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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
Who should be treated for osteoporosis?
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
What are the nondrug treatments that reduce bone loss in postmenopausal women?
Diet Smoking cessation Physical activity
27
What are the diet components that reduce bone loss in postmenopausal women?
``` High in calcium and Vit D High in fruits and vegetables Moderate protein Avoid sodas High amounts of whole grains ```
28
What are the physical activity components that reduce bone loss in postmenopausal women?
``` Exercise, activity—weight bearing exercises Running Walking Weight training Swimming—very little effect ```
29
What are the pharmacological agents used for treatment of osteoporosis?
``` Calcium Vitamin D Teriparatide Bisphosphonates Calcitonin Raloxifene Estrogen Denosumab ```
30
Calcium- types and MOA
``` 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
Calcium-indications
Hypocalcemia Calcium deficiency Osteoporosis or osteopenia
32
Calcium- Contraindications and ADRS
Contraindications Hypercalcemia ``` ADRs GI disturbances Constipation Bradycardia Arrhythmias ```
33
Calcium- Monitor
Monitor calcium levels if given IV | Usually about q 6 hrs
34
Vitamin D- inactive and active form and MOA
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
Vitamin D- ROA and Indications
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
What do anabolic agents do?
Stimulate bone formation | Directly stimulate formation by effects on osteoblast function and lifespan
37
What do antiresorptive agents do?
Inhibit bone resorption | Decreased osteoclastic bone resorption.
38
Teriparatide (Forteo)- MOA and indications
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
Teriparatide (Forteo)- contraindications and adverse effects
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
Bisphosphonates
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
Bisphosphonates- MOA
works by inhibiting bone resorption via: Inhibits osteoclastic proton pump necessary for dissolution of hydroxyapatite Decreased osteoclastic formation/activation Increased osteoclastic apoptosis
42
Bisphosphonates- efficacy and indications
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
Bisphosphonates- disadvantages and cautions/contraindications
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
Alendronate (Fosamax)
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
Zoledronic Acid (Reclast)
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
What is the biggest difference b/w alendronate and zoledronic acid?
Alendronate is given PO and zolendronic acid is given IV. Due to Alendronate being given PO it is more corrosive to the esophagus
47
Calcitonin (Miacalcin)-MOA
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
Calcitonin (Miacalcin)- function
Also improves bone architecture, relieves pain, increases function
49
Calcitonin (Miacalcin)- ROA and indications
ROA: Intranasal, SubQ ``` Indications Hypercalcemia Paget’s disease of the bone Bone pain in metastatic disease Bone pain in osteoporosis ```
50
Calcitonin (Miacalcin)- ADRs
N/V/D Flushing Tingling in the hands Nasal irritation (if given intranasally)
51
What are the advantages of calcitonin nasal spray?
Do not have to remain upright | Do not have to avoid eating
52
What are the disadvantages of calcitonin nasal spray?
Is not as good at rebuilding bone Must remember which nare medication was placed previous day. Tolerance with continued use Must keep refrigerated
53
Raloxifene- MOA
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
Evista (raloxifene)- indications
When to use: 1st line if patient postmenopausal and contraindication to bisphosphonates
55
Evista (raloxifene)- ADRs
Chest pain and peripheral edema Venous thromboembolism (3.4 fold risk) and pulmonary thromboembolism (2 fold risk) Hot flashes Weight gain
56
Estrogen- MOA
- 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
Estrogen- Disadvantages
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
Denosumab- MOA
Monoclonal antibody Slows bone breakdown but also entire bone remodeling process Twice yearly injection at the office Very expensive
59
Denosumab- indications
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
Denosumab-ADRs
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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