Safety and tolerability of denosumab for the treatment of postmenopausal osteoporosis

Drug, Healthcare and Patient Safety

Volumn 3, Issue 1, 2011, Pages 79-91

  Michael Lewiecki, E ^a  

^a Clinical Research and Osteoporosis Center   (United States)

Author keywords

Beneft; Denosumab; FDA; Osteoporosis; Risk; Safety

Indexed keywords

ALENDRONIC ACID; ALKALINE PHOSPHATASE BONE ISOENZYME; AMINO TERMINAL TELOPEPTIDE; CARBOXY TERMINAL TELOPEPTIDE; DENOSUMAB; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; MONOCLONAL ANTIBODY; OSTEOPROTEGERIN; PLACEBO;

ARTHRALGIA; ARTICLE; BACKACHE; BONE DENSITY; BONE REMODELING; BONE STRENGTH; BONE TURNOVER; CARDIOVASCULAR DISEASE; CELLULITIS; CLINICAL ARTICLE; CONTROLLED STUDY; CYSTITIS; DRUG BLOOD LEVEL; DRUG HALF LIFE; DRUG MECHANISM; DRUG SAFETY; DRUG TOLERABILITY; DUAL ENERGY X RAY ABSORPTIOMETRY; ECZEMA; EYE DISEASE; FEMALE; FEMUR FRACTURE; FLATULENCE; FRACTURE; HUMAN; HYPERCHOLESTEROLEMIA; HYPERSENSITIVITY REACTION; HYPOCALCEMIA; INJECTION SITE REACTION; JAW OSTEONECROSIS; LIMB PAIN; LONG TERM CARE; MAXIMUM PLASMA CONCENTRATION; MUSCULOSKELETAL PAIN; OSTEOLYSIS; PANCREATITIS; PATIENT COMPLIANCE; PHARMACODYNAMICS; PHASE 1 CLINICAL TRIAL; POSTMARKETING SURVEILLANCE; POSTMENOPAUSE OSTEOPOROSIS; RANDOMIZED CONTROLLED TRIAL; RISK BENEFIT ANALYSIS; RISK REDUCTION; SKIN INFECTION; UPPER RESPIRATORY TRACT INFECTION;

EID: 84855294809     PISSN: None     EISSN: 11791365     Source Type: Journal    
DOI: None     Document Type: Article

References (92)

1. NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and Therapy. Osteoporosis prevention, diagnosis, and therapy. JAMA. 2001;285(6):785-795.
2. Cooper C, Campion G, Melton LJ. Hip fractures in the elderly: a world-wide projection. Osteoporos Int. 1992;2(6):285-289.
3. European Foundation for Osteoporosis and Bone Disease, National Osteoporosis Foundation. Who are candidates for prevention and treatment for osteoporosis? Osteoporos Int. 1997;7(1):1-6.
4. Melton LJ III, Chrischilles EA, Cooper C, Lane AW, Riggs BL. Perspective. How many women have osteoporosis? J Bone Miner Res. 1992;7(9):1005-1010.
5. Center JR, Nguyen T V, Schneider D, Sambrook PN, Eisman JA. Mortality after all major types of osteoporotic fracture in men and women: an observational study. Lancet. 1999;353(9156):878-882.
6. Cooper C. The crippling consequences of fractures and their impact on quality of life. Am J Med. 1997;103(2A):12S-19S.
7. Lewiecki EM, Bilezikian J P, Khosla S, et al. Osteoporosis update from the 2010 Santa Fe bone symposium. J Clin Densitom. 2011;14(1):1-21.
8. Beaupre LA, Morrish DW, Hanley DA, et al. Oral bisphosphonates are associated with reduced mortality after hip fracture. Osteoporos Int. 2011;22(3):983-991.
9. Center JR, Bliuc D, Nguyen ND, Nguyen T V, Eisman JA. Osteoporosis medication and reduced mortality risk in elderly women and men. J Clin Endocrinol Metab. 2011;96(4):1006-1014.
10. Nurmi-Luthje I, Sund R, Juntunen M, Luthje P. Post-hip fracture use of prescribed calcium plus vitamin D or vitamin D supplements and antiosteoporotic drugs is associated with lower mortality: A nationwide study in Finland. J Bone Miner Res. 2011;26(8):1845-1853.
11. Bolland MJ, Grey AB, Gamble GD, Reid IR. Effect of osteoporosis treatment on mortality: a meta-analysis. J Clin Endocrinol Metab. 2010;95(3):1174-1181.
12. Curtis JR, Carbone L, Cheng H, et al. Longitudinal trends in use of bone mass measurement among older Americans, 1999-2005. J Bone Miner Res. 2008;23(7):1061-1067.
13. Foley KA, Foster SA, Meadows ES, Baser O, Long SR. Assessment of the clinical management of fragility fractures and implications for the new HEDIS osteoporosis measure. Med Care. 2007;45(9): 902-906.
14. McCombs JS, Thiebaud P, Laughlin-Miley C, Shi J. Compliance with drug therapies for the treatment and prevention of osteoporosis. Maturitas. 2004;48(3):271-287.
15. Caro JJ, Ishak KJ, Huybrechts KF, Raggio G, Naujoks C. The impact of compliance with osteoporosis therapy on fracture rates in actual practice. Osteoporos Int. 2004;15(12):1003-1008.
16. McHorney CA, Schousboe JT, Cline RR, Weiss T W. The impact of osteoporosis medication beliefs and side-effect experiences on non-adherence to oral bisphosphonates. Curr Med Res Opin. 2007;23(12):3137-3152.
17. Lewiecki EM. Risk communication and shared decision making in the care of patients with osteoporosis. J Clin Densitom. 2010;13(4):335-345.
18. Montori VM, Shah ND, Pencille LJ, et al. Use of a decision aid to improve treatment decisions in osteoporosis: the osteoporosis choice randomized trial. Am J Med. 2011;124(6):549-556.
19. Parftt AM. Osteonal and hemi-osteonal remodeling: the spatial and temporal framework for signal traffc in adult human bone. J Cell Biochem. 1994;55(3):273-286.
20. Burr DB. Targeted and nontargeted remodeling. Bone. 2002;30(1):2-4.
21. Collin-Osdoby P. Regulation of vascular calcification by osteo-clast regulatory factors RANKL and osteoprotegerin. Circ Res. 2004;95(11):1046-1057.
22. Hsu H, Lacey DL, Dunstan CR, et al. Tumor necrosis factor receptor family member RANK mediates osteoclast differentiation and activation induced by osteoprotegerin ligand. Proc Natl Acad Sci U S A. 1999;96(7): 3540-3545.
23. Lacey DL, Timms E, Tan HL, et al. Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell. 1998;93(2):165-176.
24. Eghbali-Fatourechi G, Khosla S, Sanyal A, Boyle WJ, Lacey DL, Riggs BL. Role of RANK ligand in mediating increased bone resorp-tion in early postmenopausal women. J Clin Invest. 2003;111(8): 1221-1230.
25. Simonet WS, Lacey DL, Dunstan CR, et al. Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell. 1997;89(2):309-319.
26. Ross AB, Bateman TA, Kostenuik PJ, et al. The effects of osteoprote-gerin on the mechanical properties of rat bone. J Mater Sci Mater Med. 2001;12(7):583-588.
27. Bekker PJ, Holloway D, Nakanishi A, Arrighi M, Leese PT, Dunstan CR. The effect of a single dose of osteoprotegerin in postmenopausal women. J Bone Miner Res. 2001;16(2):348-360.
28. Bekker PJ, Holloway DL, Rasmussen AS, et al. A single-dose placebo-controlled study of AMG 162, a fully human monoclonal antibody to RANKL, in postmenopausal women. J Bone Miner Res. 2004;19(7):1059-1066.
29. McClung MR, Lewiecki EM, Cohen SB, et al. Denosumab in post-menopausal women with low bone mineral density. N Engl J Med. 2006;354(8):821-831.
30. Lewiecki EM, Miller PD, McClung MR, et al. Two-year treatment with denosumab (AMG 162) in a randomized phase 2 study of post-menopausal women with low bone mineral density. J Bone Miner Res. 2007;22(12):1832-1841.
31. Miller PD, Bolognese MA, Lewiecki EM, et al. 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. 2008;43(2):222-229.
32. Miller PD, Wagman RB, Peacock M, et al. Effect of denosumab on bone mineral density and biochemical markers of bone turnover: six-year results of a phase 2 clinical trial. J Clin Endocrinol Metab. 2011;96(2):394-402.
33. McClung M, Lewiecki EM, Bolognese MA, et al. Effects of deno-sumab on bone mineral density and biochemical markers of bone turnover: 8-Year results of a phase 2 clinical trial. J Bone Miner Res. 2011;24(Suppl 1):S20.
34. Cummings SR, San Martin J, McClung MR, et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med. 2009;361(8):756-765.
35. Bone HG, Bolognese MA, Yuen CK, et al. Effects of denosumab on bone mineral density and bone turnover in postmenopausal women. J Clin Endocrinol Metab. 2008;93(6):2149-2157.
36. Brown J P, Prince RL, Deal C, et al. Comparison of the effect of deno-sumab 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. 2009;24(1):153-161.
37. Kendler DL, Roux C, Benhamou CL, et al. Effects of denosumab on bone mineral density and bone turnover in postmenopausal women transition-ing from alendronate therapy. J Bone Miner Res. 2010;25(1):72-81.
38. Amgen. Amgen medical information [web page on the Internet]. Thousand Oaks, CA: Amgen Inc; 2009, 2010. Available from: https://www.amgenmedinfo.com/Home. Accessed September 15, 2011.
39. ® Postmarketing Active Safety Surveillance Program [website on the Internet]. Thousand Oaks, CA: Amgen Inc; 2011. Available from: https://proliasafety.secure.force.com/prolia. Accessed August 26, 2011.
40. US Food and Drug Administration. MedWatch: The FDA Safety Information and Adverse Event Reporting Program [website on the Internet]. Silverspring, MD: FDA; 2011 [updated October 3]. Available from: http://www.fda.gov/Safety/MedWatch/default.htm. Accessed October 4, 2011.
41. ® (denosumab) risk evaluation and mitigation strategy [website on the Internet]. Thousand Oaks, CA: Amgen Inc; 2011. Available from: http://www.proliahcp.com/risk-evaluation-mitigation-strategy/. Accessed August 26, 2011.
42. ® prescribing information. Thousand Oaks, CA: Amgen Inc; 2010-2011. Available from: http://pi.amgen.com/united_states/prolia/prolia_pi.pdf. Accessed August 28, 2011.
43. ®. Thousand Oaks, CA: Amgen Inc; 2011. Available from: http://pi.amgen.com/united_states/prolia/prolia_mg.pdf. Accessed August 28, 2011.
44. ® (densoumab). [Dear healthcare professional letter.] Thousand Oaks, CA: Amgen Inc; nd. Available from: http://www.proliahcp.com/pdf/dear_healthcare_professional_letter.pdf. Accessed August 28, 2011.
45. ® (denosumab) Injection [homepage on the Internet]. Thousand Oaks, CA: Amgen Inc; 2011. Available from: http://www.prolia.com/. Accessed September 15, 2011.
46. US Food and Drug Administration. Investigational new drug safety reporting requirements for human drug and biological products and safety reporting requirements for bioavailability and bioequivalence studies in humans. Federal Register. 21 CFR Parts 312 and 320. 2010;75(188):59935-59963. Available from: http://frwebgate.access.gpo.gov/cgi-bin/getdoc.cgi?dbname=2010_register&docid=fr29se10-3.pdf. Accessed September 2, 2011.
47. US Food and Drug Administration. An FDA guide to drug safety terms [web page on the Internet]. Silverspring, MD: FDA; 2011 [updated September 9]. Available from: http://www.fda.gov/ForConsumers/ConsumerUpdates/ucm107970.htm. Accessed October 4, 2011.
48. Houghton Mifin Company. The American Heritage Dictionary. 4th ed. Boston, MA, and New York, NY: Houghton Mifin Company; 2000.
49. US Food and Drug Administration. CFR- Code of Federal Regulations Title 21. Medication Guides for Prescription Drug Products. Silverspring, MD: FDA; 2011 [updated April 1]. Available at: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=208&showFR=1. Accessed October 12, 2011.
50. US Food an Drug Admistration. CFR - Code of Federal Regulations Title 21: Food and Drugs. Part 201 - Labeling. Subpart B - Labeling Requirements for Prescription Drugs and/or Insulin. Silverspring, MD: FDA; 2011 [updated April 1]. Available from: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=201.57. Accessed August 30, 2011.
51. Rothstein A. Denosumab Safety: FDA Analysis. Silverspring, MD: FDA; nd. Available from: http://courses.washington.edu/bonephys/denosumab/Rothstein%20FDA%20deno%20safety.pdf. Accessed September 6, 2011.
52. Advisory Committee for Reproductive Health Drugs of the Center for Drug Evaluation and Research. Summary Minutes of the Advisory Committee for Reproductive Health Drugs: August 13, 2009. Washington DC North, Githersburg, MD. Available from: http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/ReproductiveHealthDrugsAdvisoryCommittee/UCM249267.pdf. Accessed September 6, 2011.
53. Dougall WC, Glaccum M, Charrier K, et al. RANK is essential for osteoclast and lymph node development. Genes Dev. 1999;13(18): 2412-2424.
54. Josien R, Wong BR, Li HL, Steinman RM, Choi Y. TRANCE, a TNF family member, is differentially expressed on T cell subsets and induces cytokine production in dendritic cells. J Immunol. 1999;162(5):2562-2568.
55. Anderson DM, Maraskovsky E, Billingsley WL, et al. A homologue of the TNF receptor and its ligand enhance T-cell growth and dendritic-cell function. Nature. 1997;390(6656):175-179.
56. Seshasayee D, Wang H, Lee W P, et al. A novel in vivo role for osteoprotegerin ligand in activation of monocyte effector function and infammatory response. J Biol Chem. 2004;279(29):30202-30209.
57. Li Y, Toraldo G, Li A, et al. B cells and T cells are critical for the preservation of bone homeostasis and attainment of peak bone mass in vivo. Blood. 2007;109(9):3839-3848.
58. Stolina M, Dwyer D, Ominsky MS, et al. Continuous RANKL inhibition in osteoprotegerin transgenic mice and rats suppresses bone resorption without impairing lymphorganogenesis or functional immune responses. J Immunol. 2007;179(11):7497-7505.
59. Stolina M, Dwyer D, Morony S, et al. Rats and mice overexpressing soluble OPG have high bone mass but no alteration in immuno-logical parameters or lymphocyte function. Arthritis Rheum. 2005; 20:S708.
60. Barbaroux JB, Beleut M, Brisken C, Mueller CG, Groves RW. Epidermal receptor activator of NF-kappaB ligand controls Langerhans cells numbers and proliferation. J Immunol. 2008;181(2):1103-1108.
61. Loser K, Mehling A, Loeser S, et al. Epidermal RANKL controls regulatory T-cell numbers via activation of dendritic cells. Nat Med. 2006;12(12):1372-1379.
62. Recker RR, Lewiecki EM, Miller PD, Reiffel J. Safety of bis-phosphonates in the treatment of osteoporosis. Am J Med. 2009; 122(2 Suppl):S22-S32.
63. Reid IR, Miller PD, Brown J P, et al. Effects of denosumab on bone histomorphometry: the FREEDOM and STAND studies. J Bone Miner Res. 2010;25(10):2256-2265.
64. Odvina C V, Zerwekh JE, Rao DS, Maalouf N, Gottschalk FA, Pak C Y. Severely suppressed bone turnover: a potential complication of alen-dronate therapy. J Clin Endocrinol Metab. 2005;90(3):1294-1301.
65. Visekruna M, Wilson D, McKiernan FE. Severely suppressed bone turnover and atypical skeletal fragility. J Clin Endocrinol Metab. 2008;93(8):2948-2952.
66. Jorgensen NR, Schwarz P. Effects of anti-osteoporosis medications on fracture healing. Curr Osteoporos Rep. 2011;9(3):149-155.
67. Marx RE, Cillo JE, Ulloa JJ. Oral bisphosphonate-induced osteone-crosis: risk factors, prediction of risk using serum CTX testing, prevention, and treatment. J Oral Maxillofac Surg. 2007;65(12): 2397-2410.
68. Rasmussen LM, Tarnow L, Hansen TK, Parving HH, Flyvbjerg A. Plasma osteoprotegerin levels are associated with glycaemic status, systolic blood pressure, kidney function and cardiovascular morbidity in type 1 diabetic patients. Eur J Endocrinol. 2006;154(1): 75-81.
69. Browner WS, Lui LY, Cummings SR. Associations of serum osteoprote-gerin levels with diabetes, stroke, bone density, fractures, and mortality in elderly women. J Clin Endocrinol Metab. 2001;86(2):631-637.
70. Kiechl S, Schett G, Wenning G, et al. Osteoprotegerin is a risk factor for progressive atherosclerosis and cardiovascular disease. Circulation. 2004;109(18):2175-2180.
71. Nitta K, Akiba T, Uchida K, et al. Serum osteoprotegerin levels and the extent of vascular calcifcation in haemodialysis patients. Nephrol Dial Transplant. 2004;19(7):1886-1889.
72. Morena M, Terrier N, Jaussent I, et al. Plasma osteoprotegerin is associated with mortality in hemodialysis patients. J Am Soc Nephrol. 2006;17(1):262-270.
73. Kearns AE, Khosla S, Kostenuik PJ. Receptor activator of nuclear factor kappaB ligand and osteoprotegerin regulation of bone remodeling in health and disease. Endocr Rev. 2008;29(2):155-192.
74. Black DM, Delmas PD, Eastell R, et al. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med. 2007;356(18):1809-1822.
75. US Food and Drug Administration. Update of safety review follow-up to the October 1, 2007. Early communication about the ongoing safety review of bisphosphonates [web page on the Internet]. Silverspring, MD: FDA; 2010 [updated March 4]. Available from: http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatient-sandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm136201.htm. Accessed August 11, 2011.
76. Smith MR, Egerdie B, Hernandez TN, et al. Denosumab in men receiving androgen-deprivation therapy for prostate cancer. N Engl J Med. 2009;361(8):745-755.
77. Division of Reproductive and Urologic Products, Office of New Drugs, Center for Drug Evaluation and Research, Food and Drug Administration. Background Document for Meeting of Advisory Committee for Reproductive Health Drugs (August 13, 2009): Deno-sumab (Proposed trade name: PROLIA), Amgen, Inc. Silverspring, MD: FDA; 2009. Available from: http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/Repro-ductiveHealthDrugsAdvisoryCommittee/UCM176605.pdf. Accessed September 15, 2011.
78. Adami S, Palacios S, Pavelka K, et al. FREEDOM trial: denosumab is not associated with fracture healing complications in postmenopausal women with osteoporosis. Osteoporos Int. 2011;22:S243.
79. Brown J P, Dempster DW, Ding B, et al. Bone remodeling in postmeno-pausal women who discontinued denosumab treatment: Off-treatment biopsy study. J Bone Miner Res. 2011. Epub 2011 Oct 20.
80. Watts NB, Roux C, Modlin J F, et al. Infections in postmenopausal women with osteoporosis treated with denosumab or placebo: coincidence or causal association? Osteoporos Int. 2011. Epub 2011 Sep 3.
81. Bone HG, Chapurlat R, Libanati C, et al. Safety observations from denosumab long-term extension and cross-over studies in postmeno-pausal women with osteoporosis. J Bone Miner Res. 2011;26:S22.
82. Bone HG, Chapurlat R, Brandi ML, et al. Denosumab treatment for 5 years of postmenopausal women with osteoporosis: results from the frst two years of the FREEDOM trial extension. American Association of Clinical Endocrinologists 20th Annual Meeting and Clinical Congress. 2011; Abstract 503.
83. von Keyserlingk C, Hopkins R, Anastasilakis A, et al. Clinical effcacy and safety of denosumab in postmenopausal women with low bone mineral density and osteoporosis: a meta-analysis. Semin Arthritis Rheum. 2011;41:178-186.
84. Ellis GK, Bone HG, Chlebowski R, et al. Randomized trial of deno-sumab in patients receiving adjuvant aromatase inhibitors for nonmeta-static breast cancer. J Clin Oncol. 2008;26(30):4875-4882.
85. Fizazi K, Carducci M, Smith M, et al. Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomised, double-blind study. Lancet. 2011;377(9768): 813-822.
86. Henry DH, Costa L, Goldwasser F, et al. 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. 2011;29(9): 1125-1132.
87. Stopeck AT, Lipton A, Body JJ, et al. 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. 2010;28(35):5132-5139.
88. Kendler DL, McClung MR, Freemantle N, et al. Adherence, preference, and satisfaction of postmenopausal women taking denosumab or alendronate. Osteoporos Int. 2011;22(6):1725-1735.
89. McClung M, Freemantle N, Kaur P, et al. The denosumab adherence, preference, satisfaction (DAPS) study: bone mineral density results at 24 months. J Clin Densitom. 2011;14:159.
90. National Osteoporosis Foundation. Clinician's Guide to Prevention and Treatment of Osteoporosis. Washington DC: National Osteoporosis Foundation; 2010. Available at: http://www.nof.org/sites/default/fles/pdfs/NOF_ClinicianGuide2009_v7.pdf. Accessed October 10, 2011.
91. Watts NB, Bilezikian J P, Camacho PM, et al. American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for the diagnosis and treatment of postmenopausal osteoporosis. Endocr Pract. 2010;16 Suppl 3:1-37.
92. Lewiecki EM. The role of risk communication in the care of osteoporosis. Curr Osteoporos Rep. 2011;9(3):141-148.