Post on 02-Apr-2015
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Overview of Cancer-Related Vertebral Compression
Fractures
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Objectives
Describe Vertebral Compression Fractures (VCF)
Describe the scope of the problem in patients with cancer
Review evidence-based interventions
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Wedge Biconcave Crush
1. Genant HK et al. J Bone Miner Res. 1993;8:1137–1148.
Vertebral Compression Fractures
VCFs are fractures of the bones of the spinal column Occur when the vertebral body fractures or collapses because the
bone is too weak Weakness can be caused by primary bone cancer, metastatic bone
disease, and cancer- or chemotherapy- related osteoporosis
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Cancer-Related VCFs
An estimated 75K-100K cancer-induced VCFs occur annually in the U.S. Stage IV breast and lung
cancers All stages of Multiple
Myeloma Stages III and IV of
prostate cancer
Additional data calculations on file, Medtronic Spine LLC. Compiled from the following articles: 1.Hortobagy et al. NEJM. 1996;335:1785-1791.2.Berenson et al. NEJM. 1996;334:488-493.3.Brincker et al. Brit J Haematol. 1998;101:280-286.4.McCloskey et al. Brit J Haematol. 1998;100:317-325.5.Melton et al. J Bone Miner Res. 2005 ;20:487-493.6.Djulbegovic et al. Cochrane Database Syst Rev. 2002; 4, CD003188:1-32.7.Berruti et al. J Urol. 2000; 164:1248-1253.8.Diamond et al. J Urol, 2004;172:529-532.
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Metastatic Bone Disease
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Regulation of Bone Metabolism
1. Roodman. NEJM. 2004;350:1655-1664. Images used with permission from NEJM.
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Metastatic Bone DiseaseEpidemiology
Definition: Tumors in bone arising from distant, non-bone sources.
Most skeletal cancers are metastatic rather than primary1
30-70% of the roughly 563,700 people who die annually of all cancers have bone metastasis.1
Patients with cancer are at elevated risk for osteoporosis and fractures because of both disease and treatment1
1. Coleman. Cancer Treat Rev. 2001;27:165-176.
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Metastatic Bone DiseaseLesion Types
Osteoblastic Increased bone density Does not change bone strength
but decrease bone stiffness Common in patients with prostate
cancer
1. Lieberman et al. ClinOrthopaed Rel Res. 2003;415S:S176-186.2. Patel, DeGroot. Ortho J. 2001;24:612-7.
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Metastatic Bone DiseaseLesion Types
Osteolytic Decrease both bone strength and
density Common in patients with
metastatic cancer and multiple myeloma 70% of multiple myeloma patients
present with osteolytic involvement of the spine1
Higher risk for fracture than blastic lesions2
1. Lieberman et al. Clin Orthopaed Rel Res. 2003;415S:S176-186.2. Patel, DeGroot. Ortho J. 2001;24:612-617.
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Metastatic Bone DiseaseRadiographic Appearance of
Skeletal Metastases
Breast Usually Osteolytic or Mixed
Prostate Usually Osteoblastic
Lung Usually Osteolytic
Thyroid Usually Osteolytic
1. Manoso, Healey. In: Cancer: Principles and Practice of Oncology. 7th ed. 2005:2368-2380.
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Metastatic Bone DiseasePrognosis
Variable survival Many live for years with bony
disease Patients live longer with bone
metastases than with both bone metastases and pulmonary metastases1
Potential for improved QoL Patients with longer median
survival will typically require treatment for skeletal complications
Disease TypeMedian Survival (months)
Multiple Myeloma2 36 – 60+
Breast1 19*
Lung1 3*
Thyroid1 19*
* After disease metastasizes to bone
1. Manoso, Healey. In: Cancer: Principles and Practice of Oncology. 7th ed. 2005:2368-2380.2. Ludwig et al. Blood. 2008 Feb 11. [Epub ahead of print]
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Metastatic Bone DiseaseDiagnostic Tools
Imaging X-ray and/or skeletal survey Computed Tomography (CT) Bone Scan Positron Emission Tomography (PET) Magnetic Resonance Imaging (MRI)
Blood Tests Calcium level, Alkaline Phosphatase, etc.
Needle Bone Biopsy1. Manoso, Healey. In: Cancer: Principles and Practice of Oncology. 7th ed. 2005:2368-2380.
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Metastatic Bone DiseaseTreatment Goals
Control pain and symptomsEradicate or reduce tumor when primary
tumors are involved Prevent neurologic complications Treat pathologic fractures and prevent
recurrent fracture
1. American Cancer Society. How is Bone Metastasis Treated? 2007. Available at: http://www.cancer.org/docroot/CRI/content/CRI_2_4_4X_How_Is_Bone_Metastasis_Treated_66.asp?sitearea=
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Surgery Open and minimally invasive
Radiation therapyRadioisotopes
Strontium Samarium Sm-153 lexidronam [Quadramet®, Cytogen]
Systemic treatment Supportive therapy
Bisphosphonates Analgesics
Metastatic Bone DiseaseAvailable Treatments1,2
1. How is Bone Metastasis Treated? 2007. Available at: http://www.cancer.org/docroot/CRI/content/CRI_2_4_4X_How_Is_Bone_Metastasis_Treated_66.asp?sitearea=
2. Manoso, Healey. In: Cancer: Principles and Practice of Oncology. 7th ed. 2005:2368-2380.
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Metastatic Bone DiseaseClinical Sequelae
Bone damage leads to bone painPathologic fracture
Vertebral compression fractures (VCFs) Long bones
Spinal cord compressionHypercalcemia
1. Roodman. NEJM. 2004;350:1655-1664.
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Vertebral Compression Fractures
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Signs of Vertebral Compression Fractures
Acute Event Sudden onset of back pain
with little or no trauma Point tenderness Girdle/belt/band-like pain Muscle spasms
Chronic Manifestation(s) Loss of height Spinal deformity - kyphosis
Protuberant abdomen
Compiled from the following articles: 1. Coleman. Cancer. 1997;80:1588-1594.2. Lavelle et al. Med Clin N Am. 2007;91:299-314.
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Biomechanics of VCF
Knees bend, pelvis tilts forward to counteract forward bendingChange in balance1
Decrease in gait velocity1
Increased muscle fatigue1
Increased risk of falls and additional fractures2,3
1. Gold, Lee, Tresolini. Working with patients to prevent, treat and manage osteoporosis, 2001.2. Ross et al. Annals Int Med, 1991; 114(11):919-23.3. Myers, Wilson. Spine. 1997;22(24 Suppl):25S-31S.
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Compiled from the following articles: 1. Gold , Silverman The Downward Spiral of Vertebral Osteoporosis: Consequences. Designated by Cedar Sinai Medical Center Press,
2003.2. Podichetty. J Musculoskel Med. 2004;21:372-378.
Radiculopathy Spinal cord
compression
Neurological Consequences
Compression of the abdominal contents
Early satiety, weight loss Kyphosis – curved back Decreased lung function Increased risk of death from
lung disease Spinal instability Risk of more fractures
Biomechanical Consequences
Consequences of Untreated VCF
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Consequences …
Chronic pain Increased
dependence Decreased ability
for activities of daily living
Partial to complete immobility
Functional Consequences
Depression or clinical anxiety or both
Sleep disorder
Psychological Consequences
Compiled from the following articles: 1. Gold, Silverman . The Downward Spiral of Vertebral Osteoporosis: Consequences. Designated by Cedar Sinai Medical Center Press, 2003.2. Podichetty et al. J Musculoskel Med. 2004;21:372-378.3. Lavelle, Carl, Lavelle, Khaleel. Med Clin N Am. 2007:91:299-314.4. Gold. Rheum Dis Clin North Am. 2001; 27:255-62.
Social Consequences
150,000 annual hospital admissions
Higher medical costs
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Future Fracture Risk
After first VCF, risk of subsequent VCF is increased:5-fold after first VCF12-fold after 2 or more VCFs75-fold after 2 or more VCFs
and low bone mass (below the 33rd percentile)
1. Ross et al. Annals Int Med. 1991; 114(11):919-23
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Tumor-Related VCFsSurgical Management
Medical Management, Radiation to the tumor Open Surgical Procedures
Vertebral column reconstruction Oncology patients are generally poor candidates for
open surgery due to soft bone/tumor mass and co-morbidities
Minimally Invasive Procedures Balloon kyphoplasty Vertebroplasty
Compiled from the following articles:
1. Yeh, Berenson. Clin Cancer Res. 2006, 10: 6279-6284.2. Lieberman, Reinhardt. Clin Orthop Relat Res. 2003;(415 Suppl):S176-186.3. Lavelle, Carl, Cavelle, Khaleel. Med Clin N Am. 2007;91:299-314.4. Pateder, Khanna, Lieberman. Orthop Clin N Am. 2007;38:409-418.
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Percutaneous Vertebroplasty
Augmentation of vertebral compression fractures with polymethylmethacrylate
Uses pressure to introduce the materialUsed successfully to treat painDoes not attempt to restore the height of the
collapsed vertebral bodyCement leakage and extravasation can be
problems
Compiled from the following articles: 1. Lieberman, Reinhardt. Clin Orthop Relat Res. 2003;(415 Suppl):S176-186.2. Lavelle, Carl, Cavelle, Khaleel. Med Clin N Am. 2007;91:299-314.3. Pateder, Khanna, Lieberman. Orthop Clin N Am. 2007;38:409-418.
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Tumor-Related VCFsVertebroplasty vs. Balloon Kyphoplasty
Vertebroplasty Balloon Kyphoplasty
Fracture Reduction
Postural Reduction Inflatable Bone Tamp (IBT)
Cavity Creation
-- Inflatable Bone Tamp
Cement Injection
High-pressure injection into interstices
Low-pressure fill into cavity created by IBT
Compiled from the following articles: 1. Lieberman, Reinhardt. Clin Orthop Relat Res. 2003;(415 Suppl):S176-186.2. Lavelle, Carl, Cavelle, Khaleel. Med Clin N Am. 2007;91:299-314.3. Pateder, Khanna, Lieberman. Orthop Clin N Am. 2007;38:409-418.
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Tumor-Related VCFsBalloon Kyphoplasty
Aimed at Stabilizing the Fracture and Correcting Spinal Deformity caused by VCFs
•Indicated for the treatment of pathological fractures of the vertebral body due to osteoporosis, cancer, or benign lesions using a balloon kyphoplasty procedure.
KYPHON® HV-R™ Bone Cement. FDA Premarket Notification Summary. Available at: http://www.fda.gov/cdrh/pdf4/k041584.pdf
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Tumor-Related VCFsBalloon Kyphoplasty Procedure
Minimally invasive Bilateral, 1 cm incisions
Typically one hour per treated fracture General or local anesthesia (supplemented
by conscious sedation) May require an overnight hospital stay
Compiled from the following articles: 1. Lieberman, Reinhardt. Clin Orthop Relat Res. 2003;(415 Suppl):S176-186.2. Lavelle, Carl, Cavelle, Khaleel. Med Clin N Am. 2007;91:299-314.3. Pateder, Khanna, Lieberman. Orthop Clin N Am. 2007;38:409-418.
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Balloon Kyphoplasty
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Vertebral Augmentation : Clinical Outcomes for Oncology Patients
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Balloon Kyphoplasty and Vertebroplasty for Vertebral Compression Fractures: A
Comparative Systematic Review of Efficacy and Safety
Taylor, Taylor, Fritzell. Spine. 2006;31:2747–2755
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Meta-Analysis of Complications
Total Procedure-Related
Complications
Cement-Related Complications
Access-Related Complications
Non-Device- Related
Complications
Balloon KyphoplastyN = 1947 patients
14(0.7%)
3(0.2%)
4(0.2%)
7(0.4%)
VertebroplastyN = 6808 patients
199(2.9%)
132(1.9%)
28(0.4%)
39(0.6%)
p-value 0.0002* <0.0001* 0.3791 0.8781
*Balloon kyphoplasty has statistically significant lower complication rates compared to vertebroplasty
Data on file, Medtronic Spine LLC.
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Taylor Study* Cement Leakage Results
p < 0.0001BK: 90/1111 = 8%VP: 614/1551 = 40%
(p-value not reported)BK: 0/1094 = 0%VP: 8/275 = 3%
Taylor, Taylor, Fritzell. Spine. 2006;31:2747–2755 – See Table 6.*Includes fracture of all etiologies. BK = balloon kyphoplasty. VP = vertebroplasty.
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Taylor Study Adverse Events
BK: 1/291 = 0.3%VP: 15/803 = 1.8%
BK: 0/195 = 0%VP: 3/631 = 0.5%
BK: 1/322 = 0.3%VP: 32/1100 = 2.5%
Taylor, Taylor, Fritzell. Spine. 2006;31:2747–2755 – See Table 6.
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Patient IdentificationPatient cancer diagnosis
Metastatic breast cancer, lung cancer, prostate cancer, and others
Multiple myelomaPatient demographics
Age, gender, type of cancer, comorbiditiesPatient self-report of symptoms
Sudden pain in the back Persistent back pain with developing other signs
Kyphosis, incontinence, respiratory difficulties, balance problems
Identification of Fractures
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Patient educationPain is NOT a necessary part of the cancer
experienceVCF treatment options, including balloon
kyphoplastyAdvocacy
Awareness and referrals Where can the procedure be done? Who is qualified to perform it?
Patient Education
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Barriers to useReimbursement
What is your patient’s insurance coverage?Comfort level of spine physician/interventionalist
Does the specialist have a full understanding of balloon kyphoplasty?
Has he/she performed it multiple times? Can she/he refer the patient to a qualified practitioner?
Barriers to Use
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Monitoring post-procedure Immediate post-surgical monitoring usually done
by surgical staffLonger term follow-up may be needed
Monitor symptoms, status changes PCP be the first to note new symptoms, new fractures
Considerations
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Balloon Kyphoplasty Case Study
Patient: 76 YO FemaleDiagnosis: Metastatic Lung CancerFracture Reduced: T8, 8 weeks old
Courtesy of Henry Small, M.D., Houston, TX
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Indications for UseNot Investigational – Indicated for Cancer-Related Fractures
KYPHON® HV-R™ Bone Cement was originally cleared for marketing un the United States in 2004 for treatment of pathologic VCFs using a balloon kyphoplasty procedure
Indicated for the treatment of pathological fractures of the vertebral body due to osteoporosis, cancer, or benign lesions using a balloon kyphoplasty procedure. Cancer includes multiple myeloma and metastatic lesions, including those arising from breast or lung cancer, or lymphoma. Benign lesions include hemangioma and giant cell tumor.
KYPHON® Inflatable Bone Tamps were originally cleared for
marketing in the United States in 1998
Intended to be used as conventional bone tamps for the reduction of fractures and/or creation of a void in cancellous bone in the spine (including use during balloon kyphoplasty with KYPHON®
HV-R™ Bone Cement), hand, tibia, radius and calcaneus.
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Risk Statement
Although the complication rate with KYPHON® Balloon Kyphoplasty has been demonstrated to be low, as with most surgical procedures, there are risks associated with the procedure, including serious complications. For complete information regarding indications for use, contraindications, warnings, precautions, adverse events, and methods of use, please reference the devices’ Instructions for Use.
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Summary
VCFs can be significant problems for patients with cancer Pain Functional impairment
Providers can identify and refer patients for appropriate therapy, including balloon kyphoplasty
Balloon kyphoplasty can provide significant pain relief, restore vertebral body height, and improve function for many patients with cancer
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Disclosures The physicians referenced may be paid consultants of, and
research cited may have been funded partially or in whole by, Medtronic.
Although the complication rate with Balloon Kyphoplasty has been demonstrated to be low, as with most surgical procedures, there are risks associated with Balloon Kyphoplasty, including serious complications. For complete information regarding indications for use, contraindications, warnings, precautions, adverse events and methods of use, please reference the devices’ Instructions for Use.
For further information, please call Medtronic at 1-877-459-7466 and/or visit Medtronic’s web site www.kyphon.com.
KYPHON is a registered trademark, and HV-R is a trademark of Medtronic.
© 2008 Medtronic Spine LLC. All rights reserved. 16001110
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Questions and Discussion
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References 1. American Cancer Society. How is Bone Metastasis Treated? 2007. Available at:
http://www.cancer.org/docroot/CRI/content/CRI_2_4_4X_How_Is_Bone_Metastasis_Treated_66.asp?sitearea=2. Andre F, Slimane K, Bachelot T, et al. Breast cancer with synchronous metastases: trends in survival during a 14-year period. J
of Clin Oncol. 2004;22:3302-3308.3. Berenson JR, Lichtenstein A, Porter L, et al. Efficacy of pamidronate in reducing skeletal events in patients with advanced
multiple myeloma. NEJM. 1996;334:488-493.4. Berruti A, Dogliotti L, Bitossi R, et al. Incidence of skeletal complications in patients with bone metastatic prostate cancer and
hormone refractory disease. J. Urol. 2000;164: 1248-1253.5. Brincker H, Westin J, Abildgaard N, et al. Failure of oral pamidronate to reduce skeletal morbidity in multiple myeloma: a double-
blind placebo controlled trial. Brit J Haematol. 1998;101:280-286.6. Body J. Effectiveness and cost of bisphosphonate therapy in tumor bone disease. Cancer. 2003;Suppl 97:859-865. 7. Clinical Trials. Gov. 2008. Identifier: NCT00211237. Available at http://www.clinicaltrials.gov/ct2/show/NCT00211237?
term=kyphoplasty&rank=28. Coleman RE. Metastatic bone disease: clinical features, pathophysiology and treatment strategies. Cancer Treat Rev.
2001;27:165-176.9. Coleman RE. Uses and abuses of bisphosphonates. Ann Oncol. 2000;11:179-184. 10. Coleman RE. Bisphosphonates: clinical experience. Oncologist. 2004;9(suppl 4):14-27.11. Compression Fractures. 2006. Available at http://health.nytimes.com/health/guides/disease/compression-fractures-of-the-back/
overview.html12. Diamond TH, Bucci J, Kersley JH, et al. Osteoporosis and spinal fractures in men with prostate cancer: risk factors and effects of
androgen deprivation therapy. J. Urol. 2004;172: 529-532.13. Djulbegovic B, Wheatley K, Ross J, et al. Bisphosphonates in multiple myeloma (Review). Cochrane Database Sys Rev. 2002;
Issue 4. Art. No.: CD003188:1-32.14. Durie B. Understanding balloon kyphoplasty and myeloma-induced vertebral compression fractures. International Myeloma
Foundation. 2006; June:16. 15. Falkmer U, Jarhult J, Wersall P, Cavallin-Shahl E. A systematic overview of radiation therapy effects in skeletal metastases. Acta
Oncologica. 2003;42:620-633. 16. Fourney D, Schomer DF, Nader R, et al. Percutaneous vertebroplasty and kyphoplasty for painful vertebral body fractures in
cancer patients. J Neurosurg (Spine 1). 2003;98:21-30. 17. Genant HK , Wu CY, vanKuijk K, Nevitt MC. Vertebral fracture assessment using a semiquantitative technique. J Bone Miner
Res. 1993;8:1137–1148.18. Gold DT, Lee LS, Tresolini CP, eds. Working with patients to prevent, treat and manage osteoporosis: a curriculum guide for the
health professions. 3rd ed. Durham, NC: Center for the Study of Aging and Human Development, Duke University; 2001.19. Gold DT. The nonskeletal consequencesof osteoporotic fractures. Psychologicand social outcomes. Rheum Dis ClinNorth Am.
2001; 27:255-62.20. Gold DT, Silverman SL. The Downward Spiral of Vertebral Osteoporosis: Consequences. Designated by Cedar Sinai Medical
Center Press, 2003.21. Hadjipavlou AG, Tzermiadianos MN, Katonis PG, Szpalski M, et al. Percutaneous vertebroplasty and balloon kyphoplasty for the
treatment of osteoporotic vertebral compression fractures and osteolytic tumours. J. Bone Joint Surg Br. 2005;87:1595-1604.
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References (continued)22. Hortobagyi GN, Theriault RL, Porter L, et al. Efficacy of pamidronate in reducing skeletal complications in patients with breast
cancer and lytic bone metastases. NEJM. 1996;335:1785-1791.23. Hortobagyi GN, Theriault RL, Lipton A, et al. Long-term prevention of skeletal complications of metastatic breast cancer with
pamidronate. J Clin Oncol. 1998;16:2038-2044.24. Hulme PA, Krebs J, Ferguson SJ, Berlemann U, et al. Vertebroplasty and kyphoplasty: a systematic review of 69 clinical studies.
Spine. 2006;31:1983-2001.25. Janjan N. Bone metastases: approaches to management. Sem Oncol. 2001;28:28-34.26. Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ. Cancer statistics, 2007. CA Cancer J Clin. 2007;57:43-66.27. Kyphon Data on File. Literature review conducted as of July, 2004, Kyphon Prospective Study.28. KYPHON® HV-R™ Bone Cement. FDA Premarket Notification Summary. 2004. Available at:
http://www.fda.gov/cdrh/pdf4/k041584.pdf29. Lane J, Hong R, Koob J, et al. (2004) Kyphoplasty enhances function and structural alignment in multiple myeloma. Clin Orthop
Rel Res. 2004;426:49-53.30. Lavelle W, Carl A, Lavelle ED, Khaleel MA. Vertebroplasty and kyphoplasty. Med Clin N Am. 2007:91:299-314.31. Lieberman I, Reinhardt MK. Vertebroplasty and kyphoplasty for osteolytic vertebral collapse. Clin Orthop Rel Res.
2003;415(S):176-186.32. Lipton A, Small E, Saad F, et al. The new bisphosphonate, Zometa (zoledronic acid), decreases skeletal complications in both
osteolytic and osteoblastic lesions: a comparison to pamidronate. Cancer Invest. 2002;20 Suppl. 2:45-54.33. Ludwig Hm Durie BG, Bolejack V, et al. Myeloma in patients under age 50 presents with more favorable features and shows
better survival: an analysis of 10,549 patients from the International Myeloma Working Group. Blood. 2008 Feb 11. [Epub ahead of print]
34. McCloskey EV, Guest JF, Kanis JA. The clinical and cost considerations of bisphosphonates in preventing bone complications in patients with metastatic breast cancer or multiple myeloma. Drugs. 2001;61:1253-1274.
35. McCloskey EV, MacLennan JC, Drayson MT, et al. (1998) A randomized trial of the effect of clodronate on skeletal morbidity in multiple myeloma. Br J. Haematol. 1998;100:317-325.
36. Melton LJ 3d, Kyle RA, Achenbach SJ, et al. Fracture risk with multiple myeloma: a population-based study. J Bone Min Res. 2005;20:487-493.
37. Manoso MM, Healey JH. Metastatic cancer to the bone. In: Cancer: Principles and Practice of Oncology. 7th ed. Philadelphia, PA: Lippincott Williams and Wilkins; 2005:2368-2380.
38. Myers ER, Wilson SE. Biomechanics of osteoporosis and vertebral fracture. Spine. 1997;22(24 Suppl):25S-31S .39. National Cancer Institute. SEER Cancer Statistics Review, 1975-2004. 2007. Available at:
http://seer.cancer.gov/csr/1975_2004/results_merged/topic_prevcounts.pdf40. Pateder DB, Khanna AJ, Lieberman IH. Vertebroplasty and kyphoplasty for the management of osteoporotic vertebral
compression fractures. Orthop Clin N Am. 2007;38:409-418 41. Patel B, DeGroot H. Evaluation of the risk of pathologic fractures secondary to metastatic bone disease. Ortho J. 2001;24:612-
617.42. Paterson AH, Powles TJ, Kanis JA, et al. (1993) Double-blind controlled trial of oral clodronate in patients with bone metastases
from breast cancer. J Clin Oncol. 1993;11:59-65.
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References (continued)43. Perez EA. management of bone metastases in advanced breast cancer. Cancer Control. 1999; 6(5 Suppl 2):28-
31.44. Podichetty V, et al. Managing vertebral compression fractures and multiple myeloma in older patients. J
Musculoskel Med. 2004;21:372-378.45. Ray NF, Chan JK, Thamer M, Melton LJ 3rd. Medical expenditures for the treatment of osteoporotic fractures in
the u.s. in 1995: report from the national osteoporosis foundation. J Bone Min Res. 1997;12:24-35.46. Roodman GD. Mechanisms of bone metastases. NEJM. 2004; 350:1655-1664.47. Ross PD, Davis JW, Epstein RS, Wasnich RD. Pre-existing fractures and bone mass predict vertebral fracture
incidence in women. Annals Int Med, 1991; 114(11):919-923.48. Sirohi B, Powles R. Seminar: multiple myeloma. Lancet. 2004;363:875-887.49. Stricker CT. Endocrine effects of breast cancer treatment. Sem Oncol Nurs. 2007;23(1):55-70.50. TaylorRS, Taylor RJ, Ftitzell P. Balloon kyphoplasty and vertebroplasty for vertebral compression fractures: a
comparative systematic review of efficacy and safety. Spine. 2006;31:2747-2755.51. Theriault RL, Lipton A, Hortobagyi GN, et al. Pamidronate reduces skeletal morbidity in women with advanced
breast cancer and lytic bone lesions: a randomized, placebo-controlled trial. Protocol 18 Aredia Breast Cancer Study Group. J Clin Oncol. 1999;17:846-854.
52. Theriault RL. Task force reports on bone health in patients with cancer. J Natl Compr Canc Netw. 2006;4 Suppl 2:S1-20; quiz S21-2.
53. Tong D, Gillick L, Hendrickson FR. The Palliation of symptomatic osseous metastases: final results of the study by the Radiation Therapy Oncology Group. Cancer. 1982;50:893-899.
54. West HJ. Onc.Talk. Bone Metastases. 2007. Available at: http://onctalk.com/2007/02/17/bone-metastases-in-lung-cancer-an-introduction/
55. Yeh HS, Berenson JR. Treatment of myeloma bone disease. Clin Cancer Res. 2006;10:6279-6284. 55. Van Staa TP, Leufkens HG, Abenhaim L, Zhang B, Cooper C. Use of oral corticosteroids and risk of fractures. J
Bone Miner Res. 2000;15:993–1000.