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Denosumab significantly increases bone mineral density and reduces bone turnover compared with monthly oral ibandronate and risedronate in postmenopausal women who remained at higher risk for fracture despite previous suboptimal treatment with an oral bisphosphonate

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Abstract

Summary

Managing osteoporotic patients suboptimally adherent to bisphosphonates (BPs) is difficult. Such patients who remained at higher risk for fracture (≥1 risk factor) were transitioned to denosumab or a monthly oral BP. Denosumab-treated subjects had significantly greater increases in bone mineral density and decreases in bone turnover in this 12-month study.

Introduction

A clinical need exists to manage patients who are suboptimally adherent to oral BPs and remain at higher risk for fracture. Here, we compare the effects on bone mineral density (BMD) and bone turnover of transitioning such patients to denosumab or monthly oral BP (ibandronate or risedronate).

Methods

In two previous multicenter, open-label studies, postmenopausal women ≥55 years previously treated with, though suboptimally adherent to, a daily or weekly BP were randomized to denosumab 60 mg subcutaneously every 6 months (N = 852) or oral BP 150 mg monthly (N = 851) for 12 months. In this combined post-hoc analysis, a subset of higher risk subjects was identified, and the percentage changes from baseline in BMD and serum C-telopeptide of type I collagen (sCTX-1) were assessed.

Results

In the overall population, denosumab was associated with greater gains in BMD at 12 months than monthly oral BP at the total hip, femoral neck, and lumbar spine (p < 0.0001 for all). In higher risk subjects, denosumab led to greater gains in BMD than oral BPs at the total hip (2.2 vs 0.8 %), femoral neck (1.8 vs 0.3 %), and lumbar spine (3.7 vs 1.4 %) (p < 0.0001 for all). Denosumab also led to greater decreases in sCTX-1 in the overall population and higher risk subjects at months 1 and 6 (p < 0.0001 for both). Adverse events and serious adverse events were generally similar between treatment groups.

Conclusions

Transitioning to denosumab was well tolerated and more effective in increasing BMD and reducing bone turnover than cycling to a monthly oral BP treatment in subjects who remained at higher fracture risk despite suboptimal BP treatment.

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References

  1. Recker RR, Gallagher R, MacCosbe PE (2005) Effect of dosing frequency on bisphosphonate medication adherence in a large longitudinal cohort of women. Mayo Clin Proc 80:856–861

    Article  PubMed  Google Scholar 

  2. Lee S, Glendenning P, Inderjeeth CA (2011) Efficacy, side effects and route of administration are more important than frequency of dosing of anti-osteoporosis treatments in determining patient adherence: a critical review of published articles from 1970 to 2009. Osteoporos Int 22:741–753

    Article  CAS  PubMed  Google Scholar 

  3. Siris ES, Harris ST, Rosen CJ, Barr CE, Arvesen JN, Abbott TA, Silverman S (2006) Adherence to bisphosphonate therapy and fracture rates in osteoporotic women: relationship to vertebral and nonvertebral fractures from 2 US claims databases. Mayo Clin Proc 81:1013–1022

    Article  PubMed  Google Scholar 

  4. Cotte FE, Fardellone P, Mercier F, Gaudin AF, Roux C (2010) Adherence to monthly and weekly oral bisphosphonates in women with osteoporosis. Osteoporos Int 21:145–155

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  5. Devine J, Trice S, Finney Z, Yarger S, Nwokeji E, Linton A, Davies W (2012) A retrospective analysis of extended-interval dosing and the impact on bisphosphonate compliance in the US Military Health System. Osteoporos Int 23:1415–1424

    Article  CAS  PubMed  Google Scholar 

  6. Briesacher BA, Andrade SE, Harrold LR, Fouayzi H, Yood RA (2010) Adoption of once-monthly oral bisphosphonates and the impact on adherence. Am J Med 123:275–280

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Caro JJ, Ishak KJ, Huybrechts KF, Raggio G, Naujoks C (2004) The impact of compliance with osteoporosis therapy on fracture rates in actual practice. Osteoporos Int 15:1003–1008

    Article  PubMed  Google Scholar 

  8. Siris ES, Selby PL, Saag KG, Borgstrom F, Herings RM, Silverman SL (2009) Impact of osteoporosis treatment adherence on fracture rates in North America and Europe. Am J Med 122:S3–S13

    Article  PubMed  Google Scholar 

  9. Sunyecz JA, Mucha L, Baser O, Barr CE, Amonkar MM (2008) Impact of compliance and persistence with bisphosphonate therapy on health care costs and utilization. Osteoporos Int 19:1421–1429

    Article  CAS  PubMed  Google Scholar 

  10. Huybrechts KF, Ishak KJ, Caro JJ (2006) Assessment of compliance with osteoporosis treatment and its consequences in a managed care population. Bone 38:922–928

    Article  PubMed  Google Scholar 

  11. Finigan J, Greenfield DM, Blumsohn A, Hannon RA, Peel NF, Jiang G, Eastell R (2008) Risk factors for vertebral and nonvertebral fracture over 10 years: a population-based study in women. J Bone Miner Res 23:75–85

    Google Scholar 

  12. Gehlbach SH, Avrunin JS, Puleo E, Spaeth R (2007) Fracture risk and antiresorptive medication use in older women in the USA. Osteoporos Int 18:805–810

    Article  CAS  PubMed  Google Scholar 

  13. McClung M, Recker R, Miller P, Fiske D, Minkoff J, Kriegman A, Zhou W, Adera M, Davis J (2007) Intravenous zoledronic acid 5 mg in the treatment of postmenopausal women with low bone density previously treated with alendronate. Bone 41:122–128

    Google Scholar 

  14. Cummings SR, Nevitt MC, Browner WS, Stone K, Fox KM, Ensrud KE, Cauley J, Black D, Vogt TM (1995) Risk factors for hip fracture in white women. Study of Osteoporotic Fractures Research Group. N Engl J Med 332:767–773

    Article  CAS  PubMed  Google Scholar 

  15. Nevitt MC, Cummings SR, Stone KL et al (2005) Risk factors for a first-incident radiographic vertebral fracture in women > or =65 years of age: the study of osteoporotic fractures. J Bone Miner Res 20:131–140

    Google Scholar 

  16. WHO (2003) Adherence to long-term therapies: evidence for action. World Health Organization. http://www.who.int/chp/knowledge/publications/adherence_report/en/ Accessed 28 Oct 2013

  17. Dempster DW, Lambing CL, Kostenuik PJ, Grauer A (2012) Role of RANK ligand and denosumab, a targeted RANK ligand inhibitor, in bone health and osteoporosis: a review of preclinical and clinical data. Clin Ther 34:521–536

    Article  CAS  PubMed  Google Scholar 

  18. Genant HK, Engelke K, Hanley DA et al (2010) Denosumab improves density and strength parameters as measured by QCT of the radius in postmenopausal women with low bone mineral density. Bone 47:131–139

    Article  CAS  PubMed  Google Scholar 

  19. Keaveny T, McClung M, Genant H et al (2014) Femoral and vertebral strength improvements in postmenopausal women with osteoporosis treated with denosumab. J Bone Mineral Res 29:158–165

    Google Scholar 

  20. Kostenuik PJ, Smith SY, Jolette J, Schroeder J, Pyrah I, Ominsky MS (2011) Decreased bone remodeling and porosity are associated with improved bone strength in ovariectomized cynomolgus monkeys treated with denosumab, a fully human RANKL antibody. Bone 49:151–161

    Article  CAS  PubMed  Google Scholar 

  21. Simon JA, Recknor C, Moffett AH Jr et al (2013) Impact of denosumab on the peripheral skeleton of postmenopausal women with osteoporosis: bone density, mass, and strength of the radius, and wrist fracture. Menopause 20:130–137

    PubMed  Google Scholar 

  22. Recknor C, Czerwinski E, Bone HG et al (2013) Denosumab compared with ibandronate in postmenopausal women previously treated with bisphosphonate therapy: a randomized open-label trial. Obstet Gynecol 121:1291–1299

    Article  CAS  PubMed  Google Scholar 

  23. Roux C, Hofbauer LC, Ho PR et al (2014) Denosumab compared with risedronate in postmenopausal women suboptimally adherent to alendronate therapy: efficacy and safety results from a randomized open-label study. Bone 58:48–54

    Article  CAS  PubMed  Google Scholar 

  24. Reynolds K, Viswanathan HN, O'Malley CD et al (2012) Psychometric properties of the Osteoporosis-specific Morisky Medication Adherence Scale in postmenopausal women with osteoporosis newly treated with bisphosphonates. Ann Pharmacother 46:659–670

    Article  PubMed  Google Scholar 

  25. Boonen S, Adachi JD, Man Z et al (2011) Treatment with denosumab reduces the incidence of new vertebral and hip fractures in postmenopausal women at high risk. J Clin Endocrinol Metab 96:1727–1736

    Article  CAS  PubMed  Google Scholar 

  26. McClung MR, Boonen S, Torring O et al (2012) Effect of denosumab treatment on the risk of fractures in subgroups of women with postmenopausal osteoporosis. J Bone Miner Res 27:211–218

    Article  CAS  PubMed  Google Scholar 

  27. Brown JP, Deal C, de Gregorio LH et al (2008) Effect of denosumab vs alendronate on bone turnover markers and bone mineral density changes at 12 months based on baseline bone turnover level [Abstract 1285]. J Bone Miner Res 23(Suppl S1):S80

  28. Miller P, Gruntmanis U, Boonen S, Yang Y, Wagman R, Hall J, Orwoll E (2012) The effect of denosumab on bone mineral density (BMD) assessed by baseline bone turnover in men with low BMD [Abstract FR0393]. J Bone Miner Res 27(Suppl 1):S123

    Google Scholar 

  29. Kendler DL, Roux C, Benhamou CL, Brown JP, Lillestol M, Siddhanti S, Man HS, San Martin J, Bone HG (2010) Effects of denosumab on bone mineral density and bone turnover in postmenopausal women transitioning from alendronate therapy. J Bone Miner Res 25:72–81

    Article  CAS  PubMed  Google Scholar 

  30. Brown JP, Prince RL, Deal C et al (2009) 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 24:153–161

    Article  CAS  PubMed  Google Scholar 

  31. Austin M, Yang YC, Vittinghoff E et al (2012) Relationship between bone mineral density changes with denosumab treatment and risk reduction for vertebral and nonvertebral fractures. J Bone Miner Res 27:687–693

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. Seeman E, Delmas PD, Hanley DA et al (2010) Microarchitectural deterioration of cortical and trabecular bone: differing effects of denosumab and alendronate. J Bone Miner Res 25:1886–1894

    Article  PubMed  Google Scholar 

  33. Zebaze RM, Libanati C, McClung MR, Zanchetta JR, Kendler DL, Høiseth A, Wang A, Ghasem-Zadeh A, Seeman E (2013) Denosumab reduces hip cortical porosity in women with osteoporosis [Abstract 1065]. J Bone Miner Res 28(Suppl S1):S23

  34. Ominsky MS, Stouch B, Schroeder J, Pyrah I, Stolina M, Smith SY, Kostenuik PJ (2011) Denosumab, a fully human RANKL antibody, reduced bone turnover markers and increased trabecular and cortical bone mass, density, and strength in ovariectomized cynomolgus monkeys. Bone 49:162–173

    Article  CAS  PubMed  Google Scholar 

  35. Miller PD, McClung MR, Macovei L et al (2005) Monthly oral ibandronate therapy in postmenopausal osteoporosis: 1-year results from the MOBILE study. J Bone Miner Res 20:1315–1322

    Article  CAS  PubMed  Google Scholar 

  36. Cummings SR, San Martin J, McClung MR et al (2009) Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med 361:756–765

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This study was sponsored by Amgen Inc. Erica Rockabrand, PhD, an employee of Amgen Inc., and Mary G. Royer, MS, a paid consultant of Amgen Inc., provided medical writing support.

Conflicts of interest

J.P. Brown received research grants and/or consulting or speaking fees from Amgen Inc., Eli Lilly, Merck, Novartis, and Warner Chilcott.

M.A. Bolognese also received research grants from Amgen Inc., Lilly, MSD, and Genentech, and is part of the advisory board or board of directors for NOF, Lilly, and Vivus.

P.R. Ho, J. Hall, I. Ferreira, P. Dakin, and R.B. Wagman are employees of Amgen Inc. and may own stock and/or stock options in Amgen Inc.

C. Roux received research grants and/or consulting or speaking fees from Amgen Inc., Bongrain, Lilly, MSD, Novartis, Roche, and Servier.

H.G. Bone received research grants from Amgen Inc., Lilly, Merck, Novartis, and Tarsa; part of the advisory board for Amgen Inc. and Merck; and received consulting fees from Amgen Inc., Merck, Novartis, and Tarsa.

S. Bonnick received research grants from Amgen Inc. and Merck.

J.P. van den Bergh received speaker fees from Amgen Inc., Eli Lilly, MSD, and Will Pharma, and part of the advisory board or board of directors for Amgen Inc. and MSD.

C. Recknor received research grants from Medi; received consulting and/or speaking fees from Amgen Inc., Eli Lilly, Novartis, and Warner Chilcott; and is shareholder in Ion Med Systems.

Author information

Authors and Affiliations

  1. CHU de Québec Research Centre and Laval University, Room S-763, 2705 Laurier Boulevard, Quebec City, QC, G1V 4G2, Canada

    J. P. Brown

  2. Paris Descartes University, Paris, France

    C. Roux

  3. Amgen Inc., Thousand Oaks, CA, USA

    P. R. Ho, J. Hall, P. Dakin & R. B. Wagman

  4. Bethesda Health Research Center, Bethesda, MD, USA

    M. A. Bolognese

  5. Michigan Bone and Mineral Clinic, Detroit, MI, USA

    H. G. Bone

  6. Clinical Research Center of North Texas, Denton, TX, USA

    S. Bonnick

  7. VieCuri Medical Centre and Maastricht University, Maastricht, The Netherlands

    J. P. van den Bergh

  8. Amgen Inc., Cambridge, UK

    I. Ferreira

  9. United Osteoporosis Centers, Gainesville, GA, USA

    C. Recknor

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  1. J. P. Brown
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  2. C. Roux
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  9. I. Ferreira
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Correspondence to J. P. Brown.

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Brown, J.P., Roux, C., Ho, P.R. et al. Denosumab significantly increases bone mineral density and reduces bone turnover compared with monthly oral ibandronate and risedronate in postmenopausal women who remained at higher risk for fracture despite previous suboptimal treatment with an oral bisphosphonate. Osteoporos Int 25, 1953–1961 (2014). https://doi.org/10.1007/s00198-014-2692-7

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  • DOI: https://doi.org/10.1007/s00198-014-2692-7

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