Bone health

New guidelines recommend zoledronate after denosumab withdrawal

Tuesday, 15 Sep 2020

Prof Bente Langdahl

Osteoporosis patients who discontinue denosumab therapy after long term use should be treated with zoledronate to prevent a rebound increase in bone turnover and a rapid bone loss, new guidelines advise.

The new advice from the European Calcified Tissue Society (ECTS) follows the publication of data from the ZOLARMAB trial, which investigated the effects of zoledronate in 61 patients with osteopenia who were discontinuing denosumab after an average of 4.6 years.

Presented at the ASBMR 2020 virtual meeting, the findings showed that there was some degree of bone mineral density loss regardless of whether zoledronate was administrated six or nine months after the last denosumab injection or based on when bone turnover (CTX levels) had increased.

Two years after the initial zoledronate dose, the average bone loss at the spine and hip were 4.2% and 3.8% respectively, without any difference between zoledronate regimens.

The study also showed that longer duration of denosumab treatment was associated with higher bone turnover at baseline and higher risk of bone loss after discontinuation.

Speaking at ASBMR, study co-investigator and past president of ECTS, Professor Bente Langdahl, said these findings and others had resulted in a revised position statement on denosumab discontinuation from the society. The new advice states that bone loss should be expected after stopping long term treatment, and therefore the aim should be to achieve higher BMD before considering stopping denosumab.

Professor Langdahl, an endocrinologist at Aarhus University Hospital, explained that the revised advice is that oral bisphosphonates may be considered to prevent the bone loss in patients who have been treated with denosumab for a short duration, whereas zoledronate is recommended for patients who have been on denosumab for longer periods.

“If your patient has been treated short term, up to two years, you could give alendronate for one to two years and monitor the response with CTX. If the patient cannot tolerate alendronate then you can give one infusion of zoledronate instead,” she said.

“However if the patients has been treated longer term with denosumab, for more than two years, we would suggest giving an infusion of zoledronate six months after the last denosumab injection.”

The new position statement also recommends monitoring the response with CTX after three, six and 12 months. If CTX again increases above the premenopausal reference, zoledronate should  be repeated. And if unable to monitor CTX, clinicians are advised to give two infusion of zoledronate six months apart.

Professor Langdahl said the revised statement, which replace the previous 2017 ECTS guidelines are under consideration for  publication in the Journal of Clinical Endocrinology and Metabolism.

In her ASBMR presentation, Professor Langdahl said the focus in osteoporosis prevention is now on sequential therapy with the evidence increasingly favouring initial treatment with a bone forming (anabolic) agent or dual action agent such as romosuzumab to achieve high BMD, followed by maintenance therapy with an anti-resorptive agent.

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