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864 > Bone Modifying Agents and Hypercalcemia > Flashcards

Bone Modifying Agents and Hypercalcemia Flashcards

1
Q

Epidemiology

20 – 30% of all cancer patients
– decreased due to increased ___ use
Most common tumor types
– Lung – 35%
– Breast – 25%
– Hematologic – 14%
– Genitourinary – 6%

A

bisphosphonate

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2
Q

Pathophysiology of HCM

  • ___ parathyroid hormone related protein (PTHrP)
  • ___ calcitriol
  • ___ resorption
  • ___ elimination
  • Bone metastases
A

increased
increased
increased
decreased

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3
Q

HCM Etiology

  1. Humoral (80% of cases)
  2. Local osteolytic hypercalcemia
    (20% of cases) Caused by cytokines and PTHrP
  3. 1, 25(OH)2D-Secreting Lymphomas
  4. . Ectopic hyperparathyroidism
    1. Renal (increased ___ reabsorption, Decreased ___ reabsorption)
A
  • calcium
  • phosphorus
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4
Q

Corrected Calcium

Serum Calcium + 0.8 (4 – Serum Albumin)

A

Normal Calcium: 8.5-10 mg/dL

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5
Q

Mild HCM (10-12 mg/dL)

Asymptomatic or mild symptoms
- Encourage hydration
- Discontinue medications that increase serum calcium or decrease renal blood flow
- Repeat calcium level in 4 weeks

Moderate symptoms
– Hydration: 200 - 400 mL/Hr of 0.9% normal saline
– Bisphosphonate: ___ or ___
* Can be repeated after 7 days if needed

A

Zoledronic acid or Pamidronate

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6
Q

Moderate HCM (12 – 14 mg/dL)

T or F: hydration reduces calcium more quickly than a bisphosphonate and Loop diuretics should be reserved for patients who develop fluid overload

A

T

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7
Q

Moderate HCM (12 – 14 mg/dL)

Bisphosphonate
- ___ Acid
- superior to pamidronate for treatment of moderate to severe hypercalcemia

A

Zoledronic

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8
Q

Severe HCM (> 14 mg/dL)

Hydration, Hydration, Hydration!!
– Typically, ___ mL/Hr

Bisphosphonates

Calcitonin
- ___ after 48 hours
- Hypersensitivity reactions, arthralgias, flushing, or nausea

A

200
Tachyphylaxis

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9
Q

FDA approved
refractory HCM

A

Denosumab

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10
Q

Chronic HCM Management

___ and ___

A

zoledronic acid, pamidronate

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11
Q

Comparison of Agents

A

NS and bisphosphonates = mild + severe
loop diuretics = moderate + severe
calcitonin = severe

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12
Q

Intravenous Bisphosphonates

Affinity for ___
Inhibit osteoclast activity through:
- Induce direct osteoclast apoptosis
- Inhibit differentiation and maturation

  • Decreasing bone ___
  • Increasing mineralization
  • Concentrate at active bone remodeling sites
A

hydroxyapatite
resorption

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13
Q

Bone in Cancer Patients

Tumor cells secrete cytokines and growth factor
* increased production of receptor activate or nuclear factor kappa B
ligand ( ___ )
* increased osteoclasts lead to more bone ___

A

RANK-L
resorption

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14
Q

Epidemiology of Bone Metastases

Cancers with affinity for bone
* ___
* ___
* Myeloma
* ___
* Kidney

  • Usually metastasizes to the ___ skeleton
A
  • breast
  • prostate
  • lung
  • axial
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15
Q

Skeletal Related Events (SRE’s)

Defined as:
1. Pathologic fracture
2. Need for bone radiation
3. Need for bone surgery
4. Spinal cord ___
5. Hyper ___

s/s
- Bony pain or tenderness

Radionucleotide bone scan > radiograph

A

compression
hypercalcemia

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16
Q

Risk Factors for Fractures

Women: Breast Cancer
* Bone mineral density < -2.5
* On aromatase inhibitors
* Age > 65
- ___ use > 6 months
* BMI < 20 kg/m 2
* Family history of hip fractures
* History of fracture before age of 50
* Smoking

Men with Prostate
Cancer
* Androgen deprivation
therapy
* Smoking

A
17
Q

Treatment of Bone Metastases

Goal: Palliation of
symptoms
* Radiation
* Chemotherapy
* IV bone modifying
agents
– Delays time to first
SRE by 50%
* Radioisotopes

A
18
Q

Radiation Therapy
* Overall response rates of 85%
* Pain relief within 1 to 2 weeks
– If pain relief not achieved by 6 weeks, unlikely
to see benefit
– No difference between single and multiple
fractions
– Limited by life-time limits of radiation within
certain areas

A
19
Q

Radioisotopes
- Delivered more specifically to the tumor
- Treatment of bone metastases from thyroid cancer with 131-Iodine
- Radium-223 chloride shown overall survival benefits in ___ cancer
- Strontium and samarium used in metastatic breast and prostate cancers
- Expensive and have toxicities ( ___ )

A

prostate
myelosuppression

20
Q

T or F: no renal adjustments are warranted if these agents (zoledronic acid and pamidronate) are for HCM

A

T

20
Q

V Bisphosphonates for SRE’s

___ :90 mg IV over 2 hours every 3 to 4 weeks
– Renal adjustment dosing needed

___ acid : 4 mg IV over 15 minutes every 3 to 4 weeks or every 12 weeks
– Renal adjustment dosing needed

A

pamidronate
zoledronic

21
Q

Bisphosphonates
– Supplement with ___ and ___

A

calcium
vitamin D

22
Q

Denosumab

Fully human monoclonal antibody with high affinity for ___
- Rapidly reduces bone turnover
- Lack of affinity for hydroxyapatite and more evenly spreads throughout bone
- May suppress residual ___ function in patients who poorly responds to bisphosphonates

Bone metastases from solid tumors - ___

For women at high risk of fracture and
receiving aromatase inhibitors for breast cancer and in men receiving androgen deprivation therapy for prostate cancer – ___

A
  • RANK-L
  • osteoclast
  • Xgeva
  • Prolia
23
Q

Denosumab Considerations

  • Correct ___ prior to initiation
  • Supplement calcium and Vitamin D daily
  • NO renal dose adjustments
A

hypocalcemia

24
Q

Adverse Effects of Therapies

Osteonecrosis of ___
- Angiogenesis suppression
- Osteocyte depletion leading to avascular necrosis

Possible treatment options:
– Palliative, pain control, chlorhexidine and/or antibiotics, conservative surgeries

Agent discontinuation may be associated with slow improvement but may not return to normal

A

jaw

25
Q

Renal Dysfunction in this Setting

Zoledronic acid > pamidronate > denosumab

Bisphosphonate
- Not recommended for CrCl < ___ mL/min

Denosumab
- Not renally eliminated
- No renal or hepatic dosing adjustments
- No specific dosing recommendations for those on dialysis

A

30

26
Q

Other Adverse Effects

Hypocalcemia:
- ___&raquo_space; zoledronic acid
- Patients should be supplemented with daily calcium and vitamin D when using for prevention of SRE’s
* Bone pain
* Nausea
* Diarrhea
* Fatigue

A

Denosumab

27
Q

Duration of Treatment

In clinical practice, typically will use every ___
month dosing

A

3

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