Denosumab, a RANKL Inhibitor, Induced Osteonecrosis of the Jaw
DOI: 10.12677/HJS.2013.31001, PDF, HTML, 下载: 2,593  浏览: 13,269  科研立项经费支持
作者: 胡龙威:上海交通大学医学院,口腔医学院,上海;徐立群:上海交通大学医学院附属第九人民医院口腔颌面外科,上海
关键词: 地诺塞麦双磷酸盐颌骨坏死Denosumab; Bisphosphonates; Osteonecrosis of the Jaw
摘要: 引起药物性颌骨坏死的主要两大类药物包括双磷酸盐及RANKL抑制剂。RANKL抑制剂地诺塞麦是一种完全人化单克隆抗体,临床上主要用于预防实体肿瘤发生骨转移患者骨相关事件的发生以及用于增加骨质疏松患者的骨密度。本文就地诺塞麦的作用机制、临床应用、副作用,与双磷酸盐比较及所致的颌骨坏死做一综述。
Abstract: The two main kinds of drugs that induced osteonecrosis of the jaw are bisphosphonates and anti-RANKL. Anti-RANKL is a fully human monoclonal antibody. It is effective to prevent skeletal-related complications in cancer patients with bone metastasis and to increase bone mineral density in patients with osteoporosis. This article summa- rizes the mechanism of action, clinical use, adverse effects of denosumab and its comparison with bisphosphonates as well as osteonecrosis of the jaw induced by it.
文章引用:胡龙威, 徐立群. RANKL抑制剂地诺塞麦所致颌骨坏死[J]. 外科, 2014, 3(1): 1-5. http://dx.doi.org/10.12677/HJS.2013.31001


[1] Vescovi, P., Merigo, E., Meleti, M., et al. (2012) Bisphosphona- tesrelated osteonecrosis of the jaws: A concise review of the li- terature and a report of a single-centre experience with 151 pa- tients. Journal of Oral Pathology & Medicine, 41, 214-221.
[2] Rustemeyer, J. and Bremerich, A. (2010) Bisphosphonate-asso- ciated osteonecrosis of the jaw: What do we currently know? A survey of knowledge given in the recent literature. Clinical Oral Investigations, 14, 59-64.
[3] Allen, M.R. and Burr, D.B. (2009) The pathogenesis of bispho- sphonatere-lated osteonecrosis of the jaw: So many hypotheses, so few data. Journal of Oral and Maxillofacial Surgery, 67, 61- 70.
[4] Wehrhan, F., et al. (2010) Expression of Msx-1 is suppressed in bisphosphonate associated osteonecrosis related jaw tissue-eti- opathology considerations respecting jaw developmental biolo- gy-related unique features. Journal of Translational Medicine, 8, 96.
[5] Hoefert, S., Schmitz, I., Tannapfel, A. and Eufinger, H. (2010) Importance of microcracks in etiology of bisphosphonate-related osteonecrosis of the jaw: A possible pathogenetic model of symptom-matic and nonsymptomatic osteonecrosis of the jaw based on scanning electron microscopy findings. Clinical Oral Investigations, 14, 271-284.
[6] Taylor, K.H., Middlefell, L.S., Mizen, K.D., et al. (2010) Os- teonecrosis of the jaws induced by anti-RANK ligand therapy. British Journal of Oral and Maxillofacial Surgery, 48, 221-223.
[7] Dougall, W.C. (2011) Molecular pathways: Osteoclast-depen- dent and osteoclast-independent roles of the RANKL/RANK/ OPG pathway in tumorigenesis and metastasis. Clinical Cancer Research, 18, 326-335.
[8] Lumachi, F., Brunello, A., Roma, A. and Basso, U. (2009) Can- cer-induced hypercalcemia. Anticancer Research, 29, 1551- 1555.
[9] Sivolella, S., Lumachi, F. and Stellini, E. (2013) Denosumab and anti-angiogenetic drug-related osteonecrosis of the jaw: An un- common but potentially severe disease. Anticancer Research, 33, 1793-1798.
[10] Cummings, S.R., San, M.J., McClung, M.R., et al. (2009) for FREEDOM Trial. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. The New England Journal of Medicine, 361, 756-765.
[11] Adler, R.A. and Gill, R.S. (2011) Clinical utility of denosumab for treatment of bone loss in men and women. Clinical Interven- tions in Aging, 6, 119-124.
[12] Amgen Incorporated, “Prolia™ (Denosumab) injection, for sub- cutaneous use: US prescribing information,” TAmgen Inc., housand Oaks, 2010. http://pi.amgen.com/united_states/prolia/prolia_pi.pdf
[13] Body, J.J., Facon, T., Coleman, R.E., et al. (2006) A study of the biological recep-tor activator of nuclear factor-kappaB ligand inhibitor, denosumab, in patients with multiple myeloma or bone metastases from breast cancer. Clinical Cancer Research, 12, 1221-1228.
[14] Smith, M.R., Kabbinavar, F., Saad, F., et al. (2005) Natural his- tory of rising serum prostate-specific antigen in men with ca- strate nonmetastatic prostate cancer. Journal of Clinical Oncol- ogy, 23, 2918-2925.
[15] National Osteoperosis Foundation (2010) Clinician’s guide to prevention and treatment of osteoporosis. National Osteoporosis Foundation, Washington DC.
[16] Smith, M.R., Saad, F., Coleman, R., et al. (2012) Denosumab and bone-metastasis-free survival in men with castration-resis- tant prostate cancer: Results of a phase 3, randomised, placebo- controlled trial. Lancet, 379, 39-46.
[17] Rothstein, A. (2009) Denosumab safety: Division of reproduc- tive and uro-logic products, center of drug evaluation and re- search at the food and drug administration. http://courses.washington.edu/bonephys/denosumab/Rothstein%20FDA%20deno%20safety.pdf
[18] Ibrahim, A., Scher, N., Williams, G., et al. (2003) Approval summary for zoledronic acid for treatment of multiple myeloma and cancer bone metastases. Clinical Cancer Research, 9, 2394- 2399.
[19] Chang, J.T., Green, L. and Beitz, J. (2003) Renal failure with the use of zoledronic acid. The New England Journal of Medicine, 349, 1676-1679; Discussion 1676-1679.
[20] Baron, R., Ferrari, S. and Russell, R.G. (2011) Denosumab and bisphosphonates: Different mechanisms of action and effects. Bone, 48, 677-692.
[21] Pazianas, M., Cooper, C., Ebetino, F.H. and Russell, R.G. (2010) Long-term treatment with bisphosphonates and their safety in postmenopausal osteoporosis. Therapeutics and Clinical Risk Management, 6, 325-343.
[22] Black, D.M., Delmas, P.D., Eastell, R., et al. (2007) Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. The New England Journal of Medicine, 356, 1809-1822.
[23] Henry, D.H., Costa, L., Goldwasser, F., et al. (2011) Randomiz- ed, double-blind study of denosumab versus zoledronic acid in the treatment of bone metastases in patients with advanced can- cer (excluding breast and prostate cancer) or multiple myeloma. Journal of Clinical Oncology, 29, 1125-1132.
[24] Ellis, G.K., Bone, H.G., Chlebowski, R., et al. (2008) Rando- mized trial of deno-sumab in patients receiving adjuvant aroma- tase inhibitors for nonmeta-static breast cancer. Journal of Clin- ical Oncology, 26, 4875-4882.
[25] Smith, M.R., Egerdie, B., Hernandez, T.N., et al. (2009) Deno- sumab in men receiving androgen-deprivation therapy for pros- tate cancer. The New England Journal of Medicine, 361, 745- 755.
[26] Stopeck, A.T., Lipton, A., Body, J.J., et al. (2010) Denosumab compared with zoledronic acid for the treatment of bone metas- tases in patients with advanced breast cancer: A randomized, double-blind study. Journal of Clinical Oncology, 28, 5132- 5139.
[27] Fizazi, K., Carducci, M., Smith, M., et al. (2011) Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant pros-tate cancer: A randomised, double- blind study. Lancet, 377, 813-822.
[28] Otto, S., Abu-Id, M.H., Fedele, S., Warnke, P.H., Becker, S.T., Kolk, A., et al. (2011) Osteoporosis and bisphosphonates-related osteonecrosis of the jaw: Not just a sporadic coincidence e a multi-centre study. Journal of Cranio-Maxillofacial Surgery, 39, 272-277.
[29] Otto, S., Schreyer, C., Hafner, S., Mast, G., Ehrenfeld, M., Stur- zenbaum, S., et al. (2012) Bisphosphonate-related osteonecrosis of the jaws e characteristics, risk factors, clinical features, loca- lization and impact on oncological treatment. Journal of Cranio- Maxillofacial Surgery, 40, 303-309.
[30] Russell, R.G., Watts, N.B., Ebetino, F.H. and Rogers, M.J. (2008) Mechanisms of action of bis-phosphonates: Similarities and dif- ferences and their potential influence on clinical efficacy. Os- teoporosis International, 19, 733-759.
[31] Groetz, K.A. and Al-Nawas, B. (2006) Persisting alveolar sock- ets: A radiologic symptom of BPONJ? Journal of Oral and Maxillofacial Surgery, 64, 1571-1572.
[32] Otto, S., et al. (2013) Successful surgical management of osteo- necrosis of the jaw due to RANK-ligand inhibitor treatment us- ing fluorescence guided bone resection. Journal of Cranio-Max- illo-Facial Surgery, 41, 694-698.
[33] Bonacina, R., Mariani, U., Villa, F., et al. (2011) Preventive stra- tegies and clinical implications for bisphosphonaterelated osteo- necrosis of the jaw: A review of 282 patients. Journal of the Canadian Dental Association, 77, b147.
[34] Ruggiero, S.L., Dodson, T.B., Assael, L.A., Landesberg, R., Marx, R.E., Mehrotra, B. and American Association of Oral and Maxillofacial Surgeons (2009) American Association of Oral and Maxillofacial Surgeonsposition paper on bisphosphonate- related osteonecrosis of the jaws—2009 update. Journal of Oral and Maxillofacial Surgery, 67, 2-12.
[35] Shenker, N.G. and Jawad, A.S. (2007) Bisphosphonates and osteonecrosis of the jaw. Rheumatology (Oxford), 46, 1049- 1051.
[36] Dunford, J.E., Thompson, K., Coxon, F.P., et al. (2001) Structu- reactivity relationships for inhibition of farnesyl diphosphate synthase in vitro and inhibition of bone resorption in vivo by ni- tro-gen-containing bisphosphonates. Journal of Pharmacology and Experimental Therapeutics, 296, 235-242.
[37] Suleman, Y.F., Meer, S., Lurie, R., et al. (2007) Bisphosphona- teinduced osteonecrosis of the jaws: Review, clinical implica- tions and case report. Head and Neck Pathology, 1, 156-164.
[38] Herbozo, P.J., Briones, D.L., Ferres, A.J., et al. (2007) Severe spontaneous cases of bisphosphonate-related osteonecrosis of the jaws. Journal of Oral and Maxillofacial Surgery, 2007, 65, 1650-1654.
[39] Han, J.W. (2011) Bisphosphonate related osteonecrosis of the jaws: Report of two cases. Imaging Science in Dentistry, 41, 129-134.
[40] Aghaloo, T.L., Felsenfeld, A.L. and Tetradis, S. (2010) Osteone- crosis of the jaw in a patient on denosumab. Journal of Oral and Maxillofacial Surgery, 68, 959-963.
[41] Saad, F., Brown, J.E., Van Poznak, C., Ibrahim, T., Stemmer, S.M., Stopeck, A.T., et al. (2012) Incidence, risk factors, and outcomes of osteonecrosis of the jaw: Integrated analysis from three blinded active-controlled phase III trials in cancer patients with bone metastases. Annals of Oncology, 23, 1341-1347.
[42] Ficarra, G. and Beninati, F. (2007) Bis-phosphonate-related os- teonecrosis of the jaws: An update on clinical, pathological and management aspects. Head and Neck Pathology, 1, 132-140.
[43] Kademani, D., Koka, S., Lacy, M.Q., et al. (2006) Primary surgi- cal therapy for osteonecrosis of the jaw secondary to bisphos- phonate therapy. Mayo Clinic Proceedings, 81, 1100-1103.
[44] Freiberger, J.J. (2009) Utility of hype rbaric oxygen in treatment of bisphosphonate-related osteonecrosis of the jaws. Journal of Oral and Maxillofacial Surgery, 67, 96-106.
[45] Romeo, U., Galanakis, A., Marias, C., et al. (2011) Observation of pain control in patients with bisphosphonate-induced osteone- crosis using low level laser therapy: Preliminary results. Photomedicine and Laser Surgery, 29, 447-452.