Osteoporosis Flashcards
What are some risk factors for Osteoporosis?
-Advanced age
-low bone mineral density
-females
-postemenopause
-small body frame/low bod weight
-falling and immobilization
-hx of parental hip fracture
-previous vertebral/fragility -fracture
-racial background
-sedentary lifestyle
-current smoking
-alcohol > 3 drinks/day
-low calcium intake
-vitamin D deficiency
-long term meds
What are the most common long term meds associated with OP? (6)
Chronic glucocorticoid use (>= 5 mg pred or equivalent for >= 3 months)
-Gonadotropin releasing hormone agonists
-cancer chemo drugs
-aromatase inhibs (anastrazole, exemestane, letrozole)
-Anticonvuls therapy > 2 yrs and age > 40
-Anticoags (> 6 months UFH/LMWH)
Associated Medical conditions: For the following conditions list a few topics
- Endocrine
- GI
- Disuse/immobility
- Chronic liver disease
- Inflamm Disorders
- Chronic Illness
- Genetic
- ovarian failure, testosterone deficiency, HYPERthyroidism, cushing’s syndrome, primary hyperparathyroid, diabetes
- Anorexia, crohn’s, celiac, chronic pancreatitis, bariatric surgery
- muscular dystrophy, MS, CVA
- RA, SLE, COPD
- CKD, malignancies, HIV/AIDS, organ transplant
- Osteogenesis imperfecta, turner syndrome, down syndrome, CF
Diagnosis requires :
History of :
Physical Exam Showing :
Labs such as :
Risk factors, secondary causes, current fractures
-loss of height
- serum ca2+, creatinine, phos, Mg2+, BUN
-CBC, LFTS, TSH, 25-OHD level, alk phos, albumin
-24 hr urinary CA2+ and creatinine
-Free testosterone (men)
Diagnosis - Dual Energy X ray Absorptiometry
- Describe the central DEXA and what it can predict
- What about the peripheral DEXA?
- Best predictor of hip fracture risk –> gold standard and definitive diagnosis . Can be used for spine and hip
- Wrist, ankle/heel and phalanges
-For screening only!
Diagnosing Osteoporosis Based on DEXA : Category Vs T Score
For each T score describe what the category is
- > -1
- -1 to -2.4 (osteopenia) + incr fracture risk determined by FRAX which is the 10 yr probability of major osteoporosis related fracture >=20% or hip fracture >=3%
- <= -2.5
- <= -2.5 with 1 or more fractures
- Normal
- Osteoporosis
- Osteoporosis
- Severe/established osteoporosis
Non Pharm tx :
-Start by achieving ___
-Life style interventions such as ? (4)
-Weight bearing __, balance exercise and ___ –> HOw long should patients be doing this for?
Peak bone mass (child-adolescent)
Sunlight exposure, smoking cessation, alcohol moderation , balanced diet!
aerobic exercise, resistance training
->= 30 mins/day for adults and >= 60 mins per day for children
Pharm tx Calcium and Vitamin D:
-What’s the recc dietary allowances for calcium for male and females 51-71+?
-Obtain as much calcium from ___ rather than via ___
-Calcium absorption is inhib when contained in foods with ___ or __ such as ??
-May be difficult to get RDA from diet if ?
1200 mg for females + males 71+, if 51-70 males = 1000mg and females = 1200 mg.
diet, supplement
oxalic, phytic acids –> spinach, rhubarb, sweet potatoes, beans, collard greens, whole grain, wheat bran
vegetarian or vegan
Calc Carb :
Generic names?
-Why is this the generally preferred salt?
-Take with ?
-Also acts as an ?
Caltrate, Tums, OsCal
-40% elemental calcium (highest of all Ca2+ salts) AND it’s the least expensive
-meals and or citrus juices (food incr acid production and acidiity is required for absorption)
Antacid (if taken on empty stomach u may have rebound gastric acidity and gastritis)
Calcium Supps :
-increases ___ but fracture prevention ONLY IF?
-Doses > 500-600 mg should be divided into?
-best to use which forms?
-Reccomend which form for older adults?
-AE’s?
-Dont exceed how many mgs per day due to risk of kidney stones and CVD/CVA?
BMD, with Vitamin D
2-3 doses/day
chewable, liquid
citrate (better absorption)
Flatulence and constipation (incr water, fiber, exercise)
> 1200-1500 mg/day
Calc Citrate :
Generic? Includes?
What % of elemental calcium?
Absorption is not affected by?
Very ___
Less ___ than carbonate
Citracal (D3)
21%
Food or acidity
soluble
constipating
Because calcium adsorbs/chelates drugs in the gut, which drugs do you have to space them apart from? (4)
How long should u space them apart?
Tetracyclines, azithro, fluoroquinolones, BIPHOSPHONATES
2 hrs
Calcium Increases intragastric pH , so u should space it apart 2 hrs from the following drugs ?
Itraconazole, ketoconazole, iron absorption
Why should patients not take PPI’s while taking calcium supps?
If you must take PPI’s while taking calcium supps, which supps should u use ??
CAlC supps may cause hypercalcemia with which drugs?
What can decr calc absorption?
PPI’s will increase hip fracture in patients > 50 years old when used greater than 1 yr. It may reduce Ca2+ absorption or inhibit activity in bone
NON CARBONATE SALTS
Thiazide diuretics
Fiber laxatives
Vitamin D :
-maximizes ___ and incr __
-Linked to ___
-Who are some individuals at risk for deficiency ?
intestinal calcium absorption , BMD
-Decr fractures
-Older adults > 70 yo
-concomitant low dose steroids
-concomitant phenytoin, CBZ, barbiturates, rifampin
-Low dietary intake
-Low UV light exposure, winter seasons
-Institutionalized or housebound
-GI malabsorption syndromes
-renal disease
-cirrhosis
Vitamin D from UV exposure :
- Recommended to get how much sunlight a day? Why do older folks have a harder time getting their adequate Vitamin D intake?
Sunlight 5-15 mins/day
-When you’re older your skin doesnt convert Vitamin D as effectively
VITAMIN D RDA:
For males and females 51-70 yrs?
>70 yrs?
- 600 IU (15 mcg)
- 800 IU (20 mcg)
Vitamin D Forms :
Ergocalciferol is ?
Cholecalciferol is?
What’s the daily dosage for supplementation?
Why is D3 usually preferred?
In which situations may u need a higher dose ?
Vit D2 (rx only , high dose for replacement tx)
Vit D3 (non rx supplementation)
-D3 1000-2000 IU (25-50 mcg)
D2 metab to active drug is impaired in older adults and cant be assayed in body. D3 more effective at raising Serum 25 (OH)D levels!
Obesity, malabsorption, older age
Vit D Replacement/Tx
What is the reference range for LOW levels VS DEFICIENCY?
What should the dose be?
Whats ur goal serum 25(OH)D concentrtaion? When should u re-check?
Low = 20-30 ng/mL
Deficiency = <20 ng/mL
50,000 IU PO qweekly x 8-12 wks , then once monthly or 1000-2000 IU PO daily thereafter
> = 30 ng/mL or 30-50 ng/mL is preferable!
after 3 months of therapy
Vitamin D ADR’s ? (2)
DDI?s ?
-Which incr metabolism? (4)
-Which decr absorption? (4)
Hypercalcemia, hypercalciuria
Phenytoin, barbiturates, CBZ, rifampins incr metabolism
Cholestyramine, colestipol, orlistat and mineral oil DECR absorption
For All women and Men with OP :
What’s the daily Calcium and Vitamin D3 dose?
COntinue both for how long?
Calcium : 1000-1200 mg daily
Vitamin D3 : 600-800 IU Daily
Indefinitely ! even if starting the rx only agent
Pharm Tx Should be considered for ?
-What kind of fracture?
-Which T score? (2)
Postmenopausal women and men older than 50 yrs who have a low trauma hip or vertebral fracture
T score <= 2.5 at the femoral neck, total hip, or spine (osteoporosis)
T score between -1 and -2.5 (osteopenia) and a FRAX10-yr probability of major osteoporosis related fracture >= 20% or hip fracture >=3%
TX recommendations :
- Pt’s with OP?
1st line?
2nd line? - Post menopausal pt’s with OP at v high risk of fracture
- Post menopausal pt’s with OSTEOpenia
- biphosphonates, denosumab (If CI to bisphos or ADR’s)
- Sclerostin inhibitor (romosozumab) or recomb PTH (teriparatide) followed by a biphosphonate
- individualized approach to reduce risk fractures
Kim, See Biphosphonates Chart
See chart
Alendronate Dosing : For Tx of postmenopausal OP or men with OP
- Fosamax (3)
- Binosto (1)
- Fosamax Plus D (Cholecalc) (2)
- 70 mg tab weekly, or 10 mg tab daily, or 1 bottle of 70 mg oral solution weekly
- 70 mg tab dissolved in 4 oz water weekly
- 70 mg/2800 IU tablet weekly
70 mg/5600 IU tablet weekly
Alendronate Dosing for PREVENTION of postmenopausal OP :
- Fosamax
Dosing for TX of GIO :
- Fosamax
-Usual Dose.
-In post menopausal pt’s not receiving estrogen?
DONT USE IF?**
- 35 mg tab weekly, or 5 mg tab daily
- -5 mg tab daily,
-10 mg tab daily in post menopausal not receiving estrogen
CrCl <= 35 mL/min
Risedronate -Dosing
- TX and PREVENTION of Postmenopausal OP? (2)
- TX of men with OP?
- TX of GIO?
DONT USE IF CRCL??***
- 150 mg monthly (75 mg tabs taken 2 days in a row)
-35 mg tab weekly - 35 mg tab once weekly
- 5 mg tab daily
<= 30 mL/min
Ibandronate (Boniva)
1. U cannot use it for tx in ?
2. it does not help reduce fracture risk in the following ? (2)
- Dosing for TX of postmenopau OP? (2)
- Dosing for Prevention of postmenopausal OP?
- DONT USE IF CRCL ?
- men or GIO
- nonvertebral or HIP
- -150 mg tab monthly (on SAME DAY)
-3 mg IV every 3 months (tx only)
-bolused over 15-30 secs at provider’s office, supplied as pre filled single use syringes 3mg/mL , stored at room temp - 150 mg tablet monthly (on same day)
- If CrCl<= 30 mL/min
Zoledronic ACid/Zoledronate (reclast)
1. Dosing? tx and prevention
2. Infused over ?
3. Dont administer quicker than __mins bc this incr the risk of?
-Ensure pt is ___ before tx
- May also reduce ___ associated with ?
- Dont use if CrCL ?
- 5 mg IV once yearly (for tx) or 5 mg IV every 2 yrs (for prevention)
- > = 15 mins at providers office
- 15 mins, Renal impairment!
-Well hydrated - Back pain , vertebral fx
- <=35 mL/min
Biphosphonates Common ADR’s ? (2)
GI - usually during first 3 months (orals only)
-Abd pain, dyspepsia
-Esophagitis, esophageal erosions, or ulcers
-Gastric or duodenal ulcers
MSK/BONE pain -Usually during first 3 months
-Occasional severe, incapacitating pain
Ibandronate (IV) AE’s? M,C,L
Zoledronic Acid (H this is a CI and AE , F,A,A,A,H)
Myalgias, cramps and limb pain
-HYPOCALCEMIA (which is a CI)
-flu like sx’s such as pyrexia, chills, myalgias (usually only after 1st infusion lasting 1-7 days), pretx with tylenol or motrin
-AFIB
-Arthritis, arthralgias, and HA’s
Biphosphonates : DDI’s ? (3)
- precaution in ? (2)
- Extreme caution in ?
Aminoglycosides, Loop diuretics, NSAIDS or other nephrotoxic drugs
- Renal impairment of CrCl<30-35 mL/min
-Kidney injury , deaths due to kidney failure
- Hypocalcemia - check levels prior to each dose
- dehyrated , older adults, or when conditions/drugs that can predispose to kidney impairment
Biphosphonates Rare but important AE?
-Common characteristics in those who develop this disease?
How do we prevent this from occurring?
ONJ (osteonecrosis of the jaw)
cancer, chemo, radiation and or glucocorticoid therapy receiving high dose IV biphosphonate therapy
maintain good oral hygiene
see dentist regularly and immediately if pain, swelling in mouth, soft tissue ulceration, parasthesias, or teeth loosening
Bisphos Rare but Important AE’s : Atypical Hip fractures
Risk increases with ?
Requires?
Risk increases with duration, particularly >5 yrs
patient medication guide
Biphos : Monitoring
-Efficacy?
-Consider changing or adding tx after 1 yr if?
-Labs?
-Patients complaints of ?
-Adherence (low with ___) –> improved with ?
Efficacy : New fractures
-consider changing /adding tx after 1 year if fractures continue, or bone or back pain develops
baseline calcium, baseline serum creatinine
adverse effects
orals , about 30% adherent at 1 year.
-weekly, monthly, and yearly dosing
Oral Biphos Patient Education :
-To reduce risk of esoph stricture/perforation/ulceration what should u do ?
For Atelvia what is the timing?
For Binosto?
DO not __ or ___ on tab
Remain ___ for how long after dosing ? Only lie down when??
Stop immediately if??
Take >= 30 mins or (>= 60 mins for ibandronate) before first food, bev, or med with a full glass of water (6-8) ounces
Atelvia : Take immed after breakfast
Binosto : Dissolve in 4 oz of room temp water
Chew or suck
upright for >=30 mins , for ibandronate its >= 60 mins
-after first food of the day
trouble or pain with swallowing, chest pain, or new/worsening heart burn sx’s
When taking Biphos with Calcium, u must space apart the calcium how far apart ??
Avoid which 2 drugs ?
How often should u get dental exams ? but try to avoid ?
What should a patient do if they miss a weekly dose?
What if they miss more than 1 day?
What if they miss a monthly dose?
> =30-60 min apart from biphos
NSAIDS and aspirin
2x/yr , dental procedures while taking biphos
Take the next morning!
Skip until next weekly dose
Take up to 7 days before next scheduled monthly dose
Biphosphonates : Duration
Effect on fracture reduction is seen within ?
If u stop using after 2-5 yrs what happens?
After 5 yrs?
If treated for 10 yrs?
However, what concerns are there with long tern use?
6-12 months
significant loss at spine and hip + increases hip fracture risk
positive effects on BMD persists for several years
significant increases in BMD (at all sites)
Atypical fractures and ONJ
Because of concern with problems with long term use, consider a drug holiday:
- When should u take a holiday from oral biphosphonates?
- Zoledronate?
- after 5 yrs if no longer high fx risk (t score > -2.5 or fx free); after 6-10 yrs if very high risk
- after 3 yrs in high risk pt’s or until risk is no longer high; continue up to 6 yrs in very high risk pt’s
Denosumab (Prolia)
- Indications for?
- What about fracture risk reduction?
- Dose?
- Tx in postmenopausal women with OP at high risk , or men with OP at high risk . GIO.
Helps with verterbral, nonvertebral, and HIP
60 mg SQ injection every 6 months : admin in upper arm, thigh, or abdomen
-Must be given in provider’s office
Denosumab (Prolia)
- Advantages? (2)
- Disadvantages? (2)
ADR’s ? (3) Common
FERD
PEMI
(4) Rare
- improved adherence, no drug holiday needed!
- expensive, if poor adherence the effects wear off
- flatulence, dermatitis, eczema , rash
- pain in back, extremities, and MSK system
- Incr cholesterol levels
-Hypocalcemia (incr with CKD)
-Incr UTI’s, serious infections
-ONJ -slightly more than biphos
-Atypical femur fractures - less than biphosphonates
Denosumab Monitoring :
In renally impaired :
-NO ___
-No fx reduction in ___
-ADmin with caution ! Why?
Monitoring :
Ensure ur pt is NOT ___ prior to therapy bc that’s a CI
-Monitor which four aspects?
-Serious ___
-Discontinue if?
-ONJ, Atypical femur fractures, and delayed healing can occur
-Doses should NOT be delayed < ___ late due to rapid ___
Dose adjustment
CKD4
Lowers bone turnover rapidly and substantially !
hypocalcemic
serum ca2+, phosphorus, Mg2+ and lipids
Infections (UTI, abdomen, ear)
severe skin reactions
1 month late, rebound in bone turnover when stopped (new vertebral fractures occur)
Teriparatide (Forteo) :
Indications in OP? (3)
Fracture risk reduction?
-What happens if you discontinue the medication?
What’s the dose?
-Store where ?
-Once opened what must u do?
-Max of ?
Tx of postmenopaus women with OP at high risk or men with OP at high risk
Tx of GIO at high risk
Can help in vertebral and nonvertebral but cannot help in hip
-Benefit is lost, follow with antiresorptive tx
-20 mcg subcutaneously daily (thigh or abdomen)
-store in fridge and inject immed
-Once opened, must be thrown away after 28 days
-Max 2 yrs of usage
Teriparatide (forteo) ADR’s
-Generally mild, (2)
-Leg __ and ___
-Hyper___
Treatment for max of ?
BBW ?
Nausea, and dizziness due to low BP
-cramps, muscle spasms
-Hypercalcemia (transient and rare)
2 yrs due to lack of efficacy and safety data
Osteosarcoma in rats!
Teriparatide : Caution if?
- active or recent hx of ?
- Severe ___
3.Orthostatic ____
Avoid if incr risk of osteosarcoma such as ?
Monitoring? (2)
kidney stones, or hypercalcemia
renal impairment/failure
hypotension
paget’s disease, previous skeletal radiation, bone metastases or skeletal malignancy, hypercalcemia
New fractures and calcium level
Teriparatide (Forteo) -Patient Ed
-Solution in pen is __ and __
-Dose is preset to ?
-Inject ___ into thigh or abdomen but rotate sites daily
-Give initial dose ____
-Remove ___ after each use
-May experience ___ within 4 hrs of injection so make sure ur lying down
clear, colorless
20mcg
once daily
lying/sitting (ortho hypo)
needle
dizziness
Abaloparatide (Tymlos)
-Indications?
-Fracture risk reduction ?
-Dose?
-prefilled pen with how many doses in each?
-Store in fridge but can leave up to how many days at room temp after first use?
Treatment of post menopaus women with OP, or men with OP , cannot treat GIO. Individuals who have failed other therapies
In verterbral and nonvertrebral only. no hip
80 mcg sq daily (abdomen)
-30 doses
-30 days
Abaloparatide (Tymlos) ADR’s?
(4)
Precautions and monitoring? (refer to Teriparatide)
Orthostatic hypotension
Palpitations
Hypercalcemia
nausea and headaches
Romosozumab (Evenity)
-Indicated for ?
-Fracture reduction risk?
-Effects will wane after how many doses?
Dose?
-Max use?
tx in postmenopau women at high risk of fracture (hx of OP fracture or mult risk factors)
-Individuals without success with or intolerant to other therapies
-NOT for men or GIO
ONLY VERTEBRAL FRACTURES
12 doses –> continue with anti-resorptive agent thereafter
210 mg sq monthly (providers office)
-Max 1 yr
Romosozumab (Evenity) ADR’s
-A,H,I
-H
-O and A
Arthalgias, HA, injection site rxns
-Hypersensitivity rxns
ONJ and atypical fractures have been reported
- Romosozumab BBW?
- Do not start if ___ within 1 yr and discontinue if event occurs
Contraindications? (1)
-if severe CKD/dialysis, must have adequate ?
- Incr risk of MACE
- MI/CVA
Hypocalcemia
CA2+ and vitamin D
Raloxifene (Evista)
-Indications?
-Not indicated for?
-Fracture risk reduction?
-However, after discontinuation….
-BUT it reduces incidence of invasive BC both during and after tx for ___ after completion
TX AND PREVENTION of postmenopaus OP (Women)
-Reduction in risk of invasive breast cancer in postmenopaus wonen with OP
-Reduction in risk of invas breast cancer in postmenopaus women at high risk for breast cancer
TX in men, GIO
ONLY VERTREBRAL
BONE BENEFIT IS LOST
5 yrs
Raloxifene Dose ?
Useful for ?
-Younger post menopaus who have higher risk for ___ than ___ and low risk of ___
-__ and ___ not appropriate
-Pt’s with high risk of?
60 mg PO daily
vertebral fracture, hip fracture, DVT.
-Biphosphonates, denosumab
-Breast cancer
Raloxifene ADR’s ? (4)
- Precautions: BBW ?
- 3x incr risk of?
- CI in ?
- Caution if at risk for ?
Well tolerated overall !
-vasomotor sx’s (hot flashes, night sweats)
-Muscle spasms, leg cramps, periph edema
- Raloxifene may rarely cause serious blood clots, especially in legs or lungs
- VTE (DVT, PE , retinal vein thrombosis)
- Active or past Hx of VTE
- CVA (incr risk of death)
Raloxifene : DDI’s? (2)
Levothyroxine -raloxifene may reduce absorption–> sep by 12 hrs
Warfarin - monitor INR wen starting or stopping raloxifene
Raloxifene : Patient Education
-May cause ___ and or ___
-Report any sudden ___,___, SOB, vision changes, ____ , loss of ___ on any side of ur body
-Stop at least ___ before and during prolonged immobilization (post surgery, prolonged bed rest)
hot flashes, night sweats
leg pain, chest pain, inability to speak or slurred speech, movement
72 hrs
DUAVEE
-Indications?
-Primarily for pt’s with ?
-Give for the ___ possible
-Increases ___ and ___ by 1.21-1.51%
Dose?
ONLY FOR PREVENTION OF POSTMENOPAUS OP
- post menopaus sx’s with an intact uterus
-Shortest time
-Lumbar spine and HIP BMD
(0.45 mg/20 mg) 1 tablet by mouth daily
DUAVEE
-CI in ?
- not recc in ?
-AE’s? (4)
hepatic impairment
renal impairment due to lack of bazedoxifene data
Muscle spasms, nausea, diarrhea, dyspepsia
Hormone Therapy Estrogen +/- Progestin
1. Indication?
-Primarily for?
-Give for?
-Once therapy is stopped what happens?
-Fracture risk reduction?
For ages < ___ or < 10 yrs past ___, low risk of __, when biphos or denosunab are innapropriate, bothersome ___ without prior __ or___, without ___
SLIGHTLY higher risk of ? (3)
Only for prevention of postmenopausal OP
-pt’s with post menopausal sx’s with an intact uterus (must give progestin if intact uterus)
-Shortest time possible
-Benefit in increased BMD lost
ALL Vertebral, non vertebral, and hip
60, menopaus, DVT, vasomotor sx’s, MI, CVA, breast cancer
stroke, breast CA, blood clots
Glucocorticoid Induced Osteoporosis (GIO) :
-At risk if ___ because ___?
-Calcium intake and Vitamin D3 dose should be?
-WHat should be done at therapy onset and every 6-12 months?
-May also need rx meds
Try first (3)
If bisphos are intolerable or there are CI’s try __ or __
Prednisone >= 5 mg/day or equivalent for >= 3 months
-Bone losses are rapid
calcium 1200-1500 mg daily + vitamin D3 800-1200 IU daily
BMD/DXA
Alendronate, risedronate, zoledronic acid
teriparatide or denosumab
