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Osteoporosis: Can zoledronate prevent bone loss in patients discontinuing denosumab?

Key clinical point: Treatment with zoledronate (ZOL) irrespective of the timing did not fully prevent loss of bone mineral density (BMD) in patients with osteopenia who discontinued long-term treatment with denosumab.

Major finding: Lumbar spine BMD decreased significantly by 2.1 ± 0.9% (mean ± standard of the mean), 4.3 ± 1.1%, and 3.0 ± 1.1% at 6 months after ZOL and by 4.8 ± 0.7%, 4.1 ± 1.1%, and 4.7 ± 1.2% at 12 months after ZOL in patients who received ZOL at 6 months (n=20), 9 months (n=20) after the last denosumab injection, and when bone turnover had increased (n=21), respectively (P less than .02; no between-group differences).

Study details: The data come from a 2-year randomized, open-label, interventional study of 61 patients with osteopenia who discontinued denosumab after 4.6 ± 1.6 years.

Disclosures: The authors disclosed financial support from Amgen, The Danish Osteoporosis Society, P. Carl Petersen’s Foundation, Torkil Steenbeck’s Foundation, Vilhelm Pedersen and wife’s Foundation, and Aarhus University during the conduct of the study.


“Because denosumab discontinuation has been associated with loss of gains in bone mineral density and increased risk of vertebral fracture, administration of an alternative therapy upon denosumab discontinuation has been recommended. However, the choice of medication and the exact timing of its administration has not been defined. This open-label, randomized interventional included 61 patients with osteopenia who discontinued denosumab after 4.6 ± 1.6 years. Zoledronate was administered either at 6 months or 9 months after the last denosumab injection or when bone turnover, measured using p-carboxy-terminal collagen cross-links (p-CTX) increased.

At 6 and 12 months post zoledronate, the lumbar spine BMD decreased significantly in all three groups. Thus, one infusion of zoledronate was not sufficient to maintain suppression of p-CTX and completely prevent bone loss in any group. Compared to the other 2 groups, in the group who received zoledronate 6 months after denosumab, initial rapid bone loss was avoided, but eventually p-CTX increased. Further studies are needed to determine whether a second dose of zoledronate administered at 3-6 months interval may mitigate bone loss after denosumab discontinuation.”

Maria I. Danila, MD, MSc, MSPH

University of Alabama at Birmingham


Sølling AS et al. J Bone Miner Res. 2020 May 27. doi: 10.1002/jbmr.4098.