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Fall 2021: Therapeutics III > Bone Modifying Agents (Weddle) > Flashcards

Bone Modifying Agents (Weddle) Flashcards

1
Q

Hypercalcemia of malignancy (HCM) occurs most frequently in which two tumor types?

A

lung and breast

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2
Q

List the five components of HCM pathophysiology.

A
  • Increased PTHrP
  • Increased calcitriol
  • Increased resorption
  • Decreased elimination
  • Bony metastases
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3
Q

80% of HCM cases are ___________.

A

humoral

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4
Q

What compound is responsible for humoral HCM?

A

PTHrP

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5
Q

20% of HCM cases are _______________.

A

local osteolytic hypercalcemia

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6
Q

What compounds are responsible for causing local osteolytic hypercalcemia?

A

cytokines and PTHrP

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7
Q

What renal symptoms are associated with mild HCM?

A

polyuria and polydipsia

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8
Q

What GI symptoms are associated with mild HCM?

A

constipation and anorexia

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9
Q

What neurologic symptoms are associated with mild HCM?

A

fatigue

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10
Q

What cardiac symptoms are associated with mild HCM?

A

none

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11
Q

What renal symptoms are associated with moderate HCM?

A

dehydration

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12
Q

What GI symptoms are associated with moderate HCM?

A

nausea and vomiting

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13
Q

What neurologic symptoms are associated with moderate HCM?

A
  • Lethargy/confusion
  • Muscle weakness
  • Loss of deep tendon reflexes
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14
Q

What cardiac symptoms are associated with moderate HCM?

A

shortened QT and widened T wave

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15
Q

What renal symptoms are associated with severe HCM?

A

decreased GFR and nephrocalcinosis

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16
Q

What GI symptoms are associated with severe HCM?

A

none

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17
Q

What neurologic symptoms are associated with severe HCM?

A

seizures, stupor, coma

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18
Q

What cardiac symptoms are associated with severe HCM?

A

heart block, arrhythmias, asystole

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19
Q

What is the corrected calcium equation?

A

serum calcium + 0.8 (4 - serum albumin)

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20
Q

What is the normal range for calcium?

A

8.5-10 mg/dL

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21
Q

What’s the corrected calcium range for mild hypercalcemia?

A

10-12 mg/dL

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22
Q

What’s the corrected calcium range for moderate hypercalcemia?

A

12-14 mg/dL

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23
Q

What’s the corrected calcium range for severe hypercalcemia?

A

> 14 mg/dL

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24
Q

A patient states they are experiencing some polyuria and fatigue. Their labs come back, with a corrected calcium of 11 mg/dL. What treatment would you recommend?

A

counsel to drink 3 L/day, and repeat calcium level in 4 weeks

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25
Q

A patient arrives to your clinic complaining of lethargy and dehydration. Upon further investigation, their EKG shows shortened QT and a calcium level of 11.6 mg/dL. What course of treatment would you recommend?

A

hydration and/or bisphosphonate

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26
Q

What corrected calcium level would warrant admission to an inpatient setting?

A

> 14 mg/dL

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27
Q

A patient arrives to the ER with a corrected calcium of 13.2 mg/dL. What course of treatment would you recommend?

A
  1. 0.9% NS IV
  2. zoledronic acid or pamidronate
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28
Q

A patient presents to the ER with seizures and general stupor. Upon further investigation, it is revealed that their corrected calcium is 16 mg/dL. What course of treatment would you recommend?

A
  1. 0.9% NS IV
  2. zoledronic acid or pamidronate
  3. probably calcitonin
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29
Q

IV bisphosphonates inhibit ________ activity.

A

osteoclast

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30
Q

What is pamidronate FDA-approved for?

A
  • SRE prevention for breast cancer & MM bony mets
  • HCM
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31
Q

What is zoledronic acid FDA-approved for?

A
  • Bony mets in all solid tumors & MM
  • HCM
32
Q

In what situation do bisphosphonates NOT need to be renally dose adjusted?

A

almost all HCM cases

33
Q

Which reduces calcium faster: hyperhydration or bisphosphonates?

A

hyperhydration

34
Q

Which bisphosphonate has been shown to be superior for the treatment of moderate to severe hypercalcemia?

A

zoledronic acid

35
Q

What complication can occur when administering calcitonin for severe hypercalcemia?

A

tachyphylaxis after 48 hours

36
Q

When would you use calcitonin for hypercalcemia?

A

severe symptoms or very high calcium or after bisphosphonate

37
Q

Which should be administered first: calcitonin or zoledronic acid?

A

zoledronic acid; calcitonin can be administered before, but barely reduces calcium

38
Q

What treatment options are available for refractory HCM?

A
  • Phosphates
  • Denosumab
  • Gallium nitrate (not really used anymore)
39
Q

What drugs can be used for chronic HCM?

A

monthly zoledronic acid or pamidronate

40
Q

In normal bone, _________ are in balance with __________.

A

osteoclasts; osteoblasts

41
Q

Increased osteoclasts lead to increased bone ______________.

A

resorption

42
Q

List some cancers that have an affinity for bone.

A
  • Breast
  • Prostate
  • Myeloma
  • Lung
  • Kidney
43
Q

What symptom is most associated with SREs?

A

bone pain or tenderness

44
Q

What scan is best for diagnosing SREs?

A

radionuclide bone scan

45
Q

Give some fracture risk factors for women with breast cancer.

A
  • Bone mineral density score < -2.5
  • AI treatment
  • > 65 YO
  • Corticosteroid use > 6 months
  • BMI < 20
  • Family hx of hip fractures
  • Hx of fracture before age 50
  • Smoking
46
Q

Give some fracture risk factors for men with prostate cancer.

A
  • Androgen deprivation therapy
  • > 65 YO
  • Corticosteroid use > 6 months
  • BMI < 20
  • Family hx of hip fractures
  • Hx of fracture before age 50
  • Smoking
47
Q

What is the overall goal for treatment of bone metastases?

A

palliation of symptoms

48
Q

What are the three treatment options for bone metastases?

A
  • Chemo
  • IV bone modifying agents
  • Radioisotopes
49
Q

What drug class is considered 1st line for SRE?

A

IV bisphosphonates

50
Q

What radioisotope can be used for treatment of bone metastases from thyroid cancer?

A

131-iodine

51
Q

What radioisotope has shown overall survival improvements in prostate cancer?

A

radium-223

52
Q

What radioisotopes have been used for metastatic breast and prostate cancers?

A

strontium and samarium

53
Q

What toxicity is associated with radioisotopes?

A

myelosuppression

54
Q

What patient factor must be considered before dosing IV bisphosphonates for SRE?

A

renal function

55
Q

Which IV bisphosphonate should NOT be used for SREs if CrCl < 30?

A

zoledronic acid

56
Q

What should be supplemented with IV zoledronic acid?

A

calcium and vitamin D

57
Q

Even though IV pamidronate is much cheaper than zoledronic acid, what is a drawback of it?

A

longer infusion time

58
Q

Does denosumab work directly on osteoclasts?

A

no

59
Q

What is a beneficial consequence of denosumab lacking affinity for hydroxyapatite?

A

spreads more evenly throughout bone

60
Q

What can occur if a patient who poorly responded to bisphosphonates in the past initiates denosumab?

A

residual osteoclast function may be suppressed

61
Q

What is Xgeva used for?

A

bone metastases from solid tumors

62
Q

What is Prolia used for?

A

osteopenia from breast cancer

63
Q

What is the Xgeva dosing for bone metastases from solid tumors?

A

120 mg SQ every 4 weeks

64
Q

What is the Prolia dosing for osteopenia from breast cancer?

A

60 mg SQ every 6 months

65
Q

What should be corrected prior to initiating denosumab?

A

hypocalcemia

66
Q

Which agent is more likely to cause hypocalcemia: densoumab or bisphosphonates?

A

denosumab

67
Q

Should denosumab be renally dose adjusted?

A

nah

68
Q

What are some risk factors for osteonecrosis of the jaw (ONJ)?

A
  • Invasive dental procedures
  • Poor oral hygiene
  • Use of dental appliances
  • Oral infection
  • Monthly bone modifying agent
  • IV bone modifying agents
69
Q

What drugs are most associated with ONJ?

A

zoledronic acid, denosumab

70
Q

What should happen to help prevent ONJ?

A

baseline dental evaluation/intervention before starting bisphosphonates and denosumab

71
Q

What are the two proposed mechanisms for ONJ?

A
  • angiogenesis suppression
  • osteocyte depletion leading to avascular necrosis
72
Q

What are the possible treatment options for ONJ?

A
  • palliative
  • pain control
  • chlorhexidine and/or antibiotics
  • conservative surgeries
  • **discontinuing bone modifying agents may be associated with slow improvement, but may not return to normal**
73
Q

Rank the bone modifying agents from most to least likely to cause renal dysfunction.

A
  1. zoledronic acid
  2. pamidronate
  3. denosumab
74
Q

Does denosumab need to be renally dose adjusted? Hepatically dose adjusted?

A

no and no

75
Q

Beyond ONJ and renal dysfunction, what are some other common adverse effects of bone modifying agents?

A
  • hypocalcemia (especially with denosumab)
  • bone pain
  • nausea
  • diarrhea
  • fatigue
76
Q

What is the extended dosing interval generally for bone modifying agents?

A

monthly for 1 year, then every 3 months

77
Q

What are the standard screening guidelines for prostate cancer?

A

none exist

Fall 2021: Therapeutics III (25 decks)

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