Osteoporosis and HRT (Quiz 2) Flashcards
Describe the pathogenesis of osteoporosis.
Loss of sex steroids leads to a shortened lifespan for osteoblasts and a delay in the cell death of osteoclasts
List 7 risk factors for osteoporosis.
- Smoking/Alcohol
- Advanced age
- Low body weight
- RA
- Disease states
- History of fractures/steroid treatment
- Family hx of hip fracture
_____ is produced by the osteoblasts and facilitates crosstalk between osteoblasts and ______ for bone remodeling.
RANK L (ligand) Osteoclasts
What cell surface receptor binds to RANKL on the osteoblast to promote osteoclast maturation?
Receptor activator of nuclear factor (RANK)
_____ promotes osteoclast cell death and osteoblast activity.
Estrogen
Polymorphisms in the ____ gene have been associated with osteoporotic fractures and differences in BMD. What is the action of this gene?
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
Low levels of ___ and ___ are associated with the pathogenesis of osteoporosis.
Calcium
Vitamin D
_____ slightly increase bone mineral density. How?
Cox-2 inhibitors
via inhibition of prostaglandins (PGE2 is responsible for resorption)
What tool is used to screen for osteoporosis? Scores?
Bone densitometry with dual energy x-ray absorptiometry (DEXA)
T-score = young normal Z-score = age matched norms
What t-score is indicative of osteopenia vs osteoporosis?
Osteopenia= -1 to -2.5 SDs
Osteoporosis = -2.5 or below SDs
___ SD equals 10-12% decrease in bone density
-1
How often should bone density be measured?
Every 1-2 years starting age 65
List 5 effects of estrogen and hormone replacement therapy.
- Female sex characteristics
- Endometrial proliferation
- Increase in HDL
- Decrease in Osteoclast activity
- Increase osteoblast activity
List 4 indications for the use of estrogen and hormone replacement therapy.
- Estrogen deficiency
- Severe vasomotor symptoms in menopause
- Postmenopausal osteoporosis
- Birth control
Birth control contains fixed amounts of ___ and ___ taken for ___ days before administration is stopped to allow for bleeding.
Estrogen and Progesterone
21 days
Estrogen was thought to be _____, but this has been disproved by later studies.
Cardioprotective
Thought that giving estrogen would decrease risk for MI because women get MIs 10 years after men.
_____ turns out to be associated with a higher risk of breast cancer and a more virulent form.
MPA (medroxyprogesterone)
What are the current recommendations for calcium intake for 19-50 years and those >50 years of age?
19-50 years = 1000mg
>50 years = 1200mg
_____ IUs of vitamin D is required for younger than 50 years but increases to ____ IU for ages 51-70.
400-800 IU for younger than 50
800-1000 IU for ages 51-70
List 3 MOAs of bisphosphonates.
- Inhibit bone reabsorption by binding to hydroxyapatite crystals in bone
- Inhibit osteoclast mediated bone resorption.
- Enhances osteoclast cell death, absorbed directly into calcium crystals
List 4 indications for the use of bisphosphonates.
- Osteoporosis
- Spinal cord injury
- Total hip replacement (for 4 months post surgery)
- Paget’s disease
Bisphosphonates have poor oral ____. Describe their dosing (3).
Poor oral BIOAVAILABILITY
- Must take oral dose with full glass of water
- Maintain upright position for 30 min
- Abstain from taking drug with food, calcium, iron, coffee, tea and orange juice
What is the most significant ADR associated with the use of bisphosphonates? What will the patient report?
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)
List 2 selective estrogen receptor modulators and their MOA.
- Tamoxifen: blocks estrogen receptors in the breast but is an agonist in bone and endometrium
- Raloxifene blocks estrogen receptors in the breast and endometrium but is an agonist in bone
True or false: Selective estrogen receptor modulators are MORE effective than estrogen.
FALSE
Less effective than estrogen
List 3 ADRs associated with the use of selective estrogen receptor modulators.
- Hot flashes
- Leg cramps
- Increased risk of thromboembolic events
_____ have been found to also enhance bone formation.
STATINS
List 4 therapy concerns when treating patients on hormone replacement therapy/estrogen.
- Monitor for thigh pain
- Enhance effect of drugs with wt bearing activities
- No modalities or exercise near daily injections
- For patients on oral bisphosphonates-avoid increasing intra-abdominal pressure
What is the MOA of oral contraceptives? (2)
- Inhibit ovulation by increasing serum levels of estrogens and progestins which in turn inhibits secretion of FSH and LH.
- Induces changes in the endometrium that impair ova implantation and an increase in cervical mucus impedes passage of sperm
List 2 ADRs associated with the use of contraceptives.
- increased risk of DVT/HTN
2. Risk of osteoporosis with low dose estrogen
List 4 ADRs associated with the use of fertility drugs.
1, Weight gain
- Edema
- Abdominal bloating
- Ovarian hyper-stimulation syndrome
What 2 activitites should be avoided with patients taking Clomid/Pergonal (fertility drugs)?
- Jumping activities
2. High impact aerobics
