Osteo TX Flashcards

(96 cards)

1
Q

Strategies to prevent fracture

A
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2
Q

Exercise stimulates

A

Stimulates osteoblast activity

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3
Q

Exercise clinical benefit

A

Lowers fall risk
Decreases risk of fractures
Possibly better maintenance of BMD

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4
Q

Exercise type s

A

Encourage a variety of types and intensities but prioritize balance, functional and resistance training > twice weekly

  • Increase over time
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5
Q

Functional exercises

A

Exercises that improve ability to perform everyday tasks, or do activities for fun or fitness (e.g., chair stands for sit-to-stand ability, stair-climbing to train for hiking).

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6
Q

Exercise that the patients wants to do

A

For patients who wish to participate in other activities (e.g, walking, impact exercise, yoga, plates) for enjoyment or other benefits
They should be encouraged if they can be done safely or modified for safety
They should be in addition to, but not instead of balance, functional and resistance training

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7
Q

Exercise guidelines

A

getting ≥ 150 min of moderate to vigorous physical activity per week, but prioritize balance, functional and resistance training.

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8
Q

Impact exercise?

A

only progress to moderate (e.g., running, racquet sports, skipping) or high (e.g., drop or high vertical jumps) impact exercise if appropriate for fracture risk or physical fitness level;
safety or efficacy is uncertain in individuals at high fracture risk

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9
Q

Reduce alcohol intake to….

A

Les sthan 2 drinks per day

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10
Q

caffeine

A

Avoidexcess - >4 cups per day may lower BMD by 4%
No fracture risk increase found

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11
Q

Calcium RDA’s

A

Men
51-70 years: 1000 mg calcium /day
> 70 years: 1200 mg calcium /day
Women:
> 50: 1200 mg calcium /day

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12
Q

Is calcium always need to be supplemented?

A

For people who meet the recommended dietary allowance for calcium with a variety of calcium-rich foods, we suggest no supplementation to prevent fractures

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13
Q

Calcium supllemnt chpoices

A
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14
Q

Calcium absorption

A

Prefer Calcium Citrate if patient on PPI or wants to take without food
Consuming ≤ 550mg elemental calcium at one time maximizes abs

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15
Q

Drug Interactions Calcium

A

PPI’s can decrease Ca absorption
Decreased absorption of ciprofloxacin, iron, protease inhibitors, tetracycline, thyroid medications

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16
Q

What is recommended: DIetary, SUpplement? Why?

A

Dietary sources are preferred over supplementation as excess supplementation can have adverse effects

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17
Q

Calcium supllement safety

A

Calcium may have safety issues if exceeding 2000mg/day
Nephrolithiasis
Cardiovascular disease
Dyspepsia
Constipation

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18
Q

Vitamin D RDAs

A

Men and women
< 70 years: 600 IU vitamin D/ day
> 70 years: 800 IU vitamin D/day

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19
Q

Health Canada recommendation for vit d supplementation

A

To meet the RDA, Health Canada recommends a supplement of 400 IU/day

For people at risk of vitamin D deficiency additional supplementation should be provided

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20
Q

Typse of vitamin? Which preferred?

A

Vitamin D3 = cholecalciferol; Vitamin D2= ergocalciferol
Vitamin D3 preferred
Usually 400iu or 1000iu tablets, also drops and liquids

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21
Q

Monitoring of vitamin D

A

Routine monitoring of Vitamin D is not necessary

Most Canadians are deficient

Possibly monitor if patient may require higher doses, eg. malabsorption disorders, sig. renal impairment, hypo/hyperparathyroidism, CF

If monitoring, do not repeat any sooner than 3 months after supplementation

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22
Q

Serum Vitamin D levels

A

The optimal serum 25-hydroxyvitamin level for bone health is uncertain, however the following definitions are widely accepted:

<30 nmol/L - high risk of vitamin D deficiency
30 to <50 nmol/L - potential risk of inadequacy for bone health
≥50 nmol/L - generally considered adequate for bone and overall health in healthy individuals
>125 nmol/L - linked to potential adverse effects

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23
Q

When to recommend pharmacotx?

A
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24
Q

First Line Mod-High

A

Bisphosphonates first line, denosumab second line

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25
Very High Risk
VERY HIGH RISK (Recommend pharmacotherapy) Recent severe vertebral fracture or >1 vertebral fracture and T-score < -2.5 Recent fracture” is defined as a fracture occurring within the past 2 yr, and “severe vertebral fracture” as vertebral body height loss of > 40%.
26
Very High Risk TX
Teraparatide or Romosumab should be followed by a bisphosphonate
27
Fracture risk guidelines re-test
5 – 10 yr if the risk of major osteoporotic fracture is < 10% 5 yr if the risk of major osteoporotic fracture is 10%–15% 3 yr if the risk of major osteoporotic fracture is > 15%. For those on pharmacotherapy 3 years A shorter retesting interval may be appropriate for those with secondary osteoporosis or new clinical risk factors, such as a fracture
28
First-line all pt's. WHy?
Bispphosphonates Halts BMD decline and slightly reverses loss Fracture risk decreases independent of BMD changes
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Indications bisphosphonates
Postmenopausal osteoporosis treatment and prevention Osteoporosis treatment in men Treatment and prevention of glucocorticoid-induced osteoporosis Paget’s disease
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Examples bisphosp
Alendronate Risedronate Zoledronic Acid
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MOA of bisphosph
Are analogues of pyrophosphate which allows for incorporation into bone Binds strongly to hydroxyapatite undergoing remodeling Inhibits osteoclast activity at site 2nd generation bisphosphonates additionally inhibit farnesyl pyrophosphate synthase  osteoclast apoptosis May also prevent osteoblast apoptosis
32
Dose Bisphosphonates
33
Bioavail Bisphosph
Extremely poor bioavailability – space from all medications
34
Admin Bisphosp
Immediate-release tablets: empty stomach with 1 cup of water, >30 minutes before food, drink and other medications. Remain upright for 30 minutes. Delayed-release tablets: take with 1 cup of liquid immediately after breakfast. Remain upright for 30 minutes. Zoledronic acid: once yearly IV infusion over 15 minutes
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Bisphosphonates Onset
Weeks to observe bone changes Years to observe clinical benefit
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Common S/e Bisphosphonates
GI complaints - Abdominal pain(7%), Dyspepsia(2%), Nausea(4%), Diarrhea/Constipation (3%) Headache (2%) Dizziness (4%) Musculoskeletal pain (5%)
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Zolderonic CAid S/E
Infusion reaction – fever, myalgia, headache, flu-like symptoms, arthralgia Free from GI issue
38
What do all bisphosphonates do?
All cause transient decrease in blood calcium levels
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Serious s/e of Bisphosphonates
Osteonecrosis of the Jaw (ONJ) Atypical sub-trochanteric fractures Severe Muscoskeletal Pain AKI Atrial FIbrilation Esophagitis, reflux, ulcers Esophogeal cancer
40
Bisphosphonate Necorosis of JAw
Complication associated with pain, swelling, exposed bone, local infection and jaw fracture Dentist should be aware of bisphosphonate therapy
41
Atypical sub-trchanteric fractures bisphosp
Changes in bone remodeling may inhibit ability of bone to heal micro-trauma Onset is typically 7 years into treatment Risk increases with duration of exposure Risk returns to baseline once discontinued May present as unusual thigh pain or dull ache Recommend further evaluation with a bone scan If atypical fracture identified: discontinue bisphosphonate, use alternate therapy
42
Muscoskletal pain Bisphos
Case reports of severe, debilitating pain Onset highly variable May not completely resolve upon discontinuation Report unusual, non-improving pain immediately
43
AKI Bisphosp
May cause small decline in CrCl, precipitating acute kidney injury in some Most prevalent with zoledronic acid Must ensure adequate hydration prior to infusion
44
Afib Bisphosp
Most data shows no association with AF Caution in those with severe AF or heart disease
45
Esophagitis Bisoph
Local irritation of esophagus Proper administration largely avoids this Avoid in patients with esophageal disorders
46
Pregancy Bisoph
Crosses the placenta and accumulates in fetal bones Animal models show harm (difficulties with delivery, bone abnormalities, hypocalcemia) Scarce human data available, but no harms noted Long half-life means use should be limited to special circumstances
47
C.I. Bisphosp
Esophageal abnormalities Inability to stand/sit up for 30 minutes Hypocalcemia CrCl <35ml/min
48
Bisphosp Duration of TX
Needs to be highly individualized Long bone half-life, less benefit with increased risks with long term use New guidelines suggest 3-6 years 6 if hx of hip, vertebral or multiple nonvertebral fractures OR new or ongoing risk factors for accelerated loss or fracture “Drug holiday”= Temporary discontinuation after a certain time period
49
Inadequate response bisphosp
If in adequate response or ongoing concern for fracture during therapy, extend or switch therapy, reassess for secondary causes and seek referral to specialist Inadequate response should be considered when > 1 fracture or substantial bone density decline (e.g., > 5%) despite adherence to tx (typically >1 year) However, fractures or bone density decline do not always indicate in adequate response to tx (secondary causes, falls, imprecise measurements)
50
Denosumab
Newer biologic agent
51
MOA Denosumab
Binds to the “Receptor Activator of Nuclear factor Kappa-B Ligand (RANKL)” RANKL naturally secreted by osteoblasts, which binds to the RANK receptor RANKL binding to RANK receptors activates osteoclasts Denosumab will bind to RANKL instead, preventing osteoclast activation
52
Denosumab main roles
Cannot adhere to dosing requirements of oral bisphosphonates Intolerance to oral bisphosphonates Severe renal impairment
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Denosumab Onset
Markers of bone resorption markedly decreased within 3 d Maximal reduction within 1 month
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Denosumab Duration
Indefinite treatment recommended Benefits of denosumab rapidly lost upon discontinuation Fracture risk sharply increases
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Denosumab Dosing
For all osteoporosis indications: 60mg administered once every 6 months
56
Denosumab Renal
Used down to CrCl 30ml/min May be cautiously used between 15-30ml/min Generally not recommended if <15ml/min or dialysis
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Common S/e Denosumab
Very well tolerated Only a few side effects greater than placebo rates: Rash / eczema MSK pain
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Serious s/e denosumab
Hypocalcemia Osteonecrosis of Jaw Atypical fractures Concern with increased infection Rebound Fracture upon d/c
59
Rebound fracture Denosumab. How to adress?
Any BMD gains made lost within 12-24 months Retreatment returns BMD levels to previous highs Vertebral fracture risk sharply increases 12 months after discontinuatio ****Sequential bisphosphonate therapy 6 months after last denosumab dose
60
Monitoring Denosumab
Calcium levels if renal impairment
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C.I. Denosumab
Hypocalcemia Pregnancy or lactation
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Raloxifene MOA
A selective estrogen receptor modulator (SERM) Binds to estrogen receptors in bone and acts as an agonist Decreases bone resorption, increases BMD Attenuates estrogen-related losses in menopause Acts as an estrogen antagonist in breast and uterine tissues
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Roloxifene Role
3rd line prevention option for postmenopausal women Patient who cannot tolerate bisphosphonates or denosumab Postmenopausal women with increased risk of invasive breast cancer
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Onset of Raloxifen
Years to observe maximum BMD changes Typically lifelong therapy No residual benefit to bone after discontinuation BMD decreases similar to placebo upon discontinuation
65
Dosing Raloxifen and renal
60 mg once daily Caution if CrCl <50ml/min
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Common side-effects Raloxifene
Flushing Flu-like symptoms Leg cramps Peripheral edema Increase in triglycerides
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Raloxifene serious s/e
VTE Stroke
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Precautiosn ramoxifen
High risk of venous thromboembolism or stroke Hypertriglyceridemia Moderate-severe renal impairment
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C.I. Raloxifene
Pregnancy History of venous thromboembolisms
70
Rolixifene Risks
Less BMD increases than bisphosphonates and denosumab Does not reduce hip fractures Ineffective in premenopausal women
71
Hormone Therapy aimedat and extra benefit?
Aimed at preventing menopausal associated bone loss Additional benefit of treating menopausal symptoms
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Hormonal Therapy for who?
Women with persistent menopausal symptoms and cannot tolerate bisphosphonates or denosumab For postmenopausal females aged < 60 yr or within 10 yr of who prioritize alleviation of substantial menopausal symptoms
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Dose Hormonal TX
Lower doses of estrogen may effectively prevent bone loss Conjugated estrogen 0.3mg oral daily Micronized estradiol 0.5mg oral daily Estradiol patch (25ug to 50ug weekly)
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Safety Concerns hormonal tx
Increased endometrial / breast cancer risk Thromboembolism risk CHD risk increase Stroke risk Urinary incontinence
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Teriparatide Role
For use in men or postmenopausal women with the highest fracture risk: Prior fragility fractures who continue to have fractures despite treatment Very low BMD BMD continues to decline on other treatments
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Teripraatide MOA
Is recombinant human parathyroid hormone Acts as an anabolic agent, similar to physiologic parathyroid hormone Stimulates osteoblast function, increases calcium uptake
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Duration Taeriparatide
Maximum approved duration of lifetime was 2 years – cancer concern; but recently changed by FDA
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Dose Teriparatide
Subcutaneous 20mcg once daily into thigh or abdomen x 24 months
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Side effects teriparatide
Nausea Dizziness Leg cramps Orthostatic hypotension / syncope
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Serious side effects teriparatide
Hypercalcemia, Hypercalciuria, Osteosarcoma
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Precautiosn teriparatide
History of renal stones Moderate renal impairment Pre-existing orthostatic hypotension
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C.I. Teriparatide
Pre-existing hypercalcemia Severe renal dysfunction Hyperparathyroidism History of bone cancers Pregnancy or lactation
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Teriparatide Monitoring
Must check Ca, SCr, PO4 and ALP prior to initiation Calcium every 3-6 months thereafter
84
D/C Teriparatide
Transitioning to a bisphosphonate or denosumab will preserve BMD gains
85
Romosozumab Role
For use in men or postmenopausal women with the highest fracture risk: Prior fragility fractures who continue to have fractures despite treatment Very low BMD continues to decline on other treatments
86
MOA Romosuzumab
humanized monoclonal antibody directed against sclerostin (an osteocyte-derived glycoprotein that inhibits bone formation Acts as an anabolic agent and anticatabolic
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RomosozumabDuration
Treatment duration is 12 months Gains in bone density are lost after stopping unless an antiremodelling agent is started
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Dose ROsu
Monthly SC injections (210 mg q month)
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S/E Rosu
Musculoskeletal /joint discomfort headache Injection site pain/erythema
90
Serious s/e rosu
Osteonecrosis of the Jaw Atypical fractures MI, stroke
91
Precautions rosu
tory of MI/stroke within the last year
92
C.I. Rosu
Pre-existing hypocalcemia Pregnancy or lactation
93
Rosu Monitoring
Baseline calcium
94
D/C Rosu
ransitioning to a bisphosphonate or denosumab will preserve BMD gains
95
Combo Tx
In general, combination therapy has BMD benefits, but no additional fracture benefit
96
Tx Failure
Defined as a BMD decreasing or a > fracture or substantial bone density decline (e.g., 5%) during therapy despite adherence and and adequate tx course (typically >1 year)