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The next step after anti-osteoporotic drug discontinuation: an up-to-date review of sequential treatment

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Abstract

Several antiresorptive drugs, like bisphosphonates and denosumab, are currently available for the treatment of osteoporosis due to their evidenced efficacy in reducing fracture risk at mid-term. Osteoanabolic therapies, like teriparatide, whose treatment duration is limited to 2 years, have also shown efficacy in the reduction of fracture risk. However, depending on the severity of osteoporosis and the presence of other associated risk factors for fracture, some patients may require long-term treatment to preserve optimal bone strength and minimize bone fracture risk. Given the limited duration of some treatments, the fact that most of the antiresorptive drugs have not been assessed beyond 10 years, and the known long-term safety issues of these drugs, including atypical femoral fractures or osteonecrosis of the jaw, the long-term management of these patients may require an approach based on drug discontinuation and/or switching. In this regard, interest in sequential osteoporosis therapy, wherein drugs are initiated and discontinued over time, has grown in recent years, although the establishment of an optimal and individualized order of therapies remains controversial. This review reports the currently available clinical evidence on the discontinuation effects of different anti-osteoporotic drugs, as well as the clinical outcomes of the different sequential treatment regimens. The objective of this article is to present up-to-date practical knowledge on this area in order to provide guidance to the clinicians involved in the management of patients with osteoporosis.

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References

  1. R.M. Martin, P.H. Correa, Bone quality and osteoporosis therapy. Arq. Bras. Endocrinol. Metab. 54(2), 186–199 (2010)

    Article  Google Scholar 

  2. N. Freemantle, C. Cooper, A. Diez-Perez, M. Gitlin, H. Radcliffe, S. Shepherd, C. Roux, Results of indirect and mixed treatment comparison of fracture efficacy for osteoporosis treatments: a meta-analysis. Osteoporos. Int. 24(1), 209–217 (2013). https://doi.org/10.1007/s00198-012-2068-9

    Article  CAS  PubMed  Google Scholar 

  3. C. Reyes, C. Tebe, D. Martinez-Laguna, M.S. Ali, A. Soria-Castro, C. Carbonell, D. Prieto-Alhambra, One and two-year persistence with different anti-osteoporosis medications: a retrospective cohort study. Osteoporos. Int. 28(10), 2997–3004 (2017). https://doi.org/10.1007/s00198-017-4144-7

    Article  CAS  PubMed  Google Scholar 

  4. Teriparatide-Summary of Product Characteristics (SPC). http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000425/WC500027994.pdf

  5. R.A. Adler, Management of Endocrine Disease: Atypical femoral fractures: risks and benefits of long-term treatment of osteoporosis with anti-resorptive therapy. Eur. J. Endocrinol. 178(3), R81–R87 (2018). https://doi.org/10.1530/EJE-17-1002

    Article  CAS  PubMed  Google Scholar 

  6. J. Gonzalez-Macias, J. Del Pino-Montes, J.M. Olmos, X. Nogues, Seiomm, e.n.d.l.C.d.R.d.l.G.d.O.d.l.: Clinical practice guidelines for posmenopausal, glucocorticoid-induced and male osteoporosis. Spanish Society for Research on Bone and Mineral Metabolism (3rd updated version 2014). Rev. Clin. Esp. 215(9), 515–526 (2015). https://doi.org/10.1016/j.rce.2015.08.003

    Article  CAS  PubMed  Google Scholar 

  7. B.Z. Leder, Optimizing sequential and combined anabolic and antiresorptive osteoporosis therapy. J. Bone Min. Res. 2(2), 62–68 (2018). https://doi.org/10.1002/jbm4.10041

    Article  Google Scholar 

  8. S. Khosla, M.J. Oursler, D.G. Monroe, Estrogen and the skeleton. Trends Endocrinol. Metab. 23(11), 576–581 (2012). https://doi.org/10.1016/j.tem.2012.03.008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. L.C. Hofbauer, M. Schoppet, Clinical implications of the osteoprotegerin/RANKL/RANK system for bone and vascular diseases. JAMA 292(4), 490–495 (2004). https://doi.org/10.1001/jama.292.4.490

    Article  CAS  PubMed  Google Scholar 

  10. W.H. Utian, D.F. Archer, G.A. Bachmann, C. Gallagher, F. Grodstein, J.R. Heiman, V.W. Henderson, H.N. Hodis, R.H. Karas, R.A. Lobo, J.E. Manson, R.L. Reid, P.J. Schmidt, C.A. Stuenkel, Estrogen and progestogen use in postmenopausal women: July 2008 position statement of The North American Menopause Society. Menopause 15(4 Pt 1), 584–602 (2008). https://doi.org/10.1097/gme.0b013e31817b076a

    Article  PubMed  Google Scholar 

  11. J.E. Rossouw, R.L. Prentice, J.E. Manson, L. Wu, D. Barad, V.M. Barnabei, M. Ko, A.Z. LaCroix, K.L. Margolis, M.L. Stefanick, Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause. JAMA 297(13), 1465–1477 (2007). https://doi.org/10.1001/jama.297.13.1465

    Article  CAS  PubMed  Google Scholar 

  12. J.E. Rossouw, G.L. Anderson, R.L. Prentice, A.Z. LaCroix, C. Kooperberg, M.L. Stefanick, R.D. Jackson, S.A. Beresford, B.V. Howard, K.C. Johnson, J.M. Kotchen, J. Ockene; Investigators, W.G.f.t.W.s.H.I., Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women’s Health Initiative randomized controlled trial. JAMA 288(3), 321–333 (2002)

    Article  CAS  PubMed  Google Scholar 

  13. J.A. Cauley, J. Robbins, Z. Chen, S.R. Cummings, R.D. Jackson, A.Z. LaCroix, M. LeBoff, C.E. Lewis, J. McGowan, J. Neuner, M. Pettinger, M.L. Stefanick, J. Wactawski-Wende, N.B. Watts; Women’s Health Initiative, I., Effects of estrogen plus progestin on risk of fracture and bone mineral density: the Women’s Health Initiative randomized trial. JAMA 290(13), 1729–1738 (2003). https://doi.org/10.1001/jama.290.13.1729

    Article  CAS  PubMed  Google Scholar 

  14. E.R. Nelson, S.E. Wardell, D.P. McDonnell, The molecular mechanisms underlying the pharmacological actions of estrogens, SERMs and oxysterols: implications for the treatment and prevention of osteoporosis. Bone 53(1), 42–50 (2013). https://doi.org/10.1016/j.bone.2012.11.011

    Article  CAS  PubMed  Google Scholar 

  15. B. Ettinger, D.M. Black, B.H. Mitlak, R.K. Knickerbocker, T. Nickelsen, H.K. Genant, C. Christiansen, P.D. Delmas, J.R. Zanchetta, J. Stakkestad, C.C. Gluer, K. Krueger, F.J. Cohen, S. Eckert, K.E. Ensrud, L.V. Avioli, P. Lips, S.R. Cummings, Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. Multiple Outcomes of Raloxifene Evaluation (MORE) Investigators. JAMA 282(7), 637–645 (1999)

    Article  CAS  PubMed  Google Scholar 

  16. S.L. Silverman, C. Christiansen, H.K. Genant, S. Vukicevic, J.R. Zanchetta, T.J. de Villiers, G.D. Constantine, A.A. Chines, Efficacy of bazedoxifene in reducing new vertebral fracture risk in postmenopausal women with osteoporosis: results from a 3-year, randomized, placebo-, and active-controlled clinical trial. J. Bone Min. Res. 23(12), 1923–1934 (2008). https://doi.org/10.1359/jbmr.080710

    Article  CAS  Google Scholar 

  17. K.E. Naylor, J.A. Clowes, J. Finigan, M.A. Paggiosi, N.F. Peel, R. Eastell, The effect of cessation of raloxifene treatment on bone turnover in postmenopausal women. Bone 46(3), 592–597 (2010). https://doi.org/10.1016/j.bone.2009.10.043

    Article  CAS  PubMed  Google Scholar 

  18. J.C. Gallagher, S. Palacios, K.A. Ryan, C.R. Yu, K. Pan, D.L. Kendler, S. Mirkin, B.S. Komm, Effect of conjugated estrogens/bazedoxifene on postmenopausal bone loss: pooled analysis of two randomized trials. Menopause 23(10), 1083–1091 (2016). https://doi.org/10.1097/GME.0000000000000694

    Article  PubMed  Google Scholar 

  19. S. Mirkin, J.V. Pinkerton, R. Kagan, J.R. Thompson, K. Pan, J.H. Pickar, B.S. Komm, D.F. Archer, Gynecologic Safety of Conjugated Estrogens Plus Bazedoxifene: Pooled Analysis of Five Phase 3 Trials. J. Women’s Health 25(5), 431–442 (2016). https://doi.org/10.1089/jwh.2015.5351

    Article  Google Scholar 

  20. B.S. Komm, J.R. Thompson, S. Mirkin, Cardiovascular safety of conjugated estrogens plus bazedoxifene: meta-analysis of the SMART trials. Climacteric 18(4), 503–511 (2015). https://doi.org/10.3109/13697137.2014.992011

    Article  CAS  PubMed  Google Scholar 

  21. R.G. Russell, Bisphosphonates: the first 40 years. Bone 49(1), 2–19 (2011). https://doi.org/10.1016/j.bone.2011.04.022

    Article  CAS  PubMed  Google Scholar 

  22. F. Cosman, S.J. de Beur, M.S. LeBoff, E.M. Lewiecki, B. Tanner, S. Randall, R. Lindsay, National Osteoporosis, F.: Clinician’s Guide to Prevention and Treatment of Osteoporosis. Osteoporos. Int. 25(10), 2359–2381 (2014). https://doi.org/10.1007/s00198-014-2794-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. D.M. Black, D.E. Thompson, D.C. Bauer, K. Ensrud, T. Musliner, M.C. Hochberg, M.C. Nevitt, S. Suryawanshi, S.R. Cummings, Fracture Intervention, T.: Fracture risk reduction with alendronate in women with osteoporosis: the Fracture Intervention Trial. FIT Research Group. J. Clin. Endocrinol. Metab. 85(11), 4118–4124 (2000). https://doi.org/10.1210/jcem.85.11.6953

    Article  CAS  PubMed  Google Scholar 

  24. S.T. Harris, N.B. Watts, H.K. Genant, C.D. McKeever, T. Hangartner, M. Keller, C.H. Chesnut 3rd, J. Brown, E.F. Eriksen, M.S. Hoseyni, D.W. Axelrod, P.D. Miller, Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: a randomized controlled trial. Vertebral Efficacy With Risedronate Therapy (VERT) Study Group. JAMA 282(14), 1344–1352 (1999)

    Article  CAS  PubMed  Google Scholar 

  25. M.R. McClung, P. Geusens, P.D. Miller, H. Zippel, W.G. Bensen, C. Roux, S. Adami, I. Fogelman, T. Diamond, R. Eastell, P.J. Meunier, J.Y. Reginster; Hip Intervention Program Study, G., Effect of risedronate on the risk of hip fracture in elderly women. Hip Intervention Program Study Group. N. Engl. J. Med. 344(5), 333–340 (2001). https://doi.org/10.1056/NEJM200102013440503

    Article  CAS  PubMed  Google Scholar 

  26. C.H. Chesnut 3rd, A. Skag, C. Christiansen, R. Recker, J.A. Stakkestad, A. Hoiseth, D. Felsenberg, H. Huss, J. Gilbride, R.C. Schimmer, P.D. Delmas, Oral Ibandronate Osteoporosis Vertebral Fracture Trial in North, A., Europe: Effects of oral ibandronate administered daily or intermittently on fracture risk in postmenopausal osteoporosis. J. Bone Min. Res. 19(8), 1241–1249 (2004). https://doi.org/10.1359/JBMR.040325

    Article  CAS  Google Scholar 

  27. D.M. Black, P.D. Delmas, R. Eastell, I.R. Reid, S. Boonen, J.A. Cauley, F. Cosman, P. Lakatos, P.C. Leung, Z. Man, C. Mautalen, P. Mesenbrink, H. Hu, J. Caminis, K. Tong, T. Rosario-Jansen, J. Krasnow, T.F. Hue, D. Sellmeyer, E.F. Eriksen, S.R. Cummings, H.P.F. Trial, Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N. Engl. J. Med. 356(18), 1809–1822 (2007). https://doi.org/10.1056/NEJMoa067312

    Article  CAS  PubMed  Google Scholar 

  28. D.M. Black, I.R. Reid, J.A. Cauley, F. Cosman, P.C. Leung, P. Lakatos, K. Lippuner, S.R. Cummings, T.F. Hue, A. Mukhopadhyay, M. Tan, R.P. Aftring, R. Eastell, The effect of 6 versus 9 years of zoledronic acid treatment in osteoporosis: a randomized second extension to the HORIZON-Pivotal Fracture Trial (PFT). J. Bone Min. Res. 30(5), 934–944 (2015). https://doi.org/10.1002/jbmr.2442

    Article  CAS  Google Scholar 

  29. R.A. Adler, G. El-Hajj Fuleihan, D.C. Bauer, P.M. Camacho, B.L. Clarke, G.A. Clines, J.E. Compston, M.T. Drake, B.J. Edwards, M.J. Favus, S.L. Greenspan, R. McKinney Jr., R.J. Pignolo, D.E. Sellmeyer, Managing Osteoporosis in Patients on Long-Term Bisphosphonate Treatment: Report of a Task Force of the American Society for Bone and Mineral Research. J. Bone Min. Res. 31(1), 16–35 (2016). https://doi.org/10.1002/jbmr.2708

    Article  CAS  Google Scholar 

  30. E. Shane, D. Burr, B. Abrahamsen, R.A. Adler, T.D. Brown, A.M. Cheung, F. Cosman, J.R. Curtis, R. Dell, D.W. Dempster, P.R. Ebeling, T.A. Einhorn, H.K. Genant, P. Geusens, K. Klaushofer, J.M. Lane, F. McKiernan, R. McKinney, A. Ng, J. Nieves, R. O’Keefe, S. Papapoulos, T.S. Howe, M.C. van der Meulen, R.S. Weinstein, M.P. Whyte, Atypical subtrochanteric and diaphyseal femoral fractures: second report of a task force of the American Society for Bone and Mineral Research. J. Bone Min. Res. 29(1), 1–23 (2014). https://doi.org/10.1002/jbmr.1998

    Article  Google Scholar 

  31. D.L. Diab, N.B. Watts, Bisphosphonate drug holiday: who, when and how long. Ther. Adv. Musculoskelet. Dis. 5(3), 107–111 (2013). https://doi.org/10.1177/1759720X13477714

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. C. Meier, B. Uebelhart, B. Aubry-Rozier, M. Birkhauser, H.A. Bischoff-Ferrari, D. Frey, R.W. Kressig, O. Lamy, K. Lippuner, P. Stute, N. Suhm, S. Ferrari, Osteoporosis drug treatment: duration and management after discontinuation. A position statement from the SVGO/ASCO. Swiss Med. Wkly. 147, w14484 (2017). https://doi.org/10.4414/smw.2017.14484

    Article  CAS  PubMed  Google Scholar 

  33. A.A. Khan, A. Morrison, D.A. Hanley, D. Felsenberg, L.K. McCauley, F. O’Ryan, I.R. Reid, S.L. Ruggiero, A. Taguchi, S. Tetradis, N.B. Watts, M.L. Brandi, E. Peters, T. Guise, R. Eastell, A.M. Cheung, S.N. Morin, B. Masri, C. Cooper, S.L. Morgan, B. Obermayer-Pietsch, B.L. Langdahl, R. Al Dabagh, K.S. Davison, D.L. Kendler, G.K. Sandor, R.G. Josse, M. Bhandari, M. El Rabbany, D.D. Pierroz, R. Sulimani, D.P. Saunders, J.P. Brown, J. Compston, International Task Force on Osteonecrosis of the, J. Diagnosis and management of osteonecrosis of the jaw: a systematic review and international consensus. J. Bone Min. Res. 30(1), 3–23 (2015). https://doi.org/10.1002/jbmr.2405

    Article  Google Scholar 

  34. S. Aljohani, R. Fliefel, J. Ihbe, J. Kuhnisch, M. Ehrenfeld, S. Otto, What is the effect of anti-resorptive drugs (ARDs) on the development of medication-related osteonecrosis of the jaw (MRONJ) in osteoporosis patients: a systematic review. J. Craniomaxillofac Surg. 45(9), 1493–1502 (2017). https://doi.org/10.1016/j.jcms.2017.05.028

    Article  PubMed  Google Scholar 

  35. B.Z. Leder, R.M. Neer, J.J. Wyland, H.W. Lee, S.M. Burnett-Bowie, J.S. Finkelstein, Effects of teriparatide treatment and discontinuation in postmenopausal women and eugonadal men with osteoporosis. J. Clin. Endocrinol. Metab. 94(8), 2915–2921 (2009). https://doi.org/10.1210/jc.2008-2630

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. D.W. Dempster, C.L. Lambing, P.J. Kostenuik, A. Grauer, 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(3), 521–536 (2012). https://doi.org/10.1016/j.clinthera.2012.02.002

    Article  CAS  PubMed  Google Scholar 

  37. M. McClung, S.T. Harris, P.D. Miller, D.C. Bauer, K.S. Davison, L. Dian, D.A. Hanley, D.L. Kendler, C.K. Yuen, E.M. Lewiecki, Bisphosphonate therapy for osteoporosis: benefits, risks, and drug holiday. Am. J. Med. 126(1), 13–20 (2013). https://doi.org/10.1016/j.amjmed.2012.06.023

    Article  CAS  PubMed  Google Scholar 

  38. A.D. Anastasilakis, S.A. Polyzos, Z.A. Efstathiadou, M. Savvidis, G.T. Sakellariou, A. Papatheodorou, P. Kokkoris, P. Makras, Denosumab in treatment-naive and pre-treated with zoledronic acid postmenopausal women with low bone mass: Effect on bone mineral density and bone turnover markers. Metabolism 64(10), 1291–1297 (2015). https://doi.org/10.1016/j.metabol.2015.06.018

    Article  CAS  PubMed  Google Scholar 

  39. A.D. Anastasilakis, S.A. Polyzos, A. Gkiomisi, Z.G. Saridakis, D. Digkas, I. Bisbinas, G.T. Sakellariou, A. Papatheodorou, P. Kokkoris, P. Makras, Denosumab versus zoledronic acid in patients previously treated with zoledronic acid. Osteoporos. Int. 26(10), 2521–2527 (2015). https://doi.org/10.1007/s00198-015-3174-2

    Article  CAS  PubMed  Google Scholar 

  40. P.D. Miller, N. Pannacciulli, J.P. Brown, E. Czerwinski, B.S. Nedergaard, M.A. Bolognese, J. Malouf, H.G. Bone, J.Y. Reginster, A. Singer, C. Wang, R.B. Wagman, S.R. Cummings, Denosumab or zoledronic acid in postmenopausal women with osteoporosis previously treated with oral bisphosphonates. J. Clin. Endocrinol. Metab. 101(8), 3163–3170 (2016). https://doi.org/10.1210/jc.2016-1801

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. A.D. Anastasilakis, S.A. Polyzos, P. Makras, B. Aubry-Rozier, S. Kaouri, O. Lamy, Clinical features of 24 patients with rebound-associated vertebral fractures after denosumab discontinuation: systematic review and additional cases. J. Bone Min. Res. 32(6), 1291–1296 (2017). https://doi.org/10.1002/jbmr.3110

    Article  CAS  Google Scholar 

  42. E. Tsourdi, B. Langdahl, M. Cohen-Solal, B. Aubry-Rozier, E.F. Eriksen, N. Guanabens, B. Obermayer-Pietsch, S.H. Ralston, R. Eastell, M.C. Zillikens, Discontinuation of Denosumab therapy for osteoporosis: a systematic review and position statement by ECTS. Bone 105, 11–17 (2017). https://doi.org/10.1016/j.bone.2017.08.003

    Article  PubMed  Google Scholar 

  43. A.D. Anastasilakis, M.P. Yavropoulou, P. Makras, G.T. Sakellariou, F. Papadopoulou, S. Gerou, S.E. Papapoulos, Increased osteoclastogenesis in patients with vertebral fractures following discontinuation of denosumab treatment. Eur. J. Endocrinol. 176(6), 677–683 (2017). https://doi.org/10.1530/EJE-16-1027

    Article  CAS  PubMed  Google Scholar 

  44. B.C. Silva, A.G. Costa, N.E. Cusano, S. Kousteni, J.P. Bilezikian, Catabolic and anabolic actions of parathyroid hormone on the skeleton. J. Endocrinol. Invest. 34(10), 801–810 (2011). https://doi.org/10.3275/7925

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. F. Cosman, J.W. Nieves, D.W. Dempster, Treatment sequence matters: anabolic and antiresorptive therapy for osteoporosis. J. Bone Min. Res. 32(2), 198–202 (2017). https://doi.org/10.1002/jbmr.3051

    Article  CAS  Google Scholar 

  46. S.Y. Lim, M.B. Bolster, Profile of romosozumab and its potential in the management of osteoporosis. Drug Des. Devel. Ther. 11, 1221–1231 (2017). https://doi.org/10.2147/DDDT.S127568

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. A.R. Wijenayaka, M. Kogawa, H.P. Lim, L.F. Bonewald, D.M. Findlay, G.J. Atkins, Sclerostin stimulates osteocyte support of osteoclast activity by a RANKL-dependent pathway. PloS ONE 6(10), e25900 (2011). https://doi.org/10.1371/journal.pone.0025900

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. X. Li, M.S. Ominsky, Q.T. Niu, N. Sun, B. Daugherty, D. D’Agostin, C. Kurahara, Y. Gao, J. Cao, J. Gong, F. Asuncion, M. Barrero, K. Warmington, D. Dwyer, M. Stolina, S. Morony, I. Sarosi, P.J. Kostenuik, D.L. Lacey, W.S. Simonet, H.Z. Ke, C. Paszty, Targeted deletion of the sclerostin gene in mice results in increased bone formation and bone strength. J. Bone Min. Res. 23(6), 860–869 (2008). https://doi.org/10.1359/jbmr.080216

    Article  Google Scholar 

  49. P. Chavassieux, R. Chapurlat, R., N. Portero-Muzy, P. Garcia, J.P. Brown, S. Horlait, C. Libanati, R. Boyce, A. Wang, A. Grauer, Effects of romosozumab in postmenopausal women with osteoporosis after 2 and 12 months: bone histomorphometry substudy. Paper presented at the ASBMR 2017 Annual Meeting, Denver

  50. K.G. Saag, J. Petersen, M.L. Brandi, A.C. Karaplis, M. Lorentzon, T. Thomas, J. Maddox, M. Fan, P.D. Meisner, A. Grauer, Romosozumab or alendronate for fracture prevention in women with osteoporosis. N. Engl. J. Med. 377(15), 1417–1427 (2017). https://doi.org/10.1056/NEJMoa1708322

    Article  CAS  PubMed  Google Scholar 

  51. S.L. Greenspan, R.D. Emkey, H.G. Bone, S.R. Weiss, N.H. Bell, R.W. Downs, C. McKeever, S.S. Miller, M. Davidson, M.A. Bolognese, A.L. Mulloy, N. Heyden, M. Wu, A. Kaur, A. Lombardi, Significant differential effects of alendronate, estrogen, or combination therapy on the rate of bone loss after discontinuation of treatment of postmenopausal osteoporosis. A randomized, double-blind, placebo-controlled trial. Ann. Intern. Med. 137(11), 875–883 (2002)

    Article  CAS  PubMed  Google Scholar 

  52. B. Ettinger, D. Grady, The waning effect of postmenopausal estrogen therapy on osteoporosis. N. Engl. J. Med. 329(16), 1192–1193 (1993). https://doi.org/10.1056/nejm199310143291610

    Article  CAS  PubMed  Google Scholar 

  53. B.H. Ascott-Evans, N. Guanabens, S. Kivinen, B.G. Stuckey, C.H. Magaril, K. Vandormael, B. Stych, M.E. Melton, Alendronate prevents loss of bone density associated with discontinuation of hormone replacement therapy: a randomized controlled trial. Arch. Intern. Med. 163(7), 789–794 (2003). https://doi.org/10.1001/archinte.163.7.789

    Article  CAS  PubMed  Google Scholar 

  54. N.B. Watts, J.A. Cauley, R.D. Jackson, A.Z. LaCroix, C.E. Lewis, J.E. Manson, J.M. Neuner, L.S. Phillips, M.L. Stefanick, J. Wactawski-Wende, C. Crandall, No increase in fractures after stopping hormone therapy: results from the women’s health initiative. J. Clin. Endocrinol. Metab. 102(1), 302–308 (2017). https://doi.org/10.1210/jc.2016-3270

    Article  PubMed  Google Scholar 

  55. D.M. Black, A.V. Schwartz, K.E. Ensrud, J.A. Cauley, S. Levis, S.A. Quandt, S. Satterfield, R.B. Wallace, D.C. Bauer, L. Palermo, L.E. Wehren, A. Lombardi, A.C. Santora, S.R. Cummings, F.R. Group, Effects of continuing or stopping alendronate after 5 years of treatment: the Fracture Intervention Trial Long-term Extension (FLEX): a randomized trial. JAMA 296(24), 2927–2938 (2006). https://doi.org/10.1001/jama.296.24.2927

    Article  CAS  PubMed  Google Scholar 

  56. D.M. Black, I.R. Reid, S. Boonen, C. Bucci-Rechtweg, J.A. Cauley, F. Cosman, S.R. Cummings, T.F. Hue, K. Lippuner, P. Lakatos, P.C. Leung, Z. Man, R.L. Martinez, M. Tan, M.E. Ruzycky, G. Su, R. Eastell, The effect of 3 versus 6 years of zoledronic acid treatment of osteoporosis: a randomized extension to the HORIZON-Pivotal Fracture Trial (PFT). J. Bone Min. Res. 27(2), 243–254 (2012). https://doi.org/10.1002/jbmr.1494

    Article  CAS  Google Scholar 

  57. J. Curtis, R. Chen, Z. Li, T. Arora, K. Saag, N. Wright, S. Daigle, M. Kilgore, E. Delzel, The impact of bisphosphonate drug holidays on fracture rates. J. Bone Min. Res. 33(Suppl 1), 2 (2018)

    Google Scholar 

  58. H.G. Bone, M.A. Bolognese, C.K. Yuen, D.L. Kendler, P.D. Miller, Y.C. Yang, L. Grazette, J. San Martin, J.C. Gallagher, 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. 96(4), 972–980 (2011). https://doi.org/10.1210/jc.2010-1502

    Article  CAS  PubMed  Google Scholar 

  59. J.P. Brown, C. Roux, O. Torring, P.R. Ho, J.E. Beck Jensen, N. Gilchrist, C. Recknor, M. Austin, A. Wang, A. Grauer, R.B. Wagman, Discontinuation of denosumab and associated fracture incidence: analysis from the Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months (FREEDOM) trial. J. Bone Min. Res. 28(4), 746–752 (2013). https://doi.org/10.1002/jbmr.1808

    Article  CAS  Google Scholar 

  60. A.D. Anastasilakis, P. Makras, Multiple clinical vertebral fractures following denosumab discontinuation. Osteoporos. Int. 27(5), 1929–1930 (2016). https://doi.org/10.1007/s00198-015-3459-5

    Article  CAS  PubMed  Google Scholar 

  61. B. Aubry-Rozier, E. Gonzalez-Rodriguez, D. Stoll, O. Lamy, Severe spontaneous vertebral fractures after denosumab discontinuation: three case reports. Osteoporos. Int. 27(5), 1923–1925 (2016). https://doi.org/10.1007/s00198-015-3380-y

    Article  CAS  PubMed  Google Scholar 

  62. O. Lamy, E. Gonzalez-Rodriguez, D. Stoll, D. Hans, B. Aubry-Rozier, Severe rebound-associated vertebral fractures after denosumab discontinuation: 9 clinical cases report. J. Clin. Endocrinol. Metab. 102(2), 354–358 (2017). https://doi.org/10.1210/jc.2016-3170

    Article  PubMed  Google Scholar 

  63. S.R. Cummings, S. Ferrari, R. Eastell, N. Gilchrist, J.B. Jensen, M. McClung, C. Roux, O. Torring, I. Valter, A.T. Wang, J.P. Brown, Vertebral fractures after discontinuation of denosumab: a post hoc analysis of the randomized placebo-controlled FREEDOM trial and its extension. J. Bone Min. Res. 33(2), 190–198 (2018). https://doi.org/10.1002/jbmr.3337

    Article  CAS  Google Scholar 

  64. E. González-Rodríguez, A.R. Bérengère, D. Stoll, D. Hans, O. Lamy, Clinical features of 35 patients with 172 spontaneous vertebral fractures after denosumab discontinuation: a single center observational study. J. Bone Min. Res. 33(Suppl 1), 3 (2018)

    Google Scholar 

  65. B. Uebelhart, R. Rizzoli, S.L. Ferrari, Retrospective evaluation of serum CTX levels after denosumab discontinuation in patients with or without prior exposure to bisphosphonates. Osteoporos. Int. 28(9), 2701–2705 (2017). https://doi.org/10.1007/s00198-017-4080-6

    Article  CAS  PubMed  Google Scholar 

  66. L. Tripto-Shkolnik, V. Rouach, Y. Marcus, P. Rotman-Pikielny, C. Benbassat, I. Vered, Vertebral fractures following denosumab discontinuation in patients with prolonged exposure to bisphosphonates. Calcif. Tissue Int. 103(1), 44–49 (2018). https://doi.org/10.1007/s00223-018-0389-1

    Article  CAS  PubMed  Google Scholar 

  67. G. Pfeiler, G.G. Steger, D. Egle, R. Greil, F. Fitzal, V. Wette, M. Balic, F. Haslbauer, E. Melbinger-Zeinitzer, V. Bjelic-Radisic, J. Bergh, R. Jakesz, C. Marth, D. Sevelda, B. Mlineritsch, R. Exner, C. Fesl, S. Frantal, C.F. Singer, M. Gnant, Fracture Risk after Stopping Adjuvant Denosumab in Hormone Receptor Positive Breast Cancer Patients on Aromatase Inhibitor Therapy – an Analysis of 3,425 Postmenopausal Patients in the Phase III ABCSG-18 trial. J. Bone Min. Res. 33(Suppl 1), 55 (2018)

    Google Scholar 

  68. I.R. Reid, A.M. Horne, B. Mihov, G.D. Gamble, Bone loss after denosumab: only partial protection with zoledronate. Calcif. Tissue Int. 101(4), 371–374 (2017). https://doi.org/10.1007/s00223-017-0288-x

    Article  CAS  PubMed  Google Scholar 

  69. R. Chapurlat, Effects and management of denosumab discontinuation. Jt. Bone Spine 85(5), 515–517 (2018). https://doi.org/10.1016/j.jbspin.2017.12.013

    Article  Google Scholar 

  70. N. Freemantle, S. Satram-Hoang, E.T. Tang, P. Kaur, D. Macarios, S. Siddhanti, J. Borenstein, D.L. Kendler, D. Investigators, Final results of the DAPS (Denosumab Adherence Preference Satisfaction) study: a 24-month, randomized, crossover comparison with alendronate in postmenopausal women. Osteoporos. Int. 23(1), 317–326 (2012). https://doi.org/10.1007/s00198-011-1780-1

    Article  CAS  PubMed  Google Scholar 

  71. ClinicalTrials.gov. (National Library of Medicine (US), Bethseda, 2000). Identifier NCT02499237, Zoledronic Acid to Maintain Bone Mass After Denosumab Discontinuation (AfterDmab). https://clinicaltrials.gov/ct2/show/NCT02499237. Accessed Jul 2015

  72. ClinicalTrials.gov. (National Library of Medicine (US), Bethseda, 2000). Identifier NCT03087851, Treatment With Zoledronic Acid Subsequent to Denosumab in Osteoporosis (ZOLARMAB). https://clinicaltrials.gov/ct2/show/NCT03087851. 13 Mar 2017

  73. D.M. Black, J.P. Bilezikian, K.E. Ensrud, S.L. Greenspan, L. Palermo, T. Hue, T.F. Lang, J.A. McGowan, C.J. Rosen, T.H.S.I. Pa, One year of alendronate after one year of parathyroid hormone (1-84) for osteoporosis. N. Engl. J. Med 353(6), 555–565 (2005). https://doi.org/10.1056/NEJMoa050336

    Article  CAS  PubMed  Google Scholar 

  74. R.M. Neer, C.D. Arnaud, J.R. Zanchetta, R. Prince, G.A. Gaich, J.Y. Reginster, A.B. Hodsman, E.F. Eriksen, S. Ish-Shalom, H.K. Genant, O. Wang, B.H. Mitlak, Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N. Engl. J. Med. 344(19), 1434–1441 (2001). https://doi.org/10.1056/NEJM200105103441904

    Article  CAS  PubMed  Google Scholar 

  75. R. Lindsay, W.H. Scheele, R. Neer, G. Pohl, S. Adami, C. Mautalen, J.Y. Reginster, J.J. Stepan, S.L. Myers, B.H. Mitlak, Sustained vertebral fracture risk reduction after withdrawal of teriparatide in postmenopausal women with osteoporosis. Arch. Intern. Med. 164(18), 2024–2030 (2004). https://doi.org/10.1001/archinte.164.18.2024

    Article  PubMed  Google Scholar 

  76. S. Adami, J. San Martin, M. Munoz-Torres, M.J. Econs, L. Xie, G.P. Dalsky, M. McClung, D. Felsenberg, J.P. Brown, M.L. Brandi, A. Sipos, Effect of raloxifene after recombinant teriparatide [hPTH(1-34)] treatment in postmenopausal women with osteoporosis. Osteoporos. Int. 19(1), 87–94 (2008). https://doi.org/10.1007/s00198-007-0485-y

    Article  CAS  PubMed  Google Scholar 

  77. B.Z. Leder, J.N. Tsai, A.V. Uihlein, P.M. Wallace, H. Lee, R.M. Neer, S.A. Burnett-Bowie, Denosumab and teriparatide transitions in postmenopausal osteoporosis (the DATA-Switch study): extension of a randomised controlled trial. Lancet 386(9999), 1147–1155 (2015). https://doi.org/10.1016/S0140-6736(15)61120-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. R. Niimi, T. Kono, A. Nishihara, M. Hasegawa, T. Kono, A. Sudo, Efficacy of switching from teriparatide to bisphosphonate or denosumab: A prospective, randomized, open-label trial. J. Bone Min. Res. 2(5), 1–6 (2018). https://doi.org/10.1002/jbm4.10054

    Article  CAS  Google Scholar 

  79. H.G. Bone, F. Cosman, P.D. Miller, G.C. Williams, G. Hattersley, M.Y. Hu, L.A. Fitzpatrick, B. Mitlak, S. Papapoulos, R. Rizzoli, R.K. Dore, J.P. Bilezikian, K.G. Saag, ACTIVExtend: 24 Months of Alendronate after 18 Months of Abaloparatide or Placebo for Postmenopausal Osteoporosis. J. Clin. Endocrinol. Metab. 103(8), 2949–2957 (2018). https://doi.org/10.1210/jc.2018-00163

    Article  PubMed  PubMed Central  Google Scholar 

  80. M.R. McClung, J.P. Brown, A. Diez-Perez, H. Resch, J. Caminis, P. Meisner, M.A. Bolognese, S. Goemaere, H.G. Bone, J.R. Zanchetta, J. Maddox, S. Bray, A. Grauer, Effects of 24 Months of Treatment With Romosozumab Followed by 12 Months of Denosumab or Placebo in Postmenopausal Women With Low Bone Mineral Density: A Randomized, Double-Blind, Phase 2, Parallel Group Study. J. Bone Min. Res. 33(8), 1397–1406 (2018). https://doi.org/10.1002/jbmr.3452

    Article  CAS  Google Scholar 

  81. R. Eastell, T. Nickelsen, F. Marin, C. Barker, P. Hadji, J. Farrerons, M. Audran, S. Boonen, K. Brixen, J.M. Gomes, B. Obermayer-Pietsch, A. Avramidis, G. Sigurdsson, C.C. Gluer, Sequential treatment of severe postmenopausal osteoporosis after teriparatide: final results of the randomized, controlled European Study of Forsteo (EUROFORS). J. Bone Min. Res. 24(4), 726–736 (2009). https://doi.org/10.1359/jbmr.081215

    Article  CAS  Google Scholar 

  82. J.N. Tsai, A.V. Uihlein, H. Lee, R. Kumbhani, E. Siwila-Sackman, E.A. McKay, S.A. Burnett-Bowie, R.M. Neer, B.Z. Leder, Teriparatide and denosumab, alone or combined, in women with postmenopausal osteoporosis: the DATA study randomised trial. Lancet 382(9886), 50–56 (2013). https://doi.org/10.1016/S0140-6736(13)60856-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. J.N. Tsai, L.A. Jiang, H. Lee, D. Hans, B.Z. Leder, Effects of Teriparatide, Denosumab, or Both on Spine Trabecular Microarchitecture in DATA-Switch: a Randomized Controlled Trial. J. Clin. Densitom. 20(4), 507–512 (2017). https://doi.org/10.1016/j.jocd.2017.05.007

    Article  PubMed  PubMed Central  Google Scholar 

  84. B.C. Silva, S.B. Broy, S. Boutroy, J.T. Schousboe, J.A. Shepherd, W.D. Leslie, Fracture Risk Prediction by Non-BMD DXA Measures: the 2015 ISCD Official Positions Part 2: Trabecular Bone Score. J. Clin. Densitom. 18(3), 309–330 (2015). https://doi.org/10.1016/j.jocd.2015.06.008

    Article  PubMed  Google Scholar 

  85. R. Prince, A. Sipos, A. Hossain, U. Syversen, S. Ish-Shalom, E. Marcinowska, J. Halse, R. Lindsay, G.P. Dalsky, B.H. Mitlak, Sustained nonvertebral fragility fracture risk reduction after discontinuation of teriparatide treatment. J. Bone Min. Res. 20(9), 1507–1513 (2005). https://doi.org/10.1359/JBMR.050501

    Article  CAS  Google Scholar 

  86. A. Fahrleitner-Pammer, B.L. Langdahl, F. Marin, F. Jakob, D. Karras, A. Barrett, O. Ljunggren, J.B. Walsh, G. Rajzbaum, C. Barker, W.F. Lems, Fracture rate and back pain during and after discontinuation of teriparatide: 36-month data from the European Forsteo Observational Study (EFOS). Osteoporos. Int. 22(10), 2709–2719 (2011). https://doi.org/10.1007/s00198-010-1498-5

    Article  CAS  PubMed  Google Scholar 

  87. P. Eiken, P. Vestergaard, Treatment of osteoporosis after alendronate or risedronate. Osteoporos. Int. 27(1), 1–12 (2016). https://doi.org/10.1007/s00198-015-3334-4

    Article  CAS  PubMed  Google Scholar 

  88. F. Cosman, Anabolic and antiresorptive therapy for osteoporosis: combination and sequential approaches. Curr. Osteoporos. Rep. 12(4), 385–395 (2014). https://doi.org/10.1007/s11914-014-0237-9

    Article  PubMed  Google Scholar 

  89. S. Boonen, F. Marin, B. Obermayer-Pietsch, M.E. Simoes, C. Barker, E.V. Glass, P. Hadji, G. Lyritis, H. Oertel, T. Nickelsen, E.V. McCloskey, E. Investigators, Effects of previous antiresorptive therapy on the bone mineral density response to two years of teriparatide treatment in postmenopausal women with osteoporosis. J. Clin. Endocrinol. Metab. 93(3), 852–860 (2008). https://doi.org/10.1210/jc.2007-0711

    Article  CAS  PubMed  Google Scholar 

  90. B. Ettinger, J. San Martin, G. Crans, I. Pavo, Differential effects of teriparatide on BMD after treatment with raloxifene or alendronate. J. Bone Min. Res. 19(5), 745–751 (2004). https://doi.org/10.1359/JBMR.040117

    Article  CAS  Google Scholar 

  91. P.D. Miller, P.D. Delmas, R. Lindsay, N.B. Watts, M. Luckey, J. Adachi, K. Saag, S.L. Greenspan, E. Seeman, S. Boonen, S. Meeves, T.F. Lang, J.P. Bilezikian; Investigators, O.-l.S.t.D.H.P.T.w.A.o.R.i.P.W.w.O.I.t.C.E.o.T., Early responsiveness of women with osteoporosis to teriparatide after therapy with alendronate or risedronate. J. Clin. Endocrinol. Metab. 93(10), 3785–3793 (2008). https://doi.org/10.1210/jc.2008-0353

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. P. Geusens, F. Marin, D.L. Kendler, L.A. Russo, C.A. Zerbini, S. Minisola, J.J. Body, E. Lespessailles, S.L. Greenspan, A. Bagur, J.J. Stepan, P. Lakatos, E. Casado, R. Moericke, P. Lopez-Romero, A. Fahrleitner-Pammer, Effects of Teriparatide Compared with Risedronate on the Risk of Fractures in Subgroups of Postmenopausal Women with Severe Osteoporosis: The VERO Trial. J. Bone Min. Res. 33(5), 783–794 (2018). https://doi.org/10.1002/jbmr.3384

    Article  CAS  Google Scholar 

  93. J.N. Tsai, K.K. Nishiyama, D. Lin, A. Yuan, H. Lee, M.L. Bouxsein, B.Z. Leder, Effects of Denosumab and Teriparatide Transitions on Bone Microarchitecture and Estimated Strength: the DATA-Switch HR-pQCT study. J. Bone Min. Res. 32(10), 2001–2009 (2017). https://doi.org/10.1002/jbmr.3198

    Article  CAS  Google Scholar 

  94. F. Cosman, R.A. Wermers, C. Recknor, K.F. Mauck, L. Xie, E.V. Glass, J.H. Krege, Effects of teriparatide in postmenopausal women with osteoporosis on prior alendronate or raloxifene: differences between stopping and continuing the antiresorptive agent. J. Clin. Endocrinol. Metab. 94(10), 3772–3780 (2009). https://doi.org/10.1210/jc.2008-2719

    Article  CAS  PubMed  Google Scholar 

  95. S.L. Greenspan, K. Vujevich, C. Britton, A. Herradura, G. Gruen, I. Tarkin, P. Siska, B. Hamlin, S. Perera, Teriparatide for treatment of patients with bisphosphonate-associated atypical fracture of the femur. Osteoporos. Int. 29(2), 501–506 (2018). https://doi.org/10.1007/s00198-017-4286-7

    Article  CAS  PubMed  Google Scholar 

  96. B.Z. Leder, L.S. O’Dea, J.R. Zanchetta, P. Kumar, K. Banks, K. McKay, C.R. Lyttle, G. Hattersley, Effects of abaloparatide, a human parathyroid hormone-related peptide analog, on bone mineral density in postmenopausal women with osteoporosis. J. Clin. Endocrinol. Metab. 100(2), 697–706 (2015). https://doi.org/10.1210/jc.2014-3718

    Article  CAS  PubMed  Google Scholar 

  97. P.D. Miller, G. Hattersley, B.J. Riis, G.C. Williams, E. Lau, L.A. Russo, P. Alexandersen, C.A. Zerbini, M.Y. Hu, A.G. Harris, L.A. Fitzpatrick, F. Cosman, C. Christiansen, A.S. Investigators, Effect of abaloparatide vs. placebo on new vertebral fractures in postmenopausal women with osteoporosis: a randomized clinical trial. JAMA 316(7), 722–733 (2016). https://doi.org/10.1001/jama.2016.11136

    Article  CAS  PubMed  Google Scholar 

  98. F. Cosman, P.D. Miller, G.C. Williams, G. Hattersley, M.Y. Hu, I. Valter, L.A. Fitzpatrick, B.J. Riis, C. Christiansen, J.P. Bilezikian, D. Black, Eighteen Months of Treatment With Subcutaneous Abaloparatide Followed by 6 Months of Treatment With Alendronate in Postmenopausal Women With Osteoporosis: Results of the ACTIVExtend Trial. Mayo Clin. Proc. 92(2), 200–210 (2017). https://doi.org/10.1016/j.mayocp.2016.10.009

    Article  CAS  PubMed  Google Scholar 

  99. F. Cosman, D.B. Crittenden, J.D. Adachi, N. Binkley, E. Czerwinski, S. Ferrari, L.C. Hofbauer, E. Lau, E.M. Lewiecki, A. Miyauchi, C.A. Zerbini, C.E. Milmont, L. Chen, J. Maddox, P.D. Meisner, C. Libanati, A. Grauer, Romosozumab Treatment in Postmenopausal Women with Osteoporosis. N. Engl. J. Med. 375(16), 1532–1543 (2016). https://doi.org/10.1056/NEJMoa1607948

    Article  CAS  PubMed  Google Scholar 

  100. F. Cosman, D.B. Crittenden, S. Ferrari, A. Khan, N.E. Lane, K. Lippuner, T. Matsumoto, C.E. Milmont, C. Libanati, A. Grauer; FRAME Study, The foundation effect of building bone with 1 year of romosozumab leads to continued lower fracture risk after transition to denosumab. J. Bone Min. Res. 33(7), 1219–1226 (2018). https://doi.org/10.1002/jbmr.3427

    Article  CAS  Google Scholar 

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Acknowledgements

We thank the following for permission to reproduce the figures that have appeared in published material: Journal of Bone and Mineral Research (John Wiley and Sons) for permission to reproduce Fig. 1 in Cummings et al. [63]; Ogilvy Healthworld Barcelona provided medical writing services (funded by Sociedad Española de Investigación Ósea y del Metabolismo Mineral, SEIOMM).

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Authors and Affiliations

  1. Metabolic Bone Diseases Unit, Department of Rheumatology, Hospital Clínic, Institut d’Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), University of Barcelona, Barcelona, Spain

    Núria Guañabens & Pilar Peris

  2. Bone Metabolism, Internal Medicine, University Hospital Infanta Leonor, Madrid, Spain

    María Jesús Moro-Álvarez

  3. Rheumatology Department, Parc Taulí University Hospital, Autonomous University of Barcelona, Sabadell, Spain

    Enrique Casado

  4. Rheumatology Service, Hospital del Mar, Barcelona, Spain

    Josep Blanch-Rubió

  5. Bone and Mineral Metabolism Unit, Central University Hospital of Asturias (HUCA), University of Oviedo, Oviedo, Spain

    Carlos Gómez-Alonso

  6. Endocrinology Service, University Hospital 12 de Octubre, Complutense University, Madrid, Spain

    Guillermo Martínez Díaz-Guerra

  7. University Hospital of Salamanca/University of Salamanca, Salamanca, Spain

    Javier del Pino-Montes

  8. University Hospital Marqués de Valdecilla, Research Institute Marqués de Valdecilla (IDIVAL), University of Cantabria, Santander, Spain

    Carmen Valero Díaz de Lamadrid

  9. Endocrinology and Nutrition Unit, Hospital Universitario San Cecilio de Granada, Department of Medicine, University of Granada, Granada, Spain

    Manuel Muñoz-Torres

  10. Instituto de Investigación Biosanitaria (Ibs.GRANADA), CIBERFES, Instituto de Salud Carlos III, Granada, Spain

    Manuel Muñoz-Torres

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  1. Núria Guañabens
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Dr. N.G. has received fees for lectures and participation in advisory boards from Amgen, Eli Lilly, Alexion, and UCB. Dr. E.C. has received fees for lectures and/or participation in advisory boards from Amgen, Lilly, UCB and Rubió. Dr. J.B.-R. has received advisory fees from Amgen and Gebro Pharma. Dr. C.G.-A. has received fees for lectures and participation in advisory boards from Amgen, Eli Lilly, Faes, Gebro, and UCB. Dr. G.M.D.-G. holds a research grant from Amgen and Shire, has received advisory fees from Amgen, UCB, Eli Lilly, and Shire and speaker honoraria from Amgen and Eli Lilly. Dr. J.d.P.-M. has received advisory and conference fees, as well as congress grants from Amgen, UCB, and FAES and conference fees from Eli Lilly and Gebro. Dr. P.P. has received lecture fees from Amgen, Eli Lilly, Alexion, and Kyowa Kirin. Dr. M.M.-T. has received fees for lectures and advisory boards from Amgen, UCB, Eli Lilly, Alexion, Shire, and Kyowa Kirin.

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Guañabens, N., Moro-Álvarez, M.J., Casado, E. et al. The next step after anti-osteoporotic drug discontinuation: an up-to-date review of sequential treatment. Endocrine 64, 441–455 (2019). https://doi.org/10.1007/s12020-019-01919-8

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