A Single Infusion of Zoledronate in Postmenopausal Women Following Denosumab Discontinuation Results in Partial Conservation of Bone Mass Gains

Everts‐Graber, Judith; Reichenbach, Stephan; Ziswiler, Hans‐Rudolf; Studer, Ueli; Lehmann, Thomas

doi:10.1002/jbmr.3962

Cited by 77 publications

(58 citation statements)

References 27 publications

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“…An observational study including 120 postmenopausal women treated with DMAB for 2 to 3 years (81%) were given a single infusion of ZOL 5 mg 6 months after the last DMAB injection. ( 16 ) Six to 36 months after ZOL treatment BMD had decreased significantly by 3.3%, 2.2%, and 1.5%, at the spine, TH, and FN, respectively. CTX and P1NP measured in a subgroup ( n = 27) at the same time point were within the reference range.…”

Section: Discussionmentioning

confidence: 87%

“…Three case series, ( 10,14,15 ) an observational study, ( 16 ) and a clinical trial ( 17 ) have investigated the effect of treatment with ZOL subsequent to DMAB. Horne and colleagues ( 15 ) found that BMD gains obtained during treatment with romosozumab for 1 year and DMAB for 2 years (Fracture Study in Postmenopausal Women with Osteoporosis [FRAME]) were maintained in 73% to 87% of patients 12 months after receiving an infusion of ZOL 8 months (median) after discontinuing DMAB.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Treatment with Zoledronate Subsequent to Denosumab in Osteoporosis: a Randomized Trial

Sølling

Harsløf

Langdahl

2020

Journal of Bone and Mineral Research

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Discontinuing denosumab is associated with bone loss and possibly increased fracture risk. We investigated if treatment with zoledronate (ZOL) could prevent bone loss and if the timing of the ZOL infusion influenced the outcome. We report on a 2-year randomized, open label, interventional study including 61 patients with osteopenia, discontinuing denosumab after 4.6 AE 1.6 years. We administrated ZOL 6 months (6M group, n = 20) or 9 months (9M group, n = 20) after the last denosumab injection or when bone turnover had increased (OBS group, n = 21). We monitored the patients with DXA and bone turnover markers. Our primary endpoints were change in lumbar spine BMD (LSBMD) 6 months after ZOL and the proportion of patients who failed to maintain BMD. The study is ongoing (clinicaltrials.gov; NCT03087851). We included 61 participants and 59 patients completed follow-up 12 months after ZOL. Six months after ZOL, LSBMD had decreased significantly by (mean AE SE) 2.1% AE 0.9%, 4.3% AE 1.1%, and 3.0% AE 1.1% in the 6M, 9M, and OBS groups, respectively, and by 4.8% AE 0.7%, 4.1% AE 1.1%, and 4.7% AE 1.2% 12 months after ZOL in the 6M, 9M, and OBS groups, respectively (p < .02, no between-group differences). BMD loss above the least significant change was seen in all groups; at the spine: 6M, n = 6 (30%); 9M, n = 9 (45%); and OBS, n = 9 (47%); and at the total hip: 6M, n = 1 (5%); 9M, n = 5 (25%); and OBS, n = 2 (11%). In the 6M group p-crosslinked C-terminal telopeptide (p-CTX) decreased initially, but increased rapidly thereafter, and 6 months after ZOL, p-CTX was 0.60 AE 0.08 g/L. p-CTX increased rapidly in the 9M and OBS groups, was suppressed by ZOL but increased again thereafter; p-CTX was 0.47 AE 0.05 μg/L and 0.47 AE 0.05 μg/L in the 9M and OBS groups 6 months after ZOL, respectively. Incident vertebral fractures were seen in two women in the 9M group. Treatment with ZOL irrespective of the timing did not fully prevent loss of BMD in patients discontinuing denosumab.

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Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Treatment with Zoledronate Subsequent to Denosumab in Osteoporosis: a Randomized Trial

Sølling

Harsløf

Langdahl

2020

Journal of Bone and Mineral Research

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“…However, multiple vertebral fractures have been described in two patients provided with alendronate after treatment with denosumab for an average of 3.5 years . In comparison to oral bisphosphonate treatment, there is conflicting evidence regarding whether zoledronic acid can prevent rebound bone loss associated with denosumab discontinuation, with most data showing this potent antiresorptive agent to be less effective at maintaining BMD when previous denosumab treatment exceeded 2 years compared with a shorter duration of denosumab therapy . Furthermore, there is controversy over the optimal timing and dosing of bisphosphonate therapy after denosumab discontinuation, although ongoing randomized controlled trials are expected to shed more light into this matter.…”

Section: Pharmacologic Osteoporosis Treatmentmentioning

confidence: 99%

Osteoporosis Management in the Era of COVID-19

Tsourdi

Clarke

et al. 2020

Journal of Bone and Mineral Research

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Osteoporosis is a chronic condition that reflects reduced bone strength and an associated increased risk for fracture. As a chronic condition, osteoporosis generally requires sustained medical intervention(s) to limit the risks for additional bone loss, compromise of skeletal integrity, and fracture occurrence. Further complicating this issue is the fact that the abrupt cessation of some therapies can be associated with an increased risk for harm. It is in this context that the COVID-19 pandemic has brought unprecedented disruption to the provision of health care globally, including near universal requirements for social distancing. In this Perspective, we provide evidence, where available, regarding the general care of patients with osteoporosis in the COVID-19 era and provide clinical recommendations based primarily on expert opinion when data are absent. Particular emphasis is placed on the transition from parenteral osteoporosis therapies. It is hoped that these recommendations can be used to safely guide care for patients with osteoporosis until a return to routine clinical care standards is available.

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“…Regarding the timing of ZOL administration, it has been reported that after Dmab administration over 2 years, ZOL was administered after 191-353 days of the last Dmab administration and BMD obtained with Dmab could be maintained 1 year later [23]. In addition, after Dmab administration over 3 years, ZOL was administered after 6 months of the last Dmab administration, and BMD obtained with Dmab could be maintained 2.5 years later [25]. In our investigation, the transitional period from the last Dmab administration to the start of the ZOL administration was 277.8 days (from 182 to 495 days), according to the patients' convenience, and the timing of ZOL administration may have been delayed.…”

Section: Discussionmentioning

confidence: 99%

“…Sequential therapy with Alendronate (ALN) maintained BMD, if the period of Dmab administration was 1 year [ 22 ]. Sequential therapy with ZOL maintained BMD, if the periods of Dmab administration were 2, 2.2 and 3 years, respectively [ 23 – 25 ]. However, sequential therapy with ALN reduced BMD, if the period of Dmab administration was 3.5 years [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

Zoledronic acid sequential therapy could avoid disadvantages due to the discontinuation of less than 3-year denosumab treatment

Kondo¹,

Okimoto²,

Yoshioka

et al. 2020

J Bone Miner Metab

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Introduction Rapid descent in bone mineral density (BMD) and ascent in bone turnover marker (BTM) occur within the short period following denosumab (Dmab) discontinuation. In addition, the incidence of vertebral fracture also rises within the short period. The purpose of this study is to investigate the effects of sequential therapy using zoledronic acid (ZOL) on any adverse events after Dmab discontinuation. Materials and methods This study was a multicenter retrospective observational study, and the subjects were osteoporosis patients who visited our institutions between 2013 and 2018. We performed sequential therapy using ZOL for 30 patients who had difficulty continuing Dmab, due to physical or social reasons, and investigated the fracture incidence and BMD/ BTM changes at 4 time points (at the start of Dmab, the start of ZOL, 6 months after ZOL and 12 months after ZOL). Results No new vertebral/nonvertebral fractures were observed at each time point after switching from Dmab to ZOL in any of the 30 patients. The BMD/BTM changes were evaluated in 18 of the 30 cases, since all data of lumbar/femoral neck BMDs and TRACP-5b at 4 time points was only available in 18 cases. BMDs significantly increased at each time point compared with that at the start of Dmab. Serum TRACP-5b significantly decreased at each time point compared with that at the start of Dmab. Conclusion It was suggested that sequential therapy using ZOL could suppress the decrease of BMD, and increase of BTM, if the period of Dmab administration was less than 3 years.

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A Single Infusion of Zoledronate in Postmenopausal Women Following Denosumab Discontinuation Results in Partial Conservation of Bone Mass Gains

Abstract: This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process which may lead to differences between this version and the Version of Record. Please cite this article as

Cited by 77 publications

References 27 publications

Treatment with Zoledronate Subsequent to Denosumab in Osteoporosis: a Randomized Trial

Treatment with Zoledronate Subsequent to Denosumab in Osteoporosis: a Randomized Trial

Osteoporosis Management in the Era of COVID-19

Zoledronic acid sequential therapy could avoid disadvantages due to the discontinuation of less than 3-year denosumab treatment

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