Discontinuation of Denosumab therapy for osteoporosis: A systematic review and position statement by ECTS

Tsourdi, Elena; Langdahl, Bente; Cohen‐Solal, Martine; Aubry‐Rozier, Bérengère; Eriksen, Erik Fink; Guañabens, Núria; Obermayer–Pietsch, Barbara; Ralston, Stuart H.; Eastell, Richard; Zillikens, M. Carola

doi:10.1016/j.bone.2017.08.003

Cited by 410 publications

(283 citation statements)

References 38 publications

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“…This is attributed to an increase in bone turnover above pretreatment values, a response described as “rebound phenomenon” probably due to upregulation of osteoclastogenesis . To prevent this sequence of events, it is recommended that patients discontinuing Dmab therapy should be administered bisphosphonates . These recommendations are mainly based on theoretical considerations of the pharmacodynamics of Dmab and bisphosphonates and limited, inconsistent evidence of clinical studies.…”

Section: Introductionmentioning

confidence: 99%

Zoledronate for the Prevention of Bone Loss in Women Discontinuing Denosumab Treatment. A Prospective 2-Year Clinical Trial

Anastasilakis

Papapoulos

Polyzos

et al. 2019

Journal of Bone and Mineral Research

119

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Cessation of denosumab treatment is associated with increases in bone turnover above baseline values and rapid bone loss. We investigated the efficacy of zoledronate to prevent this bone loss in women with postmenopausal osteoporosis who were treated with denosumab (mean duration 2.2 years) and discontinued treatment after achieving osteopenia. Women were randomized to receive a single 5‐mg infusion of zoledronate (ZOL) (n = 27) or two additional 60‐mg injections of denosumab (Dmab) (n = 30). Both groups were followed for a total period of 24 months. At 24 months lumbar spine–bone mineral density (LS‐BMD) was not different from baseline in the ZOL group, but decreased in the Dmab group by (mean ± SD) 4.82% ± 0.7% (p < 0.001) from the 12‐month value; the difference in BMD changes between the two groups, the primary endpoint of the study, was statistically significant (p = 0.025). Results of femoral neck (FN)‐BMD changes were similar. ZOL infusion was followed by small but significant increases in serum procollagen type 1 N‐terminal propeptide (P1NP) and C‐terminal telopeptide of type 1 collagen (CTX) during the first year and stabilization thereafter. In the Dmab group, bone turnover marker values did not change during the first 12 months but increased significantly at 15 months and in the majority of women these remained elevated at 24 months. Neither baseline nor 12‐month bone turnover marker values were associated with BMD changes in either group of women. In the Dmab group, three patients sustained vertebral fractures (two patients multiple clinical, one patient morphometric) whereas one patient in the ZOL group sustained clinical vertebral fractures 12 months after the infusion. In conclusion, a single intravenous infusion of ZOL given 6 months after the last Dmab injection prevents bone loss for at least 2 years independently of the rate of bone turnover. Follow‐up is recommended, because in a few patients ZOL treatment might not have the expected effect at 2 years. © 2019 American Society for Bone and Mineral Research.

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Section: Introductionmentioning

confidence: 99%

Zoledronate for the Prevention of Bone Loss in Women Discontinuing Denosumab Treatment. A Prospective 2-Year Clinical Trial

Anastasilakis

Papapoulos

Polyzos

et al. 2019

Journal of Bone and Mineral Research

119

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“…Because denosumab appears to be efficacious for up to 10 years, (10) an option that could be considered in patients who remain at very high risk of fragility fracture is to continue denosumab therapy beyond the 5-year time point, despite the fact that the incidence rate of atypical fracture after extended denosumab, while low, is currently difficult to precisely define (of note, similar recommendations were recently suggested in a position statement of the European Calcified Tissue Society). (11) Conversely, in patients in whom discontinuing therapy is desired, an intervening course of antiresorptive therapy should probably become the standard of care, despite only limited available evidence of the effectiveness of such an approach at present. (12,13) Although there are no comparative efficacy trials to suggest which antiresorptive is optimal to use after denosumab, given the relative potency of the various agents and their mechanisms of action, bisphosphonates should be strongly considered in patients without a contraindication.…”

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confidence: 99%

An Essential Warning

Leder

2017

Journal of Bone and Mineral Research

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“…More recently, denosumab was shown to increase BMD and reduce fractures into a great extent . However, discontinuation of denosumab in patients with osteoporosis or vertebral fractures is associated with a strong decrease in BMD, exceeding the initial increase in BMD shown over a period of 7–10 years, and an increased risk of vertebral fractures . Therefore, denosumab should not be stopped in these patients without considering alternative treatment.…”

Section: Discussionmentioning

confidence: 99%

Assessment and management of bone health in women with early breast cancer receiving endocrine treatment in the DATA study

Hellemond

Smorenburg

Peer³

et al. 2019

Intl Journal of Cancer

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The phase III DATA study investigates the efficacy of adjuvant anastrozole (6 vs. 3 year) in postmenopausal women with breast cancer previously treated with 2–3 years of tamoxifen. This planned side‐study assessed patterns of care regarding detection and treatment of osteopenia/osteoporosis, and trends in bone mineral density (BMD) during and after therapy. We registered all BMD measurements and bisphosphonate‐use. Time to osteopenia/osteoporosis was analysed by Kaplan Meier methodology. For the trend in T‐scores we used linear mixed models with random patients effects. Of 1860 eligible DATA patients, 910 (48.9%) had a baseline BMD measurement. Among patients with a normal baseline BMD (n = 417), osteopenia was observed in 53.5% and 55.4% in the 6‐ and 3‐year group respectively (p = 0.18), during follow‐up. Only two patients (3‐year group) developed osteoporosis. Of the patients with osteopenia at baseline (n = 408), 24.4% and 20.4% developed osteoporosis respectively (p = 0.89). Three years after randomisation 18.3% and 18.2% used bisphosphonates in the 6‐ and 3‐year groups respectively and 6 years after randomisation this was 23.7% and 20.9% respectively (p = 0.90) of which the majority used oral bisphosphonates. The yearly mean BMD‐change during anastrozole in the lumbar spine showed a T‐score decline of 0.075. After bisphosphonate addition the decline became less prominent (0.047 (p < 0.001)) and after anastrozole cessation, while continuing bisphosphonates, the mean BMD yearly increased (0.047 (p < 0.001)). In conclusion, extended anastrozole therapy was not associated with a higher incidence of osteoporosis. Anastrozole‐use was associated with a BMD decrease; however, the decline was modest and partially reversible after anastrozole cessation.

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Discontinuation of Denosumab therapy for osteoporosis: A systematic review and position statement by ECTS

Cited by 410 publications

References 38 publications

Zoledronate for the Prevention of Bone Loss in Women Discontinuing Denosumab Treatment. A Prospective 2-Year Clinical Trial

Zoledronate for the Prevention of Bone Loss in Women Discontinuing Denosumab Treatment. A Prospective 2-Year Clinical Trial

An Essential Warning

Assessment and management of bone health in women with early breast cancer receiving endocrine treatment in the DATA study

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