Osteoporosis Pharmacology Flashcards
Overview of the Bone remodeling process
clasts v blasts
role of RANK-L
- pre-clasts go to the area of interest
- osteoclasts resorb the bone: aka break it down & calcium is released within the serum
- pre-blasts enter the site
- osteoblasts being building bone: Formation & use calcium and phosphate in a mix to build
RANK-L
- a ligand for the receptor RANK
- the ligan, RANK-L is emitted from oestoblasts or clasts
- RANK-L promotes pre-osteoclast to osteoclastic development aka helps them mature to begin breakdown
- Osteoprotegerin bind to RANK-L and stops bone resoprbtion (breakdwon)
DEXA Scan and BMD levels
DEXA scan: bone mineral density scan at the lumbar spine, femoral neck and total hip
Osteopenia = T score -1.0 -> -2.5
Osteoporosis = < or equal to -2.5 on T score OR BMD 2.5 SD or more below average
WHO should recieved treatment for osteoporosis
- those who have had a previous HIP or VERTEBRAL fracture at any point (regardless of their BMD score) - unless its like a trauma or something
- those with osteoporosis: T-score < -2.5 at femoral neck, total hip or lumbar spine
- those with osteopenia (T-score -1.0 to -2.5 ) AND
-
a 10 year probability of a hip fracture >/= 3%
OR
-
a 10 year probability of a hip fracture >/= 3%
- 10-year probability of a major osteoporosis-related fracture >/= 20%
(the above fracture risk scores done with a FRAX score calculator
Medications for
- Post-menopausal women
- men
Post-Menopausal Women
very high = multiple fractures or fractures WHILE being treated & T-score < 3
high-risk = previous fracture & op.
moderate risk: Tscore & % but no fracture
if moderate/very high risk
FIRST LINE
- alendronate
- risedronate
- zoledronic acid
- denosumab
SECOND
- ibandronate
- raloxifene
- equine estrogen
if very high/high risk
- romosozumab
- ablaloparatide
- teriparatide
MEN
- moderate/high = testosterone, aldendronate, risedronate, zoledronic acid
- very high = teriparatide, zoledronic acid, denosumab
Which drugs are the Bisphosphonates
bisphosphonates = anti-respobtive: aka prevent breakdown
- alendronate
- risedronate
- Ibandronate
- Zoledronic Acid
when are drug that are anabolic used
what are they
anabolic: help to rebuild bone
these are used when the T score is very low, to help growht and rebuilding
Anabolics include
- parathyriod analongs (teriparatide & abloparatide)
- sclerostin inhibtor (romosozumab)
Which medications are utalized in treatment
v prevention
what can men use
Treatment
- bisphosphonates
- raloxifne
- calcitonin
- PTH analogs
- Denosumab
- Romozumab
NOT estrogen
Bisphosphonates and Rolxifene can be used in prevention
MEN
- bisphosphonates
- PTH analogs
- Denosumab
Vit D and Calcium Recommendations & role in preventing fractures in those with osteoporosis
mixed results: but in sum
maintain Vit-D levels > 30 & supplement with VitD3 1000-2000 IU daily to meet goals
supplement calcium until the daily intake is 1200 mg/day deit + supplements
Calcium Supplementations
what to take & how much
Calcium Carbonate
- requires an acidic environmnet so not good for those on PPIs
- 40% elemental calcium
Calcium Citrate
- does not require acidic environment
- 21% elemental calcium
women 51+ = need 1200 mg/day of calcium from deit + supplements
men 50-70 = 1000 mg/day
men > 71 years = 1200
Vitamin D supplemensand requirements
D2 v D3
D2 = ergocalciferol (plants)
D3 = cholecalciferol (animals and made in the skin when exposed to light in humans)
guidelines recommend giving and supplementing with D3
when you supplement Vit D3: you are increasing the amount of 25(OH) (which comes from the liver)
- 25(OH) is the level which is check in a blood panel & is the amoutn of VIt prior to it going to the kidneys to become active
in the kidneys: 25(OH) –> converted to 1,25 (OH) via alpha hydroxylase (the active form is 1,25(OH))
Effect of 1,25(OH) active Vit D within the body
Bones
- stimulates osteblasts (build) but NOT clasts
- but also stimulate osteoclasts by stimulating osteoblasts : promote turnover and breakdown/build up cycle
- net effect is just activates teh process to breakdown then build it back up
Kidneys
- increases calcium reabsorbtion in the renal tubules
Intestins
- increase intestinal absorbtion of the calcium from GI tract
OVERALL NET EFFECT OF VIT D IS TO INCREASE SERUM LEVELS OF CALCIUM
Vit D recommendation levels
goal of vit D is 30-50 ng/mL, get it above 30
how you replete is kinda up to you
- can use 5,000 IU D3 daily for 8-12 weeks
- can you 50,000 IU D weekly
once repleted….
- maintain levels by taking 1500-2000 IU daily
Monitoring of those with Osteoporosis
what are you monitoring
- obtain baseline DXA and then every 1-2 years repeat
- get Vit D and calcium at baseline & during treatment
- watch renal function in those with CKD being treated with bisphosphonates
- wathc adhearnce to meds and adverse reactions
Bisphosphonates
names
MOA
which are first line
prevention doses are smaller than treatment doses
Names
- Alendronate
- Ibandronate
- Risedronate
- Zoledronic Acid
MOA
- bind and deposit themselves into the bone surface; get uptaken into osteoclasts during resorbtion phase
- some get converted into ATP & induce apoptosis of the osteoclast (decrease clast activity of breakdown)
- some inihibit a FPS and cholesterol which induces apoptosis of the clast
last in the body for days-years
First Line Bisphosphonates
- Alendronate
- Risendronate
- Zoledronic Acid
essentailly, Ibandronate is not
Which bisphosphonates are used for kidney dysfunction
- depending on which CrCl
for those with a CrCl < 30 think rhoad Ilsand
- Risedronate
- Ibandronate
for those with a CrCl < 35 think AZ
- Alendronate
- Zoledronic Acid
Adverse Effects of Bisphosphonates
(remeber to take bisphosphonates on empty stomach, full glass of water first thing in the morning , sitting up) = risk of esophageal ulcerations
Adverse Reactions
- decreases serum calcium: because its stopping the breakdown of calcium from the bones which is the bodys mechanism of ususally adjusting seurm concentration levels)
- GI effects (abd pain, N/dyspepsia)
- esophageal inflammation = esophagitis
- muscle and bone pain
RARE
- osteonecrosis of the jaw & atypical femur fractures (more with IV use and long term use (malignancy)
Contraindications/DDI of Bisphosphonates
Contraindications
- those with hypocalcemia
- CrCl < 30/35 watch out
- abnormalities of the esophagus (stricture, achalasia) for risk of getting stuck in the esophagus
DDI
- no CYP!!
- some food/drinks can impact its absorbtion
- caution with those who already have GI ulcerations
Denosumab
MOA
use in who
MOA
- a RANK-L inhibitor (monthly subq)
- therefore stops RANK from signialing to osteoclasts to work (anti-resporbtive)
Who can use Denosumab
- postmenopausal women
- men
- glucocorticoid induced osteoporosis
- treating bone loss in those who are getting treated from breast/prostate cancer
Denosumab
Adverse Effects
- hypocalcemia!! : must check and correct calcium levels prior to beginning treatment
- risk of skin infection (cellulitis) & skin rashes
- MSK pain
- gas, constipation
- rapid bone loss once the drug is d/c
- ONJ (more common with malginancy treatment)
- atypical femur fractures
Denosumab
Contraindications & DDI
Contraindications
- do not use if they are hypocalcemia
DDI
- no CYP issues
- can increase immunosuppressive effects of otehr immunosuprresive drugs
Raloxifene
MOA
when is it used
Raloxifene
MOA: a SERM: selective estrogen receptor modulator
- works to increase estrogen activity at the bone: stops bone breakdown
- works to decrease estogen activty at the breast/uterus good for lowering breas cancer risk
- BUT: because its an estrogen-like med: it works at the bone like estrogen (stop breakdwon) but also works like estrogen at the coag. cascae to increased coagulation proteins
When is it used
- treament AND prevention of postmenopausal osteoporosis
- can be used for those with invasive BC
- must be used for 5 years
Raloxifene
Adverse Effects
BBW: increased risk of DVT and PE because it acts like estrogen; increased the coagulation proteins
- DO NOT USE in those iwth history of DVT or PE
- BBW: increased risk of death from stroke in women with CVD or those at risk for CVD
- hot flashes
- leg cramping/muscle spams
- flu-like symptons
- joint pain
- increased triglycerides in women with elevated TG from the start
Raloxifene
Monitoring
DDI
Contraindications
Monitoring
- Mammograms/breast exams before/during treatement (CANNOT be used if they ALREADY have breast cancer- monitor)
- lipids
- new signs/symptoms of VTE
Counceling
- do NOT use in VTE history
- weight pros/cons in those with risk of VTE
DDI
- dont use with other SERMs
Contraindciations
- DVT history ot other clotting disorders
Parathyroid Hormone Analogs (PTH analongs)
Names
MOA
when are they used
Names
- Teriparatide
- Abaloparatide
MOA
- used in low-dose pulse therapy: ebcause at the low doses the PTH hormone regulates and increase osteoblastic (building) activity (seems funny: since PTH will increased bone breakdwon, but at these pulse therapies it will actually work to increase blasts only, not the clasts)
- good for blast activity = building = good for those with low T scores
When are they Used
- Teriparatide: post-menopausal women, men and those who have glucocorticoid induce OP
- Abaloparatide: post-menopausal women and men
dont help reduce hip fractures
PTH analogs
Saftey Considerations
PTH analogs: teriparatide & abaloparatide
USED to have a BBW for osteosarcoma: now, just dont use these meds for longer ath 18-24 months
- hypercalcemia (can happen 4-6 hours after injections)
- orthostatic hypotension
- dizzy, HA
- joint pain , leg cramps, weakness
PTH analogs
contraindications & DDI
COntraindications
- shouldnt use severe renal disease and elevated PTH already
- probbaly shouldnt use in those with bone cancer hx.
no DDIs! (its a hormone!)
Romosozumab-aqqg
MOA
who can use it
MOA: a sclerostin inhibitor : monoclonal antibody
- sclerostin normally inhibits osteoblasts: so this blocks the inhibitor: allows blasts to do their thing
Who can use
- postmenopausal women
Romosozumab-aqqg
Adverse Effects
DDI
Contraindications
BBW: may increase risk of MI, stroke and CV death
- do not use in those with have had MI/stroke within 1 year prior
Adverse Reactions
- joint pain
- injection site reaction & pain
- HA, insomnia, parasethias
- hypocalcemia (correct prior to strating)
- ONJ and atypical fx. but EXTREMELY rare
DDI
- none
COntraindcations
- dont give to anyone who has had an MI in the last year
Calcitonin
(miacalcin)
MOA
Who
calcitonin
MOA: synthetic salmon-calcitonin
- for those who are postmenopausal with OP
- nasal or subq
- more potent and longer acting that human calcitonin
- calcitonin = inhibits bone resorbtion and inhibtis clast activity
Calcitonin
Adverse Reactions
DDI/CI
Adverse Effects
- allergy/hyersensitivity (anaphylaxis)
- hypocalcemia
- injection site/nasal reaction
- possible malignancy increase
no DDI
CI: those with allergy to salmon!
How long should you take each med?
- PTH analogs: no more than 2 years, then swap to BP or denosumab
- romossozumab: no more thatn 1 year, then swap to BP or denosumab
- denosumab: no limit: when it is stopped though: the BMD declines!!! (cannot take drug holiday)
Bisphosphonates
- can take drug holiday: after 3-5 years of treatment if…
low-moderater risk with T score > -2.5
- high risk = they should continue treatement
- alaboic treatment in thos who lose BMD or experice a fracture while on BP: give them an anabolic med
