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Skeletal Metastases: Optimal Management Today

  • John Kosteva*
  • Corey Langer
Chapter
Part of the Cancer Drug Discovery and Development book series (CDD&D)

Abstract

The skeletal system is a frequent site of metastatic involvement in patients with advanced malignancy, especially in those with breast and prostate cancer, lung cancer, and myeloma. Skeletal metastases involve an imbalance between the osteoclastic and osteoblastic activity of normal bone remodeling. Skeletal metastases may result in various complications, also known as skeletal-related events, including pain, pathologic fractures, hypercalcemia, and nerve or spinal cord compression. The consequences of skeletal metastases and their treatment may have a substantial impact on health care economics. Skeletal metastases can be detected by a variety of radiographic and nuclear imaging modalities. In the modern era, PET imaging may ultimately supplant bone scan as a diagnostic approach. Treatment for skeletal metastases includes rest and analgesics, bisphosphonates, radiation, radionuclides, and surgery. In addition, standard systemic approaches for the underlying cancer may help palliate osseous involvement.

Keywords:

Bone metastases Skeletal metastases Bisphosphonates Skeletal-related event Zoledronic acid Pamidronate Radiotherapy Radionuclides Economic Imaging 

References

  1. 1.
    Coleman RE. 1997; Skeletal complications of malignancy. Cancer 80:1588–1594.PubMedCrossRefGoogle Scholar
  2. 2.
    Mundy GR. 2002; Metastasis to bone: causes, consequences and therapeutic opportunities. Nat Rev Cancer 2:584–593.PubMedCrossRefGoogle Scholar
  3. 3.
    Coleman RE. 2001; Metastatic bone disease: clinical features, pathophysiology and treatment strategies. Cancer Treat Rev 27:165–176.PubMedCrossRefGoogle Scholar
  4. 4.
    Tong D, Gillick L, Hendrickson FR. 1982; The palliation of symptomatic osseous metastases: final results of the study by Radiation Therapy Oncology Group. Cancer 50:893–899.PubMedCrossRefGoogle Scholar
  5. 5.
    Batson O. 1940; The function of the vertebral veins and their role in the spread of metastases. Ann Surg 112:138.PubMedCrossRefGoogle Scholar
  6. 6.
    Kahn D, Weiner GJ, Ben-Haim S, et al. 1994; Positron emission tomographic measurement of bone marrow blood flow to the pelvis and lumbar vertebrae in young normal adults Blood 83:958–963.PubMedGoogle Scholar
  7. 7.
    Hauschka PV, Mavrakos AE, Iafrati MD, et al. 1986; Growth factors in bone matrix: isolation of multiple types by affinity chromatography on heparin-sepharose J Biol Chem 261:12665–12674.PubMedGoogle Scholar
  8. 8.
    Kodama H, Nose M, Niida S, et al. 1991; Essential role of macrophage colony-stimulating factor in the osteoclast differentiation supported by stromal cells J Exp Med 173:1291–1294.PubMedCrossRefGoogle Scholar
  9. 9.
    Lacey DL, Timms E, Tan HL, et al. 1998; Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation Cell 93:165–176.PubMedCrossRefGoogle Scholar
  10. 10.
    Blair HC, Teitelbaum SL, Ghiselli R, et al. 1989; Osteoclastic bone resorption by a polarized vacuolar proton pump Science 245:855–857.PubMedCrossRefGoogle Scholar
  11. 11.
    Mundy GR. 1997; Mechanisms of bone metastases. Cancer 80:1546.PubMedCrossRefGoogle Scholar
  12. 12.
    Sato K, Fujii Y, Kasano K, et al. 1988; Production of interleukin-1 alpha and a parathyroid hormone-like factor by a squamous cell carcinoma of the esophagus derived from a patient with hypercalcemia J Clin Endocrinol Metab 67:592.PubMedCrossRefGoogle Scholar
  13. 13.
    Cheung WC, Van Ness B. 2002; Distinct IL-6 signal transduction leads to growth arrest and death in B cells or growth promotion and cell survival in myeloma cells. Leukemia 16:1182–1188.PubMedCrossRefGoogle Scholar
  14. 14.
    Kurihara N, Bertolini D, Suda T, et al. 1990; IL-6 stimulates osteoclast-like multinucleated cell formation in long term human marrow cultures by inducing IL-1 release J Immunol 144:4226–4230.PubMedGoogle Scholar
  15. 15.
    Wo Z, Bonewald LF, Oreffo ROC, et al. 1990; The potential role of procathepsin D secreted by breast cancer cells in bone resorptionCalcium Regulation and Bone Metabolism. Elsevier. Amsterdam, 304.Google Scholar
  16. 16.
    Meyer T, Hart I. 1998; Mechanism of tumour metastasis. Eur J Cancer 34:214.PubMedCrossRefGoogle Scholar
  17. 17.
    Higinbotham N, Marcove R. 1965; Management of pathologic fractures. J Trauma 5:792.PubMedCrossRefGoogle Scholar
  18. 18.
    Rosen L, Gordon D, Tchekmedyian S, et al. 2003; Zoledronic acid versus placebo in the treatment of skeletal metastases in patients with lung cancer and other solid tumors: a phase III, double-blind, randomized trial. The Zoledronic Acid Lung Cancer and Other Solid Tumors Study Group J Clin Oncol 21:3150–3157.PubMedCrossRefGoogle Scholar
  19. 19.
    Groot MT, Boeken Kruger CG, Pelger RC, et al. 2003; Costs of prostate cancer metastatic to the bone in the Netherlands Eur Urol 43:226–232.PubMedCrossRefGoogle Scholar
  20. 20.
    Delea T, McKiernan J, Brandman J, et al. 2006; Retrospective study of the effect of skeletal complications on total medical care costs in patients with bone metastases of breast cancer seen in typical clinical practice J Support Oncol 4:341–347.PubMedGoogle Scholar
  21. 21.
    Delea T, McKiernan J, Liss M, et al. Cost of skeletal complications in patients with multiple myeloma [Abstract]. IX International Multiple Myeloma Workshop; Salamanca, Spain; May 23–27, 2003.Google Scholar
  22. 22.
    Delea T, Langer C, McKiernan J, et al. 2004; The cost of treatment of skeletal-related events in patients with bone metastases from lung cancer Oncology 67(5–6):390–396.CrossRefGoogle Scholar
  23. 23.
    Eustace S, Tello R, DeCarvalho V, et al. 1997; A comparison of whole-body turboSTIR MR imaging in planar 99mTc-methylene diphosphonate scintigraphy in the examination of patients with suspected skeletal metastases AJR Am J Roentgenol 169.:1655PubMedGoogle Scholar
  24. 24.
    Galasko C. 1969; The detection of skeletal metastases from mammary cancer by gamma camera scintigraphy. Br J Surg 56:757–764.PubMedCrossRefGoogle Scholar
  25. 25.
    Bury T, Barreto A, Daenan F, et al. 1998; Fluorine-18 deoxyglucose positron emission tomography for the detection of bone metastases in patients with non-small cell lung cancer Eur J Nucl Med 25:1244–1247.PubMedCrossRefGoogle Scholar
  26. 26.
    Gayed I, Vu T, Johnson M, et al. 2003; Comparison of bone and 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography in the evaluation of bony metastases in lung cancer. Mol Imaging Biol 5:26–31.PubMedCrossRefGoogle Scholar
  27. 27.
    Lauenstein T, Freudenberg L, Goehde S, et al. 2002; Whole-body MRI using a rolling table platform for the detection of bone metastases Eur Radiol 12:2091.PubMedGoogle Scholar
  28. 28.
    Shreve PD, Anzai Y, Wahl RL. 1999; Pitfalls in oncologic diagnosis with FDG PET imaging: physiologic and benign variants. Radiographics 19:61–77.PubMedGoogle Scholar
  29. 29.
    Marom E, McAdams HP, Erasmus J, et al. 1999; Staging non-small cell lung cancer with whole-body PET Radiology 212:803–809.PubMedGoogle Scholar
  30. 30.
    Savage P, Ward W. 2000; Medical management of metastatic skeletal disease. Orthop Clin North Am 31:545–555.PubMedCrossRefGoogle Scholar
  31. 31.
    Nishimura K, Nonomura N, Yasunaga Y, et al. 2000; Low doses of oral dexamethasone for hormone-refractory prostate carcinoma Cancer 89:2570.PubMedCrossRefGoogle Scholar
  32. 32.
    Harvey H. 1997; Issues concerning the role of chemotherapy and hormonal therapy of bone metastases from breast carcinoma. Cancer 80:1646.PubMedCrossRefGoogle Scholar
  33. 33.
    Lipton A, Theriault R, Leff R, et al. 1997; Long-term reduction of skeletal complications in breast cancer patients with osteolytic bone metastases receiving hormone therapy, by monthly 90 mg pamidronate (Aredia) infusions Proc Am Soc Clin Oncol:16A531.Google Scholar
  34. 34.
    Rogers MJ, Watts DJ, Russell RGG. 1997; Overview of bisphosphonates. Cancer 80(Suppl 8):1652–1660.CrossRefGoogle Scholar
  35. 35.
    Vincenzi B, Santini D, Dicuonzo G, et al. 2005; Zoledronic acid-related angiogenesis modifications and survival in advanced breast cancer patients J Interferon Cytokine Res 25:144–151.PubMedCrossRefGoogle Scholar
  36. 36.
    Luckman SP, Hughes DE, Coxon FP, et al. 1998; Nitrogen-containing bisphosphonates inhibit the mevalonate pathway and prevent post-translational phenylation of GTP-binding proteins including Ras J Bone Miner Res 13:581–589.PubMedCrossRefGoogle Scholar
  37. 37.
    Durie BG, Katz M, Crowley J. 2005; Osteonecrosis of the jaw and bisphosphonates. N Engl J Med 353:99–102.PubMedCrossRefGoogle Scholar
  38. 38.
    Bamias A, Kastritis E, Bamia C, et al. 2005; Osteonecrosis of the jaw in cancer after treatment with bisphosphonates: incidence and risk factors J Clin Oncol 23:8580–8587.PubMedCrossRefGoogle Scholar
  39. 39.
    Lacy MQ, Dispenzieri A, Gertz A, et al. 2006; Mayo clinic consensus statement for the use of bisphosphonates in multiple myeloma Mayo Clin Proc 81:1047–1053.PubMedCrossRefGoogle Scholar
  40. 40.
    Wong R, Witten PJ. Bisphosphonates for the relief of pain secondary to bone metastases. Cochrane Database Syst Rev 2003; 2:CD002068.Google Scholar
  41. 41.
    Hortobagyi GN, Theriault RL, Porter L, et al. 1996; Efficacy of pamidronate in reducing skeletal complications in patients with breast cancer and lytic bone metastases N Engl J Med 335:1785–1791.PubMedCrossRefGoogle Scholar
  42. 42.
    Hortobagyi GN, Theriault RL, Lipton A, et al. 1998; Long-term prevention of skeletal complications of metastatic breast cancer with pamidronate J Clin Oncol 16:2038–2044.PubMedGoogle Scholar
  43. 43.
    Theriault RL, Lipton A, Hortobagyi GN, et al. 1999; Pamidronate reduces skeletal morbidity in women with advanced breast cancer and lytic bone lesions: a randomized, placebo-controlled trial J Clin Oncol 17:846–854.PubMedGoogle Scholar
  44. 44.
    Lipton A, Theriault RL, Hortobagyi GN, et al. 2000; Pamidronate prevents skeletal complications and is effective palliative treatment in women with breast carcinoma and osteolytic bone metastases: long term follow-up of two randomized, placebo-controlled trials Cancer 88:1082–1090.PubMedCrossRefGoogle Scholar
  45. 45.
    Berenson JR, Lichtemstein A, Porter L, et al. 1998; Long-term pamidronate treatment of advanced multiple myeloma patients reduces skeletal events J Clin Oncol 16:593–602.PubMedGoogle Scholar
  46. 46.
    Vargha ZO, Glickasman AS, Boland J.. 1969; Single-dose radiation therapy in the palliation of metastastic disease Radiology 93:1181–1184.PubMedGoogle Scholar
  47. 47.
    Steenland E, Leer JW, van Houwelingen H, et al. 1999; The effect of a single fraction compared to multiple fractions on painful bone metastases: a global analysis of the Dutch Bone Metastasis Study Radiother Oncol 52:101.PubMedCrossRefGoogle Scholar
  48. 48.
    Van der Linden YM, Lok JJ, Steenland E, et al. 2004; Single fraction radiotherapy is efficacious: a further analysis of the Dutch Bone Metastasis Study controlling for the influence of retreatment Int J Radiat Oncol Biol Phys 59:528.PubMedCrossRefGoogle Scholar
  49. 49.
    Bone Pain Trial Working Party. 8 Gy single fraction radiotherapy for the treatment of metastatic skeletal pain: randomized comparison with a multifraction schedule over 12 months of patient follow-up. Radiother Oncol 1999; 52:111.Google Scholar
  50. 50.
    Hartsell WF, Scott CB, Bruner DW, et al. 2005; Randomized trial of short- versus long-course radiotherapy for palliation of painful bone metastases J Natl Cancer Inst 97:798.PubMedCrossRefGoogle Scholar
  51. 51.
    Townsend P, Rosenthal H, Smalley S, et al. 1994; Impact of postoperative radiation therapy and other perioperative factors on outcome after orthopedic stabilization of impending or pathologic fractures due to metastatic disease J Clin Oncol 12:2345.PubMedGoogle Scholar
  52. 52.
    Porter A, McEwan AJ, Powe J, et al. 1993; Results of a randomized phase-III trial to evaluate the efficacy of strontium-89 adjuvant to local field external beam irradiation in the management of endocrine resistant metastatic prostate cancer Int J Radiat Oncol Biol Phys 25:805–813.PubMedCrossRefGoogle Scholar
  53. 53.
    Quilty PM, Kirk D, Bolger JJ, et al. 1994; A comparison of the palliative effects of strontium-89 and external beam radiotherapy in metastatic prostate cancer Radiother Oncol 31:33–40.PubMedCrossRefGoogle Scholar
  54. 54.
    Serafini AN, Houston SJ, Resche I, et al. 1998; Palliation of pain associated with metastatic bone cancer using samarium-153 lexidronam: a double-blind placebo-controlled clinical trial J Clin Oncol 1998; 16:1574–1581.Google Scholar
  55. 55.
    Sartor O, Reid RH, Hoskin PJ, et al. 2004; Samarium-153-lexidronam complex for treatment of painful bone metastases in hormone-refractory prostate cancer Urology 63:940–945.PubMedCrossRefGoogle Scholar
  56. 56.
    Palmedo H, Manka-Waluch A, Albers P, et al. 2003; Repeated bone-targeted therapy for hormone refractory prostate carcinoma: randomized phase II trial with the new, high-energy radiopharmaceutical rhenium-188 hydroxyethylidenediphosphate J Clin Oncol 21:2869.PubMedCrossRefGoogle Scholar
  57. 57.
    Hipp J, Rosenberg A, Hayes W. 1992; Mechanical properties of trabecular bone within and adjacent to osseous metastases. J Bone Miner Res 7:1165.PubMedCrossRefGoogle Scholar
  58. 58.
    Murray J, Bruels M, Landberg R. 1974; Irradiation of polymethylmethacrylate. In vitro gamma radiation effect. J Bone Joint Surg Am 56:311.PubMedGoogle Scholar
  59. 59.
    Zickel R, Mourandian W. 1976; Intramedullary fixation of pathological fractures and lesions of the subtrochanteric region of the femur. J Bone Joint Surg Am 58:1061.PubMedGoogle Scholar
  60. 60.
    Jang JS, Lee SH. 2005; Efficacy of percutaneous vertebroplasty combined with radiotherapy in osteolytic metastatic spinal tumors. J Neurosurg Spine 2:243.PubMedCrossRefGoogle Scholar
  61. 61.
    Brown JE, Thomson C, Ellis S, et al. 2003; Bone resorption predicts for skeletal complications in metastatic bone disease Br J Cancer 89:2031–2037.PubMedCrossRefGoogle Scholar
  62. 62.
    Brown JE, Cook RJ, Major P, et al. 2005; Bone turnover markers as predictors of skeletal complications in prostate cancer, lung cancer, and other solid tumors J Natl Cancer Inst 97:59–69.PubMedCrossRefGoogle Scholar
  63. 63.
    Coleman RE, Major P, Lipton A, et al. 2005; The predictive value of bone resorption and formation markers in cancer patients with bone metastases receiving the bisphosphonate zoledronic acid J Clin Oncol 23:4925–4935.PubMedCrossRefGoogle Scholar
  64. 64.
    Papotti M, Kalebic T, Volante M, et al. 2006; Bone sialoprotein is predictive of bone metastases in resectable non-small-cell lung cancer: a retrospective case-control study J Clin Oncol 24:4818–4824.PubMedCrossRefGoogle Scholar
  65. 65.
    Kosteva J, Langer C. 2004; Incidence and distribution of skeletal metastases in NSCLC in the era of PET Lung Cancer 46:(Suppl 1)S45.Google Scholar

Copyright information

© Humana Press, a part of Springer Science + Business Media, LLC 2009

Authors and Affiliations

  • John Kosteva*
    • 1
  • Corey Langer
    • 1
  1. 1.Fox Chase Cancer CenterPhiladelphia

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