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Pharmacology III > Osteoporosis > Flashcards

Osteoporosis Flashcards

1
Q

What is bone comprised of?

A

Calcium and Phosphate
Protein meshwork
Collagen Matrix
Cells- Osteoblasts, osteoclasts, osteocytes

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2
Q

What do bones function to do?

A

Provide support
Enables us to carry out various physiological processes such as respiration and movement
In homeostasis of calcium and phosphate

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3
Q

What is serum calcium controlled by?

A

Parathyroid hormone (PTH) derived from the parathyroid glands

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4
Q

What do high plasma calcium concentrations do to PTH? Low plasma calcium concentrations?

A

High plasma calcium concentration suppress PTH secretion

Low plasma calcium concentration stimulates PTH secretion

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5
Q

What are the functions of PTH?

A

Maintains serum calcium
Acts on the kidney to reabsorb calcium from the tubular filtrate
Stimulates kidney to convert 25-OH-VitD to 1,25-(OH)2-VitD (calcitriol)
Directly on bone to mobilize calcium

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6
Q

What is endogenous (skin)?

A

Cholecalciferol (Vit D3)

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7
Q

What is exogenous (diet)?

A

Ergocalciferol (Vit D2)

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8
Q

Where are cholecalciferol and ergocalciferol stored and metabolized?

A

Endogenous (skin) = cholecalciferol (Vit D3) or exogenous (diet) = ergocalciferol (Vit D2) stored or metabolized in liver to 25-OH-VitD then 1,25-(OH2)-VitD which promotes intestinal absorption of calcium

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9
Q

Where does calcitonin come from and what does it do?

A

From the thyroid gland

In response to high calcium and inhibits resorptive activity of osteoclasts

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10
Q

What must be present in the intestines in order for calcium to be absorbed?

A

Vitamin D

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11
Q

What is osteopenia?

A

Early signs of osteoporosis

1 to 2.5 standard deviations below bone mass of a normal young adult

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12
Q

What is osteoporosis?

A

(Osteo)=Bone; (Porosis)=Porous

It is 2.5 or more standard deviations below the bone mass of a normal young

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13
Q

What is primary osteoporosis?

A

Postmenopausal women

Senile occurs with age, usually > 70 years of age in men and women

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14
Q

What is secondary osteoporosis?

A

Occurs in people who have other conditions
Hyperthyroidism, steroid use, chronic kidney disease (hyperparathyroidism), smoking, excessive ETOH
Often seen in younger people

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15
Q

What is the normal bone density T score?

A

T score of greater than -1.0

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16
Q

What is bone mineral density T score for osteopenia?

A

T score of less than or equal to -1.0 but greater than -2.5

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17
Q

What is the bone mineral density T score for ostepenic + other risk factors?

A

T score less than -2.0 or less than -1.5 with other risk factors for fracture.

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18
Q

What is the bone mineral density T score for osteoporosis?

A

Hx of fragility fracture or a BMD T score less than or equal to -2.5 at any site (lumbar spine, femoral neck, greater trochanter, or total hip

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19
Q

What are the modifiable risk factors for osteoporosis?

A 
Inadequate Calcium Intake
Inadequate Vitamin D Intake
Excess protein in diet
Diet
Alcohol use (chronic) 
--can cause poor nutrition 
--increased glucocorticosteroid secretion and decreased sexual function-all leading to bone loss.  
--Alcohol may also directly affect cell function.
Sedentary Lifestyle
Carbonated Drinks
Smoking
Anorexia
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20
Q

What are the non-modifiable risk factors of osteoporosis?

A

Parathyroid hormone problems
Thyroid hormone excess
Family history and genetics– Late age menarche, Early menopause (< 45years),Early surgical menopause, Low testosterone in males
Depression
Steroid use: patients taking glucocorticoids are 2x more likely to have a hip fracture and 4-5x more likely to have a fracture in the spine.
Long-term heparin, Lithium, Anticonvulsants, Thiazolidinediones
Drugs altering Ca absorption or elimination
Lack of Ovarian Function (menopause, surgery, cancer therapies)
Body Size-small thin bone women-this is one case where more weight is better. (< 128lbs)
Caucasian, Asian, Hispanic ethnicity

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21
Q

What are the drugs that may be associated with reduced bone mass in adults?

A 
Aluminum
Anticonvulsants (phenobarbital, phenytoin)
Cytotoxic drugs
Glucocorticosteroids and adrenocorticotropin
Gonadotropin-releasing hormone agonists
Immunosuppresants
Lithium
Long-term heparin use
Progesterone, parenteral, long-acting
Supraphysiologic thyroxine doses
Tamoxifen (premenopausal use)
Total parenteral nutrition
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22
Q

Who should be tested for osteoporosis?

A

All Women aged 65 or older.
Women age > 60 with risk factors.
Younger postmenopausal women with one or more risk factors, (OTHER THAN BEING FEMALE).
Men aged 70 or older
May consider screening Men > 50 with risk factors

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23
Q

What is done for the prevention of osteoporosis?

A

Maximize peak bone mass
Adequate calcium intake
Adequate vitamin D intake

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24
Q

When should an infant be supplemented with Vit D?

A

If they are exclusively or partially breastfed: IU/Day

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25
Q

Who should be treated for osteoporosis?

A

Postmenopausal women and men ≥50 yrs
Hip or vertebral fracture
T-score≤ -2.5 at femoral neck or spine after excluding secondary causes
Low bone mass (T-score -1.0 to -2.5 at femoral neck or spine)
10-year probability hip fracture ≥ 3%
OR
10-year probability major osteoporosis fracture ≥ 20%

26
Q

What are the nondrug treatments that reduce bone loss in postmenopausal women?

A

Diet
Smoking cessation
Physical activity

27
Q

What are the diet components that reduce bone loss in postmenopausal women?

A 
High in calcium and Vit D
High in fruits and vegetables
Moderate protein
Avoid sodas
High amounts of whole grains
28
Q

What are the physical activity components that reduce bone loss in postmenopausal women?

A 
Exercise, activity—weight bearing exercises
Running
Walking
Weight training
Swimming—very little effect
29
Q

What are the pharmacological agents used for treatment of osteoporosis?

A 
Calcium
Vitamin D
Teriparatide
Bisphosphonates
Calcitonin
Raloxifene
Estrogen
Denosumab
30
Q

Calcium- types and MOA

A 
Calcium gluconate IV/PO
Calcium carbonate PO- this is tums 
Calcium lactate PO
Calcium citrate PO- available in a liquid form
Calcium chloride IV
MOA:  Replace calcium deficiencies
31
Q

Calcium-indications

A

Hypocalcemia
Calcium deficiency
Osteoporosis or osteopenia

32
Q

Calcium- Contraindications and ADRS

A

Contraindications
Hypercalcemia

ADRs
GI disturbances
Constipation
Bradycardia
Arrhythmias
33
Q

Calcium- Monitor

A

Monitor calcium levels if given IV

Usually about q 6 hrs

34
Q

Vitamin D- inactive and active form and MOA

A

Inactive form—ergocalciferol (requires kidneys and liver to function to convert to active form)
Active form–calcitriol
400-800 I.U. daily
Calcium-Vit D combo available
MOA: Acts on the gut to absorb calcium from the diet

35
Q

Vitamin D- ROA and Indications

A

ROA: Oral, IV, UV reaction in skin

Indications
Hypocalcemia
Vitamin D deficiency
Postmenopausal osteoporosis
Renal failure- require primarily active form due to struggle with converting the inactive form.
36
Q

What do anabolic agents do?

A

Stimulate bone formation

Directly stimulate formation by effects on osteoblast function and lifespan

37
Q

What do antiresorptive agents do?

A

Inhibit bone resorption

Decreased osteoclastic bone resorption.

38
Q

Teriparatide (Forteo)- MOA and indications

A

MOA-Recombinant parathyroid hormone
Stimulates osteoblastic activity

Only used when:
History of osteoporotic fractures
Multiple risk factors and Failed/intolerant to other therapies

THis is not first line but only should be used when patient already has a fx or has failed other therapies. Very expensive

39
Q

Teriparatide (Forteo)- contraindications and adverse effects

A

Contraindications:
Paget’s disease, increased alkaline phosphatase, h/o radiation treatment

Adverse effects:
Dizziness, leg cramps
Transient increase in serum calcium
BLACK BOX WARNING: OSTEOSARCOMA

40
Q

Bisphosphonates

A

Approved products:
Fosamax (alendronate) PO; tx and prevention (once a week)
Actonel (risedronate) PO; tx and prevention (once a week)
Boniva (ibandronate) PO; tx and prevention (once a month)
Zometa (zoledronic acid) IV; tx hypercalcemia of malignancy
Reclast (zoledronic acid) IV; tx osteoporosis (Aug 2007) (once a year 15min infusion)

41
Q

Bisphosphonates- MOA

A

works by inhibiting bone resorption via:
Inhibits osteoclastic proton pump necessary for dissolution of hydroxyapatite
Decreased osteoclastic formation/activation
Increased osteoclastic apoptosis

42
Q

Bisphosphonates- efficacy and indications

A

Efficacy
Increase BMD
Decrease both vertebral and nonvertebral fractures

Indications
Prevention and/or treatment of osteoporosis (men/women)
Prevention of corticosteroid-induced osteoporosis
Management of hypercalcemia of malignancy

43
Q

Bisphosphonates- disadvantages and cautions/contraindications

A

Disadvantage of oral—must take 30 minutes before a meal and remain upright at least 30 minutes.

Cautions/ Contraindications
Renal impairment/ Hypocalciemia
Contraindicated CrCl < 30-35ml/min (renal impairment)

44
Q

Alendronate (Fosamax)

A

Bisphosphonate
Therapeutic effects sustained over 10 year period; D/C results in gradual loss of effects
ADRs
GI: Nausea, diarrhea, abdominal pain
Esophageal erosions
Hypocalcemia and hypophosphatemia (transient)

45
Q

Zoledronic Acid (Reclast)

A

Bisphosphonate
5mg IV infusion over 15 minutes once a year
Pretreat with APAP
Must be properly hydrated prior to infusion to prevent renal impairment
ADRs
Acute phase reactions: N/V, HA, myalgias, pyrexia, flu-like symptoms
Osteonecrosis of jaw, Afib, ocular “-itis”

46
Q

What is the biggest difference b/w alendronate and zoledronic acid?

A

Alendronate is given PO and zolendronic acid is given IV. Due to Alendronate being given PO it is more corrosive to the esophagus

47
Q

Calcitonin (Miacalcin)-MOA

A

Derived from salmon
MOA: calcitonins are hypocalcemic hormones secreted by the parafollicular cells of the human thyroid gland
Excreted in response to elevated serum calcium concentrations
Calcitonins increase mineral stores in bone
Decreases the number & activity of osteoclasts
In kidney, decreases tubular reabsorption of sodium and calcium (hypercalcemia)

48
Q

Calcitonin (Miacalcin)- function

A

Also improves bone architecture, relieves pain, increases function

49
Q

Calcitonin (Miacalcin)- ROA and indications

A

ROA: Intranasal, SubQ

Indications
Hypercalcemia
Paget’s disease of the bone
Bone pain in metastatic disease
Bone pain in osteoporosis
50
Q

Calcitonin (Miacalcin)- ADRs

A

N/V/D
Flushing
Tingling in the hands
Nasal irritation (if given intranasally)

51
Q

What are the advantages of calcitonin nasal spray?

A

Do not have to remain upright

Do not have to avoid eating

52
Q

What are the disadvantages of calcitonin nasal spray?

A

Is not as good at rebuilding bone
Must remember which nare medication was placed previous day.
Tolerance with continued use
Must keep refrigerated

53
Q

Raloxifene- MOA

A

Selective Estrogen Receptor Modulator Substances (SERMS)
Evista (raloxifene)
MOA:
It acts like an estrogen in the bone like an estrogen antagonist in the breast and uterus.
It increases bone mineral density in both spine and femoral neck
Decreases serum LDL
Does not stimulate endometrial growth. (doesn’t affect the breasts)
Decreases vertebral fractures 30 – 50%

54
Q

Evista (raloxifene)- indications

A

When to use: 1st line if patient postmenopausal and contraindication to bisphosphonates

55
Q

Evista (raloxifene)- ADRs

A

Chest pain and peripheral edema
Venous thromboembolism (3.4 fold risk) and pulmonary thromboembolism (2 fold risk)
Hot flashes
Weight gain

56
Q

Estrogen- MOA

A
  • FDA labeled indication for treatment and prevention of osteoporosis (4th line)
    Suppresses transcription of IL-6 that induces osteoclast proliferation, differentiation and activation
    Promotes apoptosis of osteoclasts
    Estrogens clearly slow the rate of bone loss in postmenopausal women
    Some studies document an INCREASE in bone density
57
Q

Estrogen- Disadvantages

A

If family history of breast cancer more risk for breast cancer
Intact uterus will need progesterone as well,
Breast tenderness and enlargement,
Increased risk of blood clots, CV events

58
Q

Denosumab- MOA

A

Monoclonal antibody
Slows bone breakdown but also entire bone remodeling process
Twice yearly injection at the office

Very expensive

59
Q

Denosumab- indications

A

Postmenopausal women with osteoporosis and high risk of fracture (that is, previous fracture due to osteoporosis or multiple fracture risk factors).
Patients with osteoporosis for whom other osteoporosis treatments have failed.
Patients who cannot tolerate other osteoporosis treatments

60
Q

Denosumab-ADRs

A

Decreased Calcium levels- must replace calcium
Back pain
Pain in the extremities
Muscle and bone pain
High cholesterol levels
Bladder infections- these can be very problematic in the elderly post-menopausal women
Possible increased risk of serious infections

Pharmacology III (19 decks)

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