The Joint Annual Scientific Meetings of the Endocrine Society of Australia and the Society for Reproductive Biology 2018

Life after denosumab: strategies to mitigate bone density loss in patients discontinuing denosumab (#249)

Manik J Mayadunne 1 , Lyn March 1 2 , Roderick Clifton-Bligh 1 2 , Christian Girgis 1 2
  1. Royal North Shore Hospital, Sydney, NSW
  2. Sydney University, Sydney, NSW, Australia

Background and aims:

Denosumab is an antiresorptive agent that acts by the unique mechanism of binding to the receptor activator of nuclear factor-κβ ligand (RANKL) on osteoclast precursors, thereby preventing their maturation into activated osteoclasts. It is a popular alternative to bisphosphonate therapy, administered as a six-monthly subcutaneous injection, which minimises the issue of medication non-compliance.

Mounting evidence suggests that denosumab discontinuation, however, results in rebound increases in bone turnover with subsequent rapid decline in bone mineral density and in some cases, spontaneous vertebral fractures [1-4]. In patients seeking to discontinue denosumab, there is uncertainty surrounding the optimal choice of post-denosumab agent and timing of its administration to mitigate bone density loss and subsequent fractures.



We report a case series of five patients who discontinued denosumab and were prescribed either an oral or intravenous bisphosphonate. Temporal patterns of BMD in relation to denosumab treatment and post-cessation antiresorptive treatment choices were assessed.



Our series includes 1 male and 4 females, with a mean age of 67 years. All demonstrated improvements in BMD over the period they received denosumab. Two of the three patients given zoledronic acid following denosumab discontinuation demonstrated reductions in BMD down to pre-denosumab levels over the subsequent 12 months, and the third demonstrated increased bone turnover markers suggesting accelerated bone resorption. In all 3 patients zoledronic acid was administered 6 months following the last injection of denosumab. In contrast, two patients who received oral bisphosphonates following denosumab cessation demonstrated gains in BMD in the follow up period. There were no spontaneous vertebral fractures in this group within the period of observation (18 months post denosumab). Further research is necessary to clarify the optimal treatment approach in this context, with this case series providing contrasting treatments and outcomes for consideration.

  1. (1) Anastasilakis AD, Polyzos SA, Makras P, et al. Clinical Features of 24 Patients With Rebound-Associated Vertebral Fractures After Denosumab Discontinuation: Systematic Review and Additional Cases. J Bone Miner Res 2017; 32:1291.
  2. (2) Lamy O, Gonzalez-Rodriguez E, Stoll D, et al. Severe Rebound-Associated Vertebral Fractures After Denosumab Discontinuation: 9 Clinical Cases Report. J Clin Endocrinol Metab 2017; 102:354.
  3. (3) Symonds C, Kline G. Warning of an increased risk of vertebral fracture after stopping denosumab. CMAJ 2018; 190:E485.
  4. (4) Cummings SR, Ferrari S, Eastell R, et al. Vertebral Fractures After Discontinuation of Denosumab: A Post Hoc Analysis of the Randomized Placebo-Controlled FREEDOM Trial and Its Extension. J Bone Miner Res 2018; 33:190.