. Ca2+ resorption from bone (inc. osetoclast # & activity)
4. increased PO4 loss in urine
5. inc. 1,25 (OH2) D3 production by kidney
6. PTH secretion triggered by low serum Ca++ levels and GPCR that binds Ca2+ (CSR)

Question 8

how can vitamin D (cholecalciferol) be obtained?

Answer 8

in the diet or via exposure to sun light

Question 9

what does increased Ca2+ and PO43- absorption from small intestine do?

Answer 9

direct (rapid) effect on brush border of intestinal mucosal cells

Question 10

what cells are there a indirect slow effect?

Answer 10

1. calbindins
2. vitamin D binding protein

Question 11

what vitamin D deals with feedback inhibition of PTH?

Answer 11

1,25(OH)2D3

Question 12

what does the fibroblast growth factor 23 do?

Answer 12

1. auto/paracrine effect on osteocytes inhibits bone mineralization
2. high levels of FGF23 correlate with poor prognosis in patients with CKD on dialysis

Question 13

what do high Ca2+, 1,25(OH2) vit D3, and FGF23 inhibit?

Answer 13

PTH secretion

Question 14

what does low Ca2+ do?

Answer 14

stimulates PTH secretion

Question 15

what does a negative regulator of serum (extracellular) Ca2+ do?

Answer 15

1. inhibit osteoclastic bone resorption
2. increase Ca2+ and PO4 loss in urine
3. stimulated by high serum calcium levels

Question 16

what are some side effects of Padgetts disease?

Answer 16

1. bone remodeling
2. bone deformities
3. loss of hearing, hypercalcemia
4. may be caused by slowly acting virus

Question 17

what are some risk factors for osteoporosis?

Answer 17

1. physical inactivity
2. age
3. low Ca2+ intake in early years
4. long term glucocorticoid therapy

Question 18

what is hyperparathyroidism?

Answer 18

1. inc. bone resorption and decreased Ca2+ excretion

Question 19

what care some reasons for malignant tumors?

Answer 19

some produce a peptide with PTH activity

Question 20

what are osme causes of CNS symtpoms?

Answer 20

depression and coma

Question 21

what is a first line treatment for osteoporosis?

Answer 21

bisphosphates/ denosumab

Question 22

what drugs for osteoporosis cause a high fracture risk?

Answer 22

teriparatide abaloparatide, romosozumab

Question 23

what is a regimen for Vitamin D in osteoporosis?

Answer 23

1. Vitamin D (800-1000 IU) + Ca2+ (>1200mg) daily can reduce fracture risk
2. also supplement for osteoporosis therapy

Question 24

what are the characteristics of bisphosphates?

Answer 24

1. inhibit bone resorption
2. 50% absorbed dose ends up in bone
3. may lead to hypocalemia so we need to supplement with Ca2+ + Vit D

Question 25

what bisphosphates are approved for padget's and cancer but not for osteoporosis?

Answer 25

1. pamidronate 2. etidronate

Question 26

what bisphosphates are approved for osteoporosis and build bone mass?

Answer 26

1. zoledronate 2. alendronate 3. risendronate 4. ibandronate

Question 27

what is the mechanism of action of bisphosphates?

Answer 27

it disrupts prenylation of proteins in osteoclasts

Question 28

what is teriparatide?

Answer 28

amino acid 1-34 of PTH produced in E.coli

Question 29

what is abaloparatide?

Answer 29

amino acids 1-34 of PTHrP produced synthetically

Question 30

where are PTH1 receptors expressed?

Answer 30

on osteoblasts and kidney cells

Question 31

what does intermittent PTH do?

Answer 31

increase bone mass and strength

Question 32

what does continuous PTH do?

Answer 32

increase bone resorption

Question 33

what are the pros of teriparatide to bisphosphates?

Answer 33

build bone mass at higher rate than bisphosphonates

Question 34

what are the cons of teriparatide to bisphosphates?

Answer 34

black box warning required by FDA for risk of bone cancer --> reserved for severe cases of osteoporosis

Question 35

tell me about prolia (denosumab)?

Answer 35

approved in June 2010 for postmenopausal osteoporosis 1. hypocalcemia risk- take calcium daily 2. increased risk of fracture upon discontinuation

Question 36

tell me about romosozumab?

Answer 36

1. MAB against sclerostin 2. osteocyte secretion increased 3. sclerostoin decreases osteoblasts and increases osteoclasts 4. ADRs--> MACE (hypersensitivity, hypocalcemia, osteonecrosis, atypical fractures)

Question 37

what is calcitonin and its characteristics?

Answer 37

1. decreased osteoclast activity, blocks renal reabsorption of PO4 and Ca2+ 2. rapid loss of efficacy in treatment of hypercalcemia 3. not the drug of choice in most causes for treatment of osteoporosis

Question 38

what is the mechanism cinacalcet?

Answer 38

1. CKD with dialysis the CSR become less responsive to Ca 2+ 2. cinacalcet is a PAM 3. when cinacalcet is bound its more responsive to Ca2+

Question 39

what are the characteristics for the second line treatment for hyperparathyroidism?

Answer 39

1. Zemplar --> stage 2&4 or dialysis --> 1-4ug 3x per week IV or oral 2. Hectorol --> dialysis --> 4ug 3x per week IV or oral --> prodrug- 25 hydroxylation by CYP 27 in live >> inhibit secretion of PTH with less effect on serum Ca2+ than 1,25(OH)2 Vit D3

Question 40

what is the treatment of hyperphosphatemia in CKD with dialysis?

Answer 40

1. calcification --> calcific uremic arteriolopathy 2. phosphate binders are complex with dietary phosphate and prevent absorption from GI 3. Sevelamer dec. serum PO43- levels selectively 4. Lanthanum Carbonate dec. serum PO43- AND Ca2+ levels

Question 41

what does calcium receptor sensitization do?

Answer 41

---decrease both serum PTH and Ca2+ levels and can help in ---many treatments such as chronic kidney disease with dialysis

Question 42

what are third line treatments for osteoporosis?

Answer 42

estrogens/ SERMs --> inc. osteoblasts and dec. osteoclasts --> risk of blood clots --> raloxifene& bazedoxifene -----> antagonist: in breast/ uterus/ brain ------> agonist: in bone/liver