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Evidence Matters
Vol.1, No. 1 • JANUARY 2007
The Use of Corticosteroids for Treating
Bone Metastasis Jennifer Johansen, PharmD, BCPS
What is the prevalence of bone metastasis?
Bone metastases are a common complication of cancer. The true prevalence of bone metastases is not fully
known. However, cancers of the breast and prostate frequently metastasize to the bone, occurring in up to
70% of patients with advanced disease. In other cancers (e.g., lung, colon, stomach, bladder, uterine, rectal,
thyroid, and kidney), bone metastases have an estimated occurrence of 15 to 30%.1 Common sites for
bone metastases are the vertebrae, pelvis, hip, femur, ribs, and skull.1,2
What is the mechanism of bone metastasis and related pain?
Normal bone subsists in a state of remodeling – constantly being broken down and rebuilt. Cancer cells that
spread to the bone disrupt the balance between the activity of cells that break down bone (osteoclasts) and cells
that make bone (osteoblasts). Bone metastases can be classified as osteolytic (which cause dissolution of bone),
osteoblastic (which fill up bone with extra cells), or mixed. Regardless of classification, the symptoms of bone
metastasis can vary from person to person.1,2
What are the symptoms and complications of bone metastasis?
The most common symptoms are pain, swelling, or tenderness in the affected area. The pain is frequently
described as deep, dull, aching, or sharp and is often constant. The pain is usually localized in a particular area
and is often worse at night or with weight-bearing activity. Possible causes of pain include irritation of the
nerves in the area of the tumor, mechanical stress, or direct destruction of the bone.
One of the complications of bone metastasis is spinal cord compression (SCC). SCC is an oncological emergency, and patients who develop symptoms of SCC should be immediately referred for medical follow-up.
Symptoms of SCC may include numbness/tingling, motor weakness, or lost of bowel/urinary function and are
dependent on where the metastasis is located in the spine. Though not indicated primarily for pain, corticosteroids play an important role in reducing the associated complications of SCC. Other complications of bone
metastases include bone marrow suppression, hypercalcemia, and fractures.2,3
What is the role of corticosteroids for bone metastasis?
There are several approaches to treating bone metastasis and related pain including (but not limited to) radiation, bisphosphonates, and chemotherapy.2,3 According to the World Health Organization guidelines on cancer
pain relief,4 non-opioid analgesics such as non-steroidal anti-inflammatory drugs (NSAIDs) are recommended
as the first step of the analgesic ladder. However, corticosteroids are effective analgesics and are a reasonable
alternative to NSAIDs for bone pain. That said, there are no comparative trials between NSAIDs and corticosteroids for bone pain. Nevertheless, corticosteroids may improve appetite, decrease fatigue, and increase the
sensation of well-being. They are always indicated in those experiencing SCC as they reduce edema and prevent
further neurological loss.3 Continuous bone pain also responds well to opioids, and these agents are recommended as either first-line therapy for moderate-to-severe pain or as adjuvants when NSAIDs or corticosteroids
are ineffective.3
How do corticosteroids exert their effect?
Corticosteroids are thought to lessen pain through their anti-inflammatory properties. By blocking prostaglandins
and leukotrienes (the predominant inflammatory substances), corticosteroids diminish the transmission of the pain
signal from the periphery to the spinal cord or the spinal cord to the brain. Corticosteroids also reduce capillary
permeability, which reduces fluid retention and, thereby, relieves the edema and discomfort associated with spinal
metastasis.3,5
Which corticosteroid should I use and what dose is appropriate?
Corticosteroids commonly used for bone pain management include dexamethasone, methylprednisolone, and
prednisone. Dexamethasone is often preferred because of its relatively high anti-inflammatory potency and low
mineralcorticoid potency; therefore, dexamethasone has a lower risk of causing salt and water retention compared to
equipotent doses of other corticosteroids. Regardless of the corticosteroid chosen, the preferred route of administration is oral, although IV/IM is available for dexamethasone and methylprednisolone.6,7
To date, only one study specifically addressed corticosteroid use for cancer-related bone pain. This study was a 14day, randomized, double-blind, placebo-controlled, crossover study comparing 32 mg of oral methylprednisolone
(MP) with placebo for symptoms in terminally ill cancer patients. After the initial 14 days, patients were continued
on MP for a treatment period of 20 days. Pain intensity was significantly lower after MP compared with baseline or
placebo in the crossover phase; 68% of patients responded that their pain control was better with MP compared to
placebo by the end of the treatment phase. Furthermore, the findings of this study suggest that MP exerts its action
rapidly, and the chances of obtaining better responses after 5 days of treatment are poor.8
For cancer patients with SCC due to bone metastasis, one study evaluated the use of corticosteroids in conjunction
with radiotherapy versus radiotherapy alone in 57 patients. For those who received corticosteroid treatment, IV
dexamethasone 96 mg was followed by oral dexamethasone 96 mg for 3 days, with subsequent tapering over 10 days.
Gait function was preserved or restored in 81% of the patients treated with both dexamethasone and radiotherapy
compared to 63% of those with radiotherapy alone.9 Since its publication, this study has been largely regarded as the
primary source for dosing recommendations in cancer-related SCC.
Although optimal drug and dosing regimens haven’t been established for bone pain management, many clinicians
initially prescribe 2 to 4 mg of dexamethasone given once or twice daily, and then titrate to response. Anecdotally, most patients respond within 48 to 72 hours of the initiation of the corticosteroid and/or the increase of dose.
Though the optimal duration of steroid therapy is unknown, many practitioners recommend that the therapy should
be stopped if no benefit is seen within 5 to 7 days.3,7,10 The following corticosteroid dose equivalents have been
published in numerous tertiary references: dexamethasone 0.75 mg: methylprednisolone 4 mg: prednisone 5 mg.
What side effects should I monitor for with corticosteroid therapy?
Although corticosteroids are beneficial in advanced cancer patients, their benefits should be weighed against their
adverse effects for each individual. Side effects that generally appear early in therapy and may be unavoidable include
insomnia, emotional lability, and enhanced appetite or weight gain. Insomnia can often be avoided or relieved by
giving corticosteroid doses early in the day (e.g., before 3pm) and emotional lability may resolve with a dose
reduction. Elevations in blood pressure (BP) and sugars, peptic ulcer disease (PUD), and acne are more common in
patients with underlying risk factors for those conditions.5 Often, changes in BP and sugars can be managed by
altering the patient’s antihypertensive or diabetic therapy. PUD has been shown to be associated with concomitant
use of other potentially ulcerogenic medications (e.g., NSAIDs), previous history of ulceration, advanced malignant
disease, chronic heavy alcohol use, and a cumulative dose of more than 140 mg of dexamethasone. Prophylaxis with
a cytoprotective agent (e.g., omeprazole) is recommended when patients have two or more of these risk factors;
however, routine use of such therapy devoid of risk factors is not warranted.11,12,13 Delayed side effects from long-term
use include impaired wound healing, increased susceptibility to infections, moon face/fat redistribution, and
osteoporosis.5 Patients receiving corticosteroids should be reevaluated regularly, and a dose reduction should be
attempted when possible.
Clinicians who partner with HP can refer to the Nociceptive Pain/Bone Pain algorithm on page 58 in the
Eighth Edition of the Hospice Pharmacia Medication Use Guidelines (MUGs) for more information on the
treatment of bone pain.
Conclusion
Bone metastases are a common complication of cancer. Pain is the most common presentation of
bone metastasis.
• Corticosteroids are thought to lessen pain through their anti-inflammatory and edema-reducing properties, and
they are a first-line alternative to NSAIDs.
• Most patients experience a reduction in pain within 48 to 72 hours of initiation or titration.
• Failure to respond to increasing doses of corticosteroids within a week should prompt a reevaluation of the
patient’s pain regimen.
• Patients should be monitored routinely for adverse effects, and a dose reduction should be attempted whenever
possible to achieve the lowest effective analgesic dose.
•
References:
1. Roodman DG. Mechanisms of bone metastasis. N Engl J Med. 2004;350 (16):1655-64.
2. Sabino MA, Mantyh PW. Pathophysiology of bone cancer pain. J Support Oncol. 2005;3(1):15-24.
3. Mercante S. Malignant bone pain: Pathophysiology and treatment. Pain. 1997;69(1-2):1-18.
4. World Health Organization. WHO’s pain ladder. Available at: www.who.int/cancer/palliative/painladder/en.
Accessed October 16, 2006.
5. Boumpas DT, Chrousos GP, Wilder RL, Cupps TR, Balow JE. Glucocorticoid therapy for immune-mediated
diseases: Basic and clinical correlates. Ann Intern Med. 1993;119(12):1198-1208.
6. Hanks GW,Trueman T, Twycross RG. Corticosteroids in terminal cancer - a prospective analysis of current
practice. Postgrad Med J. 1983;59(697):702-6.
7. Rousseau P. The palliative use of high-dose corticosteroids in three terminally ill patients with pain.
Am J Hosp Palliat Care. 2001;18(5):343-6.
8. Bruera E, Roca E, Cedaro L, Carraro S, Chacon R. Action of oral methylprednisolone in terminal cancer
patients: A prospective randomized double-blind study. Cancer Treat Rep. 1985;69(7-8):751-54.
9. Sorensen PS, Helweg-Larsen S, Mouridsen H, et al. Effect of high-dose dexamethasone in carcinomatous
metastatic spinal cord compression treated with radiotherapy: A randomized trial. Eur J Cancer. 1994;
30:22-27.
10. Mercadante S, Fulfaro F, Casuccio A. The use of corticosteroids in home palliative care. Support Care
Cancer. 2001;9(5):386-89.
11. Piper JM, Ray WA, Daugherty JR, Griffin MR. Corticosteroid use and peptic ulcer disease: Role of
nonsteroidal anti-inflammatory drugs. Ann Intern Med. 1991;114(9):735-40.
12. Talley NJ, Hu WH. Corticosteroid therapy does not induce peptic ulcer. ACP J Club. 1995;122:81.
13. Lester RS, Knowles SR, Shear NH.The risk of systemic corticosteroid use. Derm Clinics.1988;16(2):277-88.
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J A N UARY 2007
Evidence Matters is Hospice
Pharmacia’s bi-monthly newsletter devoted to sharing clinical
information and promoting
an evidence-based approach to
care in palliative medicine.
Evidence Matters
Dear Clinician,
Welcome to Hospice Pharmacia’s first edition of Evidence Matters, a newsletter devoted to
sharing clinical information and promoting an evidence-based approach to palliative medicine. Our first topic is The Use of Corticosteroids for Treating Bone Metastases.
This newsletter is a production of the Quality Outcomes team at excelleRx. Our team is
dedicated to building the evidence base and improving outcomes related to chronic illness
and palliative care. We welcome your feedback and questions as well as your suggestions
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