Osteoporosis Meds Flashcards
how many women and men over 50 will be affected by osteoporosis and experience a fx?
1 out of every 2 women and 1 out of every 4 men
majority are vertebral fxs
risk of different T scores associated with fx risk? What T score indicates osteopenia vs osteoporosis?
T score -1 = 2x risk
T score -2 = 4x the risk
T score -3 = 8x the risk
osteopenia T score -1 to -2.5
osteoporosis T score less than -2.5
*T score compares your pt to the entire population
*Z score compares your pt to ppl w/in their age group
RFs for osteoporosis?
gender - women generally have lower bone mass and lose bone more rapidly relative to men
body size - small statured women and thinner women
age - increasing age increases risk of developing osteoporosis
ethnicity - caucasian and asian women are at higher risk
Family hx - may be hereditary
diet low in Ca2+ and vit D
Sex hormones - low estrogen
inactive lifestyle or extended bed rest
excessive use of EtOH
use of certain meds like glucocorticoids and some anticonvulsants (phenytoin, dilantin), barbiturates, gonadotropin releasing hormone analogs, excessive use of aluminum-containing antacids, certain cancer txs, excessive thyroid hormones
eating disorders
main tx recommendation for osteoporosis?
lifestyle modifications - diet and exercise
variety of supplements and drugs are also available to help prevent and/or tx osteoporosis
osteoporosis prevention and tx considerations?
calcium vit D magnesium strontium bisphosphonates SERMs synthetic calcitonin hormone PTH analogs estrogen monoclonal abs/Anti-RANK ab
recommended amount of Ca intake for those 50 yo or less and for those over 50 yo? how much Ca2+ should breastfeeding women intake daily?
less than 50 yo is 1000 mg of Ca2+ per day
over 50 yo is 1200-1500 mg of Ca2+ per day
breastfeeding women should intake 2000 mg of Ca2+ a day
does calcium supplementation afford future fracture protection for women whom have already experienced a fracture?
not w/o the addition of other bone-building tx options
problem with calcium carbonate from oyster shells?
has been shown to have detectable levels of lead
soy can protect against fx at what levels?
those who ate 5 g a day decreased their fx levels, but even greater protection came at 13 grams (60 mg of soy isoflavones)
Vit D’s effect on bone health? how does it get activated?
Vit D is necessary for the absorption of Ca2+ in the stomach and GI tract
Vit D from sun exposure, food, supplements are biologically inert and have to undergo 2 hydroxylations - first occurs in the liver
recommended dosage for Vit D for individuals 1-70 yo; after 70 yo? how much do infants need per day?
1-70 yo need 600 IU a day
over 70 yo need 800 IU a day
infants need to be supplemented with 400 IU per day
what vitamins and minerals can you supplement with to help prevent osteoporosis?
magnesium
calcium
strontium
vit D
average dose of magnesium needed per day? SEs if take too much?
300 mg to 1000 mg per day
excessive magnesium intake can cause loose stool
how does strontium improve bone density?
improves osteoblastic activity (more bone getting laid down)
- strontium is incorporated in small amounts into hydroxyapatite crystal lattice where it remains bound for years or decades and may improve bone quality
- strontium atoms are adsorbed onto the surface of hydroxyapatite crystals, the probable site at which they stimulate bone formation, inhibit resorption and increase BMD
possible SEs of strontium? if taken in dosing over 2 g/d?
usu free of SEs other than mild GI upset and possible diarrhea
if more than 2 g/d taken can lead to weakened bone as it replaces bone’s calcium with strontium
medications approved by FDA for preventing and treating postmenopausal osteoporosis and in men and women with glucocoritcoid-induced osteoporosis? what class is each a part of?
bisphosphonates (alendronate)
raloxifene (a SERM)
medications approved for the tx of osteoporosis but not the prevention?
calcitonin/mialcin
teriparatide (synthetic PTH analogue) - can also be used in men who are at high risk for fracture
denosumab (human monoclonal ab approved by the FDA for tx)
medications approved for the prevention of postmenopausal osteoporosis?
estrogen or HRT
MOA of bisphosphonates? indications?
MOA: inhibit osteoclastic activity by encouraging osteoclastic apoptosis
indications: prevent bone loss, used to tx osteoporosis and similar dzs, reduce the risk of osteoporotic fxs in those w/previous fxs but not in those with previous osteoporotic fxs; osteitis deformans, bone mets, multiple myeloma, primary hyperparathyroidism, osteogenesis imperfects, bone fragility d/os
SEs of bispohosphonates? how to negative SEs?
dyspepsia, inflammation and erosions of esophagus
can decrease damage to esophageal lining by remaining standing or seated and upright for 30-60 mins after taking
systemic bioavailability of bisphosphonates? how should one take them in regards to meals?
bioavailability is extremely low, 0.6-0.7% and when you add with meals and beverages other than water it further reduces bioavailability
class of alendronate/fosamax? indications? MOA? how to give? chemically related to what, importance? what is needed to have optimal action?
class: bisphosphonate
indications: prevention and tx of osteoporosis
MOA: inhibit osteoclastic activity; inhibits bone resorption w/o any effect on mineralization; dose-dependent; deposited in the bone matrix in the inactive pyrophosphate form
chemically related to inorganic pyrophosphate (endogenous regulator of bone turnover)
for optimal absorption need enough Ca2+ and Vit D therefore hypocalcemia should be corrected before starting therapy
where does absorbed bisphosphonate go? where does the unabsorbed part go?
absorbed part (~50%) binds to exposed bone surface remainder is excreted unchanged by KDs
SEs of bisphosphonates? how to take to mitigate SEs?
SEs: GI - stomach ache, heartburn, nausea, erosive esophagitis, osetonecrosis of the jaw and atypical femur fxs
to limit esophagitis need to remain standing for 30 mins after taking and do not eat 30 min after each dose
thoughts behind using SERMs for increasing bone density? goals?
selective estrogen-receptor modulators
designed w/goal of producing same benefits that E has on bone density and on lowering cholesterol levels w/o increasing the risk for hormone-related CAs
class of raloxifene/evista? indications? MOA?
class: SERM
indications: increases bone mass and reduces risk of vertebral fx, significantly reduces risk of breast CA
MOA: selective binding to estrogen receptor sites; maintains beneficial E activity on bone and lipids and has an “anti-estrogenic” activity on endometrial and breast tissue
SEs of SERMs such as tamoxifen and raloxifene?
uterine cancer - raloxifene had fewer incidences when compared to tamoxifen however
tamoxifen also increases risk for cataracts
both increase risk for blood clots in veins and lungs (more common w/tamoxifen)
how to give raloxifene/evista? SEs? C/Is?
PO once per day
SEs: hot flashes, arthralgias, myalgias, edema, pruritis, small risk for DVT
C/I in PG and lactating women and women w/past or active hx of DVT, PE and renal vein thrombosis
declared in 2006 it was effective as tamoxifen in reducing incidence of breast CA in postmenopausal women at increased risk
calcitonin/miacalcin is analogous to what? where si the endogenous product formed? indications? MOA? reduces risk of what?
naturally occurring hormone in rx form; produced endogenously by parafollicular C cells of thyroid
MOA: involved in Ca2+ regulation and bone metabolism and diminishes osteoclastic activity
reduces risk of spinal fxs and may also reduce risk for developing hip fxs
in women at least 5 yrs past menopause, it can slow bone loss, increase spinal bone density, help alleviate pn associated w/bone fxs
class of calcitonin/miacalcin? indications? MOA? how to give? SEs?
class: synthetic hormone to increase serum Ca2+ levels
indications: tx osteoporosis
MOA: inhibits osteoclastic activity
give as a nasal spray, IV, not approved for prevention of osteoporosis
SEs: nose bleeds, sinusitis noted w/nasal spray; both nasal spray and IV routes may cause H/A, dizziness, edema, anorexia, diarrhea, skin rashes
effect of PTH on bone density?
daily high levels of pTH can cause osteoporosis, daily injections of low and intermittent doses however can actually stimulate bone production
what is the agent made from selected amino acids found in PTH that has been shown to significantly lower the risk of fx and increase bone mineral density?
teriparatide/forteo
class of teriparatide/forteo? indications? MOA?
class: synthetic PTH analogue
indications: approved for postmenopausal women and men w/osteoporosis who are high risk for fx, shown to reduce the risk of vertebral and non-vertebral fxs in postmenopausal women
MOA: PTH enhances release of Ca2+ from large reservoir contained in bones, PTH stimulates osteoblasts via increasing expression of RANKL and inhibiting expression of osteoprotegrin
MOA of teriparatide/forteo? how to give? SEs? portion of human PTH amino acid sequence?
MOA: activates bone turnover w/osteoblasts being activated to a much greater extent than osteoclasts; stimulates new bone formation in hip and spine
give once a day, approved for use for up to 24 mos
SE: MC are nausea, leg cramps, dizziness
amino acid sequence 1-34 of complete PTH
what has estrogen/HRT been shown to do? what is it approved for? how to give? can you take it alone? SEs?
reduce bone loss, increase bone density in spine and hip and reduce risk of hip and spine fxs in postmenopausal women
approved for prevention of postemenopausal osteoporosis and commonly given as pill or skin patch
woman with a uterus cannot take it on it’s own - increases risk of endometrial CA so need to give w/progestin to diminish this risk
SE: vaginal bleeding, breast tenderness, venous blood clots, increased risk for GB dz
risk associated with prempro use?
modest but definite increase in risk of breast CA, stroke, MI, ovarian CA
for solely using E/HRT tx to prevent osteoporosis what do you need to consider before using?
are they at significant risk of osteoporosis and can a non-estrogen medication be utilized to prevent bone loss instead?
estrogens effect on lipids?
lowers LDL and TGs, raises HDL and has vasodilatory properties plus an anti-inflammatory component
route of administration of estrogen in women with a hx of thromboembolic dz?
topical b/c absorbed directly into systemic circulation and avoid 1st pass in liver
class of denosumab/prolia? indications? MOA? how to give? SE?
class: human monoclonal ab
indications: osteoporosis, bone MET, rheumatoid arthritis, multiple myeloma, giant cell tumor of bone
MOA: targets RANKL, protein that acts as primary signal to promote bone removal; specifically inhibits maturation of osteoclasts by binding to and inhibiting RANKL so protects bone from degradation and helps counter progression of osteoporosis
give as SQ injections, once every 6 mos
SE: b/c part of TNF-a family it is known to increase risk of infxn; infxns of urinary and respiratory tracts, cataracts, constipation, rashes, jt pn, slightly increased risk for CA
where do you find RANK? member of what family? what is it activated by and where is this produced? activation of RANK leads to what?
on the surface of precursors to osteoclasts (pre-osteoclasts)
member of TNF family
activated by RANKL and produced by osteoblasts
activation of RANK leads to maturation of pre-osteoclasts into osteoclasts
what other class of drug, unrelated to osteoporosis, has shown some risk-lowering effects in regards to fxs?
statins
examples of phytoestrogens?
isoflavones (genistein, daidzein, glylcitein, equol)
lignans (enterolactone, enterodiol)
coumestans (coumestrol)
class of ipriflavone? possible indications?
class: synthetic isoflavone
possible indications: has shown some promise in its ability to conserve bone in postmenopausal women
9 drugs approved for use in prevention of osteoporosis?
- raloxifene/evista
- estrogen conjugated/premarin
- esterified estratab
- menest
- estradiol/estrace
- estropipate/ortho-est
- ogen
- estrogen +progestin/premphase (cyclic)
- estrogen+ progestin/prempase (continuous)
1 drug approved for treatment and prevention of osteoporosis?
alendronate/fosamax
2 drugs approved for tx of osteoporosis?
calcitonin/miacalcin
calcimar
