The Science and Practice of Bone Health in Oncology: Managing Bone Loss and Metastasis in Patients With Solid Tumors

View More View Less
  • 1 Hershey, Pennsylvania; Philadelphia, Pennsylvania; Houston, Texas; Seattle, Washington; Los Angeles, California; Pittsburgh, Pennsylvania; and Boston, Massachusetts
Restricted access

Cancer and its treatment can compromise bone health, leading to fracture, pain, loss of mobility, and hypercalcemia of malignancy. Bone metastasis occurs frequently in advanced prostate and breast cancers, and bony manifestations are commonplace in multiple myeloma. Osteoporosis and osteopenia may be consequences of androgen-deprivation therapy for prostate cancer, aromatase inhibition for breast cancer, or chemotherapy-induced ovarian failure. Osteoporotic bone loss and bone metastasis ultimately share a pathophysiologic pathway that stimulates bone resorption by increasing the formation and activity of osteoclasts. Important mediators of pathologic bone metabolism include substances produced by osteoblasts, such as RANKL, the receptor activator of nuclear factor kappa B ligand, which spurs osteoclast differentiation from myeloid cells. Available therapies are targeted to various steps in cascade of bone metastasis.

  • 1

    Theriault RL, Biermann JS, Brown E. NCCN task force report: bone health and cancer care. J Natl Compr Canc Netw 2006;4(Suppl 2):S1S22.

  • 2

    Roodman GD. Mechanisms of bone metastasis. N Engl J Med 2004;350:16551664.

  • 3

    Coleman RE. Bisphosphonates: clinical experience. Oncologist 2004;9(Suppl 4):1427.

  • 4

    Fidler IJ. Cancer metastasis. Br Med Bull 1991;47:157177.

  • 5

    Mohler J, Amling CL, Bahnson RR. NCCN clinical practice guidelines in oncology: prostate cancer, v.2.2009. Available at: http://www.nccn.org/professionals/physician_gls/PDF/prostate.pdf. Accessed May 21, 2009.

    • Search Google Scholar
    • Export Citation
  • 6

    Carlson RW, Allred DC, Anderson BO. NCCN clinical practice guidelines in oncology: breast cancer, v.1.2009. Available at: http://www.nccn.org/professionals/physician_gls/PDF/breast.pdf. Accessed May 21, 2009.

    • Search Google Scholar
    • Export Citation
  • 7

    Anderson KC, Alsina M, Bensinger W. NCCN clinical practice guidelines in oncology: multiple myeloma, v.2.2009. Available at: http://www.nccn.org/professionals/physician_gls/PDF/myeloma.pdf. Accessed May 21, 2009.

    • Search Google Scholar
    • Export Citation
  • 8

    Batson O. The role of vertebral veins in metastatic processes. Ann Intern Med 1942;16:3845.

  • 9

    Bundred N, Walker RA, Ratcliffe WA. Parathyroid hormone related protein and skeletal morbidity in breast cancer. Eur J Cancer 1992;28:690692.

    • Search Google Scholar
    • Export Citation
  • 10

    Koenders PG, Beex LV, Langens R. Steroid hormone receptor activity of primary human breast cancer and pattern of first metastasis. Breast Cancer Res Treat 1991;18:2732.

    • Search Google Scholar
    • Export Citation
  • 11

    Lipton A, Theriault RL, Hortobagyi GN. Pamidronate prevents skeletal complications and is effective palliative treatment in women with breast carcinoma and osteolytic bone metastasis: long term follow-up of two randomized, placebo-controlled trials. Cancer 2000;88:10821090.

    • Search Google Scholar
    • Export Citation
  • 12

    Joyce JA, Pollard JW. Microenvironmental regulation of metastasis. Nat Rev Cancer 2009;9:239252.

  • 13

    Coleman RE. Skeletal complications of malignancy. Cancer 1997;80(8 Suppl):15881594.

  • 14

    Galasko C. The anatomy and pathways of skeletal metastases. In: Weiss L, Gilbert A, eds. Bone Metastases. Boston: G.K. Hall; 1981:4963.

  • 15

    Krupski TL, Smith MR, Lee WC. Natural history of bone complications in men with prostate carcinoma initiating androgen deprivation therapy. Cancer 2004;101:541549.

    • Search Google Scholar
    • Export Citation
  • 16

    Shahinian VB, Kuo YF, Freeman JL, Goodwin JS. Risk of fracture after androgen deprivation for prostate cancer. N Engl J Med 2005;352:154164.

  • 17

    Smith MR, Lee WC, Brandman J. Gonadotropin-releasing hormone agonists and fracture risk: a claims-based cohort study of men with nonmetastatic prostate cancer. J Clin Oncol 2005;23:78977903.

    • Search Google Scholar
    • Export Citation
  • 18

    Malkowicz SB, Chu F, Forrest J. Prevalence of osteoporosis and osteopenia during androgen deprivation (ADT) for prostate cancer: baseline data from a large randomized controlled trial [abstract]. J Clin Oncol 2007;25(18 Suppl):Abstract 5116.

    • Search Google Scholar
    • Export Citation
  • 19

    American Cancer Society. Cancer Facts & Figures 2008. Available at: http://www.cancer.org/downloads/STT/2008CAFFfinalsecured.pdf. Accessed March 30 2009.

    • Search Google Scholar
    • Export Citation
  • 20

    Ross FP. M-CSF, c-Fms, and signaling in osteoclasts and their precursors. Ann N Y Acad Sci 2006;1068:110116.

  • 21

    Suda T, Takahashi N, Udagawa N. Modulation of osteoclast differentiation and function by the new members of the tumor necrosis factor receptor and ligand families. Endocr Rev 1999;20:345357.

    • Search Google Scholar
    • Export Citation
  • 22

    Dai J, Hall CL, Escara-Wilke J. Prostate cancer induces bone metastasis though Wnt-induced morphogenetic protein-dependent and independent mechanisms. Cancer Res 2008;68:57855794.

    • Search Google Scholar
    • Export Citation
  • 23

    Lessard L, Mes-Masson AM, Lamarre L. NF-kappa B nuclear localization and its prognostic significance in prostate cancer. BJU Int 2003;91:417420.

    • Search Google Scholar
    • Export Citation
  • 24

    Fradet V, Lessard L, Bégin LR. Nuclear factor kappa-B nuclear localization is predictive of biochemical recurrence in patients with positive margin prostate cancer. Clin Cancer Res 2004;10:84608464.

    • Search Google Scholar
    • Export Citation
  • 25

    Cook RJ, Coleman R, Brown J. Markers of bone metabolism and survival in men with hormone-refractory metastatic prostate cancer. Clin Cancer Res 2006;12:33613367.

    • Search Google Scholar
    • Export Citation
  • 26

    Hofbauer LC, Schoppet M. Clinical implications of the osteoprotegerin/RANKL/RANK system for bone and vascular diseases. JAMA 2004;292:490495.

    • Search Google Scholar
    • Export Citation
  • 27

    Brufsky A. Management of cancer-treatment-induced bone loss in postmenopausal women undergoing adjuvant breast cancer therapy: A Z-FAST update. Semin Oncol 2006;33(Suppl 7):S1317.

    • Search Google Scholar
    • Export Citation
  • 28

    Huber DM, Bendixen AC, Pathrose P. Androgens suppress osteoclast formation induced by RANKL and macrophage-colony stimulating factor. Endocrinology 2001;142:38003808.

    • Search Google Scholar
    • Export Citation
  • 29

    Farhat GN, Taioli E, Cauley JA. The association of bone mineral density with prostate cancer risk in the Osteoporotic Fractures in Men (MrOS) study. Cancer Epidemiol Biomarkers Prev 2009;18:148154.

    • Search Google Scholar
    • Export Citation
  • 30

    Hamaoka T, Madewell JE, Podoloff DA. Bone imaging in metastatic breast cancer. J Clin Oncol 2004;22:29422953.

  • 31

    Langer CJ. Early detection, management, and evidence-based clinical guidelines for bone metastases: a 2006 update. Johns Hopkins Advanced Studies in Medicine 2006;6:S10571062.

    • Search Google Scholar
    • Export Citation
  • 32

    Sadik M, Suurkula M, Höglund P. Improved classifications of planar whole-body bone scans using a computer-assisted diagnosis system: a multicenter, multiple-reader, multiple-case study. J Nucl Med 2009;50:368375.

    • Search Google Scholar
    • Export Citation
  • 33

    Tian M, Zhang H, Endo K. Whole-body FDG-PET can provide more information than Tc-99m MDP bone scintigraphy for detection of bone metastases in patients with lung cancer [abstract]. J Clin Oncol 2005;23(18 Suppl):Abstract 2023.

    • Search Google Scholar
    • Export Citation
  • 34

    Effert PJ, Bares R, Handt S. Metabolic imaging of untreated prostate cancer by positron emission tomography with 18fluorine-labeled deoxyglucose. J Urol 1996;155:994998.

    • Search Google Scholar
    • Export Citation
  • 35

    Morris MJ, Scher HI. Clinical approaches to osseous metastases in prostate cancer. Oncologist 2003;8:161173.

  • 36

    Even-Sapir E, Metser U, Mishani E. The detection of bone metastases in patients with high-risk prostate cancer: 99mTc-MDP Planar bone scintigraphy, single- and multi-field-of-view SPECT, 18F-fluoride PET, and 18F-fluoride PET/CT. J Nucl Med 2006;47:287297.

    • Search Google Scholar
    • Export Citation
  • 37

    Morrison MS, Ricketts S, Barnett J. Monitoring tumor response to ZD4190 therapy with an 18F labeled angiogenesis imaging agent [abstract]. J Clin Oncol 2007;25(18 Suppl):Abstract 10507.

    • Search Google Scholar
    • Export Citation
  • 38

    Watanabe H, Monzawa S, Adachi S. Can PET/CT substitute for bone scintigraphy in assessment of bone metastases in lung cancer patients [abstract]? J Clin Oncol 2006;24(18 Suppl):Abstract 7203.

    • Search Google Scholar
    • Export Citation
  • 39

    Beheshti M, Vali R, Waldenberger P. The use of F-18 choline PET in the assessment of bone metastases in prostate cancer: correlation with morphological changes on CT. Mol Imaging Biol 2009; in press.

    • Search Google Scholar
    • Export Citation
  • 40

    Venkitaraman R, Cook GJ, Dearnaley DP. Does magnetic resonance imaging of the spine have a role in the staging of prostate cancer? Clin Oncol (R Coll Radiol) 2009;21:3942.

    • Search Google Scholar
    • Export Citation
  • 41

    Lecouvet FE, Geukens D, Stainier A. Magnetic resonance imaging of the axial skeleton for detecting bone metastases in patients with high-risk prostate cancer: diagnostic and cost-effectiveness and comparison with current detection strategies. J Clin Oncol 2007;25:32813287.

    • Search Google Scholar
    • Export Citation
  • 42

    Frat A, Ağildere M, Gençoğlu A. Value of whole-body turbo short tau inversion recovery magnetic resonance imaging with panoramic table for detecting bone metastases: comparison with 99MTc-methylene diphosphonate scintigraphy. J Comput Assist Tomogr 2006;30:151156.

    • Search Google Scholar
    • Export Citation
  • 43

    Engelhard K, Hollenbach HP, Wohlfart K. Comparison of whole-body MRI with automatic moving table technique and bone scintigraphy for screening for bone metastases in patients with breast cancer. Eur Radiol 2004;14:99105.

    • Search Google Scholar
    • Export Citation
  • 44

    Schmidt GP, Schoenberg SO, Schmid R. Screening for bone metastases: whole-body MRI using a 32-channel system versus dual-modality PET-CT. Eur Radiol 2007;17:939949.

    • Search Google Scholar
    • Export Citation
  • 45

    Skrinskas T, Clemons M, Freedman O. Automated CT-based analysis to detect changes in the prevalence of lytic bone metastases from breast cancer. Clin Exp Metastasis 2009;26:97103.

    • Search Google Scholar
    • Export Citation
  • 46

    Nackaerts K, Harper PG, Manegold C. Management of bone metastases from lung cancer: consensus recommendations from an international panel [abstract]. J Clin Oncol 2008;26(18 Suppl):Abstract 19080.

    • Search Google Scholar
    • Export Citation
  • 47

    Coleman R, Smith P, Rubens R. Clinical course and prognostic factors following bone recurrence from breast cancer. Br J Cancer 1998;77:336340.

    • Search Google Scholar
    • Export Citation
  • 48

    Wei B, Wang J, Bourne P. Bone metastasis is strongly associated with estrogen receptor-positive/progesterone receptor-negative breast carcinomas. Hum Pathol 2008;39:18091815.

    • Search Google Scholar
    • Export Citation
  • 49

    Conforti R, Xia W, Boulet T. Cxcr4 expression and risk of bone metastasis in patients with early breast cancer [abstract]. J Clin Oncol 2007;25(18 Suppl):Abstract 10610.

    • Search Google Scholar
    • Export Citation
  • 50

    Lipton A, Chapman JW, Demers L. Use of elevated bone turnover to predict bone metastasis [abstract]. J Clin Oncol 2008;26(18 Suppl):Abstract 591.

    • Search Google Scholar
    • Export Citation
  • 51

    Bentkover JD, Shaka EC, Thomas SK. Diagnosis of bone metastases and utilization of bisphosphonates among advanced prostate cancer patients [abstract]. Presented at the 2006 ASCO Prostate Cancer Symposim; February 24–26, 2006; San Francisco, California. Abstract 165.

    • Search Google Scholar
    • Export Citation
  • 52

    Pal RP, Thiruudaian T, Khan MA. When is a bone scan study appropriate in asymptomatic men diagnosed with prostate cancer? Asian J Androl 2008;10:890895.

    • Search Google Scholar
    • Export Citation
  • 53

    Chodak GW, Vogelzang NJ, Caplan RJ. Independent prognostic factors in patients with metastatic (stage D2) prostate cancer. The Zoladex Study Group. JAMA 1991;265:618621.

    • Search Google Scholar
    • Export Citation
  • 54

    Ernst DS, Hanson J, Venner PM. Analysis of prognostic factors in men with metastatic prostate cancer. Uro-Oncology Group of Northern Alberta. J Urol 1991;146:372376.

    • Search Google Scholar
    • Export Citation
  • 55

    Akashi T, Furuya Y, Ohta S, Fuse H. Tissue factor expression and prognosis in patients with metastatic prostate cancer. Urology 2003;62:10781082.

    • Search Google Scholar
    • Export Citation
  • 56

    Smid M, Wang Y, Klijn JG. Genes associated with breast cancer metastatic to bone. J Clin Oncol 2006;24:22612267.

  • 57

    Klein A, Olendrowitz C, Schmutzler R. Identification of brain- and bone-specific breast cancer metastasis genes. Cancer Lett 2009;276:212220.

    • Search Google Scholar
    • Export Citation
  • 58

    Clar H, Langsenlehner U, Krippl P. A polymorphism in the G protein beta3-subunit gene is associated with bone metastasis risk in breast cancer patients. Breast Cancer Res Treat 2008;111:449452.

    • Search Google Scholar
    • Export Citation
  • 59

    Clar H, Renner W, Krippl P. The LCT 13910 C/T polymorphism as a risk factor for osteoporosis, has no impact on metastatic bone disease in breast cancer. Breast Cancer Res Treat 2008;112:363365.

    • Search Google Scholar
    • Export Citation
  • 60

    Kominsky SL, Davidson NE. A “bone” fide predictor of metastasis? Predicting breast cancer metastasis to bone. J Clin Oncol 2006;24:22272229.

    • Search Google Scholar
    • Export Citation
  • 61

    Kang Y, Siegel PM, Shu W. A multigenic program mediating breast cancer metastasis to bone. Cancer Cell 2003;3:537549.

  • 62

    Kumazawa T, Tsuchiya N, Wang L. Microsatellite polymorphism of steroid hormone synthesis gene CYP11A1 is associated with advanced prostate cancer. Int J Cancer 2004;110:140144.

    • Search Google Scholar
    • Export Citation
  • 63

    Brown JE, Thomson CS, Ellis SP. Bone resorption predicts for skeletal complications in metastatic bone disease. Br J Cancer 2003;89:20312037.

    • Search Google Scholar
    • Export Citation
  • 64

    Brown JE, Cook RJ, Major P. Bone turnover markers as predictors of skeletal complications in prostate cancer, lung cancer, and other solid tumors. J Natl Cancer Inst 2005;97:5969.

    • Search Google Scholar
    • Export Citation
  • 65

    Costa L, Demers LM, Gouveia-Oliveira A. Prospective evaluation of the peptide-bound collagen type I cross-links N-telopeptide and C-telopeptide in predicting bone metastases status. J Clin Oncol 2002;20:850856.

    • Search Google Scholar
    • Export Citation
  • 66

    Coleman RE, Major P, Lipton A. Predictive value of bone resorption and formation markers in cancer patients with bone metastases receiving the bisphosphonate zoledronic acid. J Clin Oncol 2005;23:49254935.

    • Search Google Scholar
    • Export Citation
  • 67

    Morris MJ, Akhurst T, Osman I. Fluorinated deoxyglucose positron emission tomography imaging in progressive metastatic prostate cancer. Urology 2002;59:913918.

    • Search Google Scholar
    • Export Citation
  • 68

    Chao TY, Lee SH, Chen MM. Tartrate-resistant acid phosphatase 5b (TRAP 5b) as a serum marker of bone metastasis in breast cancer patients [abstract]. Proc Am Soc Clin Oncol 2002;21:Abstract 3013.

    • Search Google Scholar
    • Export Citation
  • 69

    DiLiberto A, Schmidt W, Friedrich M. Prospective trial for clinical evaluation of TRACP 5b as serum marker of bone resorption and for monitoring an oral clodronate - medication in osteolytic metastases of breast carcinoma [abstract]. J Clin Oncol 2004;22(18 Suppl):Abstract 862.

    • Search Google Scholar
    • Export Citation
  • 70

    Ozu C, Nakashima J, Horiguchi Y. Prediction of bone metastases by combination of tartrate-resistant acid phosphatase, alkaline phosphatase and prostate specific antigen in patients with prostate cancer. Int J Urol 2008;15:419422.

    • Search Google Scholar
    • Export Citation
  • 71

    de Jong IJ, Koopmans N, Breeuwsma AJ. Bone turnover markers for the early detection of bone metastases in patients with prostate cancer [abstract]. Presented at the 2006 Presented at the 2006 ASCO Prostate Cancer Symposim; February 24–26, 2006; San Francisco, California. Abstract 145.

    • Search Google Scholar
    • Export Citation
  • 72

    Kataoka A, Yuasa T, Kageyama S. Diagnosis of bone metastasis in men with prostate cancer by measurement of serum ICTP in combination with alkali phosphatase and prostate-specific antigen. Clin Oncol (R Coll Radiol) 2006;18:480484.

    • Search Google Scholar
    • Export Citation
  • 73

    Costa LA, Alho I, Casimiro S. Markers of bone turnover (ICTP, NTX) and serum matrix metalloproteinase 1 (MMP1) as prognostic markers in breast cancer patients (BC) with bone metastases (BM) treated with bisphosphonates (BP) [abstract]. J Clin Oncol 2008;26(18 Suppl):Abstract 1024.

    • Search Google Scholar
    • Export Citation
  • 74

    Hall CL, Daignault SD, Shah RB. Dickkopf-1 expression increases early in prostate cancer development and decreases during progression from primary tumor to metastasis. Prostate 2008;68:13961404.

    • Search Google Scholar
    • Export Citation
  • 75

    Voorzanger-Rousselot N, Goehrig D, Journe F. Increased Dickkopf-1 expression in breast cancer bone metastases. Br J Cancer 2007;97:964970.

  • 76

    Zhang L, Hou X, Rao H. Predictive significance of bone sialoprotein and osteopontin for bone metastases in resectable non-small cell lung cancer: a retrospective study [abstract]. J Clin Oncol 2007;25(18 Suppl):Abstract 7666.

    • Search Google Scholar
    • Export Citation
  • 77

    Scagliotti G, Kalebic T, Volante M. Bone sialoprotein is predictive of bone metastases in resectable non-small cell lung cancer: a retrospective case-control study. J Clin Oncol 2006;24:48184824.

    • Search Google Scholar
    • Export Citation
  • 78

    Shoback D. Update in osteoporosis and metabolic bone disorder. J Clin Endocrinol Metab 2007;92:747753.

  • 79

    van Beek ER, Cohen LH, Leroy IM. Differentiating the mechanisms of antiresorptive action of nitrogen containing bisphosphonates. Bone 2003;33:805811.

    • Search Google Scholar
    • Export Citation
  • 80

    Alam AS, Bax CM, Shankar VS. Further studies on the mode of action of calcitonin on isolated rat osteoclasts: pharmacological evidence for a second site mediating intracellular Ca2+ mobilization and cell retraction. J Endocrinol 1993;136:715.

    • Search Google Scholar
    • Export Citation
  • 81

    McClung MR, Lewiecki EM, Cohen SB. Denosumab in postmenopausal women with low bone mineral density. N Engl J Med 2006;354:821831.

  • 82

    Reginster JY. Strontium ranelate in osteoporosis. Curr Pharm Des 2002;8:19071916.

  • 83

    Meunier PJ, Roux C, Seeman E. The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis. N Engl J Med 2004;350:459468.

    • Search Google Scholar
    • Export Citation
  • 84

    Reginster JY, Seeman E, De Vernejoul MC. Strontium ranelate reduces the risk of nonvertebral fractures in postmenopausal women with osteoporosis: Treatment of Peripheral Osteoporosis (TROPOS) study. J Clin Endocrinol Metab 2005;90:28162822.

    • Search Google Scholar
    • Export Citation
  • 85

    Miller PD. Safety of parathyroid hormone for the treatment of osteoporosis. Curr Osteoporos Rep 2008;6:1216.

  • 86

    U.S. Food and Drug Administration. Drugs@FDA: FDA Approved Drugs. Available at: http://www.accessdata.fda.gov/Scripts/cder/DrugsatFDA/index.cfm. Accessed April 13, 2009.

    • Search Google Scholar
    • Export Citation
  • 87

    Pavlakis N, Schmidt R, Stockler M. Bisphosphonates for breast cancer. Cochrane Database Syst Rev 2005;CD003474.

  • 88

    Powles T, Paterson A, McCloskey E. Reduction in bone relapse and improved survival with oral clodronate for adjuvant treatment of operable breast cancer [ISRCTN83688026]. Breast Cancer Res 2006;8:R13.

    • Search Google Scholar
    • Export Citation
  • 89

    Gnant M, Mlineritsch B, Schippinger W. Endocrine therapy plus zoledronic acid in premenopausal breast cancer. N Engl J Med 2009;360:679691.

  • 90

    Winter MC, Thorpe HC, Burkinshaw R. The addition of zoledronic acid to neoadjuvant chemotherapy may influence pathological response – exploratory evidence for direct anti-tumor activity in breast cancer [abstract]. Presented at the 2008 San Antonio Breast Cancer Symposium; December 10–14, 2008; San Antonio, Texas. Abstract 5101

    • Search Google Scholar
    • Export Citation
  • 91

    Saarto T, Vehmanen L, Virkkunen P, Blomqvist C. Ten-year follow-up of a randomized controlled trial of adjuvant clodronate treatment in node-positive breast cancer patients. Acta Oncol 2004;43:650656.

    • Search Google Scholar
    • Export Citation
  • 92

    Hiraga T, Williams PJ, Ueda A. Zoledronic acid inhibits visceral metastases in the 4T1/luc mouse breast cancer model. Clin Cancer Res 2004;10:45594567.

    • Search Google Scholar
    • Export Citation
  • 93

    Giraudo E, Inoue M, Hanahan D. An amino-bisphosphonate targets MMP-9-expressing macrophages and angiogenesis to impair cervical carcinogenesis. J Clin Invest 2004;114:623633.

    • Search Google Scholar
    • Export Citation
  • 94

    Neville-Webbe HL, Rostami-Hodjegan A, Evans CA. Sequence- and schedule-dependent enhancement of zoledronic acid induced apoptosis by doxorubicin in breast and prostate cancer cells. Int J Cancer 2005;113:364371.

    • Search Google Scholar
    • Export Citation
  • 95

    Lu S, Zhang J, Zhou Z. Synergistic inhibitory activity of zoledronate and paclitaxel on bone metastasis in nude mice. Oncol Rep 2008;20:581587.

    • Search Google Scholar
    • Export Citation
  • 96

    Rack BK, Jueckstock J, Genss EM. Effect of zoledronate on persisting isolated tumor cells in the bone marrow of patients without recurrence of early breast cancer [abstract]. Breast Cancer Res Treat 2007;106(Suppl 1):Abstract 511.

    • Search Google Scholar
    • Export Citation
  • 97

    Reid IR. Osteonecrosis of the jaw: who gets it, and why? Bone 2009;44:410.

  • 98

    Cetiner S, Sucak GT, Kahraman SA. Osteonecrosis of the jaw in patients with multiple myeloma treated with zoledronic acid. J Bone Miner Metab 2009;27:435443.

    • Search Google Scholar
    • Export Citation
  • 99

    Diel IJ, Weide R, Köppler H. Risk of renal impairment after treatment with ibandronate versus zoledronic acid: a retrospective medical records review. Support Care Cancer 2009;17:719725

    • Search Google Scholar
    • Export Citation
  • 100

    Kintzel PE. Anticancer drug-induced kidney disorders. Drug Saf 2001;24:1938

  • 101

    Ibrahim A, Scher N, Williams G. Approval summary for zoledronic acid for treatment of multiple myeloma and cancer bone metastases. Clin Cancer Res 2003;9:23942399

    • Search Google Scholar
    • Export Citation
  • 102

    Zometa [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2008

  • 103

    Aredia [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2008

  • 104

    Roodman GD. Biology of osteoclast activation in cancer. J Clin Oncol 2001;19:35623571

  • 105

    Bekker PJ, Holloway DL, Rasmussen AS. A single-dose placebo-controlled study of AMG 162, a fully human monoclonal antibody to RANKL, in postmenopausal women. J Bone Miner Res 2004;19:10591066

    • Search Google Scholar
    • Export Citation
  • 106

    Fizazi K, Lipton A, Mariette X. Randomized phase II trial of denosumab in patients with bone metastases from prostate cancer, breast cancer, or other neoplasms after intravenous bisphosphonates. J Clin Oncol 2009;27:15641571

    • Search Google Scholar
    • Export Citation
  • 107

    Le Gall C, Bonnelye E, Clézardin P. Cathepsin K inhibitors as treatment of bone metastasis. Curr Opin Support Palliat Care 2008;2:218222

  • 108

    Goblirsch M, Mathews W, Lynch C. Radiation treatment decreases bone cancer pain, osteolysis and tumor size. Radiat Res 2004;161:228234

  • 109

    Bradley DA, Hussain M, Dipaola RS, Kantoff P. Bone directed therapies for prostate cancer. J Urol 2007;178;S4248

  • 110

    Tu SM, Kim J, Pagliaro LC. Therapy tolerance in selected patients with androgen-independent prostate cancer following strontium-89 combined with chemotherapy. J Clin Oncol 2005;23:79047910

    • Search Google Scholar
    • Export Citation
  • 111

    Kyle RA, Gertz MA, Witzig TE. Review of 1027 patients with newly diagnosed multiple myeloma. Mayo Clin Proc 2003;78:2133

  • 112

    Lipton A. Pathophysiology of bone metastases: how this knowledge may lead to therapeutic intervention. J Support Oncol 2004;2:205220

  • 113

    Roodman GD. Pathogenesis of myeloma bone disease. Leukemia 2009;23:435441

  • 114

    Roodman GD. Skeletal imaging and management of bone disease. Hematology Am Soc Hematol Educ Program 2008;2008:313319

  • 115

    Lipton A. Bisphosphonates and metastatic breast carcinoma. Cancer 2003;97(3 Suppl):848853

  • 116

    Yaneva MP, Goranova-Marinova V, Goranov S. Palliative radiotherapy in patients with multiple myeloma. J BUON 2006;11:4348

  • 117

    Basile A, Giuliano G, Scuderi V. Cementoplasty in the management of painful extraspinal bone metastases: our experience. Radiol Med 2008;113:10181028

    • Search Google Scholar
    • Export Citation
  • 118

    Mont’alverne F, Vallée JN, Guillevin R. Percutaneous vertebroplasty for multiple myeloma of the cervical spine. Neuroradiology 2009;51:237242

    • Search Google Scholar
    • Export Citation
  • 119

    Hussein MA, Vrionis FD, Allison R. The role of vertebral augmentation in multiple myeloma: International Myeloma Working Group Consensus Statement. Leukemia 2008;22:14791484

    • Search Google Scholar
    • Export Citation
  • 120

    Saliou G, Lehmann P, Vallée JN. Controlled segmental balloon kyphoplasty: a new technique for patients with heterogeneous vertebral bone density. Spine 2008;33:E216220

    • Search Google Scholar
    • Export Citation
  • 121

    Ross JR, Saunders Y, Edmonds PM. A systematic review of the role of bisphosphonates in metastatic disease. Health Technol Assess 2004;8:1176

  • 122

    Berenson JR, Lichtenstein A, Porter L. Long-term pamidronate treatment of advanced multiple myeloma patients reduces skeletal events. Myeloma Aredia Study Group. J Clin Oncol 1998;16:593602

    • Search Google Scholar
    • Export Citation
  • 123

    Rosen LS, Gordon D, Kaminski M. Zoledronic acid versus pamidronate in the treatment of skeletal metastases in patients with breast cancer or osteolytic lesions of multiple myeloma: a phase III, double-blind, comparative trial. Cancer J 2001;7:377387

    • Search Google Scholar
    • Export Citation
  • 124

    Edwards BJ, Gounder M, McKoy JM. Pharmacovigilance and reporting oversight in US FDA fast-track process: bisphosphonates and osteonecrosis of the jaw. Lancet Oncol 2008;9:11661172

    • Search Google Scholar
    • Export Citation
  • 125

    Fehm T, Beck V, Banys M. Bisphosphonate-induced osteonecrosis of the jaw (ONJ): incidence and risk factors in patients with breast cancer and gynecological malignancies. Gynecol Oncol 2009;112:605609.

    • Search Google Scholar
    • Export Citation
  • 126

    Gallego L, Junquera L. Consequence of therapy discontinuation in bisphosphonate-associated osteonecrosis of the jaws. Br J Oral Maxillofac Surg 2009;47:6768

    • Search Google Scholar
    • Export Citation
  • 127

    Body JJ, Facon T, Coleman RE. A study of the biological receptor activator of nuclear factor-kappa-B ligand inhibitor, denosumab, in patients with multiple myeloma or bone metastases from breast cancer. Clin Cancer Res 2006;12:12211228

    • Search Google Scholar
    • Export Citation
  • 128

    Vij R, Horvath N, Spencer A. An open-label, phase 2 trial of denosumab in the treatment of relapsed (R) or plateau-phase (PP) multiple myeloma (MM) [abstract]. Blood 2007;110:Abstract 1054

    • Search Google Scholar
    • Export Citation
  • 129

    Yaccoby S, Ling W, Zhan F. Antibody-based inhibition of Dkk-1 suppresses tumor-induced bone resorption and multiple myeloma growth in vivo. Blood 2007;109:21062111

    • Search Google Scholar
    • Export Citation
  • 130

    Tian E, Zhan F, Walker R. The role of the Wnt/b-catenin signaling antagonist Dkk-1 in the development of osteolytic lesions in multiple myeloma. N Engl J Med 2003;349:24832494

    • Search Google Scholar
    • Export Citation
  • 131

    Oyajobi BO, Garrett IR, Gupta A. Stimulation of new bone formation by the proteasome inhibitor, bortezomib: implications for myeloma bone disease. Br J Haematol 2007;139:434438

    • Search Google Scholar
    • Export Citation
  • 132

    Garrett IR, Chen D, Gutierrez G. Selective inhibitors of the osteoblast proteasome stimulate bone formation in vivo and in vitro. J Clin Invest 2003;111:17711782

    • Search Google Scholar
    • Export Citation
  • 133

    Giuliani N, Morandi F, Tagliaferri S. The proteasome inhibitor bortezomib affects osteoblast differentiation in vitro and in vivo in multiple myeloma patients. Blood 2007;110:334338

    • Search Google Scholar
    • Export Citation
  • 134

    von Metzler I, Krebbel H, Hecht M. Bortezomib inhibits human osteoclastogenesis. Leukemia 2007;21:20252034

  • 135

    Roodman GD. Bone building with bortezomib. J Clin Invest 2008;118:462464

  • 136

    Breitkreutz I, Raab MS, Vallet S. Lenalidomide inhibits osteoclastogenesis, survival factors and bone-remodeling markers in multiple myeloma. Leukemia 2008;22:19251932

    • Search Google Scholar
    • Export Citation
  • 137

    Martin TJ, Moseley JM. Mechanisms in the skeletal complications of breast cancer. Endocr Relat Cancer 2000;7:271284

  • 138

    Hortobagyi GN. Moving into the future: treatment of bone metastases and beyond. Cancer Treat Rev 2005;31(Suppl 3):918

  • 139

    Ali SM, Leitzel K, Chinchilli VM. Relationship of serum HER-2/neu and serum CA 15-3 in patients with metastatic breast cancer. Clin Chem 2002;48:13141320

    • Search Google Scholar
    • Export Citation
  • 140

    Alexandre J, Bleuzen P, Bonneterre J. Factors predicting for efficacy and safety of docetaxel in a compassionate-use cohort of 825 heavily pretreated advanced breast cancer patients. J Clin Oncol 2000;18:562573

    • Search Google Scholar
    • Export Citation
  • 141

    Sledge GW, Neuberg D, Bernardo P. Phase III trial of doxorubicin, paclitaxel, and the combination of doxorubicin and paclitaxel as front-line chemotherapy for metastatic breast cancer: an intergroup trial (E1193). J Clin Oncol 2003;21:588592

    • Search Google Scholar
    • Export Citation
  • 142

    Mouridsen H, Gershanovich M, Sun Y. Superior efficacy of letrozole versus tamoxifen as first-line therapy for postmenopausal women with advanced breast cancer: results of a phase III study of the International Letrozole Breast Cancer Group. J Clin Oncol 2001;19:25962606

    • Search Google Scholar
    • Export Citation
  • 143

    Jacobson AF, Shapiro CL, Van den Abbeele AD, Kaplan WD. Prognostic significance of the number of bone scan abnormalities at the time of initial bone metastatic recurrence in breast carcinoma. Cancer 2001;91:1724

    • Search Google Scholar
    • Export Citation
  • 144

    Lipton A, Ali SM, Leitzel K. Elevated serum Her-2/neu level predicts decreased response to hormone therapy in metastatic breast cancer. J Clin Oncol 2002;20:14671472

    • Search Google Scholar
    • Export Citation
  • 145

    Coleman RE, Rubens RD. The clinical course of bone metastases from breast cancer. Br J Cancer 1987;55:6166

  • 146

    Budd GT. Estrogen receptor profile of patients with breast cancer metastatic to bone marrow. J Surg Oncol 1983;249:167169

  • 147

    Hillner BE, Ingle JN, Chlebowski RT. American Society of Clinical Oncology 2003 update on the role of bisphosphonates and bone health issues in women with breast cancer. J Clin Oncol 2003;21:40424057

    • Search Google Scholar
    • Export Citation
  • 148

    Tannock IF, de Wit R, Berry WR. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med 2004;351:15021512

    • Search Google Scholar
    • Export Citation
  • 149

    Petrylak DP, Tangen CM, Hussain MH. Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med 2004;351:15131520

    • Search Google Scholar
    • Export Citation
  • 150

    Kindrick AV, Grossfeld GD, Stier DM. Use of imaging tests for staging newly diagnosed prostate cancer: trends from CaPSURE database. J Urol 1998;160:21022106

    • Search Google Scholar
    • Export Citation
  • 151

    Han M, Partin AW, Zahurak M. Biochemical (prostate specific antigen) recurrence probability following radical prostatectomy for clinically localized prostate cancer. J Urol 2003;169:517523

    • Search Google Scholar
    • Export Citation
  • 152

    Dall’era MA, Hosang N, Konety B. Sociodemographic predictors of prostate cancer risk category at diagnosis: unique patterns of significant and insignificant disease. J Urol 2009;181:16221627

    • Search Google Scholar
    • Export Citation
  • 153

    Lee N, Fawaaz R, Olsson CA. Which patients with newly diagnosed prostate cancer need a radionuclide bone scan? An analysis based on 631 patients. Int J Radiat Oncol Biol Phys 2000;48:14431446

    • Search Google Scholar
    • Export Citation
  • 154

    Abuzallouf S, Dayes I, Lukka H. Baseline staging of newly diagnosed prostate cancer: a summary of the literature. J Urol 2004;171:21222127

  • 155

    Wymenga LF, Boomsma JH, Groenier K. Routine bone scans in patients with prostate cancer related to serum prostate-specific antigen and alkaline phosphatase. BJU Int 2001;88:226230

    • Search Google Scholar
    • Export Citation
  • 156

    Yap BK, Choo R, Deboer G. Are serial bone scans useful for the follow-up of clinically localized, low to intermediate grade prostate cancer managed with watchful observation alone? BJU Int 2003;91:613617

    • Search Google Scholar
    • Export Citation
  • 157

    Gomez P, Manoharan M, Kim SS, Soloway MS. Radionuclide bone scintigraphy in patients with biochemical recurrence after radical prostatectomy: when is it indicated? BJU Int 2004;94:299302

    • Search Google Scholar
    • Export Citation
  • 158

    Rigaud J, Tiguert R, Le Normand L. Prognostic value of bone scan in patients with metastatic prostate cancer treated initially with androgen deprivation therapy. J Urol 2002;168:14231426

    • Search Google Scholar
    • Export Citation
  • 159

    Sabbatini P, Larson SM, Kremer A. Prognostic significance of extent of disease in bone in patients with androgen-independent prostate cancer. J Clin Oncol 1999;17:948957

    • Search Google Scholar
    • Export Citation
  • 160

    Keller ET, Brown J. Prostate cancer bone metastases promote both osteolytic and osteoblastic activity. J Cell Biol 2004;91:718729.

  • 161

    Carlin BI, Andriole GL. The natural history, skeletal complications, and management of bone metastases in patients with prostate carcinoma. Cancer 2000;88(12 Suppl):29892994

    • Search Google Scholar
    • Export Citation
  • 162

    Wada T, Nakashima T, Hiroshi N, Penninger JM. RANKL-RANK signaling in osteoclastogenesis and bone disease. Trends Mol Med 2006;12:1725

  • 163

    Saad F, Gleason DM, Murray R. Long-term efficacy of zoledronic acid for the prevention of skeletal complications in patients with metastatic hormone-refractory prostate cancer. J Natl Cancer Inst 2004;96:879882

    • Search Google Scholar
    • Export Citation
  • 164

    Lynch CC, Hikosaka A, Acuff HB. MMP-7 promotes prostate cancer-induced osteolysis via the solubilization of RANKL. Cancer Cell 2005;7:485496

  • 165

    Lara PN Jr, Stadler WM, Longmate J. A randomized phase II trial of the matrix metalloproteinase inhibitor BMS-275291 in hormone-refractory prostate cancer patients with bone metastases. Clin Cancer Res 2006;12:15561563

    • Search Google Scholar
    • Export Citation
  • 166

    Carducci MA, Padley RJ, Breul J. Effect of endothelin-A receptor blockade with atrasentan on tumor progression in men with hormone-refractory prostate cancer: a randomized, phase II, placebo-controlled trial. J Clin Oncol 2003;21:679689

    • Search Google Scholar
    • Export Citation
  • 167

    Vogelzang NJ, Nelson JB, Schulman CC. Meta-analysis of clinical trials of atrasentan 10 mg in metastatic hormone-refractory prostate cancer [abstract]. J Clin Oncol 2005;23(18 Suppl):Abstract 4563

    • Search Google Scholar
    • Export Citation
  • 168

    National Osteoporosis Foundation. Fast facts on osteoporosis, 2008. Available at: http://www.nof.org/professionals/Fast_Facts_Osteoporosis.pdf. Accessed May 21, 2009

    • Search Google Scholar
    • Export Citation
  • 169

    Cole ZA, Dennison EM, Cooper C. Osteoporosis epidemiology update. Curr Rheumatol Rep 2008;10:9296

  • 170

    Eastell R. Treatment of postmenopausal osteoporosis. N Engl J Med 1998;338:736746

  • 171

    Guise TA. Bone loss and fracture risk associated with cancer therapy. Oncologist 2006;11:11211131

  • 172

    NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and Therapy. Osteoporosis prevention, diagnosis, and therapy. JAMA 2001;285:785795

    • Search Google Scholar
    • Export Citation
  • 173

    National Osteoporosis Foundation. Clinician’s guide to prevention and treatment of osteoporosis. Available at: http://www.nof.org/professionals/NOF_Clinicians_Guide.pdf. Accessed May 21, 2009

    • Search Google Scholar
    • Export Citation
  • 174

    Kanis JA, Johnell O, Oden A. FRAX and the assessment of fracture probability in men and women from the UK. Osteoporos Int 2008;19:385397

  • 175

    Pfeilschifter J, Diel IJ. Osteoporosis due to cancer treatment: pathogenesis and management. J Clin Oncol 2000;18:15701593

  • 176

    National Osteoporosis Foundation. Osteoporosis: men. Available at: http://www.nof.org/men/index.htm. Accessed May 21, 2009

  • 177

    American Cancer Society. Cancer Facts & Figures 2008. Atlanta: American Cancer Society; 2008

  • 178

    Hershman D, Narayanan R. Prevention and management of osteoporosis in women with breast cancer and men with prostate cancer. Curr Oncol Rep 2004;6:277284

    • Search Google Scholar
    • Export Citation
  • 179

    Hoff AO, Gagel RF. Osteoporosis in breast and prostate cancer survivors. Oncology (Williston Park) 2005;19:651658

  • 180

    Howell A, Cuzick J, Baum M. Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years’ adjuvant treatment for breast cancer. Lancet 2005;365:6062

    • Search Google Scholar
    • Export Citation
  • 181

    Baum M, Buzdar AU, Cuzick J. Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer: first results of the ATAC randomised trial. Lancet 2002;359:21312139

    • Search Google Scholar
    • Export Citation
  • 182

    Goss PE, Ingle JN, Martino S. Randomized trial of letrozole following tamoxifen as extended adjuvant therapy in receptor-positive breast cancer: updated findings from NCIC CTG MA.17. J Natl Cancer Inst 2005;97:12621271

    • Search Google Scholar
    • Export Citation
  • 183

    Perez EA, Josse RG, Pritchard KI. Effect of letrozole versus placebo on bone mineral density in women with primary breast cancer completing 5 or more years of adjuvant tamoxifen: a companion study to NCIC CTG MA.17. J Clin Oncol 2006;24:36293635

    • Search Google Scholar
    • Export Citation
  • 184

    Thürlimann B, Keshaviah A, Coates AS. A comparison of letrozole and tamoxifen in postmenopausal women with early breast cancer. N Engl J Med 2005;353:27472757

    • Search Google Scholar
    • Export Citation
  • 185

    Jakesz R, Jonat W, Gnant M. Switching of postmenopausal women with endocrine-responsive early breast cancer to anastrozole after 2 years’ adjuvant tamoxifen: combined results of ABCSG trial 8 and ARNO 95 trial. Lancet 2005;366:455462

    • Search Google Scholar
    • Export Citation
  • 186

    Aapro M, Abrahamsson PA, Body JJ. Guidance on the use of bisphosphonates in solid tumours: recommendations of an international expert panel. Ann Oncol 2008;19:420432

    • Search Google Scholar
    • Export Citation
  • 187

    Brufsky A, Dong M, Lund K. Twenty-four month follow-up of the effect of zoledronic acid on aromatase inhibitor associated bone loss in postmenopausal women with early breast cancer receiving adjuvant letrozole. Presented at the 2006 San Antonio Breast Cancer Symposium; December 14–17, 2006; San Antonio, Texas. Abstract 5060

    • Search Google Scholar
    • Export Citation
  • 188

    Brufsky A, Harker WG, Beck JT. Zoledronic acid inhibits adjuvant letrozole-induced bone loss in postmenopausal women with early breast cancer. J Clin Oncol 2007;25:829836

    • Search Google Scholar
    • Export Citation
  • 189

    Gnant MF, Mlineritsch B, Luschin-Ebengreuth G. Zoledronic acid prevents cancer treatment-induced bone loss in premenopausal women receiving adjuvant endocrine therapy for hormone-responsive breast cancer: a report from the Austrian Breast and Colorectal Cancer Study Group. J Clin Oncol 2007;25:820828

    • Search Google Scholar
    • Export Citation
  • 190

    Van Poznak C, Hannon RA, Clack G. The SABRE (Study of Anastrozole with the Bisphosphonate Risedronate) study: 12-month analysis. Presented at the 2007 San Antonio Breast Cancer Symposium; December 13–16, 2007; San Antonio, Texas. Abstract 502

    • Search Google Scholar
    • Export Citation
  • 191

    Ellis GK, Bone HG, Chlebowski R. Randomized trial of denosumab in patients receiving adjuvant aromatase inhibitors for nonmetastatic breast cancer. J Clin Oncol 2008;26:48754882

    • Search Google Scholar
    • Export Citation
  • 192

    Mittan D, Lee S, Miller E. Bone loss following hypogonadism in men with prostate cancer treated with GnRH analogs. J Clin Endocrinol Metab 2002;87:36563661

    • Search Google Scholar
    • Export Citation
  • 193

    Spry NA, Galvão DA, Davies R. Long-term effects of intermittent androgen suppression on testosterone recovery and bone mineral density: results of a 33-month observational study. BJU Int 2009;104:806812

    • Search Google Scholar
    • Export Citation
  • 194

    Smith MR, McGovern FJ, Zietman AL. Pamidronate to prevent bone loss during androgen-deprivation therapy for prostate cancer. N Engl J Med 2001;345:948955

    • Search Google Scholar
    • Export Citation
  • 195

    Smith MR, Eastham J, Gleason DM. Randomized controlled trial of zoledronic acid to prevent bone loss in men receiving androgen deprivation therapy for nonmetastatic prostate cancer. J Urol 2003;169:20082012.

    • Search Google Scholar
    • Export Citation
  • 196

    Michaelson MD, Kaufman DS, Kantoff P. Randomized phase II study of atrasentan alone or in combination with zoledronic acid in men with metastatic prostate cancer. Cancer 2006;107:530535

    • Search Google Scholar
    • Export Citation
  • 197

    Greenspan SL, Nelson JB, Trump DL, Resnick NM. Effect of once-weekly oral alendronate on bone loss in men receiving androgen deprivation therapy for prostate cancer: a randomized trial. Ann Intern Med 2007;146:416424

    • Search Google Scholar
    • Export Citation
  • 198

    Khosla S, Melton LJ III, Atkinson EJ, O’Fallon WM. Relationship of serum sex steroid levels to longitudinal changes in bone density in young versus elderly men. J Clin Endocrinol Metab 2001;86:35553561

    • Search Google Scholar
    • Export Citation
  • 199

    Smith MR, Fallon MA, Lee H, Finkelstein JS. Raloxifene to prevent gonadotropin-releasing hormone agonist-induced bone loss in men with prostate cancer: a randomized controlled trial. J Clin Endocrinol Metab 2004;89:38413846

    • Search Google Scholar
    • Export Citation
  • 200

    Smith MR, Malkowicz SB, Chu F. Toremifene increases bone mineral density in men receiving androgen deprivation therapy for prostate cancer: interim analysis of a multicenter phase 3 clinical study. J Urol 2008;179:152155

    • Search Google Scholar
    • Export Citation
  • 201

    Smith M, Morton R, Wallace H. A phase III randomized controlled trial of toremifene to prevent fractures and other adverse effects of androgen therapy in men with prostate cancer [abstract]. Presented at the 2008 American Association for Cancer Research Meeting; April 12–16, 2008; San Diego, California. Abstract LB-241

    • Search Google Scholar
    • Export Citation
  • 202

    Smith MR, Egerdie B, Hernández Toriz N. A randomized, double-blind, placebo-controlled trial of denosumab in men receiving androgen deprivation therapy for non-metastatic prostate cancer. Presented at the 2009 European Association of Urology Meeting; March 17–21, 2009; Stockholm, Sweden.

    • Search Google Scholar
    • Export Citation
All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 564 351 54
PDF Downloads 362 302 47
EPUB Downloads 0 0 0