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Antibodies for the Treatment of Bone Diseases: Clinical Data

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Principles of Osteoimmunology

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Abstract

Poor bone quality with localized or generalized reduced bone strength is associated with an increased incidence of fractures, high health care costs, and increased mortality. An increased need of analgetics, painful joint dysfunction, or insufficient fracture healing is associated with a wide spectrum of secondary disease conditions such as chronic inflammatory or malignant bone diseases (Svedbom et al. 2013). Rapidly expanding knowledge of the molecular changes underlying metabolic bone diseases has revealed novel bone targets that are currently being explored in clinical trials.

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References

  • Balemans W et al (2001) Increased bone density in sclerosteosis is due to the deficiency of a novel secreted protein (SOST). Hum Mol Genet 10:537–543

    Article  CAS  PubMed  Google Scholar 

  • Barrett-Lee P et al (2007) An audit to determine the time taken to administer intravenous bisphosphonate infusions in patients diagnosed with metastatic breast cancer to bone in a hospital setting. Curr Med Res Opin 23:1575–1582

    Article  PubMed  Google Scholar 

  • Bekker PJ et al (2004) A single-dose placebo-controlled study of AMG 162, a fully human monoclonal antibody to RANKL, in postmenopausal women. J Bone Miner Res 19:1059–1066

    Article  CAS  PubMed  Google Scholar 

  • Bone HG et al (2008) Effects of denosumab on bone mineral density and bone turnover in postmenopausal women. J Clin Endocrinol Metab 93:2149–2157

    Article  CAS  PubMed  Google Scholar 

  • Bone HG et al (2011) Effects of denosumab treatment and discontinuation on bone mineral density and bone turnover markers in postmenopausal women with low bone mass. J Clin Endocrinol Metab 96:972–980

    Article  CAS  PubMed  Google Scholar 

  • Bone HG et al (2013) The effect of three or six years of denosumab exposure in women with postmenopausal osteoporosis: results from the FREEDOM extension. J Clin Endocrinol Metab 98:4483–4492

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Branstetter DG et al (2012) Denosumab induces tumor reduction and bone formation in patients with giant-cell tumor of bone. Clin Cancer Res 18:4415–4424

    Article  CAS  PubMed  Google Scholar 

  • Brown JP et al (2009) Comparison of the effect of denosumab and alendronate on BMD and biochemical markers of bone turnover in postmenopausal women with low bone mass: a randomized, blinded, phase 3 trial. J Bone Miner Res 24:153–161

    Article  CAS  PubMed  Google Scholar 

  • Budhia S, Mikyas Y, Tang M, Badamgarav E (2012) Osteoporotic fractures: a systematic review of U.S. healthcare costs and resource utilization. Pharmacoeconomics 30:147–170

    Article  PubMed  Google Scholar 

  • Chawla S et al (2013) Safety and efficacy of denosumab for adults and skeletally mature adolescents with giant cell tumour of bone: interim analysis of an open-label, parallel-group, phase 2 study. Lancet Oncol 14:901–908

    Article  CAS  PubMed  Google Scholar 

  • Coleman RE (2001) Metastatic bone disease: clinical features, pathophysiology and treatment strategies. Cancer Treat Rev 27:165–176

    Article  CAS  PubMed  Google Scholar 

  • Cummings SR et al (2009) Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med 361:756–765

    Article  CAS  PubMed  Google Scholar 

  • Dempster DW et al (2013) Standardized nomenclature, symbols, and units for bone histomorphometry: a 2012 update of the report of the ASBMR Histomorphometry Nomenclature Committee. J Bone Miner Res 28:2–17

    Article  PubMed  PubMed Central  Google Scholar 

  • Eghbali-Fatourechi G et al (2003) Role of RANK ligand in mediating increased bone resorption in early postmenopausal women. J Clin Invest 111:1221–1230

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ellis GK et al (2009) Effect of denosumab on bone mineral density in women receiving adjuvant aromatase inhibitors for non-metastatic breast cancer: subgroup analyses of a phase 3 study. Breast Cancer Res Treat 118:81–87

    Article  CAS  PubMed  Google Scholar 

  • Emery JG et al (1998) Osteoprotegerin is a receptor for the cytotoxic ligand TRAIL. J Biol Chem 273:14363–14367

    Article  CAS  PubMed  Google Scholar 

  • Ferrari S et al (2015) Further reductions in nonvertebral fracture rate with long-term denosumab treatment in the FREEDOM open-label extension and influence of hip bone mineral density after 3 years. Osteoporos Int 26:2763–2771

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fizazi K et al (2009) 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 27:1564–1571

    Article  CAS  PubMed  Google Scholar 

  • Fizazi K et al (2011) Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomised, double-blind study. Lancet 377:813–822

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fulciniti M et al (2009) Anti-DKK1 mAb (BHQ880) as a potential therapeutic agent for multiple myeloma. Blood 114:371–379

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Genant HK et al (2010) Denosumab improves density and strength parameters as measured by QCT of the radius in postmenopausal women with low bone mineral density. Bone 47:131–139

    Article  CAS  PubMed  Google Scholar 

  • Giuliani N, Bataille R, Mancini C, Lazzaretti M, Barille S (2001a) Myeloma cells induce imbalance in the osteoprotegerin/osteoprotegerin ligand system in the human bone marrow environment. Blood 98:3527–3533

    Article  CAS  PubMed  Google Scholar 

  • Giuliani C, Napolitano G, Bucci I, Montani V, Monaco F (2001b) Nf-kB transcription factor: role in the pathogenesis of inflammatory, autoimmune, and neoplastic diseases and therapy implications. Clin Ter 152:249–253

    CAS  PubMed  Google Scholar 

  • Gnant M et al (2015) Adjuvant denosumab in breast cancer (ABCSG-18): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet 386:433–443

    Article  CAS  PubMed  Google Scholar 

  • Henry DH et al (2011) 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 29:1125–1132

    Article  CAS  PubMed  Google Scholar 

  • Hofbauer LC, Schoppet M (2004) Clinical implications of the osteoprotegerin/RANKL/RANK system for bone and vascular diseases. JAMA 292:490–495

    Article  CAS  PubMed  Google Scholar 

  • Iyer SP et al (2014) 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 167:366–375

    Article  CAS  PubMed  Google Scholar 

  • Jones DH et al (2006) Regulation of cancer cell migration and bone metastasis by RANKL. Nature 440:692–696

    Article  CAS  PubMed  Google Scholar 

  • Kendler DL et al (2010) Effects of denosumab on bone mineral density and bone turnover in postmenopausal women transitioning from alendronate therapy. J Bone Miner Res 25:72–81

    Article  CAS  PubMed  Google Scholar 

  • Lacey DL et al (2012) Bench to bedside: elucidation of the OPG-RANK-RANKL pathway and the development of denosumab. Nat Rev Drug Discov 11:401–419

    Article  CAS  PubMed  Google Scholar 

  • Langdahl BL et al (2015) A 24-month study evaluating the efficacy and safety of denosumab for the treatment of men with low bone mineral density: results from the ADAMO trial. J Clin Endocrinol Metab 100:1335–1342

    Article  CAS  PubMed  Google Scholar 

  • Leder BZ et al (2015) Denosumab and teriparatide transitions in postmenopausal osteoporosis (the DATA-Switch study): extension of a randomised controlled trial. Lancet 386:1147–1155

    Article  CAS  PubMed  Google Scholar 

  • Li X et al (2009) Sclerostin antibody treatment increases bone formation, bone mass, and bone strength in a rat model of postmenopausal osteoporosis. J Bone Miner Res 24:578–588

    Article  CAS  PubMed  Google Scholar 

  • Lipton A et al (2007) Randomized active-controlled phase II study of denosumab efficacy and safety in patients with breast cancer-related bone metastases. J Clin Oncol 25:4431–4437

    Article  CAS  PubMed  Google Scholar 

  • Lipton A et al (2008) Extended efficacy and safety of denosumab in breast cancer patients with bone metastases not receiving prior bisphosphonate therapy. Clin Cancer Res 14:6690–6696

    Article  CAS  PubMed  Google Scholar 

  • Lipton A et al (2012) 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 48:3082–3092

    Article  CAS  PubMed  Google Scholar 

  • Loots GG et al (2005) Genomic deletion of a long-range bone enhancer misregulates sclerostin in Van Buchem disease. Genome Res 15:928–935

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McClung MR et al (2006) Denosumab in postmenopausal women with low bone mineral density. N Engl J Med 354:821–831

    Article  CAS  PubMed  Google Scholar 

  • McClung MR et al (2014) Romosozumab in postmenopausal women with low bone mineral density. N Engl J Med 370:412–420

    Article  CAS  PubMed  Google Scholar 

  • McColm J, Hu L, Womack T, Tang CC, Chiang AY (2014) Single- and multiple-dose randomized studies of blosozumab, a monoclonal antibody against sclerostin, in healthy postmenopausal women. J Bone Miner Res 29:935–943

    Article  CAS  PubMed  Google Scholar 

  • Ominsky MS et al (2010) Two doses of sclerostin antibody in cynomolgus monkeys increases bone formation, bone mineral density, and bone strength. J Bone Miner Res 25:948–959

    Article  CAS  PubMed  Google Scholar 

  • Orwoll E et al (2012) A randomized, placebo-controlled study of the effects of denosumab for the treatment of men with low bone mineral density. J Clin Endocrinol Metab 97:3161–3169

    Article  CAS  PubMed  Google Scholar 

  • Padhi D, Jang G, Stouch B, Fang L, Posvar E (2011) Single-dose, placebo-controlled, randomized study of AMG 785, a sclerostin monoclonal antibody. J Bone Miner Res 26:19–26

    Article  CAS  PubMed  Google Scholar 

  • Padhi D et al (2014) Multiple doses of sclerostin antibody romosozumab in healthy men and postmenopausal women with low bone mass: a randomized, double-blind, placebo-controlled study. J Clin Pharmacol 54:168–178

    Article  CAS  PubMed  Google Scholar 

  • Papapoulos SE (2013) Bone diseases: bisphosphonates in osteoporosis--beyond 5 years. Nat Rev Rheumatol 9:263–264

    Article  CAS  PubMed  Google Scholar 

  • Papapoulos S et al (2015) The effect of 8 or 5 years of denosumab treatment in postmenopausal women with osteoporosis: results from the FREEDOM Extension study. Osteoporos Int 26:2773–2783

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Recker RR et al (2015) A randomized, double-blind phase 2 clinical trial of blosozumab, a sclerostin antibody, in postmenopausal women with low bone mineral density. J Bone Miner Res 30:216–224

    Article  CAS  PubMed  Google Scholar 

  • Recknor CP et al (2015) The effect of discontinuing treatment with blosozumab: follow-up results of a phase 2 randomized clinical trial in postmenopausal women with low bone mineral density. J Bone Miner Res 30:1717–1725

    Article  CAS  PubMed  Google Scholar 

  • Roodman GD (2004) Mechanisms of bone metastasis. N Engl J Med 350:1655–1664

    Article  CAS  PubMed  Google Scholar 

  • Schramek D et al (2010) Osteoclast differentiation factor RANKL controls development of progestin-driven mammary cancer. Nature 468:98–102

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Simonet WS et al (1997) Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell 89:309–319

    Article  CAS  PubMed  Google Scholar 

  • Smith MR et al (2012) Denosumab and bone-metastasis-free survival in men with castration-resistant prostate cancer: results of a phase 3, randomised, placebo-controlled trial. Lancet 379:39–46

    Article  CAS  PubMed  Google Scholar 

  • Stopeck AT et al (2010) 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 28:5132–5139

    Article  CAS  PubMed  Google Scholar 

  • Svedbom A et al (2013) Osteoporosis in the European Union: a compendium of country-specific reports. Arch Osteoporos 8:137

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Thomas D et al (2010a) Denosumab in patients with giant-cell tumour of bone: an open-label, phase 2 study. Lancet Oncol 11:275–280

    Article  CAS  PubMed  Google Scholar 

  • Thomas D, Carriere P, Jacobs I (2010b) Safety of denosumab in giant-cell tumour of bone. Lancet Oncol 11:815

    Article  PubMed  Google Scholar 

  • Tsai JN et al (2013) Teriparatide and denosumab, alone or combined, in women with postmenopausal osteoporosis: the DATA study randomised trial. Lancet 382:50–56

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Author information

Authors and Affiliations

  1. Division of Endocrinology, Diabetes and Bone Diseases, Medical Faculty of the Technische Universität Dresden, Dresden, Germany

    Maria Winzer MD, Martina Rauner PhD & Lorenz C. Hofbauer MD

  2. Division of Rheumatology, Department of Medicine III, Medical Faculty of the Technische Universität Dresden, Dresden, Germany

    Maria Winzer MD

Authors
  1. Maria Winzer MD
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  2. Martina Rauner PhD
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  3. Lorenz C. Hofbauer MD
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Corresponding author

Correspondence to Lorenz C. Hofbauer MD .

Editor information

Editors and Affiliations

  1. Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria

    Peter Pietschmann

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Winzer, M., Rauner, M., Hofbauer, L.C. (2016). Antibodies for the Treatment of Bone Diseases: Clinical Data. In: Pietschmann, P. (eds) Principles of Osteoimmunology. Springer, Cham. https://doi.org/10.1007/978-3-319-34238-2_10

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