Drugs Affecting Bone Mineral Homeostasis

Question 1

Bone mineral homeostasis

Answer 1

Calcium and phosphorous
Regulated by Vitamin D, PTH
(also fibroblast growth factor 23 and calcitonin)

Question 2

PTH and D

Answer 2

Stimulate preosteoblast proliferation and diffrentiation–> bone formation

Sitmulate differentiation and activation of osteoclast–> bone resorption

Question 3

Calcium

Answer 3

Acts to clotting blood, muscle contraction, ossification of bone, release of endocrine hormones and neurotransmitters

Question 4

Hypercalcemia

Answer 4

generalized muscular weakness and smooth muscle dysfunction

Question 5

Hypocalcemia

Answer 5

skeletal, cardiac, smooth muscle spasms, tetany, generalized convulsions; paresthesias

Question 6

Pharmacological uses of Ca

Answer 6

hypocalcemia, hypoparathyroidism, renal disease, hypocalcemic tetany, prophylaxis and tx of osteoporosis

toxicity- ectopic calcification

Question 7

Calcium carbonate

Answer 7

oral
cheap
need to take with food
can cause gas, bloating, constipation

Question 8

calcium citrate

Answer 8

oral
fewer GI problems
does not affect gastric pH
can take w/o food

Question 9

IV calcium

Answer 9

calcium gluconate
for severe symptomatic hypocalcemia
least irritating to veins of IV Ca preparations
rapid infusion can cause arrythmias

Question 10

Vitamin D

Answer 10

Formed in skin by UV irradiation, found in certain foods

D3 is intrinsic and dietary is D3 and D2 are inactive precursors that need to be converted to calcitriol (most active)

circulates bound to vitamin D binding protein

Question 11

Primary function of Vitamin D

Answer 11

• regulation of Ca homeostasis
• bones increase bone formation and resorption (inc Ca mobilization)
• kidneys to increase tubular reabsorption (dec Ca excretion)
• small intestines to increase Ca and phosphate absorption

Normal range 30-70 ng/mL

Question 12

Deficiency of vit D in children

Answer 12

Causes rickets resulting in abnormal and retarded bone growth

Question 13

Vit D toxicities

Answer 13

hypercalcemia and hypercalciuria–> nausea, vomiting, decreased appetite, frequent urination, renal failure

relatively uncommon

Question 14

Cholecalciferol

Answer 14

D3

hydroxylated by liver, and then kidney
longer 1/2 life- better for supplementation unless metabolism is compromised

otc
aminal source

Question 15

Ergocalciferol

Answer 15

D2
made by plants
prescription
shorter 1/2 life

Question 16

Calcitriol

Answer 16

1,25(OH)2D3

most active Vit D

Question 17

Other Vit D analogs

Answer 17

Calcipotriene, doxercalciferol, paracalcitrol

Question 18

Causes of Vit D def

Answer 18

inadequate dietary intake
inadequate exposure to sublight
renal dysfunction
administration of anticonvulsants (phenobarbital, phenytoin) that increase metabolism of 24(OH)D

Question 19

Pharma uses of vit D

Answer 19

nutritional rickets
metabolic rickets (genetic defect in renal hydroxylase or renal failure)- use calcitriol
osteoporosis and osteomalacia
psoriasis- calcipotriene (topical)
hypoparathyroidism
secondary hyperparathyroidism in renal disease- doxercalciferol, paricalitol

Question 20

bisphosphonates

Answer 20

Analogs of pyrophosphate

• suppress activity of osteoclasts by mechanism involving retardation of formation and dissolution of hydroxyapatite crystals within bone
• inhibit bone resorption and consequently bone formation

Question 21

Use of bisphosphonate

Answer 21

osteoporosis in females and males
pagets disease of bone
hypercalcemia
bone mets

Question 22

Bisphosphonates PK

Answer 22

less than 10% oral dose absorbed
oral reduced by food
take with full glass of water and remain upright for 30 min because it causes esophageal and gastric irritation

Question 23

AE of bisphosphonates

Answer 23

gastric irritation (unless IV)
adynamic bone
osteonecrosis of jaw 
renal failure 
drug holiday recommended after 5 years of treatment

Question 24

Oral bisphosphanates

Answer 24

Etidronate (daily), alendronate (daily or weekly), risedronate (daily, weekly, monthly)

Question 25

Oral or IV bisphosphanate

Answer 25

Ibandronate

monthly for oral and quarterly iv

Question 26

IV bisphosphanate

Answer 26

zoledronic acid- annual

Question 27

pamidronate

Answer 27

• pagets disease, malignancy

- iv bisphosphonate

Question 28

Teriparatide

Answer 28

tx osteopporosis
stimulates new bone that is structurally normal
not rec for use >2 yrs
warning: osteosarcoma

Question 29

Calcitonin

Answer 29

increases bone mass
not as effective as bisphosphonates or teriparatide

for osteoporosis

Question 30

Denosumab

Answer 30

RANKL inhibitor for osteoporosis

supresses bone resorption

Question 31

Estrogen

Answer 31

Not recommended for post menopausal osteoporosis due to effects on breast, uterus, and CV system

Question 32

Fluoride

Answer 32

stabilizes hydroxyapatite crystals in bone and teeth
prevents dental caries
toxicity at 3-5 mg/kg
in drinking water at 1 mg/L

Question 33

Cinacalcet

Answer 33

activates calcium sensing receptor (CaSR) in parathyroid gland
-used for secondary hyperparathyroidism in renal disease and parathyroid carcinoma

Question 34

Glucocorticoids

Answer 34

dec Ca absorption and increase excretion
blocks bone formation
can lead to osteoporosis

Question 35

thiazide diuretics

Answer 35

dec renal Ca excretion
augment effects of PTH
used for hypercalciuria