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Alendronate after denosumab discontinuation in women previously exposed to bisphosphonates was not effective in preventing the risk of spontaneous multiple vertebral fractures: two case reports

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Abstract

At denosumab discontinuation, an antiresorptive agent is indicated to reduce the high bone turnover, the rapid bone loss, and the risk of spontaneous vertebral fractures. We report two cases of postmenopausal women, previously exposed to bisphosphonates, treated with alendronate at denosumab discontinuation. Alendronate was ineffective to avoid spontaneous clinical vertebral fractures. They presented three and nine spontaneous vertebral fractures 8 and 12 months after denosumab discontinuation, respectively. Ineffectiveness of alendronate was attributed to insufficient control of the rebound as assessed by B-crosslaps measures in the first case, and partially to the high risk of fractures in the later. In both situations, the increased fracture risk may have favoured these new fractures. It is urgent to define effective therapeutic strategies to avoid spontaneous vertebral fractures after denosumab discontinuation.

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References

  1. Cummings SR, San Martin J, McClung MR, Siris ES, Eastell R, Reid IR, Delmas P, Zoog HB, Austin M, Wang A, Kutilek S, Adami S, Zanchetta J, Libanati C, Siddhanti S, Christiansen C, FREEDOM Trial (2009) Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med 361:756–765

    Article  CAS  Google Scholar 

  2. Bone HG, Wagman RB, Brandi ML, Brown JP, Chapurlat R, Cummings SR, Czerwiński E, Fahrleitner-Pammer A, Kendler DL, Lippuner K, Reginster JY, Roux C, Malouf J, Bradley MN, Daizadeh NS, Wang A, Dakin P, Pannacciulli N, Dempster DW, Papapoulos S (2017) 10 years of denosumab treatment in postmenopausal women with osteoporosis: results from the phase 3 randomised FREEDOM trial and open-label extension. Lancet Diabetes Endocrinol 5:513–523

    Article  CAS  PubMed  Google Scholar 

  3. Bone HG, Bolognese MA, Yuen CK, Kendler DL, Miller PD, Yang YC, Grazette L, San Martin J, Gallagher JC (2011) Effects of denosumab treatment and discontinuation on bone mineral density and bone turn-over markers in postmenopausal women with low bone mass. J Clin Endocrinol Metab 96:972–980

    Article  CAS  PubMed  Google Scholar 

  4. Popp AW, Varathan N, Buffat H, Senn C, Perrelet R, Lippuner K (2018) Bone mineral density changes after 1 year of denosumab discontinuation in postmenopausal women with long-term denosumab treatment for osteoporosis. Calcif Tissue Int 103:50–54. https://doi.org/10.1007/s00223-018-0394-4

    Article  CAS  PubMed  Google Scholar 

  5. Lamy O, Stoll D, Gonzalez-Rodriguez E, Hans D, Aubry-Rozier B (2017) Severe rebound-associated vertebral fractures after denosumab discontinuation: nine clinical cases report. J Clin Endocrinol Metab 102:354–358

    Article  PubMed  Google Scholar 

  6. McClung MR, Wagman RB, Miller PD, Wang A, Lewiecki EM (2017) Observations following discontinuation of long-term denosumab therapy. Osteoporos Int 28:1723–1732

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Anastasilakis AD, Polyzos SA, Makras P, Aubry-Rozier B, Kaouri S, Lamy O (2017) Clinical features of 24 patients with rebound-associated vertebral fractures after denosumab discontinuation: systematic review and additional cases. J Bone Miner Res 32:1291–1296

    Article  CAS  PubMed  Google Scholar 

  8. Cummings SR, Ferrari S, Eastell R, Gilchrist N, Jensen JEB, McClung M, Roux C, Törring O, Valter I, Wang AT, Brown JP (2018) Vertebral fractures after discontinuation of Denosumab: a post hoc analysis of the randomized placebo-controlled FREEDOM trial and its extension. J Bone Miner Res 33:190–198

    Article  CAS  Google Scholar 

  9. Lamy O, Gonzalez-Rodriguez E (2018) Underestimation of vertebral fractures after denosumab discontinuation. J Bone Miner Res 33:547

    Article  PubMed  Google Scholar 

  10. Leder B (2018) An essential warning: editorial on vertebral fractures after discontinuation of denosumab: a post hoc analysis of the randomized placebo-controlled FREEDOM trial, its extension. J Bone Miner Res 33:188–189

    Article  PubMed  Google Scholar 

  11. Meier C, Uebelhart B, Aubry-Rozier B et al (2017) Osteoporosis drug treatment: duration and management after discontinuation. A position statement from the SVGO/ASCO. Swiss Med Wkly 147:w14484

    PubMed  Google Scholar 

  12. Tsourdi E, Langdahl B, Cohen-Solal M, Aubry-Rozier B, Eriksen EF, Guañabens N, Obermayer-Pietsch B, Ralston SH, Eastell R, Zillikens MC (2017) Discontinuation of denosumab therapy for osteoporosis: a systematic review and position statement by ECTS. Bone 105:11–17

    Article  Google Scholar 

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

  14. Anastasilakis AD, Yavropoulou MP, Makras P, Sakellariou GT, Papadopoulou F, Gerou S, Papapoulos SE (2017) Increased osteoclastogenesis in patients with vertebral fractures following discontinuation of denosumab treatment. Eur J Endocrinol 176:677–683

    Article  CAS  PubMed  Google Scholar 

  15. Gonzalez-Rodriguez E, Stoll D, Lamy O (2018) Raloxifene has no efficacy in reducing the high bone turnover and the risk of spontaneous vertebral fractures after denosumab discontinuation. Case Rep Rheumatol 5432751:1–4. https://doi.org/10.1155/2018/5432751

    Article  Google Scholar 

  16. Reid IR, Horne AM, Mihov B, Gamble GD (2017) Bone loss after denosumab: only partial protection with zoledronate. Calcif Tissue Int 101:371–374

    Article  CAS  PubMed  Google Scholar 

  17. Rosen CJ, Hochberg MC, Bonnick SL, McClung M, Miller P, Broy S, Kagan R, Chen E, Petruschke RA, Thompson DE, de Papp AE, Fosamax Actonel Comparison Trial Investigators (2005) Treatment with once-weekly alendronate 70 mg compared with once-weekly risedronate 35 mg in women with postmenopausal osteoporosis: a randomized double-blind study. J Bone Miner Res 20:141–151

    Article  CAS  PubMed  Google Scholar 

  18. Reid IR, Brown JP, Burckhardt P, Horowitz Z, Richardson P, Trechsel U, Widmer A, Devogelaer JP, Kaufman JM, Jaeger P, Body JJ, Brandi ML, Broell J, di Micco R, Genazzani AR, Felsenberg D, Happ J, Hooper MJ, Ittner J, Leb G, Mallmin H, Murray T, Ortolani S, Rubinacci A, Sääf M, Samsioe G, Verbruggen L, Meunier PJ (2002) Intravenous zoledronic acid in postmenopausal women with low bone mineral density. N Engl J Med 346:653–661

    Article  CAS  PubMed  Google Scholar 

  19. Uebelhart B, Rizzoli R, Ferrari SL (2017) Retrospective evaluation of serum CTX levels after denosumab discontinuation in patients with or without prior exposure to bisphosphonates. Osteoporos Int 28:2701–2705

    Article  CAS  PubMed  Google Scholar 

  20. Anastasilakis AD, Tournis S, Yavropoulou MP, Polyzos SA, Makras P (2018) Multiple vertebral fractures following denosumab discontinuation: are we exaggerating? Calcif Tissue Int 103:107–108

    Article  CAS  PubMed  Google Scholar 

  21. Tsourdi E, Zillikens MC (2018) Certainties and uncertainties about denosumab discontinuation. Calcif Tissue Int 103:1–4

    Article  CAS  PubMed  Google Scholar 

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Lamy, O., Fernández-Fernández, E., Monjo-Henry, I. et al. Alendronate after denosumab discontinuation in women previously exposed to bisphosphonates was not effective in preventing the risk of spontaneous multiple vertebral fractures: two case reports. Osteoporos Int 30, 1111–1115 (2019). https://doi.org/10.1007/s00198-018-04820-8

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  • DOI: https://doi.org/10.1007/s00198-018-04820-8

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