Osteoporosis Pharmacology

Question 1

What controls the formation of 1,25-OH vitamin D?

Answer 1

PTH

Question 2

how does M-CSF affect bone metabolism?

Answer 2

increase osteoclast activity

Question 3

how does OPG affect bone metabolism?

Answer 3

decrease osteoclast activity

Question 4

how does RANKL affect bone metabolism?

Answer 4

increase osteoclast activity

Question 5

Which cytokines are osteoclastic?

Answer 5

IL-1, IL-6

Question 6

how do IGF-1, IGF-2 affect bone metabolism?

Answer 6

osteoblastic

Question 7

What is the recommended daily allowance for Calcium?

Answer 7

1200mg/day < RDA < 2500 mg/day

supplement may be needed in pts taking PPI’s

Question 8

What is the recommended daily allowance for Vit D3?

Answer 8

adult: 400U

low sunlight areas: 2000U/day

Question 9

When is active Vit D (calcitriol, paricalcitol) needed?

Answer 9

needed when renal pathology is present

Question 10

What are downsides of calcium preparations?

Answer 10

not effective in absence of Vit D

Constipation sometimes seen

Question 11

What is management of osteoporosis in PREmenopausal women?

Answer 11

1. Exercise (weightbearing)
2. 1200-2500 mg/day calcium
3. Vit D

Question 12

What is the management of osteoporosis in POSTmenopausal women?

Answer 12

Calcium + Vit D3 (risk of kidney stone if calcium > 2500mg/day)
-raloxifene or bisphosphonate often needed

Question 13

Whats the osteoporosis treatment efficacy from most effective to least?

Answer 13

1. Vit D, Ca2+, PTH
2. Calcitonin, Bisphosphonate
3. Estrogen, denosumab

Question 14

Although Estrogen + Progestin therapy decreases fx risk, why are they bad?

Answer 14

increases Heart attacks, strokes, breast cancer, VTE’s

Question 15

What is the recommended pharm for osteoporosis? What is the mechanism of action?

Answer 15

Raloxifene - selective estrogen receptor modulator

1. Partial agnostic at Estrogen Receptor A
2. Antagonist at Estrogen Receptor B

Question 16

Where are ERa and ERb located? what drug acts on these receptors?

Answer 16

ERa - cortical bone
ERb - trabecular bone
Raloxifene - ERa partial agnoist, ERb antagonist

Question 17

What is the physiological results of SERMs? Raloxifene

Answer 17

1. ERa agonist, ERb antagonist
2. reduce IL-6, TNF-a, M-CSF
3. decreased responsiveness of RANK receptor to RANKL
4. stimulation of OPG formation

net fx: reduce osteoclast activation, osteoblasts left unopposed

Question 18

What are potential risks of SERMs?

Answer 18

1. Teratogenesis
2. DVT, thrombotic stroke
3. hot flashes

Question 19

What is conjugated estrogen/bazedoxifene (SERM) reserved for?

Answer 19

women with a uterus

Question 20

What are the benefits of Raloxifene? (4)

Answer 20

1. increase bone density in spine/long bones
2. decrease hip/spine fx
3. reduced breast cancer
4. decrease in uterine cancer

Question 21

What is the mechanism of action of Bisphosphonates?

Answer 21

• directly incorporate into bone

- reduce osteoclastic dissolution of hydroxyapatite in bone (paget’s dissease, hyperPTH)

Question 22

What are alendronate, etidronate, zoledronic acid?

Answer 22

Bisphosphonates - osteoporosis, fracture healing

Question 23

What are side fx of bisphosphonates?

Answer 23

1. may erode esophagus
2. OSTEONECROSIS of jaw - seen w glucocorticoids, dental procedures
3. Atypical femur fracture

Question 24

What diuretic can be used in osteoporosis therapy?

Answer 24

Thiazide Diuretics - decrease Ca secretion

-rarely used primary for osteoporosis

Question 25

What is Teriparatide? What are its uses?

Answer 25

Parathormone | -reserved for high risk of fracture or sever osteoporosis or unresponsive osteoporosis

Question 26

What is Denosumab?

Answer 26

monoclonal Ab to RANK-L - prevents osteoclastic activation

Question 27

What are contraindications for Denosumab?

Answer 27

1. Multiple myeloma 2. Corticosteroids 3. Dental surgery 4. Radiation, chemo 5. inability to take Vit D, Ca

Question 28

What are Risks of Denosumab?

Answer 28

1. Mandibular necrosis | 2. Hip fractures

Question 29

Who is Denosumab used in? (3)

Answer 29

1. patients intolerant, unresponsive to bisphosphonates 2. Women on aromatase inhibitors 3. men with prostate cancer on GnRH inhibitors

Question 30

What is the Tx for osteoporosis in Pregnancy?

Answer 30

Calcium | Vit D

Question 31

What is the Tx for osteoporosis in Men?

Answer 31

Androgen if low test | same as women (exercise, Ca, Vit D, sometimes bisphosphonate) - NEVER estrogen or SERMS

Question 32

What is the Tx for osteoporosis induced by Aromatase Inhibitors?

Answer 32

SOC: Bisphosphonates Ca, Vit D consider substituting raloxifene for aromatase inhibitor

Question 33

What is the Tx for osteoporosis in short term spinal fractures?

Answer 33

Calcitonin

Question 34

What is the use of Calcitonin? (acute and chronic use)

Answer 34

Short Term - Spinal Fractures Chronic - Paget's Disease, HyperPTH -Ca and phosphate excretion in kidney increased

Question 35

What is the Tx for post-low trauma bone fx or glucocorticoid induced osteoporosis?

Answer 35

Ca + Vit D3 + (bisphosphonate or parathormone or short term calcitonin)

Question 36

What is the osteoporosis Tx with HyperPTH?

Answer 36

cinacalcet

Question 37

What are Cinacalcet, Etelcalcetide?

Answer 37

Calcimimetics - activates CASR in parathyroid gland (reduce Ca, PO3)

Question 38

What are the uses of calcimimetics?

Answer 38

HyperPTH from: 1. Chronic Kidney disease 2. Parathyroid carcinoma

Question 39

What are side fx of Calcimimetics?

Answer 39

Cardiac arrhythmia | New or worsening heart failure