A phase I study of AMGN-0007, a recombinant osteoprotegerin construct, in patients with multiple myeloma or breast carcinoma related bone metastases
Open accessAbstract
BACKGROUND: Osteoprotegerin (OPG) is a decoy receptor for OPG ligand (OPGL), or receptor activator of NF-kappaB ligand (RANKL). RANKL/RANK interaction is important in terminal differentiation and activation of osteoclasts. In binding to RANKL, OPG blocks differentiation and activation of osteoclasts. AMGN-0007 is a recombinant OPG construct developed as a potential therapeutic agent in the treatment of bone disease. METHODS: A randomized, double-blind, double-dummy, active-controlled, single-dose, dose escalation study was conducted to determine the safety and effect on bone resorption of AMGN-0007 in patients with multiple myeloma (n = 28) or breast carcinoma (n = 26) with radiologically confirmed lytic bone lesions. Patients were randomized (3:1 ratio) to receive a single dose of either AMGN-0007 (subcutaneously [SC]) or pamidronate (90 mg intravenously) and were followed for 56 days. Medications or other diseases affecting bone metabolism and chemotherapy within 28 days of dosing were exclusion criteria. Biologic activity of AMGN-0007 was assessed by measurement of the surrogate marker of bone resorption, urinary N-telopeptide of collagen (NTX). RESULTS: AMGN-0007 caused a rapid, sustained, dose-dependent decrease in NTX/creatinine levels, which was at least comparable to the profile observed with pamidronate. Four serious adverse events were reported, three in breast carcinoma patients: a fracture in the left femur (pamidronate, considered unrelated), extreme fatigue (0.3 mg/kg AMGN-0007, considered unrelated), and congestive heart failure (1.0 mg/kg AMGN-0007, considered by the investigator to be probably related to doxorubicin and radiation therapy); one event occurred in a multiple myeloma patient: Herpes zoster (pamidronate, considered unrelated). Two multiple myeloma patients (1.0 mg/kg AMGN-0007) had albumin-adjusted serum calcium levels of 1.9 mmol/L on Day 8 but without clinical symptoms. CONCLUSIONS: A single SC dose of AMGN-0007 suppressed bone resorption as indicated by a rapid, sustained, and profound decrease of urinary NTX/creatinine in multiple myeloma and breast carcinoma patients. Changes were comparable to those with pamidronate. AMGN-0007 was well tolerated.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
OPG-Fc dose-dependently reduced uNTX within 1 day, with a nadir of approximately −60% in multiple myeloma and −84% in breast cancer at 1.0 and 3.0 mg/kg.
“A dose-dependent reduction in uNTX occurred within 1 d of dosing with OPG-Fc, and uNTX reached a nadir of approximately Ϫ60 and Ϫ84% in the MM and breast cancer strata, respectively, at the higher doses (1.0 and 3.0 mg/kg).”
From Receptor Activator of Nuclear Factor κB Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease (2008) · cites this paper as [23]
Suppression of bone resorption by OPG-Fc was maintained throughout the 56-day study.
“Suppression of bone resorption was maintained throughout the duration of the study (56 d).”
From Receptor Activator of Nuclear Factor κB Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease (2008) · cites this paper as [23]
The pharmacodynamic profile of OPG-Fc was generally similar to that of pamidronate.
“The pharmacodynamic profile of OPG-Fc was generally similar to that observed with the open-label active control, pamidronate.”
From Receptor Activator of Nuclear Factor κB Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease (2008) · cites this paper as [23]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation.
Lacey, D. L., Timms, E., Tan, H.-L., Kelley, M. J., Dunstan, C. R., Burgess, T., Elliott, R., Colombero, A., Elliott, G., Scully, S., et al. (1998) · Cell · doi:10.1016/s0092-8674(00)81569-x · Cited by 5,439 · see citing works
Self-citationOsteoprotegerin: a novel secreted protein involved in the regulation of bone density.
Simonet, W. S., Lacey, D. L., Dunstan, C. R., Kelley, M., Chang, M.-S., Lüthy, R., Nguyen, H. Q., Wooden, S., Bennett, L., Boone, T., et al. (1997) · Cell · doi:10.1016/s0092-8674(00)80209-3 · Cited by 5,130 · see citing works
Self-citationYasuda, H., Shima, N., Nakagawa, N., Yamaguchi, K., Kinosaki, M., Mochizuki, S.-I., Tomoyasu, A., Yano, K., Goto, M., Murakami, A., et al. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.7.3597 · Cited by 4,224 · see citing works
Efficacy of Pamidronate in Reducing Skeletal Events in Patients with Advanced Multiple Myeloma
Berenson, J. R., Lichtenstein, A. K., Porter, L. L., Dimopoulos, M. A., Bordoni, R., George, S., Lipton, A., Keller, A. M., Ballester, O., Kovacs, M. J., et al. (1996) · New England Journal of Medicine · doi:10.1056/nejm199602223340802 · Cited by 1,075 · see citing works
Self-citationHortobágyi, G. N., Theriault, R. L., Porter, L. L., Blayney, D. W., Lipton, A., Sinoff, C., Wheeler, H. T., Simeone, J. F., Seaman, J. J., Knight, R., et al. (1996) · New England Journal of Medicine · doi:10.1056/nejm199612123352401 · Cited by 1,024 · see citing works
Self-citationIsolation of a novel cytokine from human fibroblasts that specifically inhibits osteoclastogenesis.
Tsuda, E., Goto, M., Mochizuki, S.-I., Yano, K., Kobayashi, F., Morinaga, T., & Higashio, K. (1997) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1997.6603 · Cited by 787 · see citing works
Berenson, J. R., Lichtenstein, A. K., Porter, L., Dimopoulos, M. A., Bordoni, R. E., George, S., Lipton, A., Keller, A. M., Ballester, O., Kovacs, M. J., et al. (1998) · Journal of Clinical Oncology · doi:10.1200/jco.1998.16.2.593 · Cited by 645 · see citing works
Self-citationHortobágyi, G. N., Theriault, R. L., Lipton, A., Porter, L., Blayney, D. W., Sinoff, C., Wheeler, H. T., Simeone, J. F., Seaman, J. J., Knight, R., et al. (1998) · Journal of Clinical Oncology · doi:10.1200/jco.1998.16.6.2038 · Cited by 630 · see citing works
Self-citationTheriault, R. L., Lipton, A., Hortobágyi, G. N., Leff, R., Glück, S., Stewart, J. F., Costello, S., Kennedy, I., Simeone, J. F., Seaman, J. J., et al. (1999) · Journal of Clinical Oncology · doi:10.1200/jco.1999.17.3.846 · Cited by 603 · see citing works
Self-citationHonoré, P., Luger, N. M., Sabino, M. A. C., Schwei, M. J., Rogers, S. D., Mach, D. B., O'keefe, P. F., Ramnaraine, M. L. R., Clohisy, D. R., & Mantyh, P. W. (2000) · Nature Medicine · doi:10.1038/74999 · Cited by 497 · see citing works
The effect of a single dose of osteoprotegerin in postmenopausal women.
Bekker, P. J., Holloway, D., Nakanishi, A., Arrighi, M., Leese, P. T., & Dunstan, C. R. (2001) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2001.16.2.348 · Cited by 484 · see citing works
Self-citationOsteoprotegerin inhibits the development of osteolytic bone disease in multiple myeloma
Croucher, P. I. (2001) · Blood · doi:10.1182/blood.v98.13.3534 · Cited by 375 · see citing works
Morony, S., Capparelli, C., Sarosi, I., Lacey, D. L., Dunstan, C. R., & Kostenuik, P. J. (2001) · PubMed · Cited by 289 · see citing works
Self-citationMorony, S., Capparelli, C., Lee, R., Shimamoto, G., Boone, T., Lacey, D. L., & Dunstan, C. R. (1999) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.1999.14.9.1478 · Cited by 187 · see citing works
Self-citationA Dose-Finding Study of Zoledronate in Hypercalcemic Cancer Patients
Body, J. J., Lortholary, A. H., Romieu, G., Vigneron, A.-M., & Ford, J. (1999) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.1999.14.9.1557 · Cited by 151 · see citing works
Self-citationCapparelli, C., Kostenuik, P. J., Morony, S., Starnes, C. O., Weimann, B., Van, G. Y., Scully, S. A., Qi, M., Lacey, D. L., & Dunstan, C. R. (2000) · PubMed · Cited by 147 · see citing works
Self-citationHonoré, P., Luger, N. M., Sabino, M., Schwei, M. J., Rogers, S. D., Mach, D. B., O'keefe, P. F., Ramnaraine, M. I., Clohisy, D. R., & Mantyh, P. W. (2000) · Nature Medicine · Cited by 87 · see citing works
Berenson (2001) · doi:10.1002/1097-0142(20010401)91:7
Self-citation
Flagged first, then by citations
Research works printed but not linked: 1
- Hortobagyi GN, Theriault RL, Lipton A, et al. Long-term prevention of skeletal complications of metastatic breast cancer with pamidronate. J Clin Oncol. 1998;16:2038-2044.
Cited by
Sorted by citations
Osteoclast differentiation and activation
Boyle, W. J., Simonet, W. S., & Lacey, D. L. (2003) · Nature · doi:10.1038/nature01658 · Cited by 6,670 · see citing works
Functions of RANKL/RANK/OPG in bone modeling and remodeling
Boyce, B. F., & Xing, L. (2008) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2008.03.018 · Cited by 1,844 · see citing works
Clinical Implications of the Osteoprotegerin/RANKL/RANK System for Bone and Vascular Diseases
Hofbauer, L. C. (2004) · JAMA · doi:10.1001/jama.292.4.490 · Cited by 979 · see citing works
Kearns, A. E., Khosla, S., & Kostenuik, P. J. (2008) · Endocrine Reviews · doi:10.1210/er.2007-0014 · Cited by 824 · see citing works
Bekker, P. J., Holloway, D. L., Rasmussen, A. S., Murphy, R., Martin, S. W., Leese, P. T., Holmes, G. B., Dunstan, C. R., & DePaoli, A. M. (2004) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.040305 · Cited by 770 · see citing works
Self-citationDenosumab and bisphosphonates: Different mechanisms of action and effects
Baron, R., Ferrari, S., & Russell, R. G. G. (2010) · Bone · doi:10.1016/j.bone.2010.11.020 · Cited by 716 · see citing works
Bench to bedside: elucidation of the OPG–RANK–RANKL pathway and the development of denosumab
Lacey, D. L., Boyle, W. J., Simonet, W. S., Kostenuik, P. J., Dougall, W. C., Sullivan, J. K., Martín, J. S., & Dansey, R. (2012) · Nature Reviews Drug Discovery · doi:10.1038/nrd3705 · Cited by 692 · see citing works
Theoleyre, S., Wittrant, Y., Tat, S. K., Fortun, Y., Redini, F., & Heymann, D. (2004) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2004.06.004 · Cited by 663 · see citing works
Body, J.-J., Facon, T., Coleman, R. E., Lipton, A., Geurs, F., Fan, M., Holloway, D., Peterson, M. C., & Bekker, P. J. (2006) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-05-1933 · Cited by 490 · see citing works
Self-citationClinical targeting of the TNF and TNFR superfamilies
Croft, M., Benedict, C. A., & Ware, C. F. (2013) · Nature Reviews Drug Discovery · doi:10.1038/nrd3930 · Cited by 457 · see citing works
Kostenuik, P. J., Nguyen, H. Q., McCabe, J. G., Warmington, K. S., Kurahara, C., Sun, N., Chen, C., Li, L. Z., Cattley, R., Van, G. Y., et al. (2008) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.081112 · Cited by 442 · see citing works
Terpos, E., Szydlo, R., Apperley, J. F., Hatjiharissi, E., Politou, M., Meletis, J., Viniou, N. A., Yataganas, X., Goldman, J. M., & Rahemtulla, A. (2003) · Blood · doi:10.1182/blood-2003-02-0380 · Cited by 411 · see citing works
The Cellular and Molecular Biology of Periprosthetic Osteolysis
Purdue, P. E., Koulouvaris, P., Potter, H. G., Nestor, B. J., & Sculco, T. P. (2006) · Clinical Orthopaedics and Related Research · doi:10.1097/01.blo.0000238813.95035.1b · Cited by 372 · see citing works
Breast Cancer Metastasis to Bone: Mechanisms of Osteolysis and Implications for Therapy
Kozlow, W., & Guise, T. A. (2005) · Journal of Mammary Gland Biology and Neoplasia · doi:10.1007/s10911-005-5399-8 · Cited by 338 · see citing works
Bone marrow microenvironment and the identification of new targets for myeloma therapy
Podar, K., Chauhan, D., & Anderson, K. C. (2008) · Leukemia · doi:10.1038/leu.2008.259 · Cited by 336 · see citing works
(2007) · PubMed · Cited by 337 · see citing works
Metastasis: a therapeutic target for cancer
Steeg, P. S., & Theodorescu, D. (2008) · Nature Clinical Practice Oncology · doi:10.1038/ncponc1066 · Cited by 332 · see citing works
Tanaka, S., Nakamura, K., Takahasi, N., & Suda, T. (2005) · Immunological Reviews · doi:10.1111/j.0105-2896.2005.00327.x · Cited by 321 · see citing works
Bone metastases from differentiated thyroid carcinoma
Mureşan, M., Olivier, P., Leclere, J.-C., Sirveaux, F., Brunaud, L., Klein, M., Zarnegar, R., & Weryha, G. (2008) · Endocrine Related Cancer · doi:10.1677/erc-07-0229 · Cited by 260 · see citing works
Clines, G. A., & Guise, T. A. (2005) · Endocrine Related Cancer · doi:10.1677/erc.1.00543 · Cited by 249 · see citing works
Vega, D., Maalouf, N. M., & Sakhaee, K. (2007) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2007-0646 · Cited by 246 · see citing works
Myeloma bone disease: pathophysiology and management.
Terpos, E., & Dimopoulos, M. (2005) · Annals of Oncology · doi:10.1093/annonc/mdi235 · Cited by 121 · see citing works
RANKL/RANK/OPG: new therapeutic targets in bone tumours and associated osteolysis
Wittrant, Y., Théoleyre, S., Chipoy, C., Padrines, M., Blanchard, F., Heymann, D., & Rédiní, F. (2004) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2004.05.002 · Cited by 230 · see citing works
Chen, G., Sircar, K., Aprikian, A. G., Potti, A., Goltzman, D., & Rabbani, S. A. (2006) · Cancer · doi:10.1002/cncr.21978 · Cited by 228 · see citing works
Farrugia, A. N., Atkins, G. J., To, L. B., Pan, B.-Q., Horvath, N., Kostakis, P., Findlay, D. M., Bardy, P., & Zannettino, A. C. W. (2003) · PubMed · Cited by 219 · see citing works
Novel host response therapeutic approaches to treat periodontal diseases
Kirkwood, K. L., Cirelli, J. A., Rogers, J. E., & Giannobile, W. V. (2007) · Periodontology 2000 · doi:10.1111/j.1600-0757.2006.00166.x · Cited by 210 · see citing works
Voskaridou, E., & Terpos, E. (2004) · British Journal of Haematology · doi:10.1111/j.1365-2141.2004.05143.x · Cited by 207 · see citing works
Dougall, W. C. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-10-2507 · Cited by 200 · see citing works
RANKL Inhibition Through Osteoprotegerin Blocks Bone Loss in Experimental Periodontitis
Jin, Q., Cirelli, J. A., Park, C. H., Sugai, J. V., Taba, M., Kostenuik, P. J., & Giannobile, W. V. (2007) · Journal of Periodontology · doi:10.1902/jop.2007.070073 · Cited by 198 · see citing works
RANK, RANKL and osteoprotegerin in bone biology and disease
Wright, H. L., McCarthy, H. S., Middleton, J., & Marshall, M. J. E. (2009) · Current Reviews in Musculoskeletal Medicine · doi:10.1007/s12178-009-9046-7 · Cited by 194 · see citing works
Pathogenesis of osteoblastic bone metastases from prostate cancer
Ibrahim, T., Flamini, E., Mercatali, L., Sacanna, E., Serra, P., & Amadori, D. (2010) · Cancer · doi:10.1002/cncr.24896 · Cited by 193 · see citing works
The pathogenesis of the bone disease of multiple myeloma
Edwards, C. M., Zhuang, J., & Mundy, G. R. (2008) · Bone · doi:10.1016/j.bone.2008.01.027 · Cited by 185 · see citing works
Bone Damage in Rheumatoid Arthritis: Mechanistic Insights and Approaches to Prevention
Karmakar, S., Kay, J., & Gravallese, E. M. (2010) · Rheumatic Disease Clinics of North America · doi:10.1016/j.rdc.2010.03.003 · Cited by 185 · see citing works
Classification of anticancer drugs—a new system based on therapeutic targets
Espinosa, E., Zamora, P. M., Feliú, J., & Barón, M. G. (2003) · Cancer Treatment Reviews · doi:10.1016/s0305-7372(03)00116-6 · Cited by 186 · see citing works
Sirohi, B., & Powles, R. (2004) · The Lancet · doi:10.1016/s0140-6736(04)15736-x · Cited by 184 · see citing works
Bone Disease in Multiple Myeloma: Pathophysiology and Management
Hameed, A., Brady, J. J., Dowling, P., CLYNES, M. M., & O’Gorman, P. (2014) · Cancer Growth and Metastasis · doi:10.4137/cgm.s16817 · Cited by 183 · see citing works
RANKL/RANK/OPG system beyond bone remodeling: involvement in breast cancer and clinical perspectives
Infante, M., Fabi, A., Cognetti, F., Gorini, S., Caprio, M., & Fabbri, A. (2019) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-018-1001-2 · Cited by 180 · see citing works
The Biology of Bone MetastasisPreprint
Esposito, M., Guise, T. A., & Kang, Y. (2017) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a031252 · Cited by 174 · see citing works
Advances in the Biology and Treatment of Bone Disease in Multiple Myeloma
Raje, N. S., & Roodman, G. D. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-10-1804 · Cited by 173 · see citing works
Kohli, S. S., & Kohli, V. S. (2011) · Indian Journal of Endocrinology and Metabolism · doi:10.4103/2230-8210.83401 · Cited by 170 · see citing works
Mitsiades, C. S., Mitsiades, N., Munshi, N. C., & Anderson, K. C. (2004) · Cancer Cell · doi:10.1016/j.ccr.2004.10.020 · Cited by 165 · see citing works
Targeted therapies for non-small cell lung cancer
Dempke, W. C. M., Sütö, T., & Reck, M. (2009) · Lung Cancer · doi:10.1016/j.lungcan.2009.10.012 · Cited by 165 · see citing works
Lerner, U. H. (2004) · Critical Reviews in Oral Biology & Medicine · doi:10.1177/154411130401500202 · Cited by 147 · see citing works
Zhang, J., Dai, J., Yao, Z., Lü, Y., Dougall, W. C., & Keller, E. T. (2003) · PubMed · Cited by 146 · see citing works
Bone Cancer Pain: From Model to Mechanism to Therapy
Luger, N. M., Mach, D. B., Sevcik, M. A., & Mantyh, P. W. (2005) · Journal of Pain and Symptom Management · doi:10.1016/j.jpainsymman.2005.01.008 · Cited by 144 · see citing works
Mechanisms of Disease: roles of OPG, RANKL and RANK in the pathophysiology of skeletal metastasis
Blair, J. M., Zhou, H., Seibel, M. J., & Dunstan, C. R. (2006) · Nature Clinical Practice Oncology · doi:10.1038/ncponc0381 · Cited by 140 · see citing works
Self-citationClinical development of anti-RANKL therapy
Schwarz, E. M., & Ritchlin, C. T. (2007) · Arthritis Research & Therapy · doi:10.1186/ar2171 · Cited by 138 · see citing works
(2005) · PubMed · Cited by 135 · see citing works
Transforming Growth Factor-Beta in Osteolytic Breast Cancer Bone Metastases
Guise, T. A., & Chirgwin, J. M. (2003) · Clinical Orthopaedics and Related Research · doi:10.1097/01.blo.0000093055.96273.69 · Cited by 134 · see citing works
Targeting tumor–stromal interactions in bone metastasis
Esposito, M., & Kang, Y. (2013) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2013.10.006 · Cited by 129 · see citing works
RANK ligand as a therapeutic target for bone metastases and multiple myeloma
Roodman, G. D., & Dougall, W. C. (2007) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2007.09.002 · Cited by 127 · see citing works
The RANK–RANKL–OPG System: A Multifaceted Regulator of Homeostasis, Immunity, and Cancer
León-Oliva, D. D., Barrena-Blázquez, S., Jiménez-Álvarez, L., Fraile‐Μartinez, O., Montero, C. G., López-González, L., Torres‐Carranza, D., García-Puente, L. M., Carranza, S. T., Álvarez-Mon, M. Á., et al. (2023) · Medicina · doi:10.3390/medicina59101752 · Cited by 136 · see citing works
Role of osteoprotegerin (OPG) in cancer
Holen, I., & Shipman, C. M. (2006) · Clinical Science · doi:10.1042/cs20050175 · Cited by 116 · see citing works
Giuliani, N., Colla, S., & Rizzoli, V. (2004) · Experimental Hematology · doi:10.1016/j.exphem.2004.03.015 · Cited by 116 · see citing works
Pathophysiology of bone cancer pain.
Sabino, M. A. C., & Mantyh, P. W. (2005) · PubMed · Cited by 114 · see citing works
Denosumab and Giant Cell Tumour of Bone—A Review and Future Management Considerations
Xu, S., Adams, B., Yu, X., & Xu, M. (2013) · Current Oncology · doi:10.3747/co.20.1497 · Cited by 112 · see citing works
Markers of Bone Remodeling in Metastatic Bone Disease
Fohr, B., Dunstan, C. R., & Seibel, M. J. (2003) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-030910 · Cited by 113 · see citing works
Self-citationDunn, M. D., Park, C. H., Kostenuik, P. J., Kapila, S., & Giannobile, W. V. (2007) · Bone · doi:10.1016/j.bone.2007.04.194 · Cited by 109 · see citing works
Mechanisms of invasion and metastasis in human neuroblastoma
Ara, T., & DeClerck, Y. A. (2006) · Cancer and Metastasis Reviews · doi:10.1007/s10555-006-9028-9 · Cited by 105 · see citing works
Body, J. J., Bergmann, P., Boonen, S., Boutsen, Y., Devogelaer, J.-P., Goemaere, S., Kaufman, J., Rozenberg, S., & Reginster, J.-Y. (2010) · Osteoporosis International · doi:10.1007/s00198-010-1223-4 · Cited by 103 · see citing works
Self-citationWu, X., Li, F., Dang, L., Liang, C., Lü, A., & Zhang, G. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00076 · Cited by 103 · see citing works
Translational medicine: cancer pain mechanisms and management
Delaney, A., Fleetwood-Walker, S. M., Colvin, L., & Fallon, M. (2008) · British Journal of Anaesthesia · doi:10.1093/bja/aen100 · Cited by 103 · see citing works
Denosumab in patients with cancer—a surgical strike against the osteoclast
Brown, J. E., & Coleman, R. E. (2012) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2011.197 · Cited by 99 · see citing works
Self-citationThe role of osteoprotegerin in cardiovascular disease
Montagnana, M., Lippi, G., Danese, E., & Guidi, G. C. (2012) · Annals of Medicine · doi:10.3109/07853890.2012.727019 · Cited by 98 · see citing works
Virk, M. S., & Lieberman, J. (2007) · Arthritis Research & Therapy · doi:10.1186/ar2169 · Cited by 108 · see citing works
Bekker, P. J., Holloway, D. L., Rasmussen, A. S., Murphy, R., Martin, S. W., Leese, P. T., Holmes, G. B., Dunstan, C. R., & DePaoli, A. M. (2005) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2005.20.12.2274 · Cited by 98 · see citing works
Self-citationVij, R., Horvath, N., Spencer, A. G., Taylor, K., Vadhan‐Raj, S., Vescio, R. A., Smith, J. W. G., Qian, Y., Yeh, H., & Jun, S. (2009) · American Journal of Hematology · doi:10.1002/ajh.21509 · Cited by 97 · see citing works
Smith, H. S. (2011) · Pain Physician · doi:10.36076/ppj.2011/14/e373 · Cited by 96 · see citing works
Challenges in cancer pain management–bone pain
Colvin, L., & Fallon, M. (2008) · European Journal of Cancer · doi:10.1016/j.ejca.2008.03.001 · Cited by 94 · see citing works
Assessment of therapeutic response in patients with metastatic bone disease
Clamp, A. R., Danson, S. J., Nguyen, H. D., Cole, D. E. C., & Clemons, M. J. (2004) · The Lancet Oncology · doi:10.1016/s1470-2045(04)01596-7 · Cited by 94 · see citing works
Recombinant Osteoprotegerin for Juvenile Paget's Disease
Cundy, T., Davidson, J. S., Rutland, M. D., Stewart, C., & DePaoli, A. M. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa050893 · Cited by 93 · see citing works
Cheng, X., Kinosaki, M., Takami, M., Choi, Y., Zhang, H., & Murali, R. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m309690200 · Cited by 92 · see citing works
Long-term treatment of osteoporosis: safety and efficacy appraisal of denosumab
Anastasilakis, A. D. (2012) · Therapeutics and Clinical Risk Management · doi:10.2147/tcrm.s24239 · Cited by 92 · see citing works
Treatment and prevention of bone complications from prostate cancer
Lee, R. J., Saylor, P. J., & Smith, M. R. (2010) · Bone · doi:10.1016/j.bone.2010.05.038 · Cited by 88 · see citing works
RANKL Inhibition: A Novel Strategy to Decrease Femoral Head Deformity After Ischemic Osteonecrosis
Kim, H. K., Morgan-Bagley, S., & Kostenuik, P. (2006) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.060905 · Cited by 89 · see citing works
Mechanisms of Cancer-induced Bone Pain
Middlemiss, T., Laird, B. J. A., & Fallon, M. (2011) · Clinical Oncology · doi:10.1016/j.clon.2011.03.003 · Cited by 88 · see citing works
The malignant clone and the bone-marrow environment
Podar, K., Richardson, P. G. G., Hideshima, T., Chauhan, D., & Anderson, K. C. (2007) · Best Practice & Research Clinical Haematology · doi:10.1016/j.beha.2007.08.002 · Cited by 88 · see citing works
Mountzios, G., Dimopoulos, M. A., Bamias, A., Papadopoulos, G., Kastritis, E., Syrigos, K., Pavlakis, G., & Terpos, E. (2006) · Acta Oncologica · doi:10.1080/02841860600635870 · Cited by 86 · see citing works
Targeting signaling pathways in multiple myeloma: Pathogenesis and implication for treatments
Hu, J., & Hu, W.-X. (2018) · Cancer Letters · doi:10.1016/j.canlet.2017.11.020 · Cited by 84 · see citing works
RANKL expression is related to treatment outcome of patients with localized, high‐grade osteosarcoma
Lee, J. A., Jung, J. S., Kim, D. H., Lim, J. S., Kim, M. S., Kong, C., Song, W. S., Cho, W. H., Jeon, D., Lee, S., et al. (2010) · Pediatric Blood & Cancer · doi:10.1002/pbc.22720 · Cited by 83 · see citing works
Kostenuik, P. J., Bolon, B., Morony, S., Daris, M., Geng, Z., Carter, C., & Sheng, J. (2004) · Bone · doi:10.1016/j.bone.2003.12.006 · Cited by 82 · see citing works
Heath, D. J., Vanderkerken, K., Cheng, X., Gallagher, O., Prideaux, M., Murali, R., & Croucher, P. I. (2007) · Cancer Research · doi:10.1158/0008-5472.can-06-1287 · Cited by 82 · see citing works
The role of the bone microenvironment in skeletal metastasis
Zheng, Y., Zhou, H., Dunstan, C. R., Sutherland, R. L., & Seibel, M. J. (2012) · Journal of bone oncology · doi:10.1016/j.jbo.2012.11.002 · Cited by 80 · see citing works
Self-citationKey roles of the OPG–RANK–RANKL system in bone oncology
Baud'huin, M., Duplomb, L., Velasco, C. R., Fortun, Y., Heymann, D., & Padrines, M. (2007) · Expert Review of Anticancer Therapy · doi:10.1586/14737140.7.2.221 · Cited by 87 · see citing works
A comprehensive review of denosumab for bone metastasis in patients with solid tumors
Gül, G., Şendur, M. A. N., Aksoy, S., Sever, A. R., & Altundağ, K. (2015) · Current Medical Research and Opinion · doi:10.1185/03007995.2015.1105795 · Cited by 79 · see citing works
Uday, S., Gaston, C. L., Rogers, L., Parry, M., Joffe, J., Pearson, J., SUTTON, D. R., Grimer, R. J., & Högler, W. (2017) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2017-02025 · Cited by 79 · see citing works
Ta, H. M., Nguyen, G. T. T., Jin, H. M., Choi, J., Park, H., Kim, N., Hwang, H., & Kim, K. K. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1011686107 · Cited by 78 · see citing works
The roles of osteoprotegerin in cancer, far beyond a bone player
Wang, Y., Liu, Y., Huang, Z., Chen, X., & Zhang, B. (2022) · Cell Death Discovery · doi:10.1038/s41420-022-01042-0 · Cited by 78 · see citing works
Role of RANKL in bone diseases
Anandarajah, A. (2009) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2008.10.007 · Cited by 77 · see citing works
Quan, J., Johnson, N. W., Zhou, G., Parsons, P. G., Boyle, G. M., & Gao, J. (2011) · Cancer and Metastasis Reviews · doi:10.1007/s10555-011-9335-7 · Cited by 75 · see citing works
Mori, T. (2004) · Nucleic Acids Research · doi:10.1093/nar/gkh949 · Cited by 74 · see citing works
Signaling Axis in Osteoclast Biology and Therapeutic Targeting in the RANKL/RANK/OPG System
Tanaka, S. (2007) · American Journal of Nephrology · doi:10.1159/000106484 · Cited by 73 · see citing works
Clinical development of anti-RANKL therapies for treatment and prevention of bone metastasis
Lipton, A., & Goessl, C. D. (2010) · Bone · doi:10.1016/j.bone.2010.10.161 · Cited by 71 · see citing works
Self-citationHypoxia, stem cells and bone tumor
Zeng, W., Wan, R., Zheng, Y., Singh, S. R., & Wei, Y. (2011) · Cancer Letters · doi:10.1016/j.canlet.2011.09.023 · Cited by 71 · see citing works
Myeloma Bone Disease: A Comprehensive Review
Mukkamalla, S. K. R., & Malipeddi, D. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22126208 · Cited by 70 · see citing works
Body, J. (2004) · Seminars in Nephrology · doi:10.1053/j.semnephrol.2003.08.015 · Cited by 69 · see citing works
Self-citationDesigning proteins for bone targeting
Gittens, S. A., BANSAL, G., Zernicke, R. F., & Uludağ, H. (2005) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2004.12.015 · Cited by 68 · see citing works
Novel aspects of osteoclast activation and osteoblast inhibition in myeloma bone disease
Heider, U., Hofbauer, L. C., Zavrski, I., Kaiser, M., Jakob, C., & Sezer, O. (2005) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2005.09.146 · Cited by 69 · see citing works
Myeloma bone disease: pathogenesis, current treatments and future targets.
Walker, R., Lawson, M., Buckle, C., Snowden, J., & Chantry, A. (2014) · British Medical Bulletin · doi:10.1093/bmb/ldu016 · Cited by 76 · see citing works
Emerging Therapeutic Targets in Breast Cancer Bone Metastasis
Rose, A. A. N., & Siegel, P. M. (2009) · Future Oncology · doi:10.2217/fon.09.138 · Cited by 67 · see citing works
- Authors
- Body, J.-J., Greipp, P., Coleman, R. E., Facon, T., Geurs, F., Fermand, J.-P., Harousseau, J.-L., Lipton, A., Mariette, X., Williams, C. D., Nakanishi, A., Holloway, D., Martin, S. W., Dunstan, C. R., & Bekker, P. J.
- Affiliations
- Institut Jules Bordet (BE)
- Mayo Clinic (US)
- Weston Park Cancer Centre (GB)
- Centre Hospitalier Universitaire de Lille (FR)
- Hôpital Saint-Louis (FR)
- Penn State Milton S. Hershey Medical Center (US)
- The Christie Hospital (GB)
- Amgen (United States) (US)
- Corresponding author
- Bekker, Pirow J.
- ORCID
- Venue
- Cancer
- Publisher
- Wiley
- Published
- 2003-01-23
- Volume
- 97
- Issue
- S3
- Pages
- 887-892
- ISSN
- 0008-543X (ISSN-L)
- 1097-0142
- OpenAlex
- W1986310612
- Cited by
- 383
- References
- 18
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 1 · 2022: 7 · 2021: 6 · 2020: 7 · 2019: 9 · 2018: 8 · 2017: 14 · 2016: 7 · 2015: 12 · 2014: 17 · 2013: 19 · 2012: 17
- FWCI
- 17.79
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cancer (publishedVersion)
- PubMed (publishedVersion)
- Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Bone health and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
- Keywords
- osteoprotegerin, RANKL, RANK, multiple myeloma, breast cancer, bone metastasis, osteolytic lesions, bone resorption, pamidronate, osteoclasts, drug safety, dose escalation, hypercalcemia, congestive heart failure, herpes zoster, phase I
- MeSH terms
- Pamidronate, Antineoplastic Agents, Bone Neoplasms, Bone Resorption, Breast Neoplasms, Diphosphonates, Dose-Response Relationship, Drug, Double-Blind Method, Female, Glycoproteins, Humans, Male, Middle Aged, Multiple Myeloma, Treatment Outcome, Receptors, Tumor Necrosis Factor, Receptors, Cytoplasmic and Nuclear, Osteoprotegerin
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
