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.
Open accessAbstract
PURPOSE: Receptor activator of nuclear factor-kappaB ligand (RANKL) is essential for the differentiation, function, and survival of osteoclasts, which play a key role in establishment and propagation of skeletal disease in patients with multiple myeloma or bone metastases as well as many other skeletal diseases. Denosumab (AMG 162), a fully human monoclonal antibody to RANKL, was developed to treat patients with skeletal diseases. EXPERIMENTAL DESIGN: This was a randomized, double-blind, double-dummy, active-controlled, multicenter study to determine the safety and efficacy of denosumab in patients with breast cancer (n = 29) or multiple myeloma (n = 25) with radiologically confirmed bone lesions. Patients received a single dose of either denosumab (0.1, 0.3, 1.0, or 3.0 mg/kg s.c.) or pamidronate (90 mg i.v.). Bone antiresorptive effect was assessed by changes in urinary and serum N-telopeptide levels. Pharmacokinetics of denosumab also were assessed. RESULTS: Following a single s.c. dose of denosumab, levels of urinary and serum N-telopeptide decreased within 1 day, and this decrease lasted through 84 days at the higher denosumab doses. Pamidronate also decreased bone turnover, but the effect diminished progressively through follow-up. Denosumab injections were well tolerated. Mean half-lives of denosumab were 33.3 and 46.3 days for the two highest dosages. CONCLUSIONS: A single s.c. dose of denosumab given to patients with multiple myeloma or bone metastases from breast cancer was well tolerated and reduced bone resorption for at least 84 days. The decrease in bone turnover markers was similar in magnitude but more sustained than with i.v. pamidronate.
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?
In a phase 1 study, denosumab was well tolerated with an adverse event profile not significantly different from placebo in patients with bone metastases from breast cancer and multiple myeloma.
“A recent double-blind phase 1 study of denosumab published by Body et al. (442) in patients with bone metastases from breast cancer (n ϭ 29 women) and patients with MM (n ϭ 25; 14 men and 11 women) showed that denosumab was well tolerated, with an adverse event profile that was not significantly different from placebo patients.”
From Receptor Activator of Nuclear Factor κB Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease (2008) · cites this paper as [442]
The decreases in uNTX and serum NTX were similar in magnitude but numerically longer in duration compared with intravenous pamidronate 90 mg.
“These decreases were similar in magnitude, but of numerically longer duration, vs. those observed in a comparator group receiving an iv dose of pamidronate 90 mg.”
From Receptor Activator of Nuclear Factor κB Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease (2008) · cites this paper as [442]
Denosumab therapy was associated with sustained decreases (≥84 days) in uNTX and serum NTX after a single subcutaneous dose (0.1, 0.3, 1.0, or 3.0 mg/kg).
“Denosumab therapy was associated with sustained decreases (Ն84 d) in uNTX and serum NTX after a single sc dose (0.1, 0.3, 1.0, or 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 [442]
At 3.0 mg/kg, denosumab had mean half-lives of 46.3 days in breast cancer patients and 33.3 days in multiple myeloma patients.
“At the 3.0 mg/kg dose, denosumab demonstrated mean halflives of 46.3 and 33.3 d in patients with breast cancer and MM, respectively.”
From Receptor Activator of Nuclear Factor κB Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease (2008) · cites this paper as [442]
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
Osteoprotegerin: 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
Yasuda, 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
Roodman, G. D. (2004) · New England Journal of Medicine · doi:10.1056/nejmra030831 · Cited by 2,752 · see citing works
Osteonecrosis of the jaws associated with the use of bisphosphonates: a review of 63 cases
Ruggiero, S. L., Mehrotra, B., Rosenberg, T. J., & Engroff, S. L. (2004) · Journal of Oral and Maxillofacial Surgery · doi:10.1016/j.joms.2004.02.004 · Cited by 2,034 · see citing works
Metastatic bone disease: clinical features, pathophysiology and treatment strategies
Coleman, R. E. (2001) · Cancer Treatment Reviews · doi:10.1053/ctrv.2000.0210 · Cited by 1,927 · see citing works
Self-citationEfficacy 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-citationHillner, B. E., Ingle, J. N., Chlebowski, R. T., Gralow, J. R., Yee, G. C., Janjan, N. A., Cauley, J. A., Blumenstein, B. A., Albain, K. S., Lipton, A., et al. (2003) · Journal of Clinical Oncology · doi:10.1200/jco.2003.08.017 · Cited by 969 · see citing works
Self-citationRosen, L. S., Gordon, D., Kaminski, M., Howell, A., Belch, A. R., Mackey, J. R., Apffelstaedt, J., Hussein, M., Coleman, R. E., Reitsma, D. J., et al. (2001) · PubMed · Cited by 896 · 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
The ligand for osteoprotegerin (OPGL) directly activates mature osteoclasts.
Burgess, T. L., Qian, Y.-X., Kaufman, S., Ring, B. D., Van, G., Capparelli, C., Kelley, M., Hsu, H., Boyle, W. J., Dunstan, C. R., et al. (1999) · The Journal of Cell Biology · doi:10.1083/jcb.145.3.527 · Cited by 689 · 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-citationBrown, J. E., Cook, R. J., Major, P. P., Lipton, A., Fred Saad, C., Smith, M. R., Lee, K., Zheng, M., Hei, Y., & Coleman, R. E. (2005) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/dji002 · Cited by 559 · see citing works
Self-citationBreast Cancer Cells Interact with Osteoblasts to Support Osteoclast Formation1
Thomas, R. J., Guise, T. A., Yin, J. J., Elliott, J., Horwood, N. J., Martin, T. J., & Gillespie, M. T. (1999) · Endocrinology · doi:10.1210/endo.140.10.7037 · Cited by 536 · see citing works
Honoré, 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
Giuliani, N., Bataille, R., Mancini, C., Lazzaretti, M., & Barillé, S. (2001) · Blood · doi:10.1182/blood.v98.13.3527 · Cited by 415 · see citing works
Body, J., Diel, I., Lichinitser, M. R., et al. (2003) · Annals of Oncology · doi:10.1093/annonc/mdg367 · Cited by 415 · see citing works
Self-citationTerpos, 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
Toxic acute tubular necrosis following treatment with zoledronate (Zometa)
Markowitz, G. S., Fine, P. L., Stack, J. I., Kunis, C. L., Radhakrishnan, J., Palecki, W., Park, J. K., Nasr, S. H., Hoh, S., Siegel, D. S. D., et al. (2003) · Kidney International · doi:10.1046/j.1523-1755.2003.00071.x · Cited by 384 · see citing works
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., et al. (2003) · Cancer · doi:10.1002/cncr.11138 · Cited by 383 · 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
Renal Failure with the Use of Zoledronic Acid
Chang, J. T., Green, L., & Beitz, J. G. (2003) · New England Journal of Medicine · doi:10.1056/nejm200310233491721 · Cited by 368 · see citing works
Body, J., Diel, I., Lichinitzer, M., et al. (2004) · British Journal of Cancer · doi:10.1038/sj.bjc.6601663 · Cited by 338 · see citing works
Self-citationMorony, S., Capparelli, C., Sarosi, I., Lacey, D. L., Dunstan, C. R., & Kostenuik, P. J. (2001) · PubMed · Cited by 289 · see citing works
Engineered Human IgG Antibodies with Longer Serum Half-lives in Primates
Hinton, P. R., Johlfs, M. G., Xiong, J. M., Hanestad, K., Ong, K. C., Bullock, C., Keller, S., Tang, M. T., Tso, J. Y., Vásquez, M., et al. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.c300470200 · Cited by 274 · see citing works
Vanderkerken, K., Leenheer, E. D., Shipman, C. M., Asosingh, K., Willems, A., Camp, B. V., & Croucher, P. I. (2003) · PubMed · Cited by 188 · see citing works
Bone resorption predicts for skeletal complications in metastatic bone disease
Brown, J. E., Thomson, C. S., Ellis, S. P., et al. (2003) · British Journal of Cancer · doi:10.1038/sj.bjc.6601437 · Cited by 165 · see citing works
Scanning electron microscopy in bone pathology: review of methods, potential and applications.
BOYDE, A., Maconnachie, E., Reid, S. A., et al. (1986) · PubMed · Cited by 162 · see citing works
Raju, T. S., Briggs, J. B., Chamow, S. M., Winkler, M. E., & Jones, A. J. S. (2001) · Biochemistry · doi:10.1021/bi010475i · Cited by 122 · see citing works
Hillner, B. E., Ingle, J. N., Chlebowski, R. T., et al. (2004) · Breast Diseases A Year Book Quarterly · Cited by 118 · see citing works
Michigami, T., Ihara-Watanabe, M., Yamazaki, M., & Ozono, K. (2001) · PubMed · Cited by 96 · see citing works
Nagai, M., Kyakumoto, S., & Sato, N. (2000) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2000.2314 · Cited by 93 · see citing works
Pathophysiologic interactions in skeletal metastasis
Orr, F. W., Lee, J., Duivenvoorden, W., & Singh, G. (2000) · Cancer · doi:10.1002/1097-0142(20000615)88:12+ · Cited by 79 · see citing works
Intravenous pamidronate in patients with tumor-induced osteolysis: A biochemical dose-response study
Body, J., Dumon, J. C., Piccart, M. J., et al. (1995) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.5650100808 · Cited by 25 · see citing works
Self-citationBody, J., Diel, I., Lichinitser, M., et al. (2003) · Annals of Oncology · doi:10.1093/annonc/mdh035 · Cited by 21 · see citing works
Self-citationClearance and tissue uptake following 4-hour and 24-hour infusions of pamidronate in rats.
Pongchaidecha, M., & Daley‐Yates, P. T. (1993) · Drug Metabolism and Disposition · doi:10.1016/s0090-9556(25)07310-6 · Cited by 14 · see citing works
Bisphosphonates in breast cancer and other solid tumors
Body, J., Rubens, R. D., & Mundy, G. R. (2000) · Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) · Cited by 8 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 4
- Goltzman D, Karaplis AC, Kremer R, Rabbani SA. Molecular basis of the spectrum of skeletal complica- tions of neoplasia. Cancer 2000;88:2903 ^8.
- Bekker PJ, Holloway DL, Rasmussen AS, et al. A single-doseplacebo-controlled studyof AMG162, aful- ly human monoclonal antibody to RANKL, in postmen- opausal women. JBone Miner Res 2004;19:1059 ^66.
- Body JJ, Kanis J, Diel I, Bergstrom B. Risk reduc- tions in metastatic breast cancer: multivariate Poisson regression analysis analyses of oral and i.v. ibandro- nate [abstract 184]. Proc Am Soc Clin Oncol 2003; 22:46.
- McClung MR, Cohen SB, Lewiecki EM, et al. AMG 162 increases bone mineral density and decreases bone turnover in postmenopausal women with low bone mass [abstract]. Osteoporos Int 2005;16:S14 ^5.
Cited by
Sorted by citations
Sipuleucel-T Immunotherapy for Castration-Resistant Prostate Cancer
Kantoff, P. W., Higano, C. S., Shore, N. D., Berger, E. R., Small, E. J., Penson, D. F., Redfern, C. H., Ferrari, A. C., Dreicer, R., Sims, R. B., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa1001294 · Cited by 5,572 · 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
RANK/RANKL: Regulators of Immune Responses and Bone Physiology
Leibbrandt, A., & Penninger, J. M. (2008) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1443.016 · Cited by 420 · see citing works
Lipton, A., Steger, G. G., Figueroa, J., Alvarado, C., Solal-Celigny, P., Body, J.-J., de Boer, R., Berardi, R., Gascon, P., Tonkin, K. S., et al. (2007) · Journal of Clinical Oncology · doi:10.1200/jco.2007.11.8604 · Cited by 389 · see citing works
Self-citationLewiecki, E. M., Miller, P. D., McClung, M. R., Cohen, S. B., Bolognese, M. A., Liu, Y., Wang, A., Siddhanti, S., & Fitzpatrick, L. A. (2007) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.070809 · Cited by 319 · 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
Dunn, L. K., Mohammad, K. S., Fournier, P. G. J., McKenna, C. R., Davis, H. W., Niewolna, M., Peng, X. H., Chirgwin, J. M., & Guise, T. A. (2009) · PLoS ONE · doi:10.1371/journal.pone.0006896 · Cited by 212 · see citing works
- Authors
- Body, J.-J., Facon, T., Coleman, R. E., Lipton, A., Geurs, F., Fan, M., Holloway, D., Peterson, M. C., & Bekker, P. J.
- Affiliations
- Institut Jules Bordet (BE)
- Amgen (United States) (US)
- Venue
- Clinical Cancer Research
- Published
- 2006-02-15
- Volume
- 12
- Issue
- 4
- Pages
- 1221-1228
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- OpenAlex
- W2146217561
- Cited by
- 490
- References
- 40
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 7 · 2023: 10 · 2022: 15 · 2021: 9 · 2020: 7 · 2019: 9 · 2018: 8 · 2017: 18 · 2016: 12 · 2015: 24 · 2014: 28 · 2013: 34 · 2012: 48
- FWCI
- 28.26
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Clinical Cancer Research (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 › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Keywords
- denosumab, RANKL, multiple myeloma, breast cancer bone metastasis, bone resorption, pamidronate, N-telopeptide, bone turnover markers, osteoclasts, antiresorptive therapy, pharmacokinetics, monoclonal antibodies, treatment efficacy and safety
- MeSH terms
- Denosumab, Pamidronate, Adult, Aged, Antibodies, Monoclonal, Antineoplastic Agents, Bone and Bones, Bone Neoplasms, Breast Neoplasms, Carrier Proteins, Collagen, Creatinine, Diphosphonates, Double-Blind Method, Female, Humans, Injections, Intravenous, Injections, Subcutaneous, Male, Membrane Glycoproteins, Middle Aged, Multiple Myeloma, Peptides, Time Factors, Treatment Outcome, Area Under Curve, Collagen Type I, RANK Ligand, Receptor Activator of Nuclear Factor-kappa B, Antibodies, Monoclonal, Humanized
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
