Drugs & Aging

, Volume 31, Issue 7, pp 555–576 | Cite as

Denosumab: A Review of its Use in Postmenopausal Women with Osteoporosis

Adis Drug Evaluation

Abstract

Subcutaneous denosumab (Prolia® [USA, Europe]; Pralia® [Japan]) once every 6 months is indicated in several countries for the treatment of postmenopausal women with osteoporosis at increased or high risk for fractures (featured indication). In some countries, it is also indicated for use in postmenopausal women who have failed or are intolerant to other osteoporosis treatments. In several international, phase III trials (≤3 years’ duration) involving more than 12,000 women with postmenopausal osteoporosis or low bone mineral density (BMD), including Asian studies, denosumab was an effective and generally well tolerated treatment. Relative to placebo, denosumab treatment significantly reduced the risk of vertebral, nonvertebral and hip fractures and increased BMD at all skeletal sites evaluated, including the lumbar spine and total hip. Furthermore, the benefits of denosumab treatment were generally evident after the first dose and were maintained during up to 8 years of treatment in an ongoing extension study. The tolerability profile of denosumab during this extension phase was consistent with that observed during the initial 3-year FREEDOM trial. At 12 months, denosumab treatment increased BMD at the total hip, lumbar spine and/or femoral neck and reduced markers of bone turnover to a significantly greater extent than oral bisphosphonates in women who were essentially bisphosphonate-naive and in those who had switched from alendronate to denosumab treatment. Further clinical experience, including an ongoing postmarketing safety study, will more fully define the long-term safety of denosumab. In the meantime, denosumab is an important option for the treatment of women with postmenopausal osteoporosis at increased or high-risk of fractures, including in women at increased risk of fracture who are unable to take other osteoporosis treatments.

References

  1. 1.
    World Health Organization. Prevention and management of osteoporosis: WHO Technical Report series no. 92. 2003. http://whqlibdoc.who.int/trs/who_trs_92pdf. Accessed 6 Jan 2014.
  2. 2.
    Management of osteoporosis in postmenopausal women: 2010 position statement of the North American Menopause Society. Menopause. 2010;17(1):25–54.Google Scholar
  3. 3.
    National Institute for Health and Clinical Excellence. Osteoporosis: assessing the risk of fragility fracture. NICE clinical guideline 146. 2012. http://guidance.nice.org.uk/CG146/NICEGuidance/pdf/English. Accessed 6 Jan 2014.
  4. 4.
    Johnell O, Kanis J. Epidemiology of osteoporotic fractures. Osteoporos Int. 2005;16(Suppl 2):3–7.CrossRefGoogle Scholar
  5. 5.
    Chitre M, Shechter D, Grauer A. Denosumab for treatment of postmenopausal osteoporosis. Am J Health Syst Pharm. 2011;68(15):1409–18.PubMedCrossRefGoogle Scholar
  6. 6.
    Moen MD, Keam SJ. Denosumab: a review of its use in the treatment of postmenopausal osteoporosis. Drugs Aging. 2011;28(1):63–82.PubMedCrossRefGoogle Scholar
  7. 7.
    Reginster J-Y. Antifracture efficacy of currently available therapies for postmenopausal osteoporosis. Drugs. 2011;71(1):65–78.PubMedCrossRefGoogle Scholar
  8. 8.
    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):1059–66.PubMedCrossRefGoogle Scholar
  9. 9.
    European Medicines Agency. Prolia 60 mg solution in a pre-filled syringe: summary of product characteristics. 2013. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/001120/WC500093526.pdf. Accessed 26 Nov 2013.
  10. 10.
    Amgen Manufacturing Limited. Prolia® (denosumab) injection, for subcutaneous use: US prescribing information. 2013. http://pi.amgen.com/united_states/prolia/prolia_pi.pdf. Accessed 26 Nov 2013.
  11. 11.
    Sutjandra L, Rodriguez RD, Doshi S, et al. Population pharmacokinetic meta-analysis of denosumab in healthy subjects and postmenopausal women with osteopenia or osteoporosis. Clin Pharmacokinet. 2011;50(12):793–807.PubMedCrossRefGoogle Scholar
  12. 12.
    Kumagai Y, Hasunuma T, Padhi D. A randomized, double-blind, placebo-controlled, single-dose study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of denosumab administered subcutaneously to postmenopausal Japanese women. Bone. 2011;49:1101–7.PubMedCrossRefGoogle Scholar
  13. 13.
    Lewiecki EM, Miller PD, McClung MR, et al. Two-year treatment with denosumab (AMG 162) in a randomized phase 2 study of postmenopausal women with low BMD. J Bone Miner Res. 2007;22(12):1832–41.PubMedCrossRefGoogle Scholar
  14. 14.
    McClung MR, Lewiecki EM, Cohen SB, et al. Denosumab in postmenopausal women with low bone mineral density. N Engl J Med. 2006;354(8):821–31.PubMedCrossRefGoogle Scholar
  15. 15.
    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):222–9.PubMedCrossRefGoogle Scholar
  16. 16.
    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.PubMedCrossRefGoogle Scholar
  17. 17.
    McClung MR, Lewiecki EM, Geller ML, et al. Effect of denosumab on bone mineral density and biochemical markers of bone turnover: 8-year results of a phase 2 clinical trial. Osteoporos Int. 2013;24(1):227–35.PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    Cummings SR, San Martin J, McClung MR, et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis [Erratum appears in N Engl J Med. 2009;361(19):1914]. N Engl J Med. 2009;361(8):756–65.Google Scholar
  19. 19.
    Papapoulos S, Chapurlat R, Libanati C, et al. Five years of denosumab exposure in women with postmenopausal osteoporosis: results from the first two years of the FREEDOM extension. J Bone Miner Res. 2012;27(3):694–701.PubMedCentralPubMedCrossRefGoogle Scholar
  20. 20.
    Ferrari S, Adachi JD, Zapalowski C, et al. Further reduction in the nonvertebral fracture rate is observed following 3 years of denosumab treatment: results with up to 7 years in the FREEDOM extension [abstract no. 1017]. American Society for Bone and Mineral Research Annual Meeting; 4–7 Oct 2013; Baltimore.Google Scholar
  21. 21.
    Papapoulos S, Lippuner K, Roux C, et al. Eight years of denosumab treatment in postmenopausal women with osteoporosis: results from the first five years of the FREEDOM extension [abstract no. LB-M026]. American Society for Bone and Mineral Research Annual Meeting; 4–7 Oct 2013; Baltimore.Google Scholar
  22. 22.
    Bone HG, Chapurlat R, Brandi M-L, et al. The effect of three or six years of denosumab exposure in women with postmenopausal osteoporosis: results from the FREEDOM extension. J Clin Endocrinol Met. 2013;98(11):4483–92.CrossRefGoogle Scholar
  23. 23.
    Roux C, Lippuner K, Bone HG, et al. Denosumab treatment of postmenopausal women with osteoporosis for 7 years: clinical fracture results from the first 4 years of the FREEDOM extension [abstract no. OP0250]. Ann Rheum Dis. 2013;72(Suppl 3):137.Google Scholar
  24. 24.
    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):2149–57.PubMedCrossRefGoogle Scholar
  25. 25.
    Bone HG, 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 Clin Endocrinol Metab. 2011;96(4):972–80.PubMedCrossRefGoogle Scholar
  26. 26.
    Zebaze RM, Libanati C, McClung MR, et al. Denosumab reduces hip cortical porosity in women with osteoporosis [abstract no. 1065]. American Society for Bone and Mineral Research Annual Meeting; 4–7 Oct 2013; Baltimore.Google Scholar
  27. 27.
    Bolognese MA, Teglbjaerg CS, Zanchetta JR, et al. Denosumab significantly increases DXA BMD at both trabecular and cortical sites: results from the FREEDOM study. J Clin Densitom. 2013;16(2):147–53.PubMedCrossRefGoogle Scholar
  28. 28.
    McClung MR, Boonen S, Törring O, et al. Effect of denosumab treatment on the risk of fractures in subgroups of women with postmenopausal osteoporosis. J Bone Miner Res. 2012;27(1):211–8.PubMedCrossRefGoogle Scholar
  29. 29.
    Boonen S, Adachi JD, Man Z, et al. Treatment with denosumab reduces the incidence of new vertebral and hip fractures in postmenopausal women at high risk. J Clin Endocrinol Metab. 2011;96(6):1727–36.PubMedCrossRefGoogle Scholar
  30. 30.
    Brown JP, Roux C, Törring O, et al. Discontinuation of denosumab and associated fracture incidence: analysis from the fracture reduction evaluation of denosumab in osteoporosis every 6 months (FREEDOM) trial. J Bone Miner Res. 2013;28(4):746–52.PubMedCentralPubMedCrossRefGoogle Scholar
  31. 31.
    McCloskey EV, Johansson H, Oden A, et al. Denosumab reduces the risk of osteoporotic fractures in postmenopausal women, particularly in those with moderate to high fracture risk as assessed with FRAX. J Bone Miner Res. 2012;27(7):1480–6.PubMedCrossRefGoogle Scholar
  32. 32.
    Jamal SA, Ljunggren O, Stehman-Breen C, et al. Effects of denosumab on fracture and bone mineral density by level of kidney function. J Bone Miner Res. 2011;26(8):1829–35.PubMedCrossRefGoogle Scholar
  33. 33.
    Simon JA, Recknor C, Moffett AH Jr, et al. Impact of denosumab on the peripheral skeleton of postmenopausal women with osteoporosis: bone density, mass, and strength of the radius, and wrist fracture. Menopause. 2013;20(2):130–7.PubMedGoogle Scholar
  34. 34.
    McClung MR, Zanchetta JR, Høiseth A, et al. Denosumab densitometric changes assessed by quantitative computed tomography at the spine and hip in postmenopausal women with osteoporosis. J Clin Densitom. 2013;16(2):250–6.PubMedCrossRefGoogle Scholar
  35. 35.
    Reid IR, Miller PD, Brown JP, et al. Effects of denosumab on bone histomorphometry: the FREEDOM and STAND studies. J Bone Miner Res. 2010;25(10):2256–65.PubMedCrossRefGoogle Scholar
  36. 36.
    Keaveny TM, McClung MR, Genant HK, et al. Femoral and vertebral strength improvements in postmenopausal women with osteoporosis treated with denosumab. J Bone Miner Res. 2014;29(1):158–65.PubMedCrossRefGoogle Scholar
  37. 37.
    Genant HK, Keaveny TM, Zapalowski C, et al. Cortical bone parameters at the hip in response to denosumab vs placebo and the clinical relevance of these changes in postmenopausal women with osteoporosis <75 and ≥75 years old [abstract no. SAO400]. American Society for Bone and Mineral Research Annual Meeting; 4–7 Oct 2013; Baltimore.Google Scholar
  38. 38.
    Eastell R, Christiansen C, Grauer A, et al. Effects of denosumab on bone turnover markers in postmenopausal osteoporosis. J Bone Miner Res. 2011;26(3):530–7.PubMedCrossRefGoogle Scholar
  39. 39.
    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.PubMedCrossRefGoogle Scholar
  40. 40.
    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):153–61.PubMedCrossRefGoogle Scholar
  41. 41.
    Recknor C, Czerwinski E, Bone HG, et al. Denosumab compared with ibandronate in postmenopausal women previously treated with bisphosphonate therapy: a randomized open-label trial. Obstet Gynecol. 2013;121(6):1291–9.PubMedCrossRefGoogle Scholar
  42. 42.
    Roux C, Hofbauer LC, Ho PR, et al. Denosumab compared with risedronate in postmenopausal women suboptimally adherent to alendronate therapy: efficacy and safety results from a randomized open-label study. Bone Miner. 2014;58:48–54.CrossRefGoogle Scholar
  43. 43.
    Nakamura T, Matsumoto T, Sugimoto T, et al. Effects of denosumab on fracture risk in Japanese patients with osteoporosis: results of 2-year data from the denosumab fracture intervention randomized placebo controlled trial (DIRECT) [abstract no. 1098]. J Bone Miner Res. 2012;27(Suppl 1):S32.Google Scholar
  44. 44.
    Silverman S, Viswanathan HN, Yang YC, et al. Impact of clinical fractures on health-related quality of life is dependent on time of assessment since fracture: results from the FREEDOM trial. Osteoporos Int. 2012;23:1361–9.PubMedCrossRefGoogle Scholar
  45. 45.
    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):1886–94.PubMedCrossRefGoogle Scholar
  46. 46.
    Zebaze RM, Libanati C, Austin M, et al. Differing effects of denosumab and alendronate on cortical and trabecular bone. Bone. 2014;59:173–9.PubMedCrossRefGoogle Scholar
  47. 47.
    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):837–46.PubMedCrossRefGoogle Scholar
  48. 48.
    Freemantle N, Satram-Hoang S, Tang ET, et al. Final results of the DAPS (Denosumab Adherence Preference Satisfaction) study: a 24-month, randomized, crossover comparison with alendronate in postmenopausal women. Osteoporos Int. 2012;23(1):317–26.PubMedCentralPubMedCrossRefGoogle Scholar
  49. 49.
    Kendler DL, McClung MR, Freemantle N, et al. Adherence, preference, and satisfaction of postmenopausal women taking denosumab or alendronate. Osteoporos Int. 2011;22(6):1725–35.PubMedCrossRefGoogle Scholar
  50. 50.
    Kendler DL, Macarios D, Lillestol MJ, et al. Influence of patient perceptions and preferences for osteoporosis medication on adherence behavior in the denosumab adherence preference satisfaction study. Menopause. 2014;21(1):25–32.PubMedCrossRefGoogle Scholar
  51. 51.
    Tsai JN, Uihlein AV, Lee H, et al. Teriparatide and denosumab, alone or combined, in women with postmenopausal osteoporosis: the DATA study randomised trial. Lancet. 2013;382(9886):50–6.PubMedCrossRefGoogle Scholar
  52. 52.
    Tsai J, Uihlein A, Zhu Y, et al. Comparative effects of teriparatide, denosumab, and combination therapy on peripheral compartmental bone density and microarchitecture: the DATA-HRpQCT Study [abstract no. SA0372]. American Society for Bone and Mineral Research Annual Meeting; 4–7 Oct 2013; Baltimore.Google Scholar
  53. 53.
    Koh J-M, Oh H-J, Park IH, et al. Efficacy and safety results from a six month double-blind study comparing 60 mg denosumab (DMAb) and placebo in Korean postmenopausal women with osteoporosis [abstract no. SAO386]. American Society for Bone and Mineral Research Annual Meeting; 4–7 Oct 2013; Baltimore.Google Scholar
  54. 54.
    Nakamura T, Matsumoto T, Sugimoto T, et al. Dose-response study of denosumab on bone mineral density and bone turnover markers in Japanese postmenopausal women with osteoporosis. Osteoporos Int. 2012;23(3):1131–40.PubMedCrossRefGoogle Scholar
  55. 55.
    Hiligsmann M, Ethgen O, Bruyère O, et al. Development and validation of a Markov microsimulation model for the economic evaluation of treatments in osteoporosis. Value Health. 2009;12(5):687–96.PubMedCrossRefGoogle Scholar
  56. 56.
    Parthan A, Kruse M, Yurgin N, et al. Cost effectiveness of denosumab versus oral bisphosphonates for postmenopausal osteoporosis in the US. Appl Health Econ Health Policy. 2013;11:485–97.PubMedCrossRefGoogle Scholar
  57. 57.
    Barbosa E, Machado M, Araujo G, et al. Cost-effectiveness of denosumab in preventing osteoporotic fractures in postmenopausal women from the private healthcare setting perspective in Brazil [abstract no. PMS41]. In: 15th Annual European Conference of the International Society for Pharmacoeconomics and Outcomes Research; 3–7 Nov 2012; Berlin.Google Scholar
  58. 58.
    Chau D, Becker DL, Coombes ME, et al. Cost-effectiveness of denosumab in the treatment of postmenopausal osteoporosis in Canada. J Med Econ. 2012;15(Suppl 1):3–14.PubMedCrossRefGoogle Scholar
  59. 59.
    Ström O, Jönsson B, Kanis JA. Intervention thresholds for denosumab in the UK using a FRAX®-based cost-effectiveness analysis. Osteoporos Int. 2013;24(4):1491–502.PubMedCrossRefGoogle Scholar
  60. 60.
    Ström O, Borgström F, Kleman M, et al. FRAX® and its applications in health economics: cost-effectiveness and intervention thresholds using bazedoxifene in a Swedish setting as an example. Bone. 2010;47(2):430–7.PubMedCrossRefGoogle Scholar
  61. 61.
    Watts NB, Roux C, Modlin JF, et al. Infections in postmenopausal women with osteoporosis treated with denosumab or placebo: coincidence or causal association? Osteoporos Int. 2012;23(1):327–37.PubMedCentralPubMedCrossRefGoogle Scholar
  62. 62.
    Geller M,Wagman RB, Ho PR, et al. Early findings from Prolia® post-marketing safety surveillance for atypical femoral fracture, osteonecrosis of the jaw, severe symptomatic hypocalcemia, and anaphylaxis [abstract]. International Osteoporosis Federation World Congress on Osteoporosis and 13th European Congress on Clinical and Economic Aspects of Osteoporosis and Osteoarthritis; 2–5 Apr 2014; Seville.Google Scholar
  63. 63.
    Diz P, Lopez-Cedrun L, Arenaz J, et al. Denosumab-related osteonecrosis of the jaw. J Am Dental Assoc. 2012;143(9):981–4.CrossRefGoogle Scholar
  64. 64.
    Rachner TD, Platzbecker U, Felsenberg D, et al. Osteonecrosis of the jaw after osteoporosis therapy with denosumab following long-term bisphosphonate therapy. Mayo Clin Proc. 2013;88(4):418–9.PubMedCrossRefGoogle Scholar
  65. 65.
    Neuprez A, Coste S, Rompen E, et al. Osteonecrosis of the jaw in a male osteoporotic patient treated with denosumab. Osteoporos Int. 2014;25:393–5.PubMedCentralPubMedCrossRefGoogle Scholar
  66. 66.
    Hadji P, Papaioannou NA, Gielen E, et al. 12-Month persistence with denosumab (DMab) in women with postmenopausal osteoporosis (PMO): interim results of a 24-month prospective observational study in Germany, Austria, Greece and Belgium [abstract]. International Osteoporosis Federation World Congress on Osteoporosis and 13th European Congress on Clinical and Economic Aspects of Osteoporosis and Osteoarthritis; 2–5 Apr 2014; Seville.Google Scholar
  67. 67.
    Thompson RN, Armstrong CL, Heyburn G. Bilateral atypical femoral fractures in a patient prescribed denosumab: a case report. Bone. 2014;61(1):44–7.PubMedCrossRefGoogle Scholar
  68. 68.
    Drampolos E, Skarpas G, Barbounakis N, et al. Atypical femoral fractures bilaterally in a patient receiving denosumab: a case report. Acta Orthop. 2014;85(1):3–5.CrossRefGoogle Scholar
  69. 69.
    Villiers J, Clark DW, Jeswani T, et al. An atraumatic femoral fracture in a patient with rheumatoid arthritis and osteoporosis treated with denosumab. Case Rep Rheumatol. 2013. doi:10.1155/2013/249872.
  70. 70.
    Adami S, Libanati C, Boonen S, et al. Denosumab treatment in postmenopausal women with osteoporosis does not interfere with fracture-healing: results from the FREEDOM trial. J Bone Joint Surg Am. 2012;94(23):2113–9.PubMedCrossRefGoogle Scholar
  71. 71.
    Samelson EJ, Miller PD, Christiansen C, et al. RANKL inhibition with denosumab does not influence 3-year progression of aortic calcification or incidence of adverse cardiovascular events in postmenopausal women with osteoporosis and high cardiovascular risk. J Bone Miner Res. 2014;29(2):450–7.PubMedCrossRefGoogle Scholar
  72. 72.
    Daiichi-Sankyo Company. Daiichi Sankyo receives approval in Japan for manufacturing and marketing of Pralia®, a new treatment for osteoporosis. 2013. http://www.daiichisankyo.com/media_investors/media_relations/press_releases/detail/005123.html. Accessed 26 Nov 2013.
  73. 73.
    National Osteoporosis Foundation. Clinician’s guide to prevention and treatment of osteoporosis. 2013. http://nof.org/files/nof/public/content/resource/913/files/580.pdf. Accessed 21 Jan 2014.
  74. 74.
    Kanis JA, McCloskey EV, Johansson H, et al. European guidance for the diagnosis and management of osteoporosis in potmenopausal women. Osteoporos Int. 2013;24(1):23–57.PubMedCentralPubMedCrossRefGoogle Scholar
  75. 75.
    Miller P, Derman RJ. What is the best balance of benefits and risks among anti-resorptive agents for postmenopausal osteoporosis? Osteoporos Int. 2010;21(11):1793–802.PubMedCrossRefGoogle Scholar
  76. 76.
    Silverman S, Christiansen C. Individualizing osteoporosis therapy. Osteoporos Int. 2012;23:797–809.PubMedCrossRefGoogle Scholar
  77. 77.
    Diab DL, Watts NB. Postmenopausal osteoporosis. Curr Opin Endocrinol Diabetes Obes. 2013;20:501–9.PubMedCrossRefGoogle Scholar
  78. 78.
    Lewiecki EM, Miller PD, Harris ST, et al. Understanding and communicating the benefits and risks of denosumab, raloxifene, and teriparatide for the treatment of osteoporosis. J Clin Densitom. 2013. doi:10.1016/j.jocd.2013.09.018.
  79. 79.
    Diel IJ, Bergner R, Grötz KA. Adverse effects of bisphosphonates: current issues. J Support Oncol. 2007;5(10):475–82.PubMedGoogle Scholar
  80. 80.
    Karlsson L, Lundkvist J, Psachoulia E, et al. Literature review and meta-analysis of persistence with oral bisphosphonates [abstract]. International Osteoporosis Federation World Congress on Osteoporosis and 13th European Congress on Clinical and Economic Aspects of Osteoporosis and Osteoarthritis; 2–5 Apr 2014; Seville.Google Scholar
  81. 81.
    Hadji P, Intorcia M, Psachoulia E, et al. GRAND 3: the German retrospective cohort analysis on non-adherence in osteoporotic patients: persistence analysis of female patients treated with denosumab [abstract]. International Osteoporosis Federation World Congress on Osteoporosis and 13th European Congress on Clinical and Economic Aspects of Osteoporosis and Osteoarthritis; 2–5 Apr 2014; Seville.Google Scholar
  82. 82.
    Siris ES, Harris ST, Rosen CJ, et al. Adherence to bisphosphonate therapy and fracture rates in osteoporotic women: relationship to vertebral and nonvertebral fractures from 2 US claims databases. Mayo Clin Proc. 2006;81(8):1013–22.PubMedCrossRefGoogle Scholar
  83. 83.
    Badamgarav E, Fitzpatrick LA. A new look at osteoporosis outcomes: the influence of treatment, compliance, persistence, and adherence. Mayo Clin Proc. 2006;81(8):1009–12.PubMedCrossRefGoogle Scholar
  84. 84.
    Siris ES, Selby PL, Saag KG, et al. Impact of osteoporosis treatment adherence on fracture rates in North America and Europe. Am J Med. 2009;122 Suppl l:S3–13.Google Scholar
  85. 85.
    Hadji P, Claus V, Ziller V, et al. GRAND: the German retrospective cohort analysis on compliance and persistence and the associated risk of fractures in osteoporotic women treated with oral bisphosphonates. Osteoporos Int. 2012;23(1):223–31.PubMedCrossRefGoogle Scholar
  86. 86.
    Qi W-X, Tang L-A, He A-N, et al. Risk of osteonecrosis of the jaw in cancer patients receiving denosumab: a meta-analysis of seven randomized controlled trials. Int J Clin Oncol. 2014. doi:10.1007/s10147-013-0561-6.
  87. 87.
    Xue F, Ma H, Stehman-Breen C, et al. Design and methods of a postmarketing pharmacoepidemiology study assessing long-term safety of Prolia® (denosumab) for the treatment of postmenopausal osteoporosis. Pharmacoepidemiol Drug Saf. 2013;22:1107–14.PubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  1. 1.AdisAucklandNew Zealand

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