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J Bone Miner Res. 2019 Aug 21. doi: 10.1002/jbmr.3853. [Epub ahead of print]

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

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Department of Endocrinology, 424 General Military Hospital, Thessaloniki, Greece.
Center for Bone Quality, Department of Internal Medicine, section Endocrinology, Leiden University Medical Center, Leiden, The Netherlands.
First Department of Pharmacology, Faculty of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece.
Department of Endocrinology and Diabetes and Department of Medical Research, 251 Hellenic Air Force & VA General Hospital, Athens, Greece.


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 zoledronate 5 mg infusion (n = 27) or two additional denosumab 60 mg injections (n = 30). Both groups were followed for a total period of 24 months. At 24 months LS-BMD was not different from baseline in the ZOL group, but decreased in the Dmab group by 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 FN-BMD changes were similar. Zoledronate 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 denosumab 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 denosumab group, 3 patients sustained vertebral fractures (2 patients multiple clinical, 1 patient morphometric) while 1 patient in the zoledronate group sustained clinical vertebral fractures 12 months after the infusion. In conclusion, a single intravenous infusion of zoledronate given 6 months after the last Dmab injection prevents bone loss for at least two years independently of the rate of bone turnover. Follow-up is recommended, as in a few patients ZOL treatment might not have the expected effect at 2 years. This article is protected by copyright. All rights reserved.


Denosumab; bone mineral density; discontinuation; osteoporosis; vertebral fractures; zoledronic acid


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