Novel therapies in benign and malignant bone diseases

Pharmacology and Therapeutics

Volumn 134, Issue 3, 2012, Pages 338-344

  Rachner, Tilman D ^a   Hadji, Peyman ^b   Hofbauer, Lorenz C ^a,c  

^a DRESDEN UNIVERSITY OF TECHNOLOGY   (Germany)

^b PHILIPPS UNIVERSITY MARBURG   (Germany)

^c CENTER FOR REGENERATIVE THERAPIES DRESDEN   (Germany)

Author keywords

Bone metastasis; Cathepsin K; Denosumab; Osteoporosis; RANKL; Sclerostin

Indexed keywords

ACTIVIN A; BHQ 880; CALCIUM SENSING RECEPTOR; CATHEPSIN K; DENOSUMAB; DICKKOPF 1 PROTEIN; ENDOTHELIN; GLYCERYL TRINITRATE; MK 5442; MONOCLONAL ANTIBODY; ODANACATIB; OSTEOCLAST DIFFERENTIATION FACTOR; PLACEBO; ROMOSOZUMAB; SCLEROSTIN; SOTATERCEPT; UNCLASSIFIED DRUG; WNT PROTEIN; ZOLEDRONIC ACID;

BONE CANCER; BONE DISEASE; CLINICAL TRIAL (TOPIC); DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG HALF LIFE; DRUG RESEARCH; DRUG SAFETY; DRUG TOLERABILITY; HUMAN; HYPOCALCEMIA; METASTASIS; MOLECULAR DYNAMICS; MYELOMA; NONHUMAN; OSTEOCLAST; OSTEOLYSIS; OSTEOPOROSIS; PRIORITY JOURNAL; REVIEW; TREATMENT OUTCOME;

ACTIVINS; ANIMALS; ANTIBODIES, MONOCLONAL; BONE DISEASES; BONE NEOPLASMS; CATHEPSIN K; ENDOTHELINS; HUMANS; MODELS, BIOLOGICAL; MOLECULAR TARGETED THERAPY; NITROGLYCERIN; RECEPTOR ACTIVATOR OF NUCLEAR FACTOR-KAPPA B; RECEPTORS, CALCIUM-SENSING; WNT SIGNALING PATHWAY;

EID: 84859796622     PISSN: 01637258     EISSN: 1879016X     Source Type: Journal    
DOI: 10.1016/j.pharmthera.2012.02.005     Document Type: Review

References (74)

1. Armstrong, A. P., Miller, R. E., Jones, J. C., Zhang, J., Keller, E. T., & Dougall, W. C. (2008). RANKL acts directly on RANK-expressing prostate tumor cells and mediates migration and expression of tumor metastasis genes. Prostate 68, 92-104.
2. Balan, G., Bauman, J., Bhattacharya, S., Castrodad, M., Healy, D. R., Herr, M., et al. (2009). The discovery of novel calcium sensing receptor negative allosteric modulators. Bioorg Med Chem Lett 19, 3328-3332.
3. Balemans, W., Ebeling, M., Patel, N., Van Hul, E., Olson, P., Dioszegi, M., 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. (Pubitemid 32184286)
4. Baron, R., & Rawadi, G. (2007). Wnt signaling and the regulation of bone mass. Curr Osteoporos Rep 5, 73-80. (Pubitemid 46954745)
5. Bekker, P. J., Holloway, D. L., Rasmussen, A. S., Murphy, R., Martin, S. W., Leese, P. T., 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. (Pubitemid 41110556)
6. Body, J. J., Facon, T., Coleman, R. E., Lipton, A., Geurs, F., Fan, M., et al. (2006). 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 12, 1221-1228. (Pubitemid 43342512)
7. Bone, H. G., McClung, M. R., Roux, C., Recker, R. R., Eisman, J. A., Verbruggen, N., et al. (2010). Odanacatib, a cathepsin-K inhibitor for osteoporosis: a two-year study in postmenopausal women with low bone density. J Bone Miner Res 25, 937-947.
8. Brown, J. P., Prince, R. L., Deal, C., Recker, R. R., Kiel, D. P., de Gregorio, L. H., 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.
9. Brown, J. P., Dempster, D. W., Ding, B., Dent-Acosta, R., San Martin, J., Grauer, A., et al. (2011). Bone remodeling in postmenopausal women who discontinued denosumab treatment: off-treatment biopsy study. J Bone Miner Res 26, 2737-2744.
10. Brubaker, K. D., Vessella, R. L., True, L. D., Thomas, R., & Corey, E. (2003). Cathepsin K mRNA and protein expression in prostate cancer progression. J Bone Miner Res 18, 222-230. (Pubitemid 36125914)
11. Bucay, N., Sarosi, I., Dunstan, C. R., Morony, S., Tarpley, J., Capparelli, C., et al. (1998). Osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification. Genes Dev 12, 1260-1268. (Pubitemid 28213402)
12. Capparelli, C., Kostenuik, P. J., Morony, S., Starnes, C., Weimann, B., Van, G., et al. (2000). Osteoprotegerin prevents and reverses hypercalcemia in a murine model of humoral hypercalcemia of malignancy. Cancer Res 60, 783-787. (Pubitemid 30129501)
13. Carducci, M. A., Padley, R. J., Breul, J., Vogelzang, N. J., Zonnenberg, B. A., Daliani, D. D., et al. (2003). 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 21, 679-689. (Pubitemid 46621903)
14. Chantry, A. D., Heath, D., Mulivor, A. W., Pearsall, S., Baud'huin, M., Coulton, L., et al. (2010). Inhibiting activin-A signaling stimulates bone formation and prevents cancer-induced bone destruction in vivo. J Bone Miner Res 25, 2633-2646.
15. Clines, G. A., Mohammad, K. S., Bao, Y., Stephens, O. W., Suva, L. J., Shaughnessy, J. D., Jr., et al. (2007). Dickkopf homolog 1 mediates endothelin-1-stimulated new bone formation. Mol Endocrinol 21, 486-498. (Pubitemid 46184897)
16. Cummings, S. R., San Martin, J., McClung, M. R., Siris, E. S., Eastell, R., Reid, I. R., et al. (2009). Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med 361, 756-765.
17. Eghbali-Fatourechi, G., Khosla, S., Sanyal, A., Boyle, W. J., Lacey, D. L., & Riggs, B. L. (2003). Role of RANK ligand in mediating increased bone resorption in early postmenopausal women. J Clin Invest 111, 1221-1230. (Pubitemid 36519939)
18. Eisman, J. A., Bone, H. G., Hosking, D. J., McClung, M. R., Reid, I. R., Rizzoli, R., et al. (2011). Odanacatib in the treatment of postmenopausal women with low bone mineral density: three-year continued therapy and resolution of effect. J Bone Miner Res 26, 242-251.
19. Ellis, G. K., Bone, H. G., Chlebowski, R., Paul, D., Spadafora, S., Smith, J., et al. (2008). Randomized trial of denosumab in patients receiving adjuvant aromatase inhibitors for nonmetastatic breast cancer. J Clin Oncol 26, 4875-4882.
20. Emery, J. G., McDonnell, P., Burke, M. B., Deen, K. C., Lyn, S., Silverman, C., et al. (1998). Osteoprotegerin is a receptor for the cytotoxic ligand TRAIL. J Biol Chem 273, 14363-14367. (Pubitemid 28319153)
21. Fizazi, K., Carducci, M., Smith, M., Damião, R., Brown, J., Karsh, L., 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.
22. Fulciniti, M., Tassone, P., Hideshima, T., Vallet, S., Nanjappa, P., Ettenberg, S. A., et al. (2009). Anti-DKK1 mAb (BHQ880) as a potential therapeutic agent for multiple myeloma. Blood 114, 371-379.
23. Gelb, B. D., Shi, G. P., Chapman, H. A., & Desnick, R. J. (1996). Pycnodysostosis, a lysosomal disease caused by cathepsin K deficiency. Science 273, 1236-1238.
24. Giuliani, N., Bataille, R., Mancini, C., Lazzaretti, M., & Barillé, S. (2001). Myeloma cells induce imbalance in the osteoprotegerin/osteoprotegerin ligand system in the human bone marrow environment. Blood 98, 3527-3533.
25. Gowen, M., Stroup, G. B., Dodds, R. A., James, I. E., Votta, B. J., Smith, B. R., et al. (2000). Antagonizing the parathyroid calcium receptor stimulates parathyroid hormone secretion and bone formation in osteopenic rats. J Clin Invest 105, 1595-1604. (Pubitemid 30390310)
26. Hadji, P. (2011). Clinical considerations for the use of antiresorptive agents in the treatment of metastatic bone disease. Crit Rev Oncol Hematol 80, 301-313.
27. Henry, D. H., Costa, L., Goldwasser, F., Hirsh, V., Hungria, V., Prausova, J., 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.
28. Hofbauer, L. C., & Schoppet, M. (2004). Clinical implications of the osteoprotegerin/ RANKL/RANK system for bone and vascular diseases. JAMA 292, 490-495. (Pubitemid 38988958)
29. Jamal, S. A., Browner, W. S., Bauer, D. C., & Cummings, S. R. (1998). Intermittent use of nitrates increases bone mineral density: The study of osteoporotic fractures. J Bone Miner Res 13, 1755-1759. (Pubitemid 28492006)
30. Jamal, S. A., Cummings, S. R., & Hawker, G. A. (2004). Isosorbide mononitrate increases bone formation and decreases bone resorption in postmenopausal women: A randomized trial. J Bone Miner Res 19, 1512-1517. (Pubitemid 41094353)
31. Jamal, S. A., Hamilton, C. J., Eastell, R., & Cummings, S. R. (2011). Effect of nitroglycerin ointment on bone density and strength in postmenopausal women: A randomized trial. JAMA 305, 800-807.
32. Jamal, S. A., Ljunggren, O., Stehman-Breen, C., Cummings, S. R.,McClung,M. R., Goemaere, S., et al. (2011). Effects of denosumab on fracture and bone mineral density by level of kidney function. J Bone Miner Res 26, 1829-1835.
33. Jensen, A. B.,Wynne, C., Ramirez, G., He,W., Song, Y., Berd, Y., et al. (2010). The cathepsin K inhibitor odanacatib suppresses bone resorption in women with breast cancer and established bone metastases: Results of a 4-week, double-blind, randomized, controlled trial. Clin Breast Cancer 10, 452-458.
34. Jones, D. H., Nakashima, T., Sanchez, O. H., Kozieradzki, I., Komarova, S. V., Sarosi, I., et al. (2006). Regulation of cancer cell migration and bone metastasis by RANKL. Nature 440, 692-696.
35. Khan, A. A., Sándor, G. K., Dore, E., Morrison, A. D., Alsahli, M., Amin, F., et al. (2008). Canadian consensus practice guidelines for bisphosphonate associated osteonecrosis of the jaw. J Rheumatol 35, 1391-1397. (Pubitemid 352000790)
36. Kumar, S., Matheny, C. J., Hoffman, S. J., Marquis, R.W., Schultz, M., Liang, X., et al. (2010). An orally active calcium-sensing receptor antagonist that transiently increases plasma concentrations of PTH and stimulates bone formation. Bone 46, 534-542.
37. Le Gall, C., Bellahcène, A., Bonnelye, E., Gasser, J. A., Castronovo, V., Green, J., et al. (2007). A cathepsin K inhibitor reduces breast cancer induced osteolysis and skeletal tumor burden. Cancer Res 67, 9894-9902. (Pubitemid 47621238)
38. Leto, G., Incorvaia, L., Badalamenti, G., Tumminello, F. M., Gebbia, N., Flandina, C., et al. (2006). Activin A circulating levels in patients with bone metastasis from breast or prostate cancer. Clin Exp Metastasis 23, 117-122. (Pubitemid 44440171)
39. Lewiecki, E. M., Miller, P. D., McClung, M. R., Cohen, S. B., Bolognese, M. A., Liu, Y., et al. (2007). Two-year treatment with denosumab (AMG 162) in a randomized phase 2 study of postmenopausal women with low BMD. J Bone Miner Res 22, 1832-1841. (Pubitemid 351229299)
40. Li, X., Ominsky, M. S., Warmington, K. S., Morony, S., Gong, J., Cao, J., et al. (2009). Sclerostin antibody treatment increases bone formation, bone mass, and bone strength in a ratmodel of postmenopausal osteoporosis. J BoneMiner Res 24, 578-588.
41. Littlewood-Evans, A. J., Bilbe, G., Bowler, W. B., Farley, D., Wlodarski, B., Kokubo, T., et al. (1997). The osteoclast-associated protease cathepsin K is expressed in human breast carcinoma. Cancer Res 57, 5386-5390. (Pubitemid 27516378)
42. Loots, G. G., Kneissel, M., Keller, H., Baptist, M., Chang, J., Collette, N. M., et al. (2005). Genomic deletion of a long-range bone enhancer misregulates sclerostin in Van Buchem disease. Genome Res 15, 928-935. (Pubitemid 40994212)
43. McClung, M. R., Lewiecki, E. M., Bolognese, M. A., Peacock, M., Weinstein, R., Ding, B., et al. (2011). Effects of denosumab on bone mineral density and biochemical markers of bone turnover: 8-year results of a phase 2 clinical trial. J Bone Miner Res 26 (Abstract 1061).
44. McClung, M. R., Lewiecki, E. M., Cohen, S. B., Bolognese, M. A., Woodson, G. C., Moffett, A. H., et al. (2006). Denosumab in postmenopausal women with low bone mineral density. N Engl J Med 354, 821-831. (Pubitemid 43290920)
45. Michaelson, M. D., Kaufman, D. S., Kantoff, P., Oh, W. K., & Smith, M. R. (2006). Randomized phase II study of atrasentan alone or in combination with zoledronic acid in men with metastatic prostate cancer. Cancer 107, 530-535. (Pubitemid 44107213)
46. Miller, P. D., Bolognese, M. A., Lewiecki, E. M., McClung, M. R., Ding, B., & Austin, M. (2008). Effect of denosumab on bone density and turnover in postmenopausal women with low bone mass after long-term continued, discontinued, and restarting of therapy: A randomized blinded phase 2 clinical trial. Bone 43, 222-229.
47. Nakashima, T., Hayashi, M., Fukunaga, T., Kurata, K., Oh-Hora, M., Feng, J. Q., et al. (2011). Evidence for osteocytes regulation of bone homeostasis through RANKL expression. Nat Med 17, 1231-1234.
48. Nelson, J. B., Love, W., Chin, J. L., Saad, F., Schulman, C. C., Sleep, D. J., et al. (2008). Phase 3, randomized, controlled trial of atrasentan in patients with nonmetastatic, hormone-refractory prostate cancer. Cancer 113, 2478-2487.
49. Ominsky, M. S., Vlasseros, F., Jolette, J., Smith, S. Y., Stouch, B., Doellgast, G., 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.
50. Padhi, D., Jang, G., Stouch, B., Fang, L., & Posvar, E. (2011). Single-dose, placebocontrolled, randomized study of AMG 785, a sclerostin monoclonal antibody. J Bone Miner Res 26, 19-26.
51. Peroni, A., Zini, A., Braga, V., Colato, C., Adami, S., & Girolomoni, G. (2008). Drug-induced morphea: Report of a case induced by balicatib and review of the literature. J Am Acad Dermatol 59, 125-129.
52. Rachner, T. D., Khosla, S., & Hofbauer, L. C. (2011). Osteoporosis: Now and the future. Lancet 377, 1276-1287.
53. Rejnmark, L., & Mosekilde, L. (2011). New and emerging antiresorptive treatments in osteoporosis. Curr Drug Saf 6, 75-88.
54. Rejnmark, L., Vestergaard, P., & Mosekilde, L. (2006). Decreased fracture risk in users of organic nitrates: A nationwide case-control study. J Bone Miner Res 21, 1811-1817. (Pubitemid 46141238)
55. Roodman, G. D. (2009). Pathogenesis of myeloma bone disease. Leukemia 23, 435-441.
56. Ruckle, J., Jacobs, M., Kramer, W., Pearsall, A. E., Kumar, R., Underwood, K. W., et al. (2009). Single-dose, randomized, double-blind, placebo-controlled study of ACE- 011 (ActRIIA-IgG1) in postmenopausal women. J Bone Miner Res 24, 744-752.
57. Saad, F., Adachi, J. D., Brown, J. P., Canning, L. A., Gelmon, K. A., Josse, R. G., et al. (2008). Cancer treatment-induced bone loss in breast and prostate cancer. J Clin Oncol 26, 5465-5476.
58. Saftig, P., Hunziker, E., Wehmeyer, O., Jones, S., Boyde, A., Rommerskirch, W., et al. (1998). Impaired osteoclastic bone resorption leads to osteopetrosis in cathepsin-K-deficient mice. Proc Natl Acad Sci U S A 95, 13453-13458. (Pubitemid 28522993)
59. Sambrook, P., & Cooper, C. (2006). Osteoporosis Lancet 367, 2010-2018.
60. Schramek, D., Leibbrandt, A., Sigl, V., Kenner, L., Pospisilik, J. A., Lee, H. J., et al. (2010). Osteoclast differentiation factor RANKL controls development of progestin driven mammary cancer. Nature 468, 98-102.
61. Schwetz, B. A. (2001). From the Food and Drug Administration. JAMA 286, 1569.
62. Simonet, W. S., Lacey, D. L., Dunstan, C. R., Kelley, M., Chang, M. S., Lüthy, R., et al. (1997). Osteoprotegerin: A novel secreted protein involved in the regulation of bone density. Cell 89, 309-319. (Pubitemid 27199902)
63. Smith, M. R., Egerdie, B., Hernández Toriz, N., Feldman, R., Tammela, T. L., Saad, F., et al. (2009). Denosumab in men receiving androgen-deprivation therapy for prostate cancer. N Engl J Med 361, 745-755.
64. Smith, M. R., Saad, F., Coleman, R., Shore, N., Fizazi, K., Tombal, B., 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.
65. Sorscher, S. M., & Lockhart, A. C. (2011). Ras inhibition and the survival benefit favoring zoledronic acid compared with denosumab in patients with multiple myeloma. J Clin Oncol 29, 2735-2736 (author reply 2736-2738).
66. Stoch, S. A., Zajic, S., Stone, J., Miller, D. L., Van Dyck, K., Gutierrez, M. J., et al. (2009). Effect of the cathepsin K inhibitor odanacatib on bone resorption biomarkers in healthy postmenopausal women: two double-blind, randomized, placebocontrolled phase I studies. Clin Pharmacol Ther 86, 175-182.
67. Stolina, M., Kostenuik, P. J., Dougall, W. C., Fitzpatrick, L. A., & Zack, D. J. (2007). RANKL inhibition: from mice to men (and women). Adv Exp Med Biol 602, 143-150.
68. Stopeck, A. T., Lipton, A., Body, J. J., Steger, G. G., Tonkin, K., de Boer, R. H., 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, 5132-9513.
69. Sutjandra, L., Rodriguez, R. D., Doshi, S., Ma, M., Peterson, M. C., Jang, G. R., et al. (2011). Population pharmacokinetic meta-analysis of denosumab in healthy subjects and postmenopausal women with osteopenia or osteoporosis. Clin Pharmacokinet 50, 793-807.
70. Tsourdi, E., Rachner, T. D., Rauner, M., Hamann, C., & Hofbauer, L. (2011). Denosumab for bone diseases - Translating bone biology into targeted therapy. Eur J Endocrinol (in print).
71. Vallet, S., Mukherjee, S., Vaghela, N., Hideshima, T., Fulciniti, M., Pozzi, S., et al. (2010). Activin A promotes multiple myeloma-induced osteolysis and is a promising target for myeloma bone disease. Proc Natl Acad Sci U S A 107, 5124-5129.
72. Wimalawansa, S. J., Grimes, J. P., Wilson, A. C., & Hoover, D. R. (2009). Transdermal nitroglycerin therapy may not prevent early postmenopausal bone loss. J Clin Endocrinol Metab 94, 3356-3364.
73. Xiong, J., Onal, M., Jilka, R. L., Weinstein, R. S., Manolagas, S. C., & O'Brien, C. A. (2011). Matrix-embedded cells control osteoclast formation. Nat Med 17, 1235-1241.
74. Yin, J. J., Mohammad, K. S., Käkönen, S. M., Harris, S., Wu-Wong, J. R., Wessale, J. L., et al. (2003). A causal role for endothelin-1 in the pathogenesis of osteoblastic bone metastases. Proc Natl Acad Sci U S A 100, 10954-10959. (Pubitemid 37140134)