Hypercalcemia

At the completion of this presentation the participant will be able to:
– Describe 2 side effects of hypercalcemia
– Define 2 agents utilized to treat hypercalcemia
– Describe at least 2 nursing interventions for hypercalcemia

Prevalence
Most common metabolic complication of cancer
10-20% of all cancer patients per year will be diagnosed with hypercalcemia

Lung-35% ( NSCL)- 15% occurrence
Breast- 40-50%
Multiple Myeloma-20-40%
Head and Neck-6%
Genitourinary-6%
Other/Unknown primary-15%

Bone formation and resorption (99%) in bone
GI absorption
Urinary excretion

Due to increased bone resorption and release of calcium from bone
Three mechanisms
– Osteolytic metastases with local release of cytokines
– Tumor secretion of parathyroid hormonerelated protein
– Tumor production of calcitriol

Hormonal Control
Parathyroid hormone- released from the parathyroid in response to a drop in calcium, acts directly on bone by stimulating osteoclast formation and inhibiting osteoblasts
Vitamin D (1,25-dihydroxycholecalciferol)increase calcium and phosphorous absorption from the intestinal mucosa
Calcitonin-reduces calcium release into circulation as a result of bone resorption

tumour cell activatd
TGFß
IL-6
IL-1
IL-6
TNF
TGF
EGF
PGs
PTHrP cathepsins
Imune cell
IL-1,
TNF
GM-CSF osteoblast
OIF /
OAF osteoclast mineralized bone

Osteolytic mets are the result of direct induction of local osteolysis by the tumor cells
Breast and Non –small cell lung
In Breast cancer adminstration of estrogen and antiestrogen Tamoxifen) can lead to hypercalcemia
Cytokines play a major role
– Tumor necrosis factor
– Interleukin-1

Multiple Myeloma can release these factors by tumor cells
Cytokines active in osteoclastic activity
– Interleukin-1-beta
– Lymphotoxin
– Tumor necrosis factor
– IL-6
– Macrophage colony stimulating factor
– Macrophage inflammatory protein
– Vascular cell adhesion molecule-1
– Hepatocyte growth factor ( This is produced by myeloma cells in culture)

tumour cell activatd
TGFß
IL-6
IL-1
IL-6
TNF
TGF
EGF
PGs
PTHrP cathepsins
Imune cell
IL-1,
TNF
GM-CSF osteoblast
OIF /
OAF osteoclast mineralized bone

Clinical Manifestations
Dehydration
Polydipsia
Polyuria
Gastointestinal
– Anorexia
– Nausea/Vomiting
– Constipation
– Abdominal pain

Clinical Manifestations
Bone pain
Pathologic fracture
Weakness
Lethargy
Hyporeflexia
Depression

Clinical Manifestations

Clinical Manifestations
–Polyuria
–Polydipsia
–Nocturia
–Calcium nephropathy
–Hypercalciuria
–Nephrolithiasis

Clinical Manifestations
– Hypertension
– Bradycardia
– Cardiac arrhythmias
– Cardiac arrest
– Heart block
– Digitalis sensitivity

Diagnosis
–Ionized calcium or free calcium is the physiologically active form of calcium circulating in the blood
–50% of serum calcium is ionized
–Results < 1.30

Diagnosis
Normal serum calcium 9-11mg/dl
Hypercalcemia can be estimated via a formula:
– Corrected Ca (mg/dl) = Ca divided by 4 minus albumin(gm/dl) times ) 0.8

Medical Management
–Calcium < 12
–Asymptomatic
–Therapy
Activity
Avoid salt restriction
Discontinue thiazide diuretics

Medical Management
Moderate to severe hypercalcemia
– Moderate 12-13 mg/dl
– Severe >13.5 mg/dl
– Rehydration
– Diuretics- Furosemide
– Discontinue thiazide diuretics

Medical Management
–Calcitonin
–Bisphosphonates
Etidronate-Didronel
Pamidronate- Aredia
Zoledronic acid- Zometa
Ibandronate- Boniva
Risedronate- Actonel

Mechanism of action of
Bisphosphonates inhibit osteoclast formation, migration and osteolytic activity, promote apoptosis modulate signalling from osteoblasts to osteoclasts local release during bone resorption concentrated in newly mineralizing bone and under osteoclasts

Current Therapeutic Approaches for
Skeletal Complications of Malignancies
Radiotherapy
Endocrine therapy
Chemotherapy
Orthopedic interventions
Analgesia
Bisphosphonates 1
– Treatment of choice in hypercalcaemia of malignancy
(HCM)
– Potent inhibitors of pathologic bone resorption
– Effective therapy for skeletal complications of bone metastases
1. Body JJ, et al. J Clin Oncol.
1998.

Zoledronic acid reduces bone resorption by potently inhibiting osteoclast hyperactivity
Proposed mechanisms of action include:
– Functional suppression of mature osteoclast 1
– Inhibition of osteoclast maturation 2
– Inhibition of osteoclast recruitment to the site 2
– Reduction in the production of cytokines, eg, IL-
1, IL-6 3
– Inhibition of tumour-cell invasion and adhesion to bone matrix 4,5
1. Green J, et al. J Bone Miner Res.
1994.
2. Evans CE, Braidman IP. J Bone Miner Res.
1994.
3. Derenne S, et al. J Bone Miner Res.
1999.
4. Boissier S, et al. Cancer Res. 2000.
5. Marion G, et al. Bone . 1998.

Overall Safety Conclusions
ZOMETA (4 mg) via 15-minute infusion is safe and well tolerated, with a safety profile comparable to that of pamidronate (90 mg) via
2-hour infusion, including renal tolerability
Similar overall safety profile to that of other intravenous bisphosphonates
Laboratory abnormalities (grade 3 and 4) were similar for ZOMETA and placebo

Zoledronic acid is the only bisphosphonate to be proven effective across tumor types in patients with both lytic and blastic bone lesions

Nursing Management
Education
– Patient
– Significant others
Rehydration
– I&O
– Weights
Activity
– Encourage ambulation

Nursing Management
Safety
– Falls prevention
– Do not allow patient to overstress bones
– Do not pull on arms or legs
– Have patient report all bone pain
– Be very gentle when assisting patient
– Use assistive devices
– Safety assessment for home via
PT/Home Health

Nursing Management

References
Jensen, G., “Hypercalcema of Malignancy” in
Oncology Nursing Secrets, R Gates and R Fink
(eds), Philadelphia: Hanley and Belfus,
2008,523-526
Paines , H., “How to manage metabolic emergencies”, Contemp Oncol, 3 (9), 54-57,
1993
2009 UpToDate , ‘Treatment of Hypercalcemia’ www.http://UPTODATE accessed 7/9/09