Osteoporosis

Question 1

HRT, SERMs, Biphosphonates, and Calcitonin are all what kind of agents?

Answer 1

Antiresorptive agents (inhibit the breakdown of bone)

Question 2

How do antiresorptive agents work?

Answer 2

Suppress osteoclastic bone resorption (prevent/slow bone loss)
No increase in osteoblastic activity (little net gain in bone mass)

Question 3

When is one time that BMD can still occur when using antiresorptive agents and why?

Answer 3

Initial period of therapy

d/t mineralization of resorption cavities that are produced during the period of excessive bone resorption

Question 4

How does HRT: Estrogen work to inhibit bone breakdown?

Answer 4

Suppresses transcription of genes encoding cytokines that induce osteoclast proliferation, differentiation, and activation (indirect inhibition of osteoclast activity)

Question 5

Main goals of HRT: Estrogen:

Answer 5

Maintain bone mass, slow bone loss

Question 6

Why is HRT: Estrogen no longer routinely used to prevent/slow osteoporosis?

Answer 6

CV and breast cancer risks outweigh benefits

would need to used with progestin to minimize endometrial cancer if used at all

Question 7

How do SERMs such as Raloxifene (Evista) work to treatment osteoporosis?

Answer 7

Binding to estrogen receptors

Agonist in bone, antag in endometrium and breast

Question 8

Raloxifene (Evista) prevents AND treats osteoporosis by increasing BMD of what area?

Answer 8

Vertebral and non-vertebral area

decreases vertebral fracture risk

Question 9

Raloxifene (Evista) has what effect on cholesterol?

Answer 9

Lowers LDL

Question 10

What risk, like Estrogen, does Raloxifene (Evista) have?

Answer 10

Risk of venous thromboembolism

Question 11

The most popular treatment and prevention of osteoporosis is:

Answer 11

Biophosphonates

Question 12

Examples of Biophosphonates:

Answer 12

Alendronate(Fosamax)-PO, daily or weekly
Risedronate (Actonel)-PO daily, weekly, monthly
Ibandronate (Boniva)- PO-monthly IV-q3mos
Pamidronate(Aredia)-IV
Zoledronate (Reclast, Zometa)- IV, once a year

Question 13

Clinical uses of Biophosphanates include:

Answer 13

1. Prevention/treatment of osteoporosis: increase hip and spine BMD, decrease risk of vertebral and nonvertebral fractures
2. Hypercalcemia
3. Metastatic bone disease
4. Paget’s Disease

Question 14

MOA of Biphosphonates:

Answer 14

Preferentially localize to sites of bone resorption, under osteoclasts.
Do not interfere with osteoclast recruitment/attachment but do inhibit osteoclast activity
Concentrate in bone in mineralized matrix
When bone resorption begins the matrix is dissolved and biophosphate is released
Bone formation can exceed resorption at its sites of action
(osteoclast/osteoblast activity is coupled= when bone resorption decreases, bone formation also decreases

Question 15

The net effect of biophosphonates is:

Answer 15

slowing of progression more than rebuilding of bone

Question 16

Oral biophosphonates have low bioavailability. How should they be taken?

Answer 16

On an empty stomach to maximize absorption:
Take in morning before 1st meal of the day
Take with 8oz of water
Wait at least 30 minutes after taking the medication before eating or taking other meds

Question 17

Because biophosphanates can causes reflux, esophagitis, and esophageal ulcers what should patients be counseled about?

Answer 17

Remain upright for 30 minutes after taking the medication

Have a meal before lying down

Question 18

Of absorbed biophosphonates: 70% are______ and 30% are_____

Answer 18

70% renally excreted

30% taken up by bone and can remain there indefinitely (why dosing is less frequent)

Question 19

AE of both IV and PO biophosphonates:

Answer 19

Long-term inhibition of bone turnover could lead to hypermineralization and structural changes that could adversely affect bone quality and strength
**Osteonecrosis of the jaw may occur in patients with extensive dental disease and oral surgery

Question 20

MOA of Calcitonin:

Answer 20

Binds to and activates a receptor on osteoclasts, decreasing resorptive activity

Question 21

What is Calcitonin good for treating?

Answer 21

Disease with high osteoclastic activity
Osteoporosis, hypercalcemia, Paget’s disease
Slows vertebral bone loss
Decreases incidence of vertebral fractures

Question 22

How must calcitonin be administered?

Answer 22

SubQ, IV, or intranasal (peptide-won’t absorb orally)

Derived from salmon, 40x higher affinity for calcitonin receptor than human calcitonin

Question 23

MOA of bone anabolic agents, Fluoride and PTH Teriparatide(Forteo) and which patients are they ideal in?

Answer 23

Increase bone mass rather than just prevent bone loss

Ideal over antiresorptive agents in patient who have lost a large amount of bone (BMD>3SD below normal

Question 24

At high concentration Fluoride increases:

Answer 24

Trabecular bone mass

unclear whether it is effective in preventing osteoporosis related fractures

Question 25

How is increased endogenous PTH (hyperparathyroidism) different from the administration of recombinant PTH teriparatide (Forteo)?

Answer 25

Hyperparythyroidism leads to more bone resorption than formation
Intermittent stimulation of bone by PTH by Forteo causes more bone formation than resorption (dosed daily or even less frequently)

Question 26

How is teraparatide (Forteo) administered?

Answer 26

SubQ

Question 27

Who is Forteo used in?

Answer 27

Osteoporosis in postmenopausal women and men that have significant bone loss. Not a first line treatment

Question 28

Which medication is a fully human monoclonal antibody that inhibits RANKL?

Answer 28

Denosumab (Prolia)

Question 29

What is RANKL?

Answer 29

Protein that is produced by osteoblasts and needed for the formation, function, and survival of osteoclasts

Question 30

How does the decreased estrogen post menopause affect RANKL?

Answer 30

Increases RANKL and therefore increasing osteoclast activity and bone breakdown (both cortical and trabecular bone)

Question 31

Precautions/AE of Denosumab (Prolia) include:

Answer 31

Pregnancy Category X
Always check Cr and Ca before administration
Postmenopausal osteoporosis: back pain, pain in extremity, hypercholesteremia, musculoskeletal pain, and cystitis
Bone loss d/t hormone ablation for cancer: arthralgia, musculoskeletal pain

Question 32

How is Denosumab administered and by whom?

Answer 32

SubQ every 6months by a healthcare professional