Denosumab for the management of postmenopausal osteoporosis

Postgraduate Medicine

Volumn 122, Issue 6, 2010, Pages 176-187

  Singer, Andrea ^a   Grauer, Andreas ^b  

^a GEORGETOWN UNIVERSITY MEDICAL CENTER   (United States)

^b AMGEN INC   (United States)

Author keywords

Adherence; Bone mineral density; Denosumab; DXA; Fracture; Osteoporosis

Indexed keywords

ALENDRONIC ACID; BISPHOSPHONIC ACID DERIVATIVE; CALCIUM; DENOSUMAB; GLUCOCORTICOID; IBANDRONIC ACID; PARATHYROID HORMONE[1-34]; PLACEBO; RALOXIFENE; RISEDRONIC ACID; SALCATONIN; VITAMIN D; ZOLEDRONIC ACID; MONOCLONAL ANTIBODY; OSTEOCLAST DIFFERENTIATION FACTOR;

ARTICLE; BONE DENSITOMETRY; BONE DENSITY; BONE REMODELING; BONE TURNOVER; CARDIOVASCULAR DISEASE; CELLULITIS; CLINICAL ASSESSMENT TOOL; CLINICAL PRACTICE; CLINICAL TRIAL (TOPIC); CONCUSSION; COST BENEFIT ANALYSIS; DRUG APPROVAL; DRUG BLOOD LEVEL; DRUG EFFICACY; DRUG FATALITY; DRUG HALF LIFE; DRUG MECHANISM; DRUG SAFETY; DRUG TARGETING; DRUG TOLERABILITY; DRUG WITHDRAWAL; ECZEMA; FALLING; FLATULENCE; FRACTURE NONUNION; FRACTURE RISK ASSESSMENT; FRAGILITY FRACTURE; HEALTH CARE COST; HEART ATRIUM FIBRILLATION; HIGH RISK PATIENT; HIP FRACTURE; HUMAN; HYPOCALCEMIA; INFECTION; ISCHEMIC HEART DISEASE; JAW OSTEONECROSIS; KINESIOTHERAPY; LONG TERM CARE; MORBIDITY; MORTALITY; NEOPLASM; OSTEOLYSIS; PATHOPHYSIOLOGY; PATIENT COMPLIANCE; PATIENT SATISFACTION; PERIPHERAL VASCULAR DISEASE; POSTMENOPAUSE OSTEOPOROSIS; PRACTICE GUIDELINE; PUBLIC HEALTH; RECOMMENDED DRUG DOSE; RETREATMENT; RISK ASSESSMENT; RISK BENEFIT ANALYSIS; RISK FACTOR; RISK REDUCTION; SECONDARY OSTEOPOROSIS; SIDE EFFECT; STROKE; TREATMENT PLANNING; VERTEBRA FRACTURE; WORLD HEALTH ORGANIZATION; AGED; DOSE RESPONSE; DRUG ADMINISTRATION; FEMALE; FOLLOW UP; HOSPITALIZATION; MIDDLE AGED; PATHOLOGIC FRACTURE; PHOTON ABSORPTIOMETRY; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; TREATMENT OUTCOME;

ABSORPTIOMETRY, PHOTON; AGED; ANTIBODIES, MONOCLONAL; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG ADMINISTRATION SCHEDULE; FEMALE; FOLLOW-UP STUDIES; FRACTURES, SPONTANEOUS; HUMANS; MIDDLE AGED; OSTEOPOROSIS, POSTMENOPAUSAL; RANDOMIZED CONTROLLED TRIALS AS TOPIC; RANK LIGAND; RISK ASSESSMENT; SEVERITY OF ILLNESS INDEX; TREATMENT OUTCOME;

EID: 79952196957     PISSN: 00325481     EISSN: 19419260     Source Type: Journal    
DOI: 10.3810/pgm.2010.11.2235     Document Type: Article

References (98)

1. National Osteoporosis Foundation. Clinician's Guide to Prevention and Treatment of Osteoporosis. Washington, DC: National Osteoporosis Foundation; 2008.
2. NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and Therapy. Osteoporosis prevention, diagnosis, and therapy. JAMA. 2001;285(6):785-795.
3. US Department of Health and Human Services. Bone health and osteoporosis: a report of the surgeon general. Rockville, MD: US Department of Health and Human Services, Office of the Surgeon General; 2004.
4. National Osteoporosis Foundation. America's bone health: the state of osteoporosis and low bone mass in our nation. Washington, DC: National Osteoporosis Foundation; 2002.
5. International Society for Clinical Densitometry. 2007 official positions of the International Society for Clinical Densitometry. West Hartford, CT: International Society for Clinical Densitometry; 2007.
6. American College of Obstetricians and Gynecologists, Women's Health Care Physicians. Osteoporosis ACOG practice bulletin. Clinical management guidelines for obstetrician-gynecologists. Number 50, January 2003. Obstet Gynecol. 2004;103(1):203-216.
7. World Health Organization. Prevention and management of osteoporosis: WHO technical report series 921. Geneva, Switzerland: World Health Organization; 2003.
8. North American Menopause Society. Management of osteoporosis in postmenopausal women: 2010 position statement of The North American Menopause Society. Menopause. 2010;17(1):25-54.
9. National Coalition for Osteoporosis and Related Bone Diseases. National action plan for bone health: recommendations from the Summit for a National Action Plan for Bone Health. Washington, DC: National Coalition for Osteoporosis and Related Bone Diseases; 2008.
10. National Committee for Quality Assurance. HEDIS® 2009: Healthcare effectiveness data and information set. http://www.ncqa.org/Portals/0/Newsroom/SOHC/SOHC_2009.pdf. Accessed May 20, 2010.
11. 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.
12. Boyle WJ, Simonet WS, Lacey DL. Osteoclast differentiation and activation. Nature. 2003;423(6937):337-342.
13. Abrams SA. Normal acquisition and loss of bone mass. Horm Res. 2003;60(suppl 3):71-76.
14. Riggs BL, Khosla S, Melton LJ 3rd. Sex steroids and the construction and conservation of the adult skeleton. Endocr Rev. 2002;23(3):279-302.
15. 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.
16. 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.
17. Dougall WC, Glaccum M, Charrier K, et al. RANK is essential for osteoclast and lymph node development. Genes Dev. 1999;13(18):2412-2424.
18. Fuller K, Wong B, Fox S, Choi Y, Chambers TJ. TRANCE is necessary and sufficient for osteoblast-mediated activation of bone resorption in osteoclasts. J Exp Med. 1998;188(5):997-1001.
19. Kong YY, Yoshida H, Sarosi I, et al. OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis. Nature. 1999;397(6717):315-323.
20. Lacey DL, Tan HL, Lu J, et al. Osteoprotegerin ligand modulates murine osteoclast survival in vitro and in vivo. Am J Pathol. 2000;157(2):435-448.
21. 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.
22. Li J, Sarosi I, Yan XQ, et al. RANK is the intrinsic hematopoietic cell surface receptor that controls osteoclastogenesis and regulation of bone mass and calcium metabolism. Proc Natl Acad Sci. 2000;97(4):1566-1571.
23. Yasuda H, Shima N, Nakagawa N, et al. Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. Proc Natl Acad Sci. 1998;95(7):3597-3602.
24. Hofbauer LC, Khosla S, Dunstan CR, Lacey DL, Spelsberg TC, Riggs BL. Estrogen stimulates gene expression and protein production of osteoprotegerin in human osteoblastic cells. Endocrinology. 1999;140(9):4367-4370.
25. D'Amelio P, Grimaldi A, Di Bella S, et al. Estrogen deficiency increases osteoclastogenesis up-regulating T cells activity: a key mechanism in osteoporosis. Bone. 2008;43(1):92-100.
26. Eghbali-Fatourechi G, Khosla S, Sanyal A, Boyle WJ, Lacey DL, Riggs BL. Role of RANK ligand in mediating increased bone resorption in early postmenopausal women. J Clin Invest. 2003;111(8):1221-1230.
27. Hodgson SF, Watts NB, Bilezikian JP, et al; AACE Osteoporosis Task Force. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the prevention and treatment of postmenopausal osteoporosis: 2001 edition, with selected updates for 2003. Endocr Pract. 2003;9(6):544-564.
28. Cooper C, Melton LJ 3rd. Epidemiology of osteoporosis. Trends Endocrinol Metab. 1992;3(6):224-229.
29. Burge R, Dawson-Hughes B, Solomon DH, Wong JB, King A, Tosteson A. Incidence and economic burden of osteoporosis-related fractures in the United States, 2005-2025. J Bone Miner Res. 2007;22(3):465-475.
30. Klotzbuecher CM, Ross PD, Landsman PB, Abbott TA 3rd, Berger M. Patients with prior fractures have an increased risk of future fractures: a summary of the literature and statistical synthesis. J Bone Miner Res. 2000;15(4):721-739.
31. Nevitt MC, Thompson DE, Black DM, et al. Effect of alendronate on limited-activity days and bed-disability days caused by back pain in postmenopausal women with existing vertebral fractures. Fracture Intervention Trial Research Group. Arch Intern Med. 2000;160(1):77-85.
32. Papaioannou A, Watts NB, Kendler DL, Yuen CK, Adachi JD, Ferko N. Diagnosis and management of vertebral fractures in elderly adults. Am J Med. 2002;113(3):220-228.
33. Lindsay R, Silverman SL, Cooper C, et al. Risk of new vertebral fracture in the year following a fracture. JAMA. 2001;285(3):320-323.
34. Roux C, Fechtenbaum J, Kolta S, Briot K, Girard M. Mild prevalent and incident vertebral fractures are risk factors for new fractures. Osteoporos Int. 2007;18(12):1617-1624.
35. Cree M, Soskolne CL, Belseck E, et al. Mortality and institutionalization following hip fracture. J Am Geriatr Soc. 2000;48(3):283-288.
36. Cummings SR, Melton LJ. Epidemiology and outcomes of osteoporotic fractures. Lancet. 2002;359(9319):1761-1767.
37. Cooper C, Atkinson EJ, Jacobsen SJ, O'Fallon WM, Melton LJ 3rd. Population-based study of survival after osteoporotic fractures. Am J Epidemiol. 1993;137(9):1001-1005.
38. Leibson CL, Tosteson AN, Gabriel SE, Ransom JE, Melton LJ. Mortality, disability, and nursing home use for persons with and without hip fracture: a population-based study. J Am Geriatr Soc. 2002;50(10):1644-1650.
39. Magaziner J, Lydick E, Hawkes W, et al. Excess mortality attributable to hip fracture in white women aged 70years and older. Am J Public Health. 1997;87(10):1630-1636.
40. Haentjens P, Magaziner J, Colon-Emeric CS, et al. Meta-analysis: excess mortality after hip fracture among older women and men. Ann Intern Med. 2010;152(6):380-390.
41. Habib ZA, Havstad SL, Wells K, Divine G, Pladevall M, Williams LK. Thiazolidinedione use and the longitudinal risk of fractures in patients with type 2 diabetes mellitus. J Clin Endocrinol Metab. 2010;95(2):592-600.
42. Meier C, Kraenzlin ME, Bodmer M, Jick SS, Jick H, Meier CR. Use of thiazolidinediones and fracture risk. Arch Intern Med. 2008;168(8):820-825.
43. Gray SL, LaCroix AZ, Larson J, et al. Proton pump inhibitor use, hip fracture, and change in bone mineral density in postmenopausal women: results from the Women's Health Initiative. Arch Intern Med. 2010;170(9):765-771.
44. Targownik LE, Lix LM, Metge CJ, Prior HJ, Leung S, Leslie WD. Use of proton pump inhibitors and risk of osteoporosis-related fractures. CMAJ. 2008;179(4):319-326.
45. Kanis JA, Borgstrom F, De Laet C, et al. Assessment of fracture risk. Osteoporos Int. 2005;16(6):581-589.
46. Wainwright SA, Marshall LM, Ensrud KE, et al; Study of Osteoporotic Fractures Research Group. Hip fracture in women without osteoporosis. J Clin Endocrinol Metab. 2005;90(5):2787-2793.
47. Siris ES, Chen YT, Abbott TA, et al. Bone mineral density thresholds for pharmacological intervention to prevent fractures. Arch Intern Med. 2004;164(10):1108-1112.
48. World Health Organization. FRAX: WHO Fracture Risk Assessment Tool. http://www.shef.ac.uk/FRAX/index.htm. Accessed January 21, 2010.
49. Ettinger B, Ettinger KM. FRAX: Using the new fracture risk assessment tool. Contemporary OB/GYN. 2009;54(7):22-28.
50. Watts NB, Lewiecki EM, Miller PD, Baim S. National Osteoporosis Foundation 2008 Clinician's Guide to Prevention and Treatment of Osteoporosis and the World Health Organization Fracture Risk Assessment Tool (FRAX): what they mean to the bone densitometrist and bone technologist. J Clin Densitom. 2008;11(4):473-477.
51. Roux C, Thomas T. Optimal use of FRAX. Joint Bone Spine. 2009;76(1):1-3.
52. Fitzpatrick LA. Secondary causes of osteoporosis. Mayo Clin Proc. 2002;77(5):453-468.
53. Odabasi E, Turan M, Tekbas F, Kutlu M. Evaluation of secondary causes that may lead to bone loss in women with osteoporosis: a retrospective study. Arch Gynecol Obstet. 2009;279(6):863-867.
54. Tannenbaum C, Clark J, Schwartzman K, et al. Yield of laboratory testing to identify secondary contributors to osteoporosis in otherwise healthy women. J Clin Endocrinol Metab. 2002;87(10):4431-4437.
55. Luckey M, Tannenbaum C. Authors' response: recommended testing in patients with low bone density. J Clin Endocrinol Metab. 2003;88(3):1402-1405.
56. National Osteoporosis Foundation. Physician's prevention and treatment of osteoporosis. Washington, DC: National Osteoporosis Foundation; 2003.
57. Dawson-Hughes B, Tosteson AN, Melton LJ 3rd, et al; National Osteoporosis Foundation Guide Committee. Implications of absolute fracture risk assessment for osteoporosis practice guidelines in the USA. Osteoporos Int. 2008;19(4):449-458.
58. Guideline for the prevention of falls in older persons. American Geriatrics Society, British Geriatrics Society, and American Academy of Orthopaedic Surgeons Panel on Falls Prevention. J Am Geriatr Soc. 2001;49(5):664-672.
59. Bonura F. Prevention, screening, and management of osteoporosis: an overview of the current strategies. Postgrad Med. 2009;121(4):5-17.
60. American Society for Bone and Mineral Research. American Society for Bone and Mineral Research statement on potential cardiovascular risks associated with calcium supplements. August, 12, 2010.
61. Recker RR, Lewiecki EM, Miller PD, Reiffel J. Safety of bisphosphonates in the treatment of osteoporosis. Am J Med. 2009;122(2suppl):S22-S32.
62. Solomon DH, Rekedal L, Cadarette SM. Osteoporosis treatments and adverse events. Curr Opin Rheumatol. 2009;21(4):363-368.
63. Silverman SL, Landesberg R. Osteonecrosis of the jaw and the role of bisphosphonates: a critical review. Am J Med. 2009;122(2 suppl):S33-S45.
64. Cooper A, Drake J, Brankin E; PERSIST Investigators. Treatment persistence with once-monthly ibandronate and patient support vs. once-weekly alendronate: results from the PERSIST study. Int J Clin Pract. 2006;60(8):896-905.
65. Cotte FE, Fardellone P, Mercier F, Gaudin AF, Roux C. Adherence to monthly and weekly oral bisphosphonates in women with osteoporosis. Osteoporos Int. 2010;21(1):145-155.
66. Siris ES, Selby PL, Saag KG, Borgstrom F, Herings RM, Silverman SL. Impact of osteoporosis treatment adherence on fracture rates in North America and Europe. Am J Med. 2009;122(2suppl):S3-13.
67. ProliaTM (denosumab) [package insert]. Thousand Oaks, CA: Amgen Inc; 2010.
68. 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.
69. Kostenuik PJ, Nguyen HQ, McCabe J, et al. Denosumab, a fully human monoclonal antibody to RANKL, inhibits bone resorption and increases BMD in knock-in mice that express chimeric (murine/human) RANKL. J Bone Miner Res. 2009;24(2):182-195.
70. Lonberg N. Human antibodies from transgenic animals. Nat Biotechnol. 2005;23(9):1117-1125.
71. Weiner LM. Fully human therapeutic monoclonal antibodies. J Immunother. 2006;29(1):1-9.
72. Jang G, Peterson M. Denosumab an inhibitor of RANKL has pharmacokinetics similiar to other monoclonal antibodies. J Bone Miner Res. 2006;21(suppl 1). http://www.abstractsonline.com/viewer/searchAdvanced.asp?MKey={FC197A55-D8DD-4F3D-9994-290B64584CCB}&AKey={D0C01D4F-E23B-45E2-ACD4-0AF8AC866B8B}. Accessed July 15, 2010.
73. Peterson M, Stouch B, Martin S. The pharmacokinetics of denosumab (AMG162) following various multiple subcutaneous dosing regimens in postmenopausal women with low bone mass. J Bone Miner Res. 2005;20(suppl 1). http://www.abstractsonline.com/viewer/?mkey=%7B70A6304C%2DA41B%2D49FC%2DA4DF%2DC147A5E943F0%7D%20. Accessed July 15, 2010.
74. McClung MR, Lewiecki EM, Cohen SB, et al. Denosumab in postmenopausal women with low bone mineral density. N Engl J Med. 2006;354(8):821-831.
75. Cummings SR, San Martin J, McClung MR, et al; FREEDOM trial. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med. 2009;361(8):756-765.
76. Boonen S, McClung M, Minisola S, et al. Effect of denosumab on the incidence of hip, new vertebral, and nonvertebral fractures over 3 years among postmenopausal women with higher fracture risk: a subgroup analysis from the FREEDOM study. J Bone Miner Res. 2009;24(suppl 1). http://www.asbmr.org/Meetings/AnnualMeeting/Abstracts09.aspx. Accessed July 15, 2010.
77. Bone H, Bolognese MA, Yuen CK, et al. Effects of denosumab treatment and discontinuation on bone mineral density and bone turnover markers in postmenopausal women with low bone mass. J Bone Miner Res. 2009;24(suppl 1). http://www.asbmr.org/Meetings/AnnualMeeting/Abstracts09.aspx. Accessed July 15, 2010.
78. Miller PD, Bolognese MA, Lewiecki EM, et al; AMG 162 Bone Loss Study Group. 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.
79. Kendler DL, Roux C, Benhamou CL, et al. Effects of denosumab on bone mineral density and bone turnover in postmenopausal women transitioning from alendronate therapy. J Bone Miner Res. 2010;25(1):72-81.
80. Brown JP, Prince RL, Deal C, et al. 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. 2009;24(1):153-161.
81. 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.
82. Riggs BL, Wahner HW, Dunn WL, Mazess RB, Offord KP, Melton LJ 3rd. Differential changes in bone mineral density of the appendicular and axial skeleton with aging: relationship to spinal osteoporosis. J Clin Invest. 1981;67(2):328-335.
83. Zebaze RM, Ghasem-Zadeh A, Bohte A, et al. Intracortical remodelling and porosity in the distal radius and post-mortem femurs of women: a cross-sectional study. Lancet. 2010;375(9727):1729-1736.
84. Seeman E, Delmas PD, Hanley DA, et al. Microarchitectural deterioration of cortical and trabecular bone: differing effects of denosumab and alendronate. J Bone Miner Res. 2010;25(8):1886-1894.
85. Miller PD, Bolognese MA, Lewiecki EM, et al. Effects of denosumab on bone mineral density and biochemical markers of bone turnover: 6year results of a phase 2 clinical trial. J Bone Miner Res. 2009;24(suppl 1). http://www.asbmr.org/Meetings/AnnualMeeting/Abstracts09.aspx. Accessed July 15, 2010.
86. Kendler DL, Bessette L, Hill CD, et al. Preference and satisfaction with a 6-month subcutaneous injection versus a weekly tablet for treatment of low bone mass. Osteoporos Int. 2010;21(5):837-846.
87. Papapoulos S, Bone HG, Brandi ML, et al. Four years of denosumab exposure in women with postmenopausal osteoporosis: results from the first year extension of the FREEDOM trial. Presented at: The American Society of Bone and Mineral Research; October 15-19, 2010; Toronto, Canada.
88. Fosamax® (alendronate sodium) [package insert]. Whitehouse Station, NJ: Merck and Co Inc; 2008.
89. Pols HA, Felsenberg D, Hanley DA, et al. Multinational, placebo-controlled, randomized trial of the effects of alendronate on bone density and fracture risk in postmenopausal women with low bone mass: results of the FOSIT study. Fosamax International Trial Study Group. Osteoporos Int. 1999;9(5):461-468.
90. Boniva® Injection (ibandronate sodium) [package insert]. Nutley, NJ: Roche Laboratories, Inc; 2009.
91. Boniva® tablets (ibandronate sodium) [package insert]. Nutley, NJ: Roche Laboratories, Inc; 2010.
92. Actonel® (risedronate sodium) [package insert]. Cincinnati, OH: Procter and Gamble Pharmaceuticals, Inc; 2009.
93. McClung MR, Geusens P, Miller PD, et al. Effect of risedronate on the risk of hip fracture in elderly women. Hip Intervention Program Study Group. N Engl J Med. 2001;344(5):333-340.
94. Reclast® (zoledronic acid) [package insert]. East Hanover, NJ: Novartis Pharmaceutical Corp; 2009.
95. Evista® (raloxifene hydrochloride) [package insert]. Indianapolis, IN: Eli Lilly and Company; 2008.
96. Fortical® (calcitonin-salmon) [package isnert]. Minneapolis, MN: Upsher-Smith Laboratories, Inc; 2009.
97. Chesnut CH 3rd, Silverman S, Andriano K, et al. A randomized trial of nasal spray salmon calcitonin in postmenopausal women with established osteoporosis: the prevent recurrence of osteoporotic fractures study. PROOF Study Group. Am J Med. 2000;109(4):267-276.
98. Forteo® (teriparatide) [package insert]. Indianapolis, IN: Eli Lilly and Company; 2009.