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Published in: Osteoporosis International 5/2019

01-05-2019 | Bisphosphonate | Case Report

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

Authors: O. Lamy, E. Fernández-Fernández, I. Monjo-Henry, D. Stoll, B. Aubry-Rozier, D. Benavent-Núñez, P. Aguado, E. Gonzalez-Rodriguez

Published in: Osteoporosis International | Issue 5/2019

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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.
Literature
1.
go back to reference 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 361:756–765CrossRef 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 361:756–765CrossRef
2.
go back to reference 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 5:513–523CrossRefPubMed 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 5:513–523CrossRefPubMed
3.
go back to reference 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 96:972–980CrossRefPubMed 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 96:972–980CrossRefPubMed
5.
go back to reference 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 102:354–358CrossRefPubMed 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 102:354–358CrossRefPubMed
6.
go back to reference McClung MR, Wagman RB, Miller PD, Wang A, Lewiecki EM (2017) Observations following discontinuation of long-term denosumab therapy. Osteoporos Int 28:1723–1732CrossRefPubMedPubMedCentral McClung MR, Wagman RB, Miller PD, Wang A, Lewiecki EM (2017) Observations following discontinuation of long-term denosumab therapy. Osteoporos Int 28:1723–1732CrossRefPubMedPubMedCentral
7.
go back to reference 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 32:1291–1296CrossRefPubMed 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 32:1291–1296CrossRefPubMed
8.
go back to reference 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 33:190–198CrossRef 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 33:190–198CrossRef
9.
go back to reference Lamy O, Gonzalez-Rodriguez E (2018) Underestimation of vertebral fractures after denosumab discontinuation. J Bone Miner Res 33:547CrossRefPubMed Lamy O, Gonzalez-Rodriguez E (2018) Underestimation of vertebral fractures after denosumab discontinuation. J Bone Miner Res 33:547CrossRefPubMed
10.
go back to reference 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 33:188–189CrossRefPubMed 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 33:188–189CrossRefPubMed
11.
go back to reference 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:w14484PubMed 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:w14484PubMed
12.
go back to reference 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 105:11–17CrossRef 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 105:11–17CrossRef
14.
go back to reference 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 176:677–683CrossRefPubMed 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 176:677–683CrossRefPubMed
16.
go back to reference Reid IR, Horne AM, Mihov B, Gamble GD (2017) Bone loss after denosumab: only partial protection with zoledronate. Calcif Tissue Int 101:371–374CrossRefPubMed Reid IR, Horne AM, Mihov B, Gamble GD (2017) Bone loss after denosumab: only partial protection with zoledronate. Calcif Tissue Int 101:371–374CrossRefPubMed
17.
go back to reference 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 20:141–151CrossRefPubMed 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 20:141–151CrossRefPubMed
18.
go back to reference 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 346:653–661CrossRefPubMed 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 346:653–661CrossRefPubMed
19.
go back to reference 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 28:2701–2705CrossRefPubMed 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 28:2701–2705CrossRefPubMed
20.
go back to reference Anastasilakis AD, Tournis S, Yavropoulou MP, Polyzos SA, Makras P (2018) Multiple vertebral fractures following denosumab discontinuation: are we exaggerating? Calcif Tissue Int 103:107–108CrossRefPubMed Anastasilakis AD, Tournis S, Yavropoulou MP, Polyzos SA, Makras P (2018) Multiple vertebral fractures following denosumab discontinuation: are we exaggerating? Calcif Tissue Int 103:107–108CrossRefPubMed
21.
go back to reference Tsourdi E, Zillikens MC (2018) Certainties and uncertainties about denosumab discontinuation. Calcif Tissue Int 103:1–4CrossRefPubMed Tsourdi E, Zillikens MC (2018) Certainties and uncertainties about denosumab discontinuation. Calcif Tissue Int 103:1–4CrossRefPubMed
Metadata
Title
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
Authors
O. Lamy
E. Fernández-Fernández
I. Monjo-Henry
D. Stoll
B. Aubry-Rozier
D. Benavent-Núñez
P. Aguado
E. Gonzalez-Rodriguez
Publication date
01-05-2019
Publisher
Springer London
Published in
Osteoporosis International / Issue 5/2019
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-018-04820-8

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