The use of bisphosphonates in multiple myeloma: Recommendations of an expert panel on behalf of the European Myeloma Network

Annals of Oncology

Volumn 20, Issue 8, 2009, Pages 1303-1317

  Terpos, E ^a,b   Sezer, O ^c   Croucher, P I ^d   Garcia Sanz R ^e   Boccadoro, M ^f   San Miguel, J ^e   Ashcroft, J ^g   Blade J ^h,i   Cavo, M ^j   Delforge, M ^k   Dimopoulos, M A ^a   Facon, T ^l   Macro, M ^m   Waage, A ⁿ   Sonneveld, P ^o  

^a UNIVERSITY OF ATHENS MEDICAL SCHOOL   (Greece)

^b IMPERIAL COLLEGE LONDON   (United Kingdom)

^c CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

^d UNIVERSITY OF SHEFFIELD   (United Kingdom)

^e HOSPITAL UNIVERSITARIO DE SALAMANCA   (Spain)

^f UNIVERSITY OF TURIN   (Italy)

^g UNIVERSITY OF LEEDS   (United Kingdom)

^h HOSPITAL CLÍNIC   (Spain)

ⁱ INSTITUT D INVESTIGACIONS BIOMÈDIQUES AUGUST PI I SUNYER IDIBAPS   (Spain)

^j UNIVERSITY OF BOLOGNA   (Italy)

^k UNIVERSITY HOSPITALS LEUVEN   (Belgium)

^l LILLE UNIVERSITY HOSPITAL   (France)

^m CAEN UNIVERSITY HOSPITAL   (France)

ⁿ TRONDHEIM UNIVERSITY HOSPITAL   (Norway)

^o ERASMUS MEDICAL CENTER   (Netherlands)

more..

Author keywords

Bisphosphonates; Multiple myeloma; Osteonecrosis of the jaw; Recommendations; Renal impairment

Indexed keywords

BISPHOSPHONIC ACID DERIVATIVE; CALCIUM; CLODRONIC ACID; CREATINE; OSTEOCLAST DIFFERENTIATION FACTOR; PAMIDRONIC ACID; TUMOR NECROSIS FACTOR; VITAMIN D; ZOLEDRONIC ACID;

ABDOMINAL PAIN; ANTINEOPLASTIC ACTIVITY; ARTHRALGIA; BONE DISEASE; BONE METABOLISM; BONE PAIN; BONE RADIOGRAPHY; CLINICAL TRIAL; CONTINUOUS INFUSION; CREATININE BLOOD LEVEL; DENTAL CARE; DIARRHEA; DRUG BIOAVAILABILITY; DRUG CONTRAINDICATION; DRUG DOSE COMPARISON; DRUG EFFICACY; DRUG POTENTIATION; DRUG TOLERABILITY; DUAL ENERGY X RAY ABSORPTIOMETRY; ESOPHAGITIS; FEVER; GASTROINTESTINAL SYMPTOM; HUMAN; HYPERTHERMIA; HYPOCALCEMIA; HYPOPHOSPHATEMIA; INJECTION SITE PAIN; INJECTION SITE REACTION; INJECTION SITE SWELLING; JAW OSTEONECROSIS; MULTIPLE MYELOMA; MYALGIA; NAUSEA; NEPHROTOXICITY; NONHUMAN; NUCLEAR MAGNETIC RESONANCE IMAGING; OSTEOLYSIS; PATIENT COMPLIANCE; PHLEBITIS; POSITRON EMISSION TOMOGRAPHY; PRACTICE GUIDELINE; PRIORITY JOURNAL; QUALITY OF LIFE; REVIEW; SINGLE DRUG DOSE; SURVIVAL TIME; TREATMENT DURATION; ULCER; BONE TUMOR; PATHOLOGY;

BONE NEOPLASMS; DIPHOSPHONATES; HUMANS; MULTIPLE MYELOMA;

EID: 69449108135     PISSN: 09237534     EISSN: 15698041     Source Type: Journal    
DOI: 10.1093/annonc/mdn796     Document Type: Review

References (193)

1. UK Myeloma Forum. British Committee for Standards in Haematology. Haematology BCfSi. Diagnosis and management of multiple myeloma. Br J Haematol 2001; 115(3): 522-540.
2. Ferlay J, Bray F, Sankila R, Parkin DM. EUCAN: Cancer Incidence, Mortality and Prevalence in the European Union 1998, version 5.0. IARC CancerBase No 4 Lyon, France: IARCPress 1999 http://www-dep.iarc.fr/ eucan/eucan.htm (17 March 2003, date last accessed).
3. Parker SL, Davis KJ, Wingo PA et al. Cancer statistics by race and ethnicity. CA Cancer J Clin 1998; 48(1): 31-48.
4. Ries L, Melbert D, Krapcho M (eds), et al. SEER Cancer Statistics Review, 1975-2004. Bethesda, MD: National Cancer Institute 2007; http://seer.cancer.gov/csr/1975_2004/, based on November 2006 SEER data submission, posted to the SEER web site.
5. Brenner H, Gondos A, Pulte D. Recent major improvement in long-term survival of younger patients with multiple myeloma. Blood 2008; 111(5): 2521-2526.
6. Kumar SK, Rajkumar SV, Dispenzieri A et al. Improved survival in multiple myeloma and the impact of novel therapies. Blood 2008; 111(5): 2516-2520.
7. Kyle RA, Gertz MA, Witzig TE et al. Review of 1027 patients with newly diagnosed multiple myeloma. Mayo Clin Proc 2003; 78(1): 21-33.
8. Gridelli C. The use of bisphosphonates in elderly cancer patients. Oncologist 2007; 12(1): 62-71.
9. Coleman RE. Skeletal complications of malignancy. Cancer 1997; 80 (8 Suppl): 1588-1594.
10. Terpos E, Dimopoulos MA. Myeloma bone disease: Pathophysiology and management. Ann Oncol 2005; 16(8): 1223-1231.
11. Croucher PI, Apperley JF. Bone disease in multiple myeloma. Br J Haematol 1998; 103(4): 902-910.
12. Jakob C, Sterz J, Liebisch P et al. Incorporation of the bone marker carboxyterminal telopeptide of type-1 collagen improves prognostic information of the International Staging System in newly diagnosed symptomatic multiple myeloma. Leukemia 2008; 22(9): 1767-1772.
13. Vogel CL, Yanagihara RH, Wood AJ et al. Safety and pain palliation of zoledronic acid in patients with breast cancer, prostate cancer, or multiple myeloma who previously received bisphosphonate therapy. Oncologist 2004; 9(6): 687-695.
14. Terpos E, Rahemtulla A. Bisphosphonate treatment for multiple myeloma. Drugs Today (Barc) 2004; 40(1): 29-40.
15. Cocks K, Cohen D, Wisloff F et al. An international field study of the reliability and validity of a disease-specific questionnaire module (the QLQ-MY20) in assessing the quality of life of patients with multiple myeloma. Eur J Cancer 2007; 43(11): 1670-1678.
16. Bruce NJ, McCloskey EV, Kanis JA, Guest JF. Economic impact of using clodronate in the management of patients with multiple myeloma. Br J Haematol 1999; 104(2): 358-364.
17. McCloskey EV, MacLennan IC, Drayson MT et al. A randomized trial of the effect of clodronate on skeletal morbidity in multiple myeloma. MRC Working Party on Leukaemia in Adults. Br J Haematol 1998; 100(2): 317-325.
18. Perry CM, Figgitt DP. Zoledronic acid: A review of its use in patients with advanced cancer. Drugs 2004; 64(11): 1197-1211.
19. Hillner BE, Ingle JN, Berenson JR et al. American Society of Clinical Oncology guideline on the role of bisphosphonates in breast cancer. American Society of Clinical Oncology Bisphosphonates Expert Panel. J Clin Oncol 2000; 18(6): 1378-1391.
20. Berenson JR, Hillner BE, Kyle RA et al. American Society of Clinical Oncology clinical practice guidelines: The role of bisphosphonates in multiple myeloma. J Clin Oncol 2002; 20(17): 3719-3736.
21. Heider U, Hofbauer LC, Zavrski I et al. Novel aspects of osteoclast activation and osteoblast inhibition in myeloma bone disease. Biochem Biophys Res Commun 2005; 338(2): 687-693.
22. Terpos E, Dimopoulos MA, Sezer O. The effect of novel anti-myeloma agents on bone metabolism of patients with multiple myeloma. Leukemia 2007; 21(9): 1875-1884.
23. Giuliani N, Rizzoli V, Roodman GD. Multiple myeloma bone disease: pathophysiology of osteoblast inhibition. Blood 2006; 108(13): 3992-3996.
24. Silvestris F, Cafforio P, Calvani N, Dammacco F. Impaired osteoblastogenesis in myeloma bone disease: Role of upregulated apoptosis by cytokines and malignant plasma cells. Br J Haematol 2004; 126(4): 475-486.
25. Tian E, Zhan F, Walker R et al. The role of the Wnt-signaling antagonist DKK1 in the development of osteolytic lesions in multiple myeloma. N Engl J Med 2003; 349(26): 2483-2494.
26. Oshima T, Abe M, Asano J et al. Myeloma cells suppress bone formation by secreting a soluble Wnt inhibitor, sFRP-2. Blood 2005; 106(9): 3160-3165.
27. Giuliani N, Colla S, Morandi F et al. Myeloma cells block RUNX2/CBFA1 activity in human bone marrow osteoblast progenitors and inhibit osteoblast formation and differentiation. Blood 2005; 106(7): 2472-2483.
28. Ehrlich LA, Chung HY, Ghobrial I et al. IL-3 is a potential inhibitor of osteoblast differentiation in multiple myeloma. Blood 2005; 106(4): 1407-1414.
29. Franchimont N, Rydziel S, Canalis E. Transforming growth factor-beta increases interleukin-6 transcripts in osteoblasts. Bone 2000; 26(3): 249-253.
30. Hayashi T, Hideshima T, Nguyen AN et al. Transforming growth factor beta receptor I kinase inhibitor down-regulates cytokine secretion and multiple myeloma cell growth in the bone marrow microenvironment. Clin Cancer Res 2004; 10(22): 7540-7546.
31. Silvestris F, Cafforio P, Tucci M et al. Upregulation of osteoblast apoptosis by malignant plasma cells: A role in myeloma bone disease. Br J Haematol 2003; 122(1): 39-52.
32. Chauhan D, Uchiyama H, Akbarali Y et al. Multiple myeloma cell adhesioninduced interleukin-6 expression in bone marrow stromal cells involves activation of NF-kappa B. Blood 1996; 87(3): 1104-1112.
33. Uchiyama H, Barut BA, Mohrbacher AF et al. Adhesion of human myeloma-derived cell lines to bone marrow stromal cells stimulates interleukin-6 secretion. Blood 1993; 82(12): 3712-3720.
34. Sati HIA, Greaves M, Apperley JF et al. Expression of interleukin-1b and tumour necrosis factor-alpha in plasma cells from patients with multiple myeloma. Br J Haematol 1999; 104(2): 350-357.
35. Roux S, Mariette X. The high rate of bone resorption in multiple myeloma is due to RANK (receptor activator of nuclear factor-Kb) and RANK ligand expression. Leuk Lymphoma 2004; 45(6): 1111-1118.
36. Oyajobi BO, Mundy GR. Receptor activator of NF-kappaB ligand, macrophage inflammatory protein-1alpha, and the proteasome: Novel therapeutic targets in myeloma. Cancer 2003; 97 (3 Suppl): 813-817.
37. Mitsiades CS, Mitsiades N, Hideshima T et al. Proteasome inhibition as a new therapeutic principle in hematological malignancies. Curr Drug Targets 2006; 7(10): 1341-1347.
38. Tanaka Y, Abe M, Hiasa M et al. Myeloma cell-osteoclast interaction enhances angiogenesis together with bone resorption: A role for vascular endothelial cell growth factor and osteopontin. Clin Cancer Res 2007; 13(3): 816-823.
39. Terpos E, Politou M, Rahemtulla A. New insights into the pathophysiology and management of bone disease in multiple myeloma. Br J Haematol 2003; 123(5): 758-769.
40. Sezer O, Heider U, Zavrski I et al. RANK ligand and osteoprotegerin in myeloma bone disease. Blood 2003; 101(6): 2094-2098.
41. Vanderkerken K, Asosingh K, Croucher P, Van Camp B. Multiple myeloma biology: Lessons from the 5TMM models. Immunol Rev 2003; 194: 196-206.
42. Rogers MJ, Gordon S, Benford HL et al. Cellular and molecular mechanisms of action of bisphosphonates. Cancer 2000; 88 (12 Suppl): 2961-2978.
43. Russell RG, Bisaz S, Fleisch H et al. Inorganic pyrophosphate in plasma, urine, and synovial fluid of patients with pyrophosphate arthropathy (chondrocalcinosis or pseudogout). Lancet 1970; 2(7679): 899-902.
44. Boonekamp PM, van der Wee-Pals LJ, van Wijk-van Lennep MM et al. Two modes of action of bisphosphonates on osteoclastic resorption of mineralized matrix. Bone Miner 1986; 1(1): 27-39.
45. Rowe DJ, Etre LA, Lovdahl MJ, Pietrzyk DJ. Relationship between bisphosphonate concentration and osteoclast activity and viability. In Vitro Cell Dev Biol Anim 1999; 35(7): 383-388.
46. Frith JC, Monkkonen J, Blackburn GM et al. Clodronate and liposomeencapsulated clodronate are metabolized to a toxic ATP analog, adenosine 5′-(beta, gamma-dichloromethylene) triphosphate, by mammalian cells in vitro. J Bone Miner Res 1997; 12(9): 1358-1367.
47. Hughes DE, Wright KR, Uy HL et al. Bisphosphonates promote apoptosis in murine osteoclasts in vitro and in vivo. J Bone Miner Res 1995; 10(10): 1478-1487.
48. Selander KS, Monkkonen J, Karhukorpi EK et al. Characteristics of clodronate-induced apoptosis in osteoclasts and macrophages. Mol Pharmacol 1996; 50(5): 1127-1138.
49. Coleman RE. Bisphosphonates: Clinical experience. Oncologist 2004; 9 (Suppl 4): 14-27.
50. Dunford JE, Thompson K, Coxon FP et al. Structure-activity relationships for inhibition of farnesyl diphosphate synthase in vitro and inhibition of bone resorption in vivo by nitrogen-containing bisphosphonates. J Pharmacol Exp Ther 2001; 296(2): 235-242.
51. Russell RG, Xia Z, Dunford JE et al. Bisphosphonates: An update on mechanisms of action and how these relate to clinical efficacy. Ann N Y Acad Sci 2007; 1117: 209-257.
52. van Beek E, Pieterman E, Cohen L et al. Nitrogen-containing bisphosphonates inhibit isopentenyl pyrophosphate isomerase/farnesyl pyrophosphate synthase activity with relative potencies corresponding to their antiresorptive potencies in vitro and in vivo. Biochem Biophys Res Commun 1999; 255(2): 491-494.
53. Luckman SP, Hughes DE, Coxon FP et al. Nitrogen-containing bisphosphonates inhibit the mevalonate pathway and prevent post-translational prenylation of GTP-binding proteins, including Ras. J Bone Miner Res 1998; 13(4): 581-589.
54. Dunford JE, Rogers MJ, Ebetino FH et al. Inhibition of protein prenylation by bisphosphonates causes sustained activation of Rac, Cdc42, and Rho GTPases. J Bone Miner Res 2006; 21(5): 684-694.
55. Belch AR, Bergsagel DE, Wilson K et al. Effect of daily etidronate on the osteolysis of multiple myeloma. J Clin Oncol 1991; 9(8): 1397-1402.
56. Daragon A, Humez C, Michot C et al. Treatment of multiple myeloma with etidronate: Results of a multicentre double-blind study. Groupe d'Etudes et de Recherches sur le Myelome (GERM). Eur J Med 1993; 2(8): 449-452.
57. Lahtinen R, Laakso M, Palva I et al. Randomised, placebo-controlled multicentre trial of clodronate in multiple myeloma. Finnish Leukaemia Group. Lancet 1992; 340(8827): 1049-1052.
58. Laakso M, Lahtinen R, Virkkunen P, Elomaa I. Subgroup and cost-benefit analysis of the Finnish multicentre trial of clodronate in multiple myeloma. Finnish Leukaemia Group. Br J Haematol 1994; 87(4): 725-729.
59. McCloskey EV, Dunn JA, Kanis JA et al. Long-term follow-up of a prospective, double-blind, placebo-controlled randomized trial of clodronate in multiple myeloma. Br J Haematol 2001; 113(4): 1035-1043.
60. 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. Danish-Swedish co-operative study group. Br J Haematol 1998; 101(2): 280-286.
61. Berenson JR, Lichtenstein A, Porter L et al. Efficacy of pamidronate in reducing skeletal events in patients with advanced multiple myeloma. Myeloma Aredia Study Group. N Engl J Med 1996; 334(8): 488-493.
62. Berenson JR, Lichtenstein A, Porter L et al. Long-term pamidronate treatment of advanced multiple myeloma patients reduces skeletal events. Myeloma Aredia Study Group. J Clin Oncol 1998; 16(2): 593-602.
63. Menssen HD, Sakalova A, Fontana A et al. Effects of long-term intravenous ibandronate therapy on skeletal-related events, survival, and bone resorption markers in patients with advanced multiple myeloma. J Clin Oncol 2002; 20(9): 2353-2359.
64. Berenson JR, Rosen LS, Howell A et al. Zoledronic acid reduces skeletal-related events in patients with osteolytic metastases. Cancer 2001; 91(7): 1191-1200.
65. Rosen LS, Gordon D, Kaminski M et al. 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(5): 377-387.
66. Rosen LS, Gordon D, Kaminski M et al. 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(8): 1735-1744.
67. Anderson K, Alsina M, Bensinger W et al. National Comprehensive Cancer Network (NCCN). Multiple myeloma guidelines. J Natl Compr Canc Netw 2007; 5: 118.
68. Kyle RA, Yee GC, Somerfield MR et al. American Society of Clinical Oncology 2007 clinical practice guideline update on the role of bisphosphonates in multiple myeloma. J Clin Oncol 2007; 25(17): 2464-2472.
69. Lacy MQ, Dispenzieri A, Gertz MA et al. Mayo clinic consensus statement for the use of bisphosphonates in multiple myeloma. Mayo Clin Proc 2006; 81(8): 1047-1053.
70. Harrouseau JL, Greil R, Kloke O. ESMO minimum clinical recommendations for diagnosis, treatment and follow-up of multiple myeloma. Ann Oncol 2005; 16 (Suppl 1): I45-i47.
71. Durie BG. Use of bisphosphonates in multiple myeloma: IMWG response to Mayo Clinic consensus statement. Mayo Clin Proc 2007; 82(4): 516-517; author reply 517-518.
72. Green JR. Bisphosphonates: Preclinical review. Oncologist 2004; 9 (Suppl 4): 3-13.
73. Aapro M, Abrahamsson PA, Body JJ et al. Guidance on the use of bisphosphonates in solid tumours: Recommendations of an international expert panel. Ann Oncol 2008; 19(3): 420-432.
74. Gralow J, Tripathy D. Managing metastatic bone pain: The role of bisphosphonates. J Pain Symptom Manage 2007; 33(4): 462-472.
75. Wong R, Wiffen PJ. Bisphosphonates for the relief of pain secondary to bone metastases. Cochrane Database Syst Rev 2002; (2): CD002068.
76. Terpos E, Palermos J, Tsionos K et al. Effect of pamidronate administration on markers of bone turnover and disease activity in multiple myeloma. Eur J Haematol 2000; 65(5): 331-336.
77. WHO's pain relief ladder http://www.who.int/cancer/palliative/painladder/ en/ (19 May 2009, data last accessed).
78. McDonald RJ, Trout AT, Gray LA et al. Vertebroplasty in multiple myeloma: Outcomes in a large patient series. AJNR Am J Neuroradiol 2008; 29(4): 642-648.
79. Dudeney S, Lieberman IH, Reinhardt MK, Hussein M. Kyphoplasty in the treatment of osteolytic vertebral compression fractures as a result of multiple myeloma. J Clin Oncol 2002; 20(9): 2382-2387.
80. Lieberman I, Reinhardt MK. Vertebroplasty and kyphoplasty for osteolytic vertebral collapse. Clin Orthop Relat Res 2003; 415 (Suppl): S176-S186.
81. Chow E, Harris K, Tharmalingam S et al. Early phase in the development of a bone metastases quality of life module. Clin Oncol (R Coll Radiol) 2007; 19(3): S26.
82. Berenson JR, Rajdev L, Broder M. Bone complications in multiple myeloma. Cancer Biol Ther 2006; 5(9): 1082-1085.
83. Villikka K, Perttunen K, Rosnell J et al. The absolute bioavailability of clodronate from two different oral doses. Bone 2002; 31(3): 418-421.
84. Cramer JA, Gold DT, Silverman SL, Lewiecki EM. A systematic review of persistence and compliance with bisphosphonates for osteoporosis. Osteoporos Int 2007; 18(8): 1023-1031.
85. Gold DT, Safi W, Trinh H. Patient preference and adherence: Comparative US studies between two bisphosphonates, weekly risedronate and monthly ibandronate. Curr Med Res Opin 2006; 22(12): 2383-2391.
86. Cameron D. Patient management issues in metastatic bone disease. Semin Oncol 2004; 31 (5 Suppl 10): 79-82.
87. Robertson AG, Reed NS, Ralston SH. Effect of oral clodronate on metastatic bone pain: A double-blind, placebo-controlled study. J Clin Oncol 1995; 13(9): 2427-2430.
88. Göl D, Hoer A, Brandman J et al. Poor persistancy with oral bisphosphonates in cancer patients with bone metastasis. Cancer Treat Rev 2005; 31 (Suppl): S49-S50 (Abstr 93).
89. Mangiapane S, Hoer A, Gothe H et al. Higher persistency with i.v. bisphosphonates in patients with bone metastasis. ASCO Meeting Abstracts. J Clin Oncol 2006; 24 (18 Suppl): (Abstr 18623).
90. Chern B, Joseph D, Joshua D et al. Bisphosphonate infusions: Patient preference, safety and clinic use. Support Care Cancer 2004; 12(6): 463-466.
91. Saad F, Gleason DM, Murray R et al. 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(11): 879-882.
92. Rosen LS, Gordon DH, Dugan W Jr et al. Zoledronic acid is superior to pamidronate for the treatment of bone metastases in breast carcinoma patients with at least one osteolytic lesion. Cancer 2004; 100(1): 36-43.
93. McCloskey E, Paterson AHG, Powles TJ. Oral clodronate maintains bone mass in women with primary breast cancer. Proc Am Soc Clin Oncol 2005; 23: (Abstr 535A).
94. Gulley J, Dahut WL. Clodronate in the prevention and treatment of skeletal metastasis. Expert Rev Anticancer Ther 2005; 5(2): 221-230.
95. Guay DR. Ibandronate, an experimental intravenous bisphosphonate for osteoporosis, bone metastases, and hypercalcemia of malignancy. Pharmacotherapy 2006; 26(5): 655-673.
96. Kraj M, Poglod R, Maj S et al. Comparative evaluation of safety and efficacy of pamidronate and zoledronic acid in multiple myeloma patients (single center experience). Acta Pol Pharm 2002; 59(6): 478-482.
97. Coleman RE. Efficacy of zoledronic acid and pamidronate in breast cancer patients: A comparative analysis of randomized phase III trials. Am J Clin Oncol 2002; 25 (6 Suppl 1): S25-S31.
98. Summary of product characteristics (SmPC) clodronate, Bonefos-. Swissmedic (50957, 50958). 2006. http://www.kompendium.ch/ Search.aspx?lang=de.
99. Wardley A, Davidson N, Barrett-Lee P et al. Zoledronic acid significantly improves pain scores and quality of life in breast cancer patients with bone metastases: A randomised, crossover study of community vs hospital bisphosphonate administration. Br J Cancer 2005; 92(10): 1869-1876.
100. SmPC clodronate http://www.compendium.ch/ MonographieTxt.aspx?lang=de&MonType=fi.
101. SmPC zoledronic acid http://www.compendium.ch/ MonographieTxt.aspx?lang=de&MonType=fi.
102. Gimsing P, Carlson K, Fayers P et al. Randomised study on prophylactic pamidronate 30 mg versus 90 mg in multiple myeloma. Blood 2007; 110(11): (Abstr 533).
103. Caparrotti G, Catalano L, Feo C et al. Perspective study on pamidronate in stage I multiple myeloma. Hematol J 2003; 4(6): 459-460.
104. Musto P, Falcone A, Sanpaolo G et al. Pamidronate reduces skeletal events but does not improve progression-free survival in early-stage untreated myeloma: Results of a randomized trial. Leuk Lymphoma 2003; 44(9): 1545-1548.
105. Tassone P, Forciniti S, Galea E et al. Growth inhibition and synergistic induction of apoptosis by zoledronate and dexamethasone in human myeloma cell lines. Leukemia 2000; 14(5): 841-844.
106. Kuroda J, Kimura S, Segawa H et al. p53-independent anti-tumor effects of the nitrogen-containing bisphosphonate zoledronic acid. Cancer Sci 2004; 95(2): 186-192.
107. Corso A, Ferretti E, Lazzarino M. Zoledronic acid exerts its antitumor effect in multiple myeloma interfering with the bone marrow microenvironment. Hematology 2005; 10(3): 215-224.
108. Aparicio A, Gardner A, Tu Y et al. In vitro cytoreductive effects on multiple myeloma cells induced by bisphosphonates. Leukemia 1998; 12(2): 220-229.
109. Shipman CM, Rogers MJ, Apperley JF et al. Bisphosphonates induce apoptosis in human myeloma cell lines: A novel anti-tumour activity. Br J Haematol 1997; 98(3): 665-672.
110. Baulch-Brown C, Molloy TJ, Yeh SL et al. Inhibitors of the mevalonate pathway as potential therapeutic agents in multiple myeloma. Leuk Res 2007; 31(3): 341-352.
111. Wilhelm M, Kunzmann V, Eckstein S et al. Gammadelta T cells for immune therapy of patients with lymphoid malignancies. Blood 2003; 102(1): 200-206.
112. Yaccoby S, Pearse RN, Johnson CL et al. Myeloma interacts with the bone marrow microenvironment to induce osteoclastogenesis and is dependent on osteoclast activity. Br J Haematol 2002; 116(2): 278-290.
113. Yaccoby S, Wezeman MJ, Zangari M et al. Inhibitory effects of osteoblasts and increased bone formation on myeloma in novel culture systems and a myelomatous mouse model. Haematologica 2006; 91(2): 192-199.
114. Croucher PI, De Hendrik R, Perry MJ et al. Zoledronic acid treatment of 5T2MM-bearing mice inhibits the development of myeloma bone disease: evidence for decreased osteolysis, tumor burden and angiogenesis, and increased survival. J Bone Miner Res 2003; 18(3): 482-492.
115. Dhodapkar MV, Singh J, Mehta J et al. Anti-myeloma activity of pamidronate in vivo. Br J Haematol 1998; 103(2): 530-532.
116. Kondo H, Mori A. Anti-tumor activity of pamidronate in human multiple myeloma. Leuk Lymphoma 2002; 43(4): 919-921.
117. Shipman CM, Vanderkerken K, Rogers MJ et al. The potent bisphosphonate ibandronate does not induce myeloma cell apoptosis in a murine model of established multiple myeloma. Br J Haematol 2000; 111(1): 283-286.
118. Dallas SL, Garrett IR, Oyajobi BO et al. Ibandronate reduces osteolytic lesions but not tumor burden in a murine model of myeloma bone disease. Blood 1999; 93(5): 1697-1706.
119. Cruz JC, Alsina M, Craig F et al. Ibandronate decreases bone disease development and osteoclast stimulatory activity in an in vivo model of human myeloma. Exp Hematol 2001; 29(4): 441-447.
120. Terpos E, Heath DJ, Rahemtulla A et al. Bortezomib reduces serum dickkopf-1 and receptor activator of nuclear factor-kappaB ligand concentrations and normalises indices of bone remodelling in patients with relapsed multiple myeloma. Br J Haematol 2006; 135(5): 688-692.
121. Tosi P, Zamagni E, Cellini C et al. First-line therapy with thalidomide, dexamethasone and zoledronic acid decreases bone resorption markers in patients with multiple myeloma. Eur J Haematol 2006; 76(5): 399-404.
122. Terpos E, de la Fuente J, Szydlo R et al. Tartrate-resistant acid phosphatase isoform 5b: A novel serum marker for monitoring bone disease in multiple myeloma. Int J Cancer 2003; 106(3): 455-457.
123. Terpos E, Viniou N, de la Fuente J et al. Pamidronate is superior to ibandronate in decreasing bone resorption, interleukin-6 and beta 2-microglobulin in multiple myeloma. Eur J Haematol 2003; 70(1): 34-42.
124. Martin A, Garcia-Sanz R, Hernandez J et al. Pamidronate induces bone formation in patients with smouldering or indolent myeloma, with no significant anti-tumour effect. Br J Haematol 2002; 118(1): 239-242.
125. Terpos E, Mihou D, Szydlo R et al. The combination of intermediate doses of thalidomide with dexamethasone is an effective treatment for patients with refractory/relapsed multiple myeloma and normalizes abnormal bone remodeling, through the reduction of sRANKL/osteoprotegerin ratio. Leukemia 2005; 19(11): 1969-1976.
126. Dunstan C, Felsenberg D, Seibel MJ. Therapy insight: The risks and benefits of bisphosphonates for the treatment of tumor-induced bone disease. Nat Clin Pract Oncol 2006; 4(1): 42-55.
127. Siris ES, Sherman WH, Baquiran DC et al. Effects of dichloromethylene diphosphonate on skeletal mobilization of calcium in multiple myeloma. N Engl J Med 1980; 302(6): 310-315.
128. Smith JA Jr. Palliation of painful bone metastases from prostate cancer using sodium etidronate: Results of a randomized, prospective, double-blind, placebocontrolled study. J Urol 1989; 141(1): 85-87.
129. Lufkin EG, Argueta R, Whitaker MD et al. Pamidronate: An unrecognized problem in gastrointestinal tolerability. Osteoporos Int 1994; 4(6): 320-322.
130. de Groen PC, Lubbe DF, Hirsch LJ et al. Esophagitis associated with the use of alendronate. N Engl J Med 1996; 335(14): 1016-1021.
131. Alves F, Prado JD, Rocha AC. Clinical features and management of jaw osteonecrosis in patients receiving bisphosphonate therapy. ASH Annual Meeting Abstracts. Blood 2007; 110(11 Suppl/part 2): 267b (Abstr 4775).
132. Saad F, Gleason DM, Murray R et al. A randomized, placebo-controlled trial of zoledronic acid in patients with hormone-refractory metastatic prostate carcinoma. J Natl Cancer Inst 2002; 94(19): 1458-1468.
133. Smith MR. Complementary and alternative therapies for advanced prostate cancer. Hematol Oncol Clin North Am 2001; 15(3): 559-571.
134. Tanvetyanon T, Stiff PJ. Management of the adverse effects associated with intravenous bisphosphonates. Ann Oncol 2006; 17(6): 897-907.
135. Sorscher SM. Electrolyte abnormalities with zoledronic acid therapy. Cancer J 2002; 8(4): 348; author reply 348-349.
136. Mercadante S, Fulfaro F. An unusual coma after therapy for bone pain. J Pain Symptom Manage 2000; 19(5): 323-324.
137. Sims EC, Rogers PB, Besser GM, Plowman PN. Severe prolonged hypocalcaemia following pamidronate for malignant hypercalcaemia. Clin Oncol (R Coll Radiol) 1998; 10(6): 407-409.
138. Peter R, Mishra V, Fraser WD. Severe hypocalcaemia after being given intravenous bisphosphonate. BMJ 2004; 328(7435): 335-336.
139. Lipton A. Efficacy and safety of intravenous bisphosphonates in patients with bone metastases caused by metastatic breast cancer. Clin Breast Cancer 2007; 7 (Suppl 1): S14-S20.
140. Markowitz GS, Fine PL, Stack JI et al. Toxic acute tubular necrosis following treatment with zoledronate (Zometa). Kidney Int 2003; 64(1): 281-289.
141. Chang JT, Green L, Beitz J. Renal failure with the use of zoledronic acid. N Engl J Med 2003; 349(17): 1676-1679; discussion 1676-1679.
142. Rosen LS, Gordon D, Tchekmedyian NS et al. 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(12): 2613-2621.
143. Rosen LS, Gordon D, Tchekmedyian S et al. 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 2003; 21(16): 3150-3157.
144. Francis M, Marttrodam R. Chemical, biochemical, and medical properties of the diphosphonates. In Hilderbrand RL (ed.), The Role of Phosphonates in Living Systems. Boca Raton, FL: CRC Press 1983; 55-59.
145. Pecherstorfer M, Diel IJ. Rapid administration of ibandronate does not affect renal functioning: Evidence from clinical studies in metastatic bone disease and hypercalcaemia of malignancy. Support Care Cancer 2004; 12(12): 877-881.
146. Bergner R, Henrich DM, Hoffmann M et al. Renal safety and pharmacokinetics of ibandronate in multiple myeloma patients with or without impaired renal function. J Clin Pharmacol 2007; 47(8): 942-950.
147. Bounameaux HM, Schifferli J, Montani JP et al. Renal failure associated with intravenous diphosphonates. Lancet 1983; 1(8322): 471.
148. Conte P, Guarneri V. Safety of intravenous and oral bisphosphonates and compliance with dosing regimens. Oncologist 2004; 9 (Suppl 4): 28-37.
149. Markowitz GS, Fine PL, D'Agati VD. Nephrotic syndrome after treatment with pamidronate. Am J Kidney Dis 2002; 39(5): 1118-1122.
150. Shreedhara M, Fenves AZ, Benavides D, Stone MJ. Reversibility of pamidronate-associated glomerulosclerosis. Proc (Bayl Univ Med Cent) 2007; 20(3): 249-253.
151. Hansen T, Kunkel M, Weber A, James Kirkpatrick C. Osteonecrosis of the jaws in patients treated with bisphosphonates-histomorphologic analysis in comparison with infected osteoradionecrosis. J Oral Pathol Med 2006; 35(3): 155-160.
152. Weitzman R, Sauter N, Eriksen EF et al. 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(2): 148-152.
153. Bamias A, Kastritis E, Bamia C et al. Osteonecrosis of the jaw in cancer after treatment with bisphosphonates: Incidence and risk factors. J Clin Oncol 2005; 23(34): 8580-8587.
154. Marx RE. Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: A growing epidemic. J Oral Maxillofac Surg 2003; 61(9): 1115-1117.
155. Melo MD, Obeid G. Osteonecrosis of the jaws in patients with a history of receiving bisphosphonate therapy: Strategies for prevention and early recognition. J Am Dent Assoc 2005; 136(12): 1675-1681.
156. Ruggiero SL, Mehrotra B, Rosenberg TJ, Engroff SL. Osteonecrosis of the jaws associated with the use of bisphosphonates: A review of 63 cases. J Oral Maxillofac Surg 2004; 62(5): 527-534.
157. Dimopoulos MA, Kastritis E, Anagnostopoulos A et al. Osteonecrosis of the jaw in patients with multiple myeloma treated with bisphosphonates: evidence of increased risk after treatment with zoledronic acid. Haematologica 2006; 91(7): 968-971.
158. Zervas K, Verrou E, Teleioudis Z et al. Incidence, risk factors and management of osteonecrosis of the jaw in patients with multiple myeloma: A single-centre experience in 303 patients. Br J Haematol 2006; 134(6): 620-623.
159. Badros A, Weikel D, Salama A et al. Osteonecrosis of the jaw in multiple myeloma patients: Clinical features and risk factors. J Clin Oncol 2006; 24(6): 945-952.
160. Durie BG, Katz M, Crowley J. Osteonecrosis of the jaw and bisphosphonates. N Engl J Med 2005; 353(1): 99-102; discussion 99-102.
161. Mehrotra B, Ruggiero S. Bisphosphonate complications including osteonecrosis of the jaw. Hematology Am Soc Hematol Educ Program 2006: 356-360.
162. Montazeri AH, Erskine JG, McQuaker IG. Oral sodium clodronate induced osteonecrosis of the jaw in a patient with myeloma. Eur J Haematol 2007; 79(1): 69-71.
163. Brooks JK, Gilson AJ, Sindler AJ et al. Osteonecrosis of the jaws associated with use of risedronate: Report of 2 new cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007; 103(6): 780-786.
164. Yarom N, Yahalom R, Shoshani Y et al. Osteonecrosis of the jaw induced by orally administered bisphosphonates: Incidence, clinical features, predisposing factors and treatment outcome. Osteoporos Int 2007; 18(10): 1363-1370.
165. Mavrokokki T, Cheng A, Stein B, Goss A. Nature and frequency of bisphosphonate-associated osteonecrosis of the jaws in Australia. J Oral Maxillofac Surg 2007; 65(3): 415-423.
166. Corso A, Varettoni M, Zappasodi P et al. A different schedule of zoledronic acid can reduce the risk of the osteonecrosis of the jaw in patients with multiple myeloma. Leukemia 2007; 21(7): 1545-1548.
167. Adam Z, Kozumplikova M, Pour L, Machalka M. [Osteonecrosis of the jaw in the course of multiple myeloma treatment and bisphosphonate administration]. Vnitr Lek 2006; 52(2): 176-180.
168. Woo SB, Hellstein JW, Kalmar JR. Narrative [corrected] review: bisphosphonates and osteonecrosis of the jaws. Ann Intern Med 2006; 144(10): 753-761.
169. Badros A, Terpos E, Katodritou E et al. Natural history of osteonecrosis of the jaw in patients with multiple myeloma. J Clin Oncol 2008; 26(36): 5904-5909.
170. Ripamonti CI, Maniezzo M, Campa T et al. Decreased occurrence of osteonecrosis of the jaw after implementation of dental preventive measures in solid tumour patients with bone metastases treated with bisphosphonates. The experience of the National Cancer Institute of Milan. Ann Oncol 2009; 20: 137-145.
171. Montefusco V, Gay F, Spina F et al. Antibiotic prophylaxis before dental procedures may reduce the incidence of osteonecrosis of the jaw in patients with multiple myeloma treated with bisphosphonates. Leuk Lymphoma 2008; 49(11): 2156-2162.
172. Dimopoulos MA, Kastritis E, Bamia C et al. Reduction of osteonecrosis of the jaw (ONJ) after implementation of preventive measures in patients with multiple myeloma treated with zoledronic acid. Ann Oncol 2009; 20: 117-120.
173. Coleman RE, Major P, Lipton A et al. Predictive value of bone resorption and formation markers in cancer patients with bone metastases receiving the bisphosphonate zoledronic acid. J Clin Oncol 2005; 23(22): 4925-4935.
174. Attal M, Harousseau JL, Leyvraz S et al. Maintenance therapy with thalidomide improves survival in patients with multiple myeloma. Blood 2006; 108(10): 3289-3294.
175. Terpos E, Palermos J, Viniou N et al. Pamidronate increases markers of bone formation in patients with multiple myeloma in plateau phase under interferonalpha treatment. Calcif Tissue Int 2001; 68(5): 285-290.
176. Abildgaard N, Brixen K, Eriksen EF et al. Sequential analysis of biochemical markers of bone resorption and bone densitometry in multiple myeloma. Haematologica 2004; 89(5): 567-577.
177. Terpos E, Politou M, Rahemtulla A. The role of markers of bone remodeling in multiple myeloma. Blood Rev 2005; 19(3): 125-142.
178. Heider U, Fleissner C, Zavrski I et al. Bone markers in multiple myeloma. Eur J Cancer 2006; 42(11): 1544-1553.
179. Lipton A, Cook RJ, Coleman RE et al. Clinical utility of biochemical markers of bone metabolism for improving the management of patients with advanced multiple myeloma. Clin Lymphoma Myeloma 2007; 7(5): 346-353.
180. Jakob C, Zavrski I, Heider U et al. Bone resorption parameters [carboxyterminal telopeptide of type-I collagen (ICTP), amino-terminal collagen type-I telopeptide (NTx), and deoxypyridinoline (Dpd)] in MGUS and multiple myeloma. Eur J Haematol 2002; 69(1): 37-42.
181. Hernandez JM, Suquia B, Queizan JA et al. Bone remodelation markers are useful in the management of monoclonal gammopathies. Hematol J 2004; 5(6): 480-488.
182. Jakob C, Zavrski I, Heider U et al. Serum levels of carboxy-terminal telopeptide of type-I collagen are elevated in patients with multiple myeloma showing skeletal manifestations in magnetic resonance imaging but lacking lytic bone lesions in conventional radiography. Clin Cancer Res 2003; 9(8): 3047-3051.
183. Zangari M, Esseltine D, Cavallo F et al. Predictive value of alkaline phosphatase for response and time to progression in bortezomib-treated multiple myeloma patients. Am J Hematol 2007; 82(9): 831-833.
184. von Metzler I, Krebbel H, Hecht M et al. Bortezomib inhibits human osteoclastogenesis. Leukemia 2007; 21(9): 2025-2034.
185. Heider U, Kaiser M, Muller C et al. Bortezomib increases osteoblast activity in myeloma patients irrespective of response to treatment. Eur J Haematol 2006; 77(3): 233-238.
186. Mulligan ME, Badros AZ. PET/CT and MR imaging in myeloma. Skeletal Radiol 2007; 36(1): 5-16.
187. Edelstyn GA, Gillespie PJ, Grebbell FS. The radiological demonstration of osseous metastases. Experimental observations. Clin Radiol 1967; 18(2): 158-162.
188. Bredella MA, Steinbach L, Caputo G et al. Value of FDG PET in the assessment of patients with multiple myeloma. AJR Am J Roentgenol 2005; 184(4): 1199-1204.
189. Coleman RE, Banks LM, Girgis SI et al. Skeletal effects of exemestane on bonemineral density, bone biomarkers, and fracture incidence in postmenopausal women with early breast cancer participating in the Intergroup Exemestane Study (IES): A randomised controlled study. Lancet Oncol 2007; 8(2): 119-127.
190. Fulfaro F, Leto G, Badalamenti G et al. The use of zoledronic acid in patients with bone metastases from prostate carcinoma: Effect on analgesic response and bone metabolism biomarkers. J Chemother 2005; 17(5): 555-559.
191. Weininger M, Lauterbach B, Knop S et al. Whole-body MRI of multiple myeloma: Comparison of different MRI sequences in assessment of different growth patterns. Eur J Radiol 2009; in press.
192. Durie BG. The role of anatomic and functional staging in myeloma: description of Durie/Salmon plus staging system. Eur J Cancer 2006; 42(11): 1539-1543.
193. Baur-Melnyk A, Buhmann S, Durr HR, Reiser M. Role of MRI for the diagnosis and prognosis of multiple myeloma. Eur J Radiol 2005; 55(1): 56-63.