B6.052 Prework 6: Osteoporosis Pharmacology

Question 1

prevention and treatment of postmenopausal osteoporosis

Answer 1

appropriate calcium and vit D intake (esp prior to achieving PBM)
exercise
pharm agents

Question 2

pharm agents for osteoporosis

Answer 2

bisphosphonates
denosumab
teriparatide
raloxifene

Question 3

effectiveness of Ca and vit d in treating osteoporosis

Answer 3

beneficial effect on bone density in postmenopausal women and older men
benefit on reduction of fracture rates is variable

Question 4

vit D and Ca guidelines

Answer 4

vit D supplements: 1000 IU/d
Ca diet + supplements: 1000 mg
for adults over 65

Question 5

types of bisphosphonates

Answer 5

alendronate- weekly
risedronate- weekly, monthly
ibandronate- monthly, IV every 3 months
zolendronic acid- IV annually

Question 6

mechanism of bisphosphonates

Answer 6

direct inhibition of bone resorption

• concentrate at sites of active remodeling, remains in matrix until the bone is remodeled
• released in acid environment of the resorption lacunae and induces apoptosis in osteoclasts
• inhibits cholesterol biosynthetic pathway which contributes to anti-resorptive activty

Question 7

adverse reactions with bisphosphonates

Answer 7

hypocalcemia
osteonecrosis of the jaw
atypical femur fractures
gastric symptoms

Question 8

mechanism of denosumab

Answer 8

fully human monoclonal Ab to RANKL

binds/inhibits ability of RANKL to mature osteoclasts from osteoclast precursors (similar to OPG)

Question 9

use of denosumab

Answer 9

twice yearly sc injection
if stopped, bone lost rapidly if another agent is not used
has applications in cancer treatment

Question 10

adverse effects of denosumab

Answer 10

osteonecrosis of the jaw
atypical femur fractures
hypocalcemia
skin infection (usually cellulitis of the lower extremity)
derm reactions

Question 11

raloxifene drug class

Answer 11

SERM

selective estrogen receptor modulator

Question 12

how do SERMs work?

Answer 12

not “pure” agonists of estrogen receptor, have different effects in different tissues
-produce different structural changes in receptor upon binding, alters the co-factors with which ER interacts

Question 13

mechanism of raloxifene

Answer 13

partially replaces missing estrogen post-menopause w respect to bone remodeling
less effect than seen with estrogens

Question 14

effectiveness of raloxifene

Answer 14

reduces occurrence of vertebral fracture by 30-50%

no data for reduced risk of nonvertebral fractures over 8 years of observation

Question 15

side effects of raloxifene

Answer 15

NO effect on heart disease, NOT associated with increased risk of uterine cancer/ benign uterine disease
65% reduction in invasive breast cancer (mainly decreased ER-positive)

Question 16

effects of calcitonin

Answer 16

bone:
-stimulates osteoblasts
-inhibits osteoclasts
kidney:
-transient increase in Ca secretion

Question 17

what is teriparatide

Answer 17

recombinant human PTH

amino acids 1-34 of the 84 AA endogenous PTH

Question 18

mechanism of teriparatide

Answer 18

first approved anabolic agent
stimulates osteoblastic bone formation
with short duration of action, most likely activates osteoblasts without activating osteoclasts

Question 19

effectiveness of teriparatide

Answer 19

increases predominantly trabecular bone at lumbar spine and femoral neck (less significant at cortical sites)

Question 20

administration of teriparatide

Answer 20

administered once daily by subq injection in thigh or abdominal wall
use for 2 years in men and post menopausal women with osteoporosis
-followed w anti-resorptive agent to maintain BMD gain
-no fracture reduction benefit from second course of teriparatide

Question 21

calcitonin administration

Answer 21

injection or nasal spray

Question 22

what is calcitonin

Answer 22

32 ss peptide with sequence of calcitonin from salmon, 30x potency of human calcitonin

Question 23

effectiveness of calcitonin

Answer 23

effects assessed by high res MRI
benefit in maintaining trabecular microarchitecture at multiple skeletal sites
reduced incidence of vertebral compression fractures by about 40% in osteoporotic women

Question 24

on graph, drugs from best to worst

Answer 24

teriparatide
PTH + estradiol
alendronate
estradiol
raloxifene
calcitonin