1. 16001110 Overview of Cancer-Related Vertebral Compression Fractures

2. 16001110 Objectives Describe Vertebral Compression Fractures (VCF) Describe the scope of the problem in patients with cancer Review evidence-based interventions

3. 16001110 WedgeBiconcaveCrush 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

4. 16001110 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.

5. 16001110 Metastatic Bone Disease

6. 16001110 Regulation of Bone Metabolism 1.Roodman. NEJM. 2004;350:1655-1664. Images used with permission from NEJM.

7. 16001110 Metastatic Bone Disease Epidemiology Definition: Tumors in bone arising from distant, non-bone sources. Most skeletal cancers are metastatic rather than primary 1 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 treatment 1 1.Coleman. Cancer Treat Rev. 2001;27:165-176.

8. 16001110 Metastatic Bone Disease Lesion 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.

9. 16001110 Metastatic Bone Disease Lesion 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 spine 1  Higher risk for fracture than blastic lesions 2 1. Lieberman et al. Clin Orthopaed Rel Res. 2003;415S:S176-186. 2. Patel, DeGroot. Ortho J. 2001;24:612-617.

10. 16001110 Metastatic Bone Disease Radiographic Appearance of Skeletal Metastases BreastUsually Osteolytic or Mixed ProstateUsually Osteoblastic LungUsually Osteolytic ThyroidUsually Osteolytic 1.Manoso, Healey. In: Cancer: Principles and Practice of Oncology. 7th ed. 2005:2368-2380.

11. 16001110 Metastatic Bone Disease Prognosis Variable survival  Many live for years with bony disease  Patients live longer with bone metastases than with both bone metastases and pulmonary metastases 1 Potential for improved QoL  Patients with longer median survival will typically require treatment for skeletal complications Disease Type Median Survival (months) Multiple Myeloma 2 36 – 60+ Breast 1 19* Lung 1 3* Thyroid 1 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]

12. 16001110 Metastatic Bone Disease Diagnostic 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 Biopsy 1.Manoso, Healey. In: Cancer: Principles and Practice of Oncology. 7th ed. 2005:2368-2380.

13. 16001110 Metastatic Bone Disease Treatment Goals Control pain and symptoms Eradicate 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=

14. 16001110 Surgery  Open and minimally invasive Radiation therapy Radioisotopes  Strontium  Samarium Sm-153 lexidronam [ Quadramet ®, Cytogen ] Systemic treatment Supportive therapy  Bisphosphonates  Analgesics Metastatic Bone Disease Available Treatments 1,2 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= 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.

15. 16001110 Metastatic Bone Disease Clinical Sequelae Bone damage leads to bone pain Pathologic fracture  Vertebral compression fractures (VCFs)  Long bones Spinal cord compression Hypercalcemia 1.Roodman. NEJM. 2004;350:1655-1664.

16. 16001110 Vertebral Compression Fractures

17. 16001110 Signs of Vertebral Compression Fractures Acute Event n Sudden onset of back pain with little or no trauma n Point tenderness n Girdle/belt/band-like pain n Muscle spasms Chronic Manifestation(s) n Loss of height n Spinal deformity - kyphosis n 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.

18. 16001110 Biomechanics of VCF Knees bend, pelvis tilts forward to counteract forward bending  Change in balance 1  Decrease in gait velocity 1  Increased muscle fatigue 1  Increased risk of falls and additional fractures 2,3 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.

19. 16001110 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

20. 16001110 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

21. 16001110 Future Fracture Risk After first VCF, risk of subsequent VCF is increased:  5-fold after first VCF  12-fold after 2 or more VCFs  75-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

22. 16001110 Tumor-Related VCFs Surgical 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.

23. 16001110 Percutaneous Vertebroplasty Augmentation of vertebral compression fractures with polymethylmethacrylate Uses pressure to introduce the material Used successfully to treat pain Does not attempt to restore the height of the collapsed vertebral body Cement 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.

24. 16001110 Tumor-Related VCFs Vertebroplasty vs. Balloon Kyphoplasty VertebroplastyBalloon Kyphoplasty Fracture Reduction Postural ReductionInflatable 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.

25. 16001110 Tumor-Related VCFs Balloon 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

26. 16001110 Tumor-Related VCFs Balloon 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.

27. 16001110 Balloon Kyphoplasty

28. 16001110 Vertebral Augmentation : Clinical Outcomes for Oncology Patients

29. 16001110 Balloon Kyphoplasty and Vertebroplasty for Vertebral Compression Fractures: A Comparative Systematic Review of Efficacy and Safety Taylor, Taylor, Fritzell. Spine. 2006;31:2747–2755

30. 16001110 Meta-Analysis of Complications Total Procedure- Related Complications Cement-Related Complications Access-Related Complications Non-Device- Related Complications Balloon Kyphoplasty N = 1947 patients 14 (0.7%) 3 (0.2%) 4 (0.2%) 7 (0.4%) Vertebroplasty N = 6808 patients 199 (2.9%) 132 (1.9%) 28 (0.4%) 39 (0.6%) p-value 0.0002*<0.0001*0.37910.8781 *Balloon kyphoplasty has statistically significant lower complication rates compared to vertebroplasty Data on file, Medtronic Spine LLC.

31. 16001110 Taylor Study* Cement Leakage Results p < 0.0001 BK: 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.

32. 16001110 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.

33. 16001110 Patient Identification  Patient cancer diagnosis Metastatic breast cancer, lung cancer, prostate cancer, and others Multiple myeloma  Patient demographics Age, gender, type of cancer, comorbidities  Patient 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

34. 16001110 Patient education  Pain is NOT a necessary part of the cancer experience  VCF treatment options, including balloon kyphoplasty Advocacy  Awareness and referrals Where can the procedure be done? Who is qualified to perform it? Patient Education

35. 16001110 Barriers to use  Reimbursement 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

36. 16001110 Monitoring post-procedure  Immediate post-surgical monitoring usually done by surgical staff  Longer term follow-up may be needed Monitor symptoms, status changes PCP be the first to note new symptoms, new fractures Considerations

37. 16001110 Balloon Kyphoplasty Case Study Patient: 76 YO Female Diagnosis: Metastatic Lung Cancer Fracture Reduced: T8, 8 weeks old Courtesy of Henry Small, M.D., Houston, TX

38. 16001110 Indications for Use Not 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.

39. 16001110 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.

40. 16001110 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

41. 16001110 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.www.kyphon.com  KYPHON is a registered trademark, and HV-R is a trademark of Medtronic. © 2008 Medtronic Spine LLC. All rights reserved. 16001110

42. 16001110 Questions and Discussion

43. 16001110 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=2 8.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.html 12.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.

44. 16001110 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.pdf 29.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.pdf 40.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.

45. 16001110 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.