Risk factors for vertebral fractures and bone loss after denosumab discontinuation: a real-world observational study

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Everts-Graber, J.¹; Reichenbach, S.^2,3; Gahl, B.⁴; Ziswiler, H.R.¹; Studer, U.¹; Lehmann, T.¹

Risk factors for vertebral fractures and bone loss after denosumab discontinuation: a real-world observational study

Bone. March 2021;144:115830

©2020 Elsevier Inc. All rights reserved.

Affiliations

¹OsteoRheuma Bern, Bahnhofplatz 1, Bern, Switzerland

²Department of Rheumatology, Immunology and Allergology, University Hospital, Bern, Switzerland

³Institute for Social and Preventive Medicine, University of Bern, Switzerland

⁴Clinical Trial Unit (CTU) Bern, University of Bern, Switzerland
Abstract and keywords

Background: Denosumab discontinuation without subsequent bisphosphonates (BPs) is associated with bone loss and multiple vertebral fractures.

Objective: Identifying risk factors for bone loss and vertebral fractures after denosumab discontinuation.

Methods: This retrospective study measured the outcome of 219 women with osteoporosis who discontinued denosumab treatment and received subsequent treatment with zoledronate, other BPs or a selective estrogen receptor modulator (SERM), or no therapy. Fracture rate, longitudinal bone mineral density (BMD) changes and bone turnover markers (BTMs) within 2 years after denosumab discontinuation were analysed. Linear regression analysis evaluated loss of BMD and age, BMI (kg/m2), denosumab treatment duration, pre-treatment, prior fracture state, baseline T-scores, use of glucocorticoids or aromatase inhibitors and BMD gains under denosumab therapy.

Results: 171 women received zoledronate after denosumab discontinuation, 26 had no subsequent treatment and 22 received other therapies (other BPs or a SERM). Zoledronate was associated with the fewest vertebral fractures (hazard ratio 0.16, p = 0.02) and all subsequent therapies retained BMD at all sites to some extent. Higher BMD loss was associated with younger age, lower BMI, longer denosumab treatment, lack of prior antiresorptive treatment and BMD gain under denosumab treatment. BTM levels correlated with denosumab treatment duration and bone loss at the total hip, but not the lumbar spine.

Conclusions: Compared to no subsequent therapy, zoledronate was associated with fewer vertebral fractures after denosumab. Further, BMD loss depended on denosumab treatment duration, age, prior BP therapy and BMD gain under denosumab therapy, whereas BTM levels were associated with bone loss at the total hip and denosumab treatment duration.

Keywords: Denosumab; Discontinuation; Fracture; Osteoporosis; Bisphosphonates
Links

DOI: 10.1016/j.bone.2020.115830

PubMed: 33359006

WoS: 000615747100001
History

Received: 2020-05-25

Revised: 2020-12-17

Accepted: 2020-12-17

Online: 2020-12-26

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Cited By (6)

Year	Entry
2022	Everts-Graber J, Reichenbach S, Gahl B, Häuselmann H, Ziswiler H-R, Studer U, Lehmann T. Effects of zoledronate on bone mineral density and bone turnover after long-term denosumab therapy: observations in a real-world setting. Bone. October 2022;163:116498.
2023	Liebich G, Lamy O, Aubry-Rozier B, Gonzalez-Rodriguez E. Maintenance of bone resorption markers in the low premenopausal range during the year following denosumab discontinuation is associated to bone density preservation: the ReoLaus study. Bone. July 2023;172:116764.
2023	Cruchelow KR, Peter ME, Chakrabarti A, Gipson HM, Gregory WT, DeClercq J, Choi L, Tanner SB. Denosumab treatment lapses, discontinuation, and off-treatment fracture risk: a retrospective study of patients with osteoporosis in a real-world clinical setting. Bone. December 2023;177:116925.
2022	Everts-Graber J, Lehmann D, Burkard J-P, Schaller B, Gahl B, Häuselmann H, Studer U, Ziswiler H-R, Reichenbach S, Lehmann T. Risk of osteonecrosis of the jaw under denosumab compared to bisphosphonates in patients with osteoporosis. J Bone Miner Res. February 2022;37(2):340-348.
2022	Everts-Graber J, Burkhard J-P, Schaller B, Reichenbach S, Lehmann T. Reply to potential issues with the use of teriparatide after denosumab-related osteonecrosis of the jaw. J Bone Miner Res. October 2022;37(10):2046-2047.
2022	Cosman F, Huang S, McDermott M, Cummings SR. Multiple vertebral fractures after denosumab discontinuation: FREEDOM and FREEDOM extension trials additional post hoc analyses. J Bone Miner Res. November 2022;37(11):2112-2120.