Zoledronic Acid to Maintain Bone Mass After Denosumab Discontinuation (AfterDmab)

The Effect of Zoledronic Acid Infusion in the Bone Loss Observed Following Denosumab Discontinuation in Postmenopausal Women With Low Bone Mass

In contrast with bisphosphonates,discontinuation of denosumab results in gradual loss of bone mineral density gains. The investigators aim to evaluate whether in patients treated with denosumab, a single zoledronic acid infusion would prevent the anticipated bone loss.

Discontinuation of denosumab results in a rebound rise of bone turnover markers and gradual loss of the achieved bone mineral density gains. In contrast, bisphosphonates, such as zoledronic acid, remain within the skeleton acting for several months or even years after discontinuation while maintaining bone mineral density despite the cessation of treatment. In this study, the investigators aim to evaluate changes in bone mineral density of the lumbar spine and the femoral neck, as well as in bone turnover markers one year after treatment discontinuation both in denosumab-treated women and in denosumab-treated women who switched to zoledronic acid infusion one year before treatment discontinuation.

Patients with low bone mass, being treated only with denosumab in the past, who will receive another year of treatment with denosumab and subsequently discontinue treatment for one year

Patients with low bone mass, being treated only with denosumab in the past, who will receive a single infusion of zoledronic acid and subsequently discontinue treatment for another year

Treatment of low bone mass with subcutaneous injections of denosumab 60 mg every 6 months for one year

differences between the 2 arms in the changes of lumbar spine bone mineral density measured by dual-energy X-ray absorptiometry

differences between the 2 arms in the changes of femoral neck bone mineral density measured by dual-energy X-ray absorptiometry

differences between the 2 arms in the changes of lumbar spine bone mineral density measured by dual-energy X-ray absorptiometry

differences between the 2 arms in the changes of femoral neck bone mineral density measured by dual-energy X-ray absorptiometry

Inclusion Criteria: postmenopausal women osteopenic (T-score > -2.5 but < -1.0) after treatment with denosumab Exclusion Criteria: secondary osteoporosis; diseases that could affect bone metabolism; medications that could affect bone metabolism; history of any antiosteoporotic treatment other than denosumab prior to randomization severe liver or kidney disease (creatinine clearance < 60ml/min/1.73m2)

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Bone HG, Bolognese MA, Yuen CK, Kendler DL, Miller PD, Yang YC, Grazette L, San Martin J, Gallagher JC. Effects of denosumab treatment and discontinuation on bone mineral density and bone turnover markers in postmenopausal women with low bone mass. J Clin Endocrinol Metab. 2011 Apr;96(4):972-80. doi: 10.1210/jc.2010-1502. Epub 2011 Feb 2.

Black DM, Bauer DC, Schwartz AV, Cummings SR, Rosen CJ. Continuing bisphosphonate treatment for osteoporosis--for whom and for how long? N Engl J Med. 2012 May 31;366(22):2051-3. doi: 10.1056/NEJMp1202623. Epub 2012 May 9. No abstract available.

Whitaker M, Guo J, Kehoe T, Benson G. Bisphosphonates for osteoporosis--where do we go from here? N Engl J Med. 2012 May 31;366(22):2048-51. doi: 10.1056/NEJMp1202619. Epub 2012 May 9. No abstract available.

Anastasilakis AD, Polyzos SA, Yavropoulou MP, Appelman-Dijkstra NM, Ntenti C, Mandanas S, Papatheodorou A, Makras P. Comparative Effect of Zoledronate at 6 Versus 18 Months Following Denosumab Discontinuation. Calcif Tissue Int. 2021 May;108(5):587-594. doi: 10.1007/s00223-020-00785-1. Epub 2021 Jan 2.