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PHAR 255 > Osteoporosis > Flashcards

Osteoporosis Flashcards

1
Q

What is osteoporosis?

A

A systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissues, leading to enhanced bone fragility and a consequent increase in fracture risk

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2
Q

How many patients need treatment for osteoporosis?

A

1/3 of elderly population will require treatment

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3
Q

What is a fragility fracture?

A

They occur from falls at standing height or when force is applied to the bone judged to be insignificant to fracture a normal bone

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4
Q

What are the four major osteoporotic fractures?

A
  1. Hip
  2. Vertebra
  3. Humerus
  4. Distal forearm

1/3 of women and 1/5 of men will suffer from an osteoporotic fracture

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5
Q

What are the mortality rates by sex for hip fractures?

A

28% of women and 33% of men who suffer a hip fracture will die within the following year

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6
Q

Are fractures of the hands considered major osteoporotic fractures?

A

No, alongside the feet and craniofacial bones

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7
Q

How many patients are affected by osteoporosis?

A

2.3 million Canadians over the age of 40 (women are affected more than men)

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8
Q

What are the two types of bone?

A

Cortical

Cancellous

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9
Q

What are the characteristics of cortical bone?

A
  • 80% of weight of the adult skeleton
  • Dense, forms outer shell
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10
Q

What are the characteristics of cancellous bone?

A
  • 20% of weight of the adult skeleton
  • Porous, forms interior structures
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11
Q

What are the three types of bone cells?

A
  • Osteoblasts (“bone builder”)
  • Osteoclasts
  • Osteocytes (bone mineralization regulatory functions)
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12
Q

What happens when bone remodelling balance becomes negative in favour of osteoclasts?

A

Bone mineral density (BMD) decreases progressively as long as bone remodelling stays in the favour of osteoclasts

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13
Q

What does advancing age do to bone remodelling?

A
  • Oxidative stress (free radicals and low grade inflammation results in resorption)
  • Osteoblasts senescence (halted production of osteoblasts)
  • Autophagy delines (quality control)
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14
Q

What is the impact of sex steroids on bone remodelling?

A
  • Estrogen (due to reduced estrogen in menopause, there is a reduction in BMD)
  • Androgens (Men achieve a higher BMD due to the effect of androgens)
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15
Q

What is the function of parathyroid hormone in bone remodelling?

A

PTH takes Ca2+ from bone and puts it into the blood

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16
Q

What is the function of calcitonin in bone remodelling?

A

Calcitonin pulls Ca2+ from blood to bone (calcitonin = “tone down”)

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17
Q

What is the role of Ca2+ in bone remodelling?

A

Ca2+ is required for mineralization of bone

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18
Q

What is the role of Vit D in bone remodelling?

A

Vit D helps regulate Ca2+

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19
Q

What happens in hypocalcemia?

A
  1. Parathyroid releases PTH
  2. PTH stimulates release of Ca2+ and phosphorus (P) from bone and reabsorption of Ca2+ in the kidneys
  3. Vit D is activated in the kidneys to increase Ca2+, PO4, and Mg absorption by the intestine
  4. Vit D is also an inhibitor of PTH, closing the negative feedback loop
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20
Q

What happens in hypercalcemia?

A
  1. Calcitonin is released by thyroid
  2. Calcitonin inhibits intestinal absorption of Ca2+ and phosphorus
  3. Calcitonin also stimulates Ca2+ excretion in the kidneys

Overall, this pathway attempts to reduce Ca2+ in the blood. Hypercalcemic patients are unlikely to see bone resorption.

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21
Q

What happens to osteocytes to cause osteoporosis?

A

Osteocyte death accelerates with age (need mechanical stress to keep osteocytes healthy)

Osteocyte death is linked to the following:
- Increased surface remodelling
- Replacement with weaker mineralized connective tissue
- Disruption in repair signalling
- Decrease in bone vascularity

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22
Q

What is the etiology of osteoporosis?

A

After age 35, BMD reaches peak and starts to decline by 0.5% per year (2-3%/year during menopause due to shift in estrogen levels)

Women, on average, lose 50% of trabecular and 35% of cortical bone, while losses experienced by men are 2/3s of what women experience.

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23
Q

What is the most common type of fracture due to osteoporosis?

A

Vertebral fractures (contribute to kyphosis) account for 50%, followed by hip and distal forearm fractures

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24
Q

What are some risk factors associated with osteoporosis?

A
  • Race (Whites and Asians are at increased risk)
  • Ca2+ intake during growth
  • Age
  • Menopause (especially in women with early menopause, under 45)
  • Family History (history of hip fractures in older adults)
  • Sex (less common in men)
  • Small stature (low body weight or fine bone structure)
  • Weight (mechanical stress on bones is beneficial for increasing BMD)
  • Secondary causes (medical conditions, drugs, lifestyle, previous falls and fractures)
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25
Q

What are some medical conditions that increase risk of osteoporosis?

A
  • Oophorectomy (removal of ovaries = less estrogen = reduced BMD)
  • Hypogonadism
  • Hyperparathyroidism
  • Cushing’s
  • Multiple myeloma
  • Malabsorption syndrome
  • Chronic inflammatory diseases
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26
Q

What are some types of drugs that predispose patients to a higher risk of developing osteoporosis?

A
  • Androgen deprivation therapy (reduce BMD)
  • Anticoagulants (heparin, LWMH, warfarin)
  • Antidepressants (SSRIs, SNRIs, lithium)
  • Antiepileptics (phenytoin, carbemazepine)
  • Anti-neoplastics (aromatase inhibitors)
  • Antiretrovirals (increase osteoclast activity and reduced osteoblast activity)
  • Calcineurin inhibitors (associated with increased osteoclast activity)
  • SGLT2i (Canagliflozin)
  • Glucocorticoid therapy
  • Loop diuretics
  • Medroxyprogesterone
  • PPIs (less acidic = less Ca2+ absorption)
  • Thyroid supplementation
  • Vit A excess (increased fracture risk)
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27
Q

What are some lifestyle risk factors for developing osteoporosis?

A
  • Nutrition
  • Exercise (weight-bearing exercise and increase flexibility)
  • Alcohol
  • Smoking (inhibits estrogen)
  • Caffeine
  • Sunshine (aids Vit D production)
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28
Q

What are some risk factors for falls and fractures?

A
  • Age-related fractures
  • Environmental hazards (tripping hazards)
  • Drug-falls (psychotropic, antihypertensive)
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29
Q

What is the common presentation of osteoporosis?

A

No symptomatic manifestation until a fracture occurs (broken bone can be painful)

Vertebral fractures are the most common in osteoporosis patients

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30
Q

What are some osteoporosis diagnosis criteria?

A

Vertebral compression fracture, hip fracture, or more than one fragility fracture in patients over 50

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31
Q

How are osteoporosis and osteopenia differentiated?

A

Using a BMD T-score

Osteoporosis: more than -2.5 standard deviations from normal peak

Osteopenia: between -1 and -2.5 standard deviations from normal peak

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32
Q

What patient profiles should be screened for osteoporosis?

A

Men and women (especially post-menopausal) over 50 should begin routine assessment of risk factors for osteoporosis and fracture

If screened and at low risk, retest in 5 years

If moderate risk (and not treating), reassess in 1 to 3 years

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33
Q

What are the elements of osteoporosis risk screening?

A
  • Detailed History (identify risk factors for low BMD, future fractures and falls)
  • Physical Examination
  • Biochemical tests
  • BMD in select individuals
  • Use of Risk Assessment Tools (CAROC and FRAX)
  • Vertebral imaging in selected individuals
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34
Q

What are some elements of the physical exam for evaluating osteoporosis risk?

A
  • Measure weight (weight loss of more than 10% since age 25 is significant or total weight below 60kg)
  • Measure height annually (prospective loss more than 2cm, and historic loss more than 6cm is indicative of osteoporosis)
  • Assess fall risk by using Get-Up-and-Go Test
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35
Q

What are some recommended biochemical tests for osteoporosis?

A
  • Calcium, corrected for albumin
  • Phosphate
  • Creatinine
  • ALP (increase bone turnover)
  • TSH
  • Vit D
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36
Q

What is Paget’s disease?

A

It is a disorder in bone remodelling

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37
Q

What are the three locations where bone mineral density is reported on a DXA scan?

A
  • Total hip
  • Femoral neck
  • Lumbar spine
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38
Q

What is the most commonly used BMD scale when performing a DXA scan?

A

T-score is used for adults over 50 who have received a DXA scan

The t-score is measures as number of standard deviations the person’s BMD is above or below a control value

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39
Q

What patient profiles should get a DXA scan for BMD testing?

A

Postmenopausal women and men:
- Age 50-64 with previous osteoporotic-related fracture or more than 2 clinical risk factors for fracture
- Age over 65 with one clinical risk factor
- Age over 70, regardless of risk factors

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40
Q

What clinical risk factors warrant a DXA scan to get an estimate of BMD?

A
  • Previous fracture (after age 40)
  • Glucocorticoids (long-term use)
  • Falls (more than 2 in the last year)
  • BMI below 20
  • Secondary osteoporosis
  • Current smoking
  • Alcohol use
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41
Q

What are the risk assessment tools for osteoporosis?

A

CAROC (Canadian Association of Radiologists and Osteoporosis Canada)

FRAX (Fracture Risk Assessment Tool developed by the World Health Organization)

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42
Q

What are some characteristics of the CAROC score?

A
  • Validated for postmenopausal women and men over 50
  • Easier to understand the T-score as determined from DXA score
  • Basal risk category is based from age, sex, and T-score from the femoral neck alone (discard readings from other sites)
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43
Q

What are some characteristics of the FRAX score?

A

It computes the 10-year probability of hip fracture and major fracture probability

  • Incorporates more factors than CAROC (prior fracture, prolonged corticosteroid use, etc.)
  • Canadian specific FRAX is the preferred tool
  • Can be used without BMD (less accurate though)
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44
Q

What are some limitations of risk assessment scores used in osteoporosis?

A
  • Calculate risk for treatment-naive patients only
  • Cannot be used to monitor response to therapy
  • May underestimate risk in the presence of specific factors (recurrent falls, low BMD at non-femoral neck sites)
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45
Q

Besides the DXA scan, what are some alternative methods of determining BMD and osteoporotic risk?

A

Qualitative ultrasound

Bone turnover markers (ex. urinary C-terminal telopeptide, needs more research to be used reliably)

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46
Q

How often should BMD testing be completed according to FRAX scores?

A

10-year fracture risk over 15% or on pharmacotherapy: In 3 years

10-year fracture risk between 10 and 15%: In 5 years

10-year fracture risk less than 10%: In 5 to 10 years

May need to repeat earlier if secondary causes of osteoporosis, new fractures or new clinical risk factors associated with rapid bone loss

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47
Q

What are the goals of treatment for osteoporosis?

A
  • Prevent fractures
  • Prevent disability and loss of independence
  • Preserve or improve BMD
  • Reduce modifiable risk factors
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48
Q

What are the types of pharmacological agents used to treat osteoporosis?

A

1st line:
- Bisphosphonates
- Denosumab

2nd line:
- Raloxifene
- Teriparatide
- Hormone Therapy

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49
Q

What are the advantages of exercise in osteoporosis therapy?

A
  • Stimulates osteoblast activity
  • Improves QOL, physical function, pain, strength and balance

Encourage a variety of types and intensities, but prioritize balance, functional and resistance training more than 2 times weekly

50
Q

What are some balance exercises?

A
  • Shifting body weight to the limits of stability
  • Reacting to things that upset your balance (catching and throwing a ball)
  • Maintaining balance while moving (ex. Tai Chi, heel raises)
  • Reducing base of support (standing on one foot)
51
Q

What are some functional exercises?

A

Exercises that improve the ability to perform everyday tasks or do activities for fun or fitness

These exercises ultimately prevent injuries

52
Q

What is resistance training?

A

Exercises where major muscle groups (upper and lower extremities, chest, shoulders, back) work against resistance

ex. Squats, lunges, and push-ups

Many resistance training exercises can be considered functional exercises

53
Q

What are some measures that can help prevent falls?

A
  • Patient education
  • Home safety assessments
  • Hip protectors
  • Bars, canes, walkers, etc.
  • Remove tripping hazards
  • Improve balance and strength
  • Avoid drugs associated with increased fall risk (many drugs on BEERS list)
54
Q

What is the impact of smoking on BMD?

A
  • 1-pack-per-day history leads to approximately 10% reduction in BMD

Negates the protective effect of HRT (estrogen replacement) in women

55
Q

What is the impact of alcohol consumption on BMD?

A

More than 4 drinks per day may lower BMD by 4%

56
Q

Is oversupplementation of Ca2+ reccomended for prevention of fractures?

A

No, oversupplementation of Ca2+ does not reduce fracture risk on its own

57
Q

What are the RDAs for Ca2+ in older adults?

A

Men:
- 50-70 yo: 1000mg/day
- More than 70yo: 1200mg/day

Women:
- Over 50yo: 1200mg/day

58
Q

What are the different types of calcium salt supplements and how much elemental Ca2+ do they contain?

A
  • Calcium carbonate: 40%
  • Calcium citrate: 21%
  • Calcium lactate: 13%
  • Calcium gluconate: 9%
59
Q

What are some non-traditional calcium supplements?

A
  • Bone meal (not reccomended by pharmacists)
  • Dolomite
  • Chelated calcium
  • Oyster shell (can contain Pb)
60
Q

What are some drug interactions associated with calcium supplementation?

A
  • PPIs reduce absoroption of Ca2+
  • Decreased absorption of cipro, iron, protease inhibitors, tetracycline, thyroid medications
61
Q

If the patient is on a PPI, what is the best type of calcium supplementation?

A

Calcium citrate is best

Can also be used in patients that want to take their Ca2+ supplement without food

62
Q

Can the entire daily RDA of calcium be taken in one administration for best efficacy?

A

No, it is best that the daily Ca2+ supplementation is taken in 2 doses (best absorption occurs for doses below 550mg of elemental Ca2+)

63
Q

What are the concerns of oversupplementation of Ca2+ (more than 2000mg/day)?

A
  • Nephrolithiasis
  • CV disease
  • Dyspepsia
  • Constipation
64
Q

What is the RDA for Vitamin D?

A

Men and women:
- Under 70: 600 IU vitamin D/day
- Over 70: 800 IU vitamin D/day

65
Q

What is the preferred Vitamin D supplement form?

A

Cholecalciferol

66
Q

What are some natural sources of Vitamin D?

A

Few food sources
- Fatty fish (salmon, rainbow trout)
- Fortified foods (cow milk, plant-based beverages)
- Eggs

  • Sun exposure
67
Q

Is Vitamin D level monitoring done commonly in osteoporotic patients?

A

No, it is not necessary in most patients (expensive)

If we are monitoring Vit D, do not retest until 3 months after supplementation

68
Q

What are the ideal Vitamin D levels for good bone health in healthy individuals?

A

Between 50 and 125 nmoL/L

69
Q

What are antiresorptive therapeutic agents used in osteoporosis?

A

Prevent break down of bone
- Bisphosphonates
- Denosumab
- Raloxifene
- Hormone Therapy

70
Q

What are the anabolic therapeutic agents used in osteoporosis?

A

Help build bone
- Teriparatide
- Romosozumab
- Combination therapy

71
Q

When should pharmacological treatment for osteoporosis be initiated?

A

Low risk (T-score less than 15%)

Intermediate risk (T-score between 15 and 30%)

High risk (T-score more than 20%)

72
Q

What are the first-line treatments for osteoporosis?

A

Bisphosphonates and denosumab

73
Q

What is the recommended treatment for osteoporosis in patients that have had a recent severe vertebral fracture (in the last 2 years)?

A

Teraparatide or Rosmosumab + Bisphosphonate

74
Q

How often should patients on osteoporosis therapy have their BMD tested?

A

3 years

A shorter retesting interval may be appropriate for those with secondary osteoporosis

75
Q

What is the effect of bisphosponate therapy in osteoporosis?

A

Halts BMD decline and slightly reverses loss

Fracture risk decreases are independent of BMD changes (2-6% increase in BMD, but 40-60% reduction in fracture risk)

76
Q

What are some indications for bisphosphonates?

A
  • Postmenopausal osteoporosis treatment and prevention
  • Osteoporosis in men
  • Treatment and prevention of glucocorticoid-induced osteoporosis
  • Paget’s disease
77
Q

What are some examples of bisphosphonates?

A
  • Alendronate
  • Risedronate
  • Zoledronic Acid (IV form, the rest are oral agents)
78
Q

What is the mechanism of action for bisphosphonates?

A
  • They are analogues of pyrophosphate which allows for incorporation into bone
  • Binds strongly to hydroxypatite undergoing remodelling
  • Inhibits osteoclast activity at site
  • Can also prevent osteoblast apoptosis
79
Q

What are some commonly used Alendronate doses?

A

10mg OD

OR

70mg weekly

80
Q

What are some commonly used Risedronate doses?

A

5mg OD

OR

35mg weekly

OR

150mg monthly

81
Q

What is the dose for Zoledronic acid?

A

5mg/100mL administered IV once yearly

82
Q

What are some dosing considerations for bisphosphonates?

A
  • Extremely poor bioavailability (space administration from all drugs, food, drink, etc.)
  • Remain upright for 30 minutes
83
Q

What is the onset of effect for bisphosphonates?

A
  • Weeks to observe bone changes
  • Years to observe clinical benefit
84
Q

What is the clinical benefit of bisphosphonate therapy?

A
  • 20-30 fewer vertebral fractures/1000 people
  • 10 fewer nonvertebral fractures/1000 people
  • 3 fewer hip fractures/1000 people
85
Q

What are some common side effects associated with bisphosphonate use?

A
  • GI complaints (abdominal pain, dyspepsia, nausea, diarrhea)
  • Headache
  • Dizziness
  • Musculoskeletal pain
  • Transient decrease in blood calcium
86
Q

What are some common side effects associated with zoledronic acid?

A

Infusion reaction: fever, myalgia, headache, flu-like symptoms, arthralgia

87
Q

What are some serious side effects associated with bisphosphonate use?

A
  • Osteonecrosis of the Jaw (especially concerning if dental surgery patient is on bisphosphonate therapy)
  • Atypical sub-trochanteric fractures
  • Severe musculoskeletal pain
  • Acute renal injury
  • Atrial fibrillation
  • Esophagitis, reflex and ulcers
  • Esophageal cancer
88
Q

What is the concern for bisphosphonate use in pregnancy?

A
  • Crosses the placenta and accumulates in fetal bones
  • Animal models show harm (difficulties with delivery, bone abnormalities, hypocalcemia)
  • Women who want to get pregnant should stop talking bisphosphonates for 1 year before concieving
89
Q

What is the duration of therapy for bisphosphonates?

A

Needs to be highly individualized (most patients use them for 3 years, up to 6 years)

  • Long bone half-lives, less benefit with long-term use (therefore drug holidays are reccomended)
90
Q

What is the mechanism of action for Denosumab?

A
  • Binds to RANKL (released by osteoblasts)
  • RANKL is prevented from activating osteoclasts by Denosumab
91
Q

Why is Denosumab used instead of bisphosphonates?

A
  • Cannot adhere to dosing requirements of oral bisphosphonates
  • Intolerance to oral bisphosphonates
  • Severe renal impairment
92
Q

What is the onset of effect for Denosumab?

A
  • Markers of bone resorption markedly decreased within 3 days
  • Maximal reduction within 1 month
93
Q

What is the duration of therapy for Denosumab?

A

Indefinite treatment (benefits of denosumab rapidly lost after discontinuation)

94
Q

How is Denosumab dosed?

A

60mg administered once every 6 months

Can be used down to CrCl of 30mL/min

95
Q

What are some common side effects associated with denosumab?

A
  • Very well tolerated (maybe rash/eczema or musculoskeletal pain)
96
Q

What are some serious side effects associated with denosumab?

A
  • Hypocalcemia
  • Osteonecrosis of the jaw
  • Atypical fractures
  • Effect on the immune system
  • Rebound fracture risk upon discontinuation (any gains are lost within 12-24 months)
97
Q

What is the efficacy of Denosumab?

A

Observational data suggests similar fracture risk reduction vs. bisphosphonates

98
Q

What is the mechanism of action for Raloxifene?

A
  • Binds to estrogen receptors in bone and acts as an agonist (increases BMD)
  • Acts asn estrogen antagonist in breast and uterine tissues (protective against cancer)
99
Q

What is the onset of effect for Raloxifene?

A

Years to observe maximum BMD changes

100
Q

How long is Raloxifene used for in osteoporosis treatment?

A

Life-long therapy

101
Q

What are some common side effects associated with raloxifene use?

A
  • Flushing
  • Flu-like symptoms
  • Leg cramps
  • Peripheral edema
  • Increase in TGs
102
Q

What are some serious side effects associated with raloxifene?

A

Venous thromboembolism and stroke

103
Q

What are some drug interactions associated with raloxifene use?

A
  • No CYP enzyme interactions
  • Bile acid sequestrants decrease absorption of raloxifene
  • Raloxifene decrease absorption of levothyroxine
104
Q

What is the efficacy of raloxifene?

A

Less BMD increases than Bisphosphonates and Denosumab

Beneficial in reducing risk for verterbral fractures (does not reduce risk for hip fractures)

Reduces risk of invasive breast cancer

105
Q

What is the target population of hormone therapy in osteoporosis treatment?

A

Women with persistant menopausal symptoms and cannot tolerate bisphosphonates or denosumab

106
Q

How long is hormone therapy for osteoporosis?

A

Maximum protection if used longer term and initiated shortly after menopause (not used indefinitely and needs to be reassessed every 1-12 months)

107
Q

What are some safety concerns associated with hormone therapy?

A
  • Increased endometrial/breast cancer risk
  • Thromboembolism risk
  • CHD risk increase
  • Stroke risk
  • Urinary incontinence
108
Q

What is the efficacy of Teriparatide?

A
  • More potent than bisphosphonates and denosumab (very expensive)
109
Q

What is the mechanism of action for Teriparatide?

A
  • Recombinant form of PTH (stimulates bone formation more than resorption)
110
Q

How is Teriparatide dosed?

A

Most patients are on Teriparatide is used for only 2 years and it is dosed daily

111
Q

What are some common side effects associated with Teriparatide?

A
  • Nausea
  • Dizziness
  • Leg cramps
  • Orthostatic hypotension/syncope
112
Q

What are some serious side effects associated with Teriparatide use?

A
  • Hypercalcemia (Ca2+ levels increase 10x, and drop to baseline after 4h)
  • Hypercalciuria (risk of precipitating renal stones)
113
Q

What are some contraindications for the use of Teriparatide?

A
  • Pre-existing hypercalcemia
  • Severe renal dysfunction
  • HyperPTH
  • History of bone cancers
  • Pregnancy
114
Q

What is done at the end of Teriparatide therapy to maintain the gains in BMD?

A

Patient is transitioned to a bisphosphonate or denosumab

115
Q

What is the efficacy of Romosozumab?

A

More potent than bisphosphonates and denosumab

116
Q

What is the mechanism of action for Romosozumab?

A

Humanized monoclonal antibody directed against sclerostin (targets regulation of osteoblasts and osteoclasts)
- Acts as an anabolic agent and anticatabolic

117
Q

How long is Romosozumab used for?

A
  • Treatment duration is 12 months
118
Q

What are some common side effects associated with romosozumab use?

A
  • Musculoskeletal/joint discomfort
  • Headache
  • Injection site pain/erythema
119
Q

What is the efficacy of Romosozumab?

A

Similar to Teriparatide

120
Q

Are combination therapies for osteoporosis useful?

A

While they do increase BMD, there are no additional fracture benefit

121
Q
A

PHAR 255 (15 decks)

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