Effects of zoledronate on bone mineral density and bone turnover after long-term denosumab therapy: Observations in a real-world setting.

Everts-Graber, Judith; Reichenbach, Stephan; Gahl, Brigitta; Häuselmann, HansJörg; Ziswiler, Hans-Rudolf; Studer, Ueli; Lehmann, Thomas (2022). Effects of zoledronate on bone mineral density and bone turnover after long-term denosumab therapy: Observations in a real-world setting. Bone, 163, p. 116498. Elsevier 10.1016/j.bone.2022.116498

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BACKGROUND

The rebound effect after denosumab discontinuation is lessened with subsequent zoledronate therapy. However, it is unclear whether this mitigation is sufficient after long-term denosumab treatment.

OBJECTIVE

This retrospective observational study analysed bone mineral density (BMD) and bone turnover marker (BTM) changes after denosumab therapy according to treatment duration and subsequent zoledronate regimen.

METHODS

We measured the outcomes of 282 women with postmenopausal osteoporosis who discontinued denosumab and received zoledronate 6 months later. In patients with longer denosumab therapy (≥5 years), BTMs were measured every 3 months and a second zoledronate infusion was administered if BTM levels increased by ≥2-fold. The BMD of all women was measured before denosumab therapy, at the last injection and 1 to 2 years after the first zoledronate.

RESULTS

Bone loss after switching from denosumab to zoledronate was higher in patients with 10 ± 2 denosumab injections (n = 84) compared to 5 ± 2 injections (n = 144, p < 0.001 for lumbar spine and femoral neck), but there was no further increase with treatment durations of ≥15 ± 2 injections (n = 54, p = 0.35 and p = 0.20, respectively). BTMs in patients with ≥10 denosumab injections were elevated 6 months after zoledronate in some patients, but not all. Twenty-four women received a second zoledronate dose 6 months after the first one. BTMs in these patients were subsequently lower, but bone loss at both the lumbar spine and hip was comparable to that in patients with only one zoledronate dose (p = 0.37 for lumbar spine and p = 0.97 for femoral neck).

CONCLUSIONS

Rebound-associated bone loss reached a plateau after denosumab treatment durations of 4-6 years, irrespective of the frequency of subsequent zoledronate therapy.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Department of Clinical Research (DCR)
04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Rheumatology and Immunology
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Social and Preventive Medicine (ISPM)

UniBE Contributor:

Everts-Graber, Judith, Reichenbach, Stephan, Gahl, Brigitta

Subjects:

600 Technology > 610 Medicine & health
300 Social sciences, sociology & anthropology > 360 Social problems & social services

ISSN:

8756-3282

Publisher:

Elsevier

Language:

English

Submitter:

Pubmed Import

Date Deposited:

28 Jul 2022 09:49

Last Modified:

20 Feb 2024 14:15

Publisher DOI:

10.1016/j.bone.2022.116498

PubMed ID:

35882310

Uncontrolled Keywords:

Denosumab Discontinuation Osteoporosis Rebound Zoledronate

BORIS DOI:

10.48350/171566

URI:

https://boris.unibe.ch/id/eprint/171566

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