Fitzy: Osteoporosis Flashcards
What is the definition of osteoporosis?
- 2.5 standard deviations from the mean bone density on DEXA scan
- 1-5 to 2.5 is osteopenia
How T-score is calculated
(Patient’s BMD- young adult mean BMD)/(1 SD of young-adult Mean BMD)
-<2.5 is osteoporosis
What does the drugs’ efficacy for prevention and tx of osteoporosis depend on?
-adequate intake of Vit D and calcium
What are the 2 calcium supplements that a person can take?
- Calcium carbonate
- calcium citrate
Describe calcium carbonate
- 40% calcium, needs acid to dissolve and for absortion
- take “at” or “after” meals
- less stomach acid with aging
describe Calcium citrate
- 20% calcium, no need for stomach acid for absorption
- may be taken between meals
- higher cost
What does 1,25 (OH)3 Vit D promote?
-intestinal Ca2+ absorption
What is the sufficient level of serum Vit D3
30-50
What are the drugs that lower serum Ca2+?
- prednisone, methylprednisolone
- budesonide, inhlaed
- carbamazepine
- phenytoin
- Furosemide
So, if we are going to initiate glucocorticoid therapy, what would we have to do first?
- a Bone densitometry and T-score
- glucocorticoids can impair Vit D absorption and metabolic activation n liver and kidney
What does Vit D make us do?
-absorb Ca2+ in the GI tract
what are the SERMs?
- Raloxifene
- Tamoxifen
What are the Bisphosphonates
- alendronate
- ibandronate
- pamidronate
- resedronate
- zolendronate
Biologicals
- teraparatide
- calcitonin
Antibodies
-denosumab
What cells do osteoclasts come from?
-HSC’s
What cells do osteoblasts come from?
-Mesenchymal stem cells
What drugs inhibit osteoclasts?
- SERMs
- Bisphosphonates
- calcitonin
- Antibodies: denosumab
What causes osteoporosis in older women?
- loss of estrogen during the aging process and at menopause
- E deficit leads to incrased rate ofbone resorption by osteoclasts
What does estrogen normally do?
-it’s usually a restrain on osteoclastic activity
Why is thrombosis such a big deal with estrogens?
-they stimulate the liver to make procoagulants
What class of drugs do we use for prevention and tx of osteoporosis?
- selective estrogen receptor modulators
- Raloxifene
- tamoxifen
Which drugs are for tx only?
- Calcitonin
- teriparatide
- denosumab
Where are the receptors that SERMS are estrogen agonists at?
-the ER in OSTEOCLASTS
Where are SERMS antagonists at ER’s
- the breast epithelium
- the ER’s there are occupied by RIx
When is Raloxifene usually chosen for osteoporosis prevention?
-when there is an independent need for breast cancer prophylaxis
What is the risk with using tamoxifen?
- increased uterine bleeding and cancer
- Raloxifene is not associated with vaginal bleeding or an increased risk of endometrial hyperplasia or cancer
What other class of drugs do we use for prevention and tx of osteoporosis?
-aminobisphosphonates
What do bisphosphonates do?
- bind to hydroxyapatite crystals in bone and inhibit bone resorption through effects on osteoclasts
- not metabolized, but either bind to hydroxyapatite in bone or are excreted unchanged into urine
What is the required for the release of bisphosphonates from the body?
- bone resorption
- they inhibit that… so they have a long time in bone
What is the amino bisphosphonate prototype?
-alendronate
What does alendronate accumulate in?
- osteoCLASTS
- sequestered by bone near remodeling sites
- remember they just go into osteoclasts and make them do apoptosis
What does osteoclast survival require?
- G protein prenylation (for signal transduction)
- FPP synthase does this
- BP’s block FPP.. there ya go
- more specifically, blocks conversion of Geranyl-PP to Farnesyl-PP
What is a contraindication for BP’s?
- pre-existing hypocalcemia
- we need bone, but we might also need the calcium from bone
What are well recognized adverse events associated with oral bisphosphonates?
-Esophagitis and esophageal ulcer
What do all of the BP’s end in?
-“dronate”
Why do you NOT want to eat or drink anything for at least 30 min after taking BP’s
-you also do NOT want to lie down for at least 30 minutes
-you want to avoid esophagitis
What is a rare but serious complication of BP’s that mainly happens in pts recieving it IV?
-Osteonecrosis of the Jaw (ONJ)
What are the treatment only anti resorption therapies?
- Calcitonin
- Denosumab
Denosumab
- monoclonal antibody
- against RANKL
- inhibits osteoclast formation b/c RANKL is a receptor activator of NFKB which is an osteoclast differentiating factor
- so, normally, RANKL on the osteoblast will bind to RANK on a pre-osteoclast to make it turn into an actual osteoclast
Calcitonin
- inhibits osteoclast action… anti-resorptive
- modest effect< BP
- decreases pain with acute vertebral compression fracture***
What is the Anabolic therapy that is used for tx only?
-Teriparatide (PTH fragment)
What does teriparatide do?
- stimulated osteoblast activity
- intermittent administration
What is teriparatide reserved for?
- high risk patients
- it has a greater increase in bone density as compared to alendrolate
What are the indications for teriparatide?
- postmenopausal women with osteoporosis at high risk for frature
- high risk for fracture
- high frisk for fracture!!!
What fractures are more common in older men?
-incidence of hip fractures increases exponentially with age
What drugs are effective in men?
-BP’s
What is Cinacalcet?
-A Calcium sensing receptor (CaSR) activator
What is Cinacalcet?
- a calcimimetic agent
- lowers PTH levels by increasing the sensitivity of the CaSR to extracellular Ca2+
What is Cinacalcet used for?
- treating an overactive parathyroid gland in dialysis pts with chronic kidney disease
- it is also used to treat high blood Ca2+ levels in pts with parathyroid cancer
