Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 Feb;21(1):95-103.
doi: 10.1007/s11914-022-00771-6. Epub 2022 Dec 24.

Denosumab Discontinuation

Anne Sophie Sølling  1   2 , Elena Tsourdi  3 , Torben Harsløf  1 , Bente L Langdahl  4
Affiliations
Review

Denosumab Discontinuation

Anne Sophie Sølling et al. Curr Osteoporos Rep. 2023 Feb.

Abstract

Purpose of review: To review the pathophysiology, the clinical consequences as well as way of mitigating the effects of denosumab discontinuation.

Recent findings: Treatment with denosumab (DMAB) is reversible and upon discontinuation there is a rapid increase in bone turnover and a subsequent bone loss. During this phase of high bone turnover, an increased risk of fractures has been reported. Therefore, treatment with DMAB could be considered life-long. However, side-effects may prompt the need for discontinuation and moreover, treatment with DMAB may have increased BMD to levels where continuing treatment does not provide further fracture risk reduction. Patients stopping DMAB should be offered subsequent antiresorptive treatment with an intense monitoring regimen during the initial year as most of the bone loss occurs within these initial 12 months. In this review, we evaluated the literature published over the past 1 to 3 years investigating DMAB withdrawal with focus on bone turnover markers, bone mineral density, and fracture risk and the transition to other anti-osteoporosis therapies. Furthermore, we summarized the current recommendations of international guidelines. In this review, we evaluated the literature published over the past 1 to 3 years investigating denosumab (DMAB) discontinuation and the transition to other anti-osteoporosis therapies. Additionally, we summarized the current recommendations of international guidelines.

Keywords: Bone mineral density; Bone turnover markers; Denosumab; Fracture; Osteoporosis.

PubMed Disclaimer

References

Papers of particular interest, published recently, have been highlighted as: • Of importance
    1. Lacey DL, Boyle WJ, Simonet WS, Kostenuik PJ, Dougall WC, Sullivan JK, Martin JS, Dansey R. Bench to bedside: elucidation of the OPG-RANK-RANKL pathway and the development of denosumab. Nat. Rev. Drug Discov. 2012;11(5):401–19. - PubMed - DOI
    1. 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. 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(7):513–23. - PubMed - DOI
    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(2):222–9. - PubMed - DOI
    1. • Bone HG, et al. 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. 2011;96(4):972–80. Describes the overshoot bone turnover and bone loss following discontinuation of denosumab - PubMed - DOI
    1. Anastasilakis AD, Polyzos SA, Makras P, Aubry-Rozier B, Kaouri S, Lamy O. Clinical Features of 24 Patients With Rebound-Associated Vertebral Fractures After Denosumab Discontinuation: Systematic Review and Additional Cases. J Bone Min. Res. 2017;32(6):1291–6. - DOI