Bone metastases are a very common problem in prostate cancer. They are associated with considerable morbidity, adversely affect quality of life and frequently lead to advanced bone events (so-called skeletal-related events, SREs); SREs include fractures, spinal cord compression and the requirement for bone surgery or bone radiation. The aim of this paper was to evaluate currently available treatment options in the prevention and management of SREs and bone metastases in men with castration-resistant prostate cancer and to outline the importance of interdisciplinary management strategies. It also discusses the diagnostic workup of osseous metastases and practical considerations for the utilization of bone-targeted therapies in accordance with current guidelines to provide a consensus for special and/or difficult clinical situations.

1.
Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM: Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010;127:2893-2917.
2.
Townsend MF, Sanders WH, Northway RO, Graham SD Jr: Bone fractures associated with luteinizing hormone-releasing hormone agonists used in the treatment of prostate carcinoma. Cancer 1997;79:545-550.
3.
Collinson MP, Tyrell CJ, Hutton C: Osteoporosis occurring in two patients receiving LHRH analogs for carcinoma of the prostate. Calcif Tissue Int 1994;54:327-328.
4.
Weinfurt KP, Li Y, Castel LD, Saad F, Timbie JW, Glendenning GA, Schulman KA: The significance of skeletal-related events for the health-related quality of life of patients with metastatic prostate cancer. Ann Oncol 2005;16:579-584.
5.
Smith MR, Egerdie B, Hernández Toriz N, Feldman R, Tammela TL, Saad F, Heracek J, Szwedowski M, Ke C, Kupic A, Leder BZ, Goessl C; Denosumab HALT Prostate Cancer Study Group: Denosumab in men receiving androgen-deprivation therapy for prostate cancer. N Engl J Med 2009;361:745-755.
6.
Rigaud J, Tiguert R, Le Normand L, Karam G, Glemain P, Buzelin JM, Bouchot O: Prognostic value of bone scan in patients with metastatic prostate cancer treated initially with androgen deprivation therapy. J Urol 2002;168:1423-1426.
7.
Soloway MS, Hardeman SW, Hickey D, Raymond J, Todd B, Soloway S, Moinuddin M: Stratification of patients with metastatic prostate cancer based on extent of disease on initial bone scan. Cancer 1988;61:195-202.
8.
Saad F, Gleason DM, Murray R, Tchekmedyian S, Venner P, Lacombe L, Chin JL, Vinholes JJ, Goas JA, Zheng M; Zoledronic Acid Prostate Cancer Study Group: 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;96:879-882.
9.
Halvorson KG, Sevcik MA, Ghilardi JR, Rosol TJ, Mantyh PW: Similarities and differences in tumor growth, skeletal remodeling and pain in an osteolytic and osteoblastic model of bone cancer. Clin J Pain 2006;22:587-600.
10.
Charhon SA, Chapuy MC, Delvin EE, Valentin-Opran A, Edouard CM, Meunier PJ: Histomorphometric analysis of sclerotic bone metastases from prostatic carcinoma with special reference to osteomalacia. Cancer 1983;51:918-924.
11.
Clarke NW, McClure J, George NJ: Morphometric evidence for bone resorption and replacement in prostate cancer. Br J Urol 1991;68:74-80.
12.
Clarke NW, McClure J, George NJ: Disodium pamidronate identifies differential osteoclastic bone resorption in metastatic prostate cancer. Br J Urol 1992;69:64-70.
13.
Percival RC, Urwin GH, Harris S, Yates AJ, Williams JL, Beneton M, Kanis JA: Biochemical and histological evidence that carcinoma of the prostate is associated with increased bone resorption. Eur J Surg Oncol 1987;13:41-49.
14.
Stenzl A: RANK ligand: a key role in cancer-induced bone destruction? Eur Urol Suppl 2009;8:823-828.
15.
Boyle WJ, Simonet WS, Lacey DL: Osteoclast differentiation and activation. Nature 2003;423:337-342.
16.
Roodman GD: Mechanisms of bone metastasis. N Engl J Med 2004;350:1655-1664.
17.
Mundy GR: Metastasis to bone: causes, consequences and therapeutic opportunities. Nat Rev Cancer 2002;2:584-593.
18.
Johnson JR, Williams G, Pazdur R: End points and United States Food and Drug Administration approval of oncology drugs. J Clin Oncol 2003;21:1404-1411.
19.
US Food and Drug Administration, Center for Drug Evaluation and Research: Guidance for Industry. Clinical Trial Endpoints for the Approval of Cancer Drugs and Biologics. 2007. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm071590.pdf (accessed February 25, 2011).
20.
Hanson DA, Weis MA, Bollen AM, Maslan SL, Singer FR, Eyre DR: A specific immunoassay for monitoring human bone resorption: quantitation of type I collagen cross-linked N-telopeptides in urine. J Bone Miner Res 1992;7:1251-1258.
21.
Ureña P, Hruby M, Ferreira A, Ang KS, de Vernejoul MC: Plasma total versus bone alkaline phosphatase as markers of bone turnover in hemodialysis patients. J Am Soc Nephrol 1996;7:506-512.
22.
Coleman RE, Major P, Lipton A, Brown JE, Lee KA, Smith M, Saad F, Zheng M, Hei YJ, Seaman J, Cook R: Predictive value of bone resorption and formation markers in cancer patients with bone metastases receiving the bisphosphonate zoledronic acid. J Clin Oncol 2005;23:4925-4935.
23.
de la Piedra C, Alcaraz A, Bellmunt J, Meseguer C, Gómez-Caamano A, Ribal MJ, Vázquez F, Anido U, Samper P, Esteban E, Álvarez-Ossorio JL, Lara PC, San José LA, Contreras JA, del Alba AG, González-Gragera B, Tabernero AJ, González-Enguita C, Fernández JM, García-Escudero A, Gómez-Veiga F, Méndez MJ, Segarra J, Virizuela JA, Carles J, Lassa A, Calderero V, Constela M, Delgado D, Mañas A, Murias A, Reynes G, Rodriguez B, Rubio G, Sánchez E, Unda M, Solsona E, Martínez-Javaloyas JM, Comet-Batlle J, Quicios C, Martín-Fernández M, Mahillo-Fernández I, Morote J: Usefulness of bone turnover markers as predictors of mortality risk, disease progression and skeletal-related events appearance in patients with prostate cancer with bone metastases following treatment with zoledronic acid: TUGAMO study. Br J Cancer 2013;108:2565-2572.
24.
Ibrahim T, Farolfi A, Mercatali L, Ricci M, Amadori D: Metastatic bone disease in the era of bone-targeted therapy: clinical impact. Tumori 2013;99:1-9.
25.
Rybak LD, Rosenthal DI: Radiological imaging for the diagnosis of bone metastases. Q J Nucl Med 2001;45:53-64.
26.
Heidenreich A, Albers P, Classen J, Graefen M, Gschwend J, Kotzerke J, Krege S, Lehmann J, Rohde D, Schmidberger H, Uder M, Zeeb H; Association of Urologic Oncology of the German Cancer Society: Imaging studies in metastatic urogenital cancer patients undergoing systemic therapy: recommendations of a multidisciplinary consensus meeting of the Association of Urological Oncology of the German Cancer Society. Urol Int 2010;85:1-10.
27.
National Comprehensive Cancer Network: Clinical Practice Guidelines in Oncology. Prostate Cancer, vol 1, 2011.
28.
Heidenreich A, Bastian PJ, Bellmunt J, Bolla M, Joniau S, Mason MD, Matveev V, Mottet N, van der Kwast TH, Wiegel T, Zattoni F: Guidelines on Prostate Cancer. European Association of Urology 2013, update March 2013. http://www.uroweb.org/gls/pdf/09_Prostate_Cancer_LR.pdf.
29.
Rosenthal DI: Radiologic diagnosis of bone metastases. Cancer 1997;80(8 suppl):1595- 1607.
30.
Schaffer DL, Pendergrass HP: Comparison of enzyme, clinical, radiographic, and radionuclide methods of detecting bone metastases from carcinoma of the prostate. Radiology 1976;121:431-434.
31.
Gralow JR, Biermann JS, Farooki A, Fornier MN, Gagel RF, Kumar RN, Shapiro CL, Shields A, Smith MR, Srinivas S, van Poznak CH: NCCN task force report: bone health in cancer care. J Natl Compr Canc Netw 2009;7(suppl 3):S1-S32; quiz S33-S35.
32.
Yu HH, Tsai YY, Hoffe SE: Overview of diagnosis and management of metastatic disease to bone. Cancer Control 2012;19:84-91.
33.
Tombal B, Lecouvet F: Modern detection of prostate cancer's bone metastasis: is the bone scan era over? Adv Urol 2012;2012:893193.
34.
Stopeck AT, Lipton A, Body JJ, Steger GG, Tonkin K, de Boer RH, Lichinitser M, Fujiwara Y, Yardley DA, Viniegra M, Fan M, Jiang Q, Dansey R, Jun S, Braun A: Denosumab compared with zoledronic acid for the treatment of bone metastases in patients with advanced breast cancer: a randomized, double-blind study. J Clin Oncol 2010;28:5132-5139.
35.
National Comprehensive Cancer Network: NCCN Clinical Practice Guidelines in Oncology 2011. http://www.nccn.org/professionals/physician_gls/f_guidelines.asp (accessed November 26, 2012).
36.
Saad F, Hotte SJ: Guidelines for the management of castrate-resistant prostate cancer. Can Urol Assoc J 2010;4:380-384.
37.
Heidenreich A, Witjes WP, Bjerklund-Johansen TE, Patel A; EAU Research Foundation: Therapies used in prostate cancer patients by European urologists: data on indication with a focus on expectations, perceived barriers and guideline compliance related to the use of bisphosphonates. Urol Int 2012;89:30-38.
38.
So A, Chin J, Fleshner N, Saad F: Management of skeletal-related events in patients with advanced prostate cancer and bone metastases: incorporating new agents into clinical practice. Can Urol Assoc J 2012;6:465-470.
39.
Ripamonti CI, Santini D, Maranzano E, Berti M, Roila F; ESMO Guidelines Working Group: Management of cancer pain: ESMO Clinical Practice Guidelines. Ann Oncol 2012;23(suppl 7):vii139-vii154.
40.
Hartsell WF, Scott CB, Bruner DW, Scarantino CW, Ivker RA, Roach M 3rd, Suh JH, Demas WF, Movsas B, Petersen IA, Konski AA, Cleeland CS, Janjan NA, DeSilvio M: Randomized trial of short- versus long-course radiotherapy for palliation of painful bone metastases. J Natl Cancer Inst 2005;97:798-804.
41.
Foro Arnalot P, Fontanals AV, Galcerán JC, Lynd F, Latiesas XS, de Dios NR, Castillejo AR, Bassols ML, Galán JL, Conejo IM, López MA: Randomized clinical trial with two palliative radiotherapy regimens in painful bone metastases: 30 Gy in 10 fractions compared with 8 Gy in single fraction. Radiother Oncol 2008;89:150-155.
42.
Sande TA, Ruenes R, Lund JA, Bruland OS, Hornslien K, Bremnes R, Kaasa S: Long-term follow-up of cancer patients receiving radiotherapy for bone metastases: results from a randomised multicentre trial. Radiother Oncol 2009;91:261-266.
43.
Dearnaley DP, Bayly RJ, A'Hern RP, Gadd J, Zivanovic MM, Lewington VJ: Palliation of bone metastases in prostate cancer. Hemibody irradiation or strontium-89? Clin Oncol (R Coll Radiol) 1992;4:101-107.
44.
Salazar OM, Sandhu T, da Motta NW, Escutia MA, Lanzós-Gonzales E, Mouelle-Sone A, Moscol A, Zaharia M, Zaman S: Fractionated half-body irradiation (HBI) for the rapid palliation of widespread, symptomatic, metastatic bone disease: a randomized phase III trial of the International Atomic Energy Agency (IAEA). Int J Radiat Oncol Biol Phys 2001;50:765-775.
45.
Porter AT, McEwan AJ, Powe JE, Reid R, McGowan DG, Lukka H, Sathyanarayana JR, Yakemchuk VN, Thomas GM, Erlich LE, et al: 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 1993;25:805-813.
46.
Parker C, Nilsson S, Heinrich D, Helle SI, O'Sullivan JM, Fosså SD, Chodacki A, Wiechno P, Logue J, Seke M, Widmark A, Johannessen DC, Hoskin P, Bottomley D, James ND, Solberg A, Syndikus I, Kliment J, Wedel S, Boehmer S, Dall'Oglio M, Franzén L, Coleman R, Vogelzang NJ, O'Bryan-Tear CG, Staudacher K, Garcia-Vargas J, Shan M, Bruland ØS, Sartor O; ALSYMPCA Investigators: Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med 2013;369:213-223.
47.
Bickels J, Kollender Y, Wittig JC, Meller I, Malawer MM: Function after resection of humeral metastases: analysis of 59 consecutive patients. Clin Orthop Relat Res 2005;437:201-208.
48.
Harrington KD: Impending pathologic fractures from metastatic malignancy: evaluation and management. Instr Course Lect 1986;35:357-381.
49.
Kollender Y, Bickels J, Price WM, Kellar KL, Chen J, Merimsky O, Meller I, Malawer MM: Metastatic renal cell carcinoma of bone: indications and technique of surgical intervention. J Urol 2000;164:1505-1508.
50.
Ward WG, Holsenbeck S, Dorey FJ, Spang J, Howe D: Metastatic disease of the femur: surgical treatment. Clin Orthop Relat Res 2003;415(suppl):S230-S244.
51.
Rades D, Huttenlocher S, Dunst J, Bajrovic A, Karstens JH, Rudat V, Schild SE: Matched pair analysis comparing surgery followed by radiotherapy and radiotherapy alone for metastatic spinal cord compression. J Clin Oncol 2010;28:3597-3604.
52.
Patchell RA, Tibbs PA, Regine WF, Payne R, Saris S, Kryscio RJ, Mohiuddin M, Young B: Direct decompressive surgical resection in the treatment of spinal cord compression caused by metastatic cancer: a randomised trial. Lancet 2005;366:643-648.
53.
Klimo P Jr, Thompson CJ, Kestle JR, Schmidt MH: A meta-analysis of surgery versus conventional radiotherapy for the treatment of metastatic spinal epidural disease. Neuro Oncol 2005;7:64-76.
54.
Bickels J, Dadia S, Lidar Z: Surgical management of metastatic bone disease. J Bone Joint Surg Am 2009;91:1503-1516.
55.
Sahgal A, Larson DA, Chang EL: Stereotactic body radiosurgery for spinal metastases: a critical review. Int J Radiat Oncol Biol Phys 2008;71:652-655.
56.
Chang EL, Shiu AS, Mendel E, Mathews LA, Mahajan A, Allen PK, Weinberg JS, Brown BW, Wang XS, Woo SY, Cleeland C, Maor MH, Rhines LD: Phase I/II study of stereotactic body radiotherapy for spinal metastasis and its pattern of failure. J Neurosurg Spine 2007;7:151-160.
57.
Coleman RE, Rathbone E, Brown JE: Management of cancer treatment-induced bone loss. Nat Rev Rheumatol 2013;9:365-374.
58.
Saad F, Gleason DM, Murray R, Tchekmedyian S, Venner P, Lacombe L, Chin JL, Vinholes JJ, Goas JA, Chen B; Zoledronic Acid Prostate Cancer Study Group: A randomized, placebo-controlled trial of zoledronic acid in patients with hormone-refractory metastatic prostate carcinoma. J Natl Cancer Inst 2002;94:1458-1468.
59.
Dearnaley DP, Sydes MR, Mason MD, Stott M, Powell CS, Robinson AC, Thompson PM, Moffat LE, Naylor SL, Parmar MK; Mrc Pr05 Collaborators: A double-blind, placebo-controlled, randomized trial of oral sodium clodronate for metastatic prostate cancer (MRC PR05 Trial). J Natl Cancer Inst 2003;95:1300-1311.
60.
Small EJ, Smith MR, Seaman JJ, Petrone S, Kowalski MO: Combined analysis of two multicenter, randomized, placebo-controlled studies of pamidronate disodium for the palliation of bone pain in men with metastatic prostate cancer. J Clin Oncol 2003;21:4277-4284.
61.
Dearnaley DP, Mason MD, Parmar MK, Sanders K, Sydes MR: Adjuvant therapy with oral sodium clodronate in locally advanced and metastatic prostate cancer: long-term overall survival results from the MRC PR04 and PR05 randomised controlled trials. Lancet Oncol 2009;10:872-876.
62.
Body JJ, Facon T, Coleman RE, Lipton A, Geurs F, Fan M, Holloway D, Peterson MC, Bekker PJ: A study of the biological receptor activator of nuclear factor-kappaB ligand inhibitor, denosumab, in patients with multiple myeloma or bone metastases from breast cancer. Clin Cancer Res 2006;12:1221-1228.
63.
Fizazi K, Carducci M, Smith M, Damião R, Brown J, Karsh L, Milecki P, Shore N, Rader M, Wang H, Jiang Q, Tadros S, Dansey R, Goessl C: Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomised, double-blind study. Lancet 2011;377:813-822.
64.
Brown JE, Cleeland CS, Fallowfield LJ, Patrick DL, Fizazi K, Smith MR, Maroto JP, Michel MS, Feng A, Goessl C, Chung K: Pain outcomes in patients with bone metastases from castrate-resistant prostate cancer: results from a phase 3 trial of denosumab vs. zoledronic acid. Eur Urol 2011;10(2 suppl): 336.
65.
Smith MR, Saad F, Coleman R, Shore N, Fizazi K, Tombal B, Miller K, Sieber P, Karsh L, Damião R, Tammela TL, Egerdie B, van Poppel H, Chin J, Morote J, Gómez-Veiga F, Borkowski T, Ye Z, Kupic A, Dansey R, Goessl C: Denosumab and bone-metastasis-free survival in men with castration-resistant prostate cancer: results of a phase 3, randomised, placebo-controlled trial. Lancet 2012;379:39-46.
66.
Bock O, Boerst H, Thomasius FE, Degner C, Stephan-Oelkers M, Valentine SM, Felsenberg D: Common musculoskeletal adverse effects of oral treatment with once weekly alendronate and risedronate in patients with osteoporosis and ways for their prevention. J Musculoskelet Neuronal Interact 2007; 7:144-148.
67.
Maxwell C, Swift R, Goode M, Doane L, Rogers M: Advances in supportive care of patients with cancer and bone metastases: nursing implications of zoledronic acid. Clin J Oncol Nurs 2003;7:403-408.
68.
Olson K, van Poznak C: Significance and impact of bisphosphonate-induced acute phase responses. J Oncol Pharm Pract 2007;13:223-229.
69.
Adami S, Bhalla AK, Dorizzi R, Montesanti F, Rosini S, Salvagno G, Lo Cascio V: The acute-phase response after bisphosphonate administration. Calcif Tissue Int 1987;41:326-331.
70.
Gallacher SJ, Ralston SH, Patel U, Boyle IT: Side-effects of pamidronate. Lancet 1989;2:42-43.
71.
Rosen LS, Gordon D, Kaminski M, Howell A, Belch A, Mackey J, Apffelstaedt J, Hussein MA, Coleman RE, Reitsma DJ, Chen BL, Seaman JJ: Long-term efficacy and safety of zoledronic acid compared with pamidronate disodium in the treatment of skeletal complications in patients with advanced multiple myeloma or breast carcinoma: a randomized, double-blind, multicenter, comparative trial. Cancer 2003;98:1735-1744.
72.
Rosen LS, Gordon D, Tchekmedyian NS, Yanagihara R, Hirsh V, Krzakowski M, Pawlicki M, De Souza P, Zheng M, Urbanowitz G, Reitsma D, Seaman J: Long-term efficacy and safety of zoledronic acid in the treatment of skeletal metastases in patients with nonsmall cell lung carcinoma and other solid tumors: a randomized, phase III, double-blind, placebo-controlled trial. Cancer 2004;100:2613-2621.
73.
Stopeck A, Fallowfield L, Patrick D, Cleeland CS, De Boer RH, Steger GG, Qian Y, Jiang Q, Dansey RD, Chung K: Effects of denosumab versus zoledronic acid (ZA) on pain in patients (pts) with metastatic breast cancer: results from a phase III clinical trial (abstract). J Clin Oncol 2010;28(suppl 15):A1024.
74.
Henry DH, Costa L, Goldwasser F, Hirsh V, Hungria V, Prausova J, Scagliotti GV, Sleeboom H, Spencer A, Vadhan-Raj S, von Moos R, Willenbacher W, Woll PJ, Wang J, Jiang Q, Jun S, Dansey R, Yeh H: Randomized, double-blind study of denosumab versus zoledronic acid in the treatment of bone metastases in patients with advanced cancer (excluding breast and prostate cancer) or multiple myeloma. J Clin Oncol 2011;29:1125-1132.
75.
Skugor M: Hypocalcemia. Cleveland, The Cleveland Clinic Foundation, 2004. http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/endocrinology/hypocalcemia/.
76.
European Medicines Agency: Assessment Report for XGEVA. European Medicines Agency, 2011. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/002173/WC500110384.pdf.
77.
Hadji P, Aapro M, Costa L, Gnant M: Antiresorptive treatment options and bone health in cancer patients - safety profiles and clinical considerations. Cancer Treat Rev 2012;38:815-824.
78.
Fizazi K, Lipton A, Mariette X, Body JJ, Rahim Y, Gralow JR, Gao G, Wu L, Sohn W, Jun S: 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;27:1564-1571.
79.
Ellis GK, Bone HG, Chlebowski R, Paul D, Spadafora S, Smith J, Fan M, Jun S: Randomized trial of denosumab in patients receiving adjuvant aromatase inhibitors for nonmetastatic breast cancer. J Clin Oncol 2008;26:4875-4882.
80.
Lipton A, Steger GG, Figueroa J, Alvarado C, Solal-Celigny P, Body JJ, de Boer R, Berardi R, Gascon P, Tonkin KS, Coleman R, Paterson AH, Peterson MC, Fan M, Kinsey A, Jun S: Randomized active-controlled phase II study of denosumab efficacy and safety in patients with breast cancer-related bone metastases. J Clin Oncol 2007;25:4431-4437.
81.
Estilo CL, van Poznak CH, Wiliams T, Bohle GC, Lwin PT, Zhou Q, Riedel ER, Carlson DL, Schoder H, Farooki A, Fornier M, Halpern JL, Tunick SJ, Huryn JM: Osteonecrosis of the maxilla and mandible in patients with advanced cancer treated with bisphosphonate therapy. Oncologist 2008;13:911-920.
82.
Hoff AO, Toth BB, Altundag K, Johnson MM, Warneke CL, Hu M, Nooka A, Sayegh G, Guarneri V, Desrouleaux K, Cui J, Adamus A, Gagel RF, Hortobagyi GN: Frequency and risk factors associated with osteonecrosis of the jaw in cancer patients treated with intravenous bisphosphonates. J Bone Miner Res 2008;23:826-836.
83.
Migliorati CA, Siegel MA, Elting LS: Bisphosphonate-associated osteonecrosis: a long-term complication of bisphosphonate treatment. Lancet Oncol 2006;7:508-514.
84.
Weitzman R, Sauter N, Eriksen EF, Tarassoff PG, Lacerna LV, Dias R, Altmeyer A, Csermak-Renner K, McGrath L, Lantwicki L, Hohneker JA: Critical review: updated recommendations for the prevention, diagnosis, and treatment of osteonecrosis of the jaw in cancer patients - May 2006. Crit Rev Oncol Hematol 2007;62:148-152.
85.
Bamias A, Kastritis E, Bamia C, Moulopoulos LA, Melakopoulos I, Bozas G, Koutsoukou V, Gika D, Anagnostopoulos A, Papadimitriou C, Terpos E, Dimopoulos MA: Osteonecrosis of the jaw in cancer after treatment with bisphosphonates: incidence and risk factors. J Clin Oncol 2005;23:8580-8587.
86.
Badros A, Weikel D, Salama A, Goloubeva O, Schneider A, Rapoport A, Fenton R, Gahres N, Sausville E, Ord R, Meiller T: Osteonecrosis of the jaw in multiple myeloma patients: clinical features and risk factors. J Clin Oncol 2006;24:945-952.
87.
Lipton A: The safety of zoledronic acid. Expert Opin Drug Saf 2007;6:305-313.
88.
Lipton A, Fizazi K, Stopeck AT, Henry DH, Brown JE, Yardley DA, Richardson GE, Siena S, Maroto P, Clemens M, Bilynskyy B, Charu V, Beuzeboc P, Rader M, Viniegra M, Saad F, Ke C, Braun A, Jun S: Superiority of denosumab to zoledronic acid for prevention of skeletal-related events: a combined analysis of 3 pivotal, randomised, phase 3 trials. Eur J Cancer 2012;48:3082-3092.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.