Osteoporosis and HRT (Quiz 2)

Question 1

Describe the pathogenesis of osteoporosis.

Answer 1

Loss of sex steroids leads to a shortened lifespan for osteoblasts and a delay in the cell death of osteoclasts

Question 2

List 7 risk factors for osteoporosis.

Answer 2

1. Smoking/Alcohol
2. Advanced age
3. Low body weight
4. RA
5. Disease states
6. History of fractures/steroid treatment
7. Family hx of hip fracture

Question 3

_____ is produced by the osteoblasts and facilitates crosstalk between osteoblasts and ______ for bone remodeling.

Answer 3

RANK L (ligand) 
Osteoclasts

Question 4

What cell surface receptor binds to RANKL on the osteoblast to promote osteoclast maturation?

Answer 4

Receptor activator of nuclear factor (RANK)

Question 5

_____ promotes osteoclast cell death and osteoblast activity.

Answer 5

Estrogen

Question 6

Polymorphisms in the ____ gene have been associated with osteoporotic fractures and differences in BMD. What is the action of this gene?

Answer 6

Osteoprotegerin (OPG)

Action: OPG is an endogenous RANK-L inhibitor, so it blocks RANK from binding to the RANK ligand (RANK-L) and prevents osteoclast maturation

Question 7

Low levels of ___ and ___ are associated with the pathogenesis of osteoporosis.

Answer 7

Calcium

Vitamin D

Question 8

_____ slightly increase bone mineral density. How?

Answer 8

Cox-2 inhibitors

via inhibition of prostaglandins (PGE2 is responsible for resorption)

Question 9

What tool is used to screen for osteoporosis? Scores?

Answer 9

Bone densitometry with dual energy x-ray absorptiometry (DEXA)

T-score = young normal
Z-score = age matched norms

Question 10

What t-score is indicative of osteopenia vs osteoporosis?

Answer 10

Osteopenia= -1 to -2.5 SDs

Osteoporosis = -2.5 or below SDs

Question 11

___ SD equals 10-12% decrease in bone density

Answer 11

-1

Question 12

How often should bone density be measured?

Answer 12

Every 1-2 years starting age 65

Question 13

List 5 effects of estrogen and hormone replacement therapy.

Answer 13

1. Female sex characteristics
2. Endometrial proliferation
3. Increase in HDL
4. Decrease in Osteoclast activity
5. Increase osteoblast activity

Question 14

List 4 indications for the use of estrogen and hormone replacement therapy.

Answer 14

1. Estrogen deficiency
2. Severe vasomotor symptoms in menopause
3. Postmenopausal osteoporosis
4. Birth control

Question 15

Birth control contains fixed amounts of ___ and ___ taken for ___ days before administration is stopped to allow for bleeding.

Answer 15

Estrogen and Progesterone

21 days

Question 16

Estrogen was thought to be _____, but this has been disproved by later studies.

Answer 16

Cardioprotective

Thought that giving estrogen would decrease risk for MI because women get MIs 10 years after men.

Question 17

_____ turns out to be associated with a higher risk of breast cancer and a more virulent form.

Answer 17

MPA (medroxyprogesterone)

Question 18

What are the current recommendations for calcium intake for 19-50 years and those >50 years of age?

Answer 18

19-50 years = 1000mg

>50 years = 1200mg

Question 19

_____ IUs of vitamin D is required for younger than 50 years but increases to ____ IU for ages 51-70.

Answer 19

400-800 IU for younger than 50

800-1000 IU for ages 51-70

Question 20

List 3 MOAs of bisphosphonates.

Answer 20

1. Inhibit bone reabsorption by binding to hydroxyapatite crystals in bone
2. Inhibit osteoclast mediated bone resorption.
3. Enhances osteoclast cell death, absorbed directly into calcium crystals

Question 21

List 4 indications for the use of bisphosphonates.

Answer 21

1. Osteoporosis
2. Spinal cord injury
3. Total hip replacement (for 4 months post surgery)
4. Paget’s disease

Question 22

Bisphosphonates have poor oral ____. Describe their dosing (3).

Answer 22

Poor oral BIOAVAILABILITY

1. Must take oral dose with full glass of water
2. Maintain upright position for 30 min
3. Abstain from taking drug with food, calcium, iron, coffee, tea and orange juice

Question 23

What is the most significant ADR associated with the use of bisphosphonates? What will the patient report?

Answer 23

Rare atypical fractures with minimal impact (diaphyseal mid shaft fx of the femur) in patients who have taken drugs 10 yrs.

Patient reports dull aching pain in thigh/groin before fx occurs (watch for unexplained joint pain)

Question 24

List 2 selective estrogen receptor modulators and their MOA.

Answer 24

1. Tamoxifen: blocks estrogen receptors in the breast but is an agonist in bone and endometrium
2. Raloxifene blocks estrogen receptors in the breast and endometrium but is an agonist in bone

Question 25

True or false: Selective estrogen receptor modulators are MORE effective than estrogen.

Answer 25

FALSE

Less effective than estrogen

Question 26

List 3 ADRs associated with the use of selective estrogen receptor modulators.

Answer 26

1. Hot flashes
2. Leg cramps
3. Increased risk of thromboembolic events

Question 27

_____ have been found to also enhance bone formation.

Answer 27

STATINS

Question 28

List 4 therapy concerns when treating patients on hormone replacement therapy/estrogen.

Answer 28

1. Monitor for thigh pain
2. Enhance effect of drugs with wt bearing activities
3. No modalities or exercise near daily injections
4. For patients on oral bisphosphonates-avoid increasing intra-abdominal pressure

Question 29

What is the MOA of oral contraceptives? (2)

Answer 29

1. Inhibit ovulation by increasing serum levels of estrogens and progestins which in turn inhibits secretion of FSH and LH.
2. Induces changes in the endometrium that impair ova implantation and an increase in cervical mucus impedes passage of sperm

Question 30

List 2 ADRs associated with the use of contraceptives.

Answer 30

1. increased risk of DVT/HTN

2. Risk of osteoporosis with low dose estrogen

Question 31

List 4 ADRs associated with the use of fertility drugs.

Answer 31

1, Weight gain

2. Edema
3. Abdominal bloating
4. Ovarian hyper-stimulation syndrome

Question 32

What 2 activitites should be avoided with patients taking Clomid/Pergonal (fertility drugs)?

Answer 32

1. Jumping activities

2. High impact aerobics