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. 2023 Mar;34(3):573-584.
doi: 10.1007/s00198-022-06648-9. Epub 2023 Jan 5.

Bone loss after denosumab discontinuation is prevented by alendronate and zoledronic acid but not risedronate: a retrospective study

Teerapat Tutaworn  1   2 , Jeri W Nieves  1   3 , Zhaorui Wang  4 , Justin E Levin  1 , Jae E Yoo  1 , Joseph M Lane  5   6   7
Affiliations

Bone loss after denosumab discontinuation is prevented by alendronate and zoledronic acid but not risedronate: a retrospective study

Teerapat Tutaworn et al. Osteoporos Int. 2023 Mar.

Abstract

A retrospective study of 121 patients who stopped denosumab (Dmab) then received no treatment (NT), risedronate (RIS), alendronate (ALN), or zoledronic acid (ZOL). Bone density (spine and hip) during and after Dmab discontinuation was measured. Treatment with ALN or ZOL, not NT and RIS, mitigated BMD loss after Dmab discontinuation.

Introduction: Denosumab (Dmab) discontinuation is associated with bone loss and multiple vertebral fractures. The purpose was to compare bone mineral density (BMD) change in patients following Dmab discontinuation with no subsequent treatment (NT) and three bisphosphonate (BP) treatments: risedronate (RIS), alendronate (ALN), and zoledronic acid (ZOL).

Methods: In a review of 121 patients aged 71.2 ± 8.1 years, discontinuing Dmab (mean 5.4 doses), 33 received NT and 88 received BP (22 RIS; 34 ALN; 32 ZOL). BMD change after 1 year was compared between groups at the lumbar spine (LS), femoral neck (FN), and total hip (TH). Risk factors for bone loss after Dmab discontinuation were compared between groups and incidence of vertebral fractures was determined.

Results: Following Dmab discontinuation, LS mean change (g/cm2; 95% CI) was for NT: - 0.041 (- 0.062 to - 0.021); RIS: - 0.035 (- 0.052 to - 0.017); ALN: - 0.005 (- 0.020 to 0.009); and ZOL: - 0.009 (- 0.025 to 0.008). Differences in LS were found between NT and ALN (p = 0.015), and NT and ZOL (p=0.037), but not between NT and RIS. The only significant difference in TH was found between NT and ZOL (p 0.034) with no group differences in FN. BMD gains during Dmab treatment were associated with BMD loss after Dmab discontinuation. In a subset, discontinuation after Dmab treatment (> 5 doses) followed by ALN (n = 22) and ZOL (n = 11) showed no difference in BMD. Five of 7 vertebral fractures occurred after Dmab discontinuation in NT.

Conclusion: Subsequent treatment with ALN or ZOL but not NT and RIS mitigates BMD loss after Dmab discontinuation.

Keywords: Bisphosphonates; Bone mineral density; Denosumab; Discontinuation; Osteoporosis; Subsequent treatment.

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Conflict of interest statement

ZW, JEL, and JEY have nothing to declare. TT has received a speaker honorarium from Amgen. JWN has received study medication from Eli Lilly and Radius. JML was paid as a consultant from ON Foundation, Kuros, Lenoss, Radius Health, Merck, Terumo BCT, and Mesentech. JML has received a research support from Merck, Novartis, and Radius Health. JML is a board member/committee appointment of ON Foundation, UCB/Amgen, and Lenoss.

Figures

Fig. 1
Fig. 1
The study flowchart. Dmab, denosumab; DXA, dual-energy X-ray absorptiometry; BP, bisphosphonates
Fig. 2
Fig. 2
Absolute change (mean ± SEM) in LS, FN, and TH BMD during denosumab treatment and after receiving no subsequent therapy or received subsequent treatment with risedronate, alendronate, or zoledronic acid. DXA1 (baseline), BMD at the time of Dmab initiation; DXA2-DXA1, BMD gained during Dmab treatment; DXA3-DXA1, BMD after Dmab discontinuation (± subsequent therapy) when compared to DXA1 (baseline); SEM, standard error of the mean; LS, lumbar spine; FN, femoral neck; TH, total hip; BMD, bone mineral density; DXA, dual-energy X-ray absorptiometry; Dmab, denosumab. Differences were compared using paired t-tests. *Significant change when compared to Dmab initiation (*p value < 0.05; **p value < 0.01; ***p value < 0.001). #Significant change when compared to Dmab discontinuation (#p value < 0.05; # #p value < 0.01)
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References

    1. Cummings SR, San Martin J, McClung MR, et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med. 2009;361:756–765. doi: 10.1056/NEJMoa0809493. - DOI - PubMed
    1. Bone HG, Wagman RB, Brandi ML, et al. 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. 2017;5:513–523. doi: 10.1016/s2213-8587(17)30138-9. - DOI - PubMed
    1. McClung MR, Wagman RB, Miller PD, Wang A, Lewiecki EM. Observations following discontinuation of long-term denosumab therapy. Osteoporos Int. 2017;28:1723–1732. doi: 10.1007/s00198-017-3919-1. - DOI - PMC - PubMed
    1. Zanchetta MB, Boailchuk J, Massari F, Silveira F, Bogado C, Zanchetta JR. Significant bone loss after stopping long-term denosumab treatment: a post FREEDOM study. Osteoporos Int. 2018;29:41–47. doi: 10.1007/s00198-017-4242-6. - DOI - PubMed
    1. Miller PD, Bolognese MA, Lewiecki EM, McClung MR, Ding B, Austin M, Liu Y, San Martin J. 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;43:222–229. doi: 10.1016/j.bone.2008.04.007. - DOI - PubMed

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