Chapter 6 – Bone disease

Contributor: Evangelos Terpos


1 Christoulas D, Terpos E, Dimopoulos MA. Pathogenesis and management of myeloma bone disease. Expert Rev Hematol. 2009;2:385-398.
2 Terpos E, Christoulas D. Effects of proteasome inhibitors on bone cancer. BoneKEy Reports. 2013;2:395.
3 Terpos E, Szydlo R, Apperley JF, et al. Soluble receptor activator of nuclear factor kappaB ligand osteoprotegerin ratio predicts survival in multiple myeloma: proposal for a novel prognostic index. Blood. 2003;102:1064–1069.
4 Sugatani T, Alvarez UM, Hruska KA. Activin A stimulates IkappaB-alpha/NFkappaB and RANK expression for osteoclast differentiation, but not AKT survival pathway in osteoclast precursors. J Cell Biochem. 2003;90:59-67.

5 Terpos E, Kastritis E, Christoulas D, et al. Circulating activin-A is elevated in patients with advanced multiple myeloma and correlates with extensive bone involvement and inferior survival; no alterations post-lenalidomide and dexamethasone therapy. Ann Oncol. 2012;23:2681-2686.
6 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;349:2483-2494.
7 Moester MJ, Papapoulos SE, Löwik CW, van Bezooijen RL. Sclerostin: current knowledge and future perspectives. Calcif Tissue Int. 2010;87:99-107.
8 Terpos E, Christoulas D, Katodritou, E et al. Elevated circulating sclerostin correlates with advanced disease features and abnormal bone remodeling in symptomatic myeloma: reduction post-bortezomib monotherapy. Int J Cancer. 2012;131:1466-1471.
9 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;25:2464-2472.
10 Lacy MQ, Dispenzieri A, Gertz MA, et al. Mayo clinic consensus statement for the use of bisphosphonates in multiple myeloma. Mayo Clin Proc. 2006;81:1047-1053.
11 Harousseau JL, Greil R, Kloke O. ESMO Minimum Clinical Recommendations for diagnosis, treatment, and follow-up of multiple myeloma. Ann Oncol. 2005;16:i45-i47.
12 Terpos E, Sezer O, Croucher PI, et al. The use of bisphosphonates in multiple myeloma: recommendations of an expert panel on behalf of the European Myeloma Network. Ann Oncol. 2009;20:1303-1317.
13 Terpos E, Morgan G, Dimopoulos MA, et al. International Myeloma Working Group recommendations for the treatment of multiple myeloma-related bone disease. J Clin Oncol. 2013;31:2347-2357.
14 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;334:488-493.
15 Berenson JR, Rosen LS, Howell A, et al. Zoledronic acid reduces skeletal-related events in patients with osteolytic metastases. Cancer. 2001;91:1191-1200.
16 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;98:1735-1744.
17 Morgan GJ, Davies FE, Gregory WM, et al. First-line treatment with zoledronic acid as compared with clodronic acid in multiple myeloma (MRC Myeloma IX): a randomised controlled trial. Lancet. 2010;376:1989-1999.
18 Morgan GJ, Child JA, Gregory WM, et al. Effects of zoledronic acid versus clodronic acid on skeletal morbidity in patients with newly diagnosed multiple myeloma (MRC Myeloma IX): secondary outcomes from a randomised controlled trial. Lancet Oncol. 2011;12:743-752.
19 Morgan GJ, Davies FE, Gregory WM, et al. Effects of induction and maintenance plus long-term bisphosphonates on bone disease in patients with multiple myeloma: the Medical Research Council Myeloma IX trial. Blood. 2012;119:5374-5383.
20 D’Arena G, Gobbi PG, Broglia C, et al. Pamidronate versus observation in asymptomatic myeloma: final results with long-term follow-up of a randomized study. Leuk Lymphoma. 2011;52:771-775.
21 Musto P, Petrucci MT, Bringhen S, et al. A multicenter, randomized clinical trial comparing zoledronic acid versus observation in patients with asymptomatic myeloma. Cancer. 2008;113:1588-1595.
22 Berenson JR, Yellin O, Boccia RV, et al. Zoledronic acid markedly improves bone mineral density for patients with monoclonal gammopathy of undetermined significance and bone loss. Clin Cancer Res. 2008;14:6289-6295.
23 Fechtner K, Hillengass J, Delorme S, et al. Staging monoclonal plasma cell disease: comparison of the Durie-Salmon and the Durie-Salmon PLUS staging systems. Radiology. 2010;257:195-204.
24 Badros A, Goloubeva O, Terpos E, Milliron T, Baer MR, Streeten E. Prevalence and significance of vitamin D deficiency in multiple myeloma patients. Br J Haematol. 2008;142:492-494.
25 Munier A, Gras V, Andrejak M, et al. Zoledronic acid and renal toxicity: data from French adverse effect reporting database. Ann Pharmacother. 2005;39:1194-1197.
26 Banerjee D, Asif A, Striker L, Preston RA, Bourgoignie JJ, Roth D. Short-term, high-dose pamidronate-induced acute tubular necrosis: the postulated mechanisms of bisphosphonate nephrotoxicity. Am J Kidney Dis. 2003;41:E18.
27 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;23:8580-8587.
28 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;91:968-971.
29 Migliorati CA, Casiglia J, Epstein J, Jacobsen PL, Siegel MA, Woo SB. Managing the care of patients with bisphosphonate-associated osteonecrosis: an American Academy of Oral Medicine position paper. J Am Dent Assoc. 2005;136:1658-1668.
30 Berenson J, Pflugmacher R, Jarzem P, et al. Balloon kyphoplasty versus non-surgical fracture management for treatment of painful vertebral body compression fractures in patients with cancer: a multicentre, randomised controlled trial. Lancet Oncol. 2011;12:225-235.
31 Bhargava A, Trivedi D, Kalva L, Tumas M, Hooks M, Speth J. Management of cancer-related vertebral compression fracture: comparison of treatment options: a literature meta-analysis. J Clin Oncol. 2009;27:e20529.
32 Utzschneider S, Schmidt H, Weber P, Schmidt GP, Jansson V, Dürr HR. Surgical therapy of skeletal complications in multiple myeloma. Int Orthop. 2011;35:1209-1213.
33 Fizazi K, Lipton A, Mariette X, et al. 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.
34 Lipton A, Fizazi K, Stopeck AT, et al. 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.
35 Abdulkadyrov KM, Salogub GN, Khuazheva NK, et al. Sotatercept in patients with osteolytic lesions of multiple myeloma. Br J Haematol. 2014;165:814-823.
36 Terpos E, Christoulas D, Papatheodorou A, et al. Dickkopf-1 is elevated in newly-diagnosed, symptomatic patients and in relapsed patients with multiple myeloma. Correlations with advanced disease features: a single-center experience in 284 patients. Haematologica. 2010;95:384, abstr 0926.
37 Iyer SP, Beck JT, Stewart AK, et al. A Phase IB multicentre dose-determination study of BHQ880 in combination with anti-myeloma therapy and zoledronic acid in patients with relapsed or refractory multiple myeloma and prior skeletal-related events. Br J Haematol. 2014;167:366-375.
38 McClung MR, Grauer A, Boonen S, et al. Romosozumab in postmenopausal women with low bone mineral density. N Engl J Med. 2014;370:412-420.
39 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;135:688–692.
40 Giuliani N, Morandi F, Tagliaferri S, et al. The proteasome inhibitor bortezomib affects osteoblast differentiation in vitro and in vivo in multiple myeloma patients. Blood. 2007;110:334-338.
41 Heider U, Kaiser M, Muller C, et al. Bortezomib increases osteoblast activity in myeloma patients irrespective of response to treatment. Eur J Haematol. 2006;77:233-238.
42 Zangari M, Aujay M, Zhan F, et al. Alkaline phosphatase variation during carfilzomib treatment is associated with best response in multiple myeloma patients. Eur J Haematol. 2011;86:484-487.
43 Mitsiades N, Mitsiades CS, Poulaki V, et al. Apoptotic signaling induced by immunomodulatory thalidomide analogs in human multiple myeloma cells: therapeutic implications. Blood. 2002;99:4525–4530.
44 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;19:1969-1976.
45 Terpos E, Christoulas D, Kastritis E, et al. The combination of lenalidomide and dexamethasone reduces bone resorption in responding patients with relapsed/refractory multiple myeloma but has no effect on bone formation: final results on 205 patients of the Greek myeloma study group. Am J Hematol. 2014;89:34-40.