Effect of Zoledronate on Bone Loss After Romosozumab/Denosumab: 2-Year Follow-up

Excerpt

Romosozumab and denosumab are monoclonal antibodies for the treatment of osteoporosis. Both have a rapid offset of effect, resulting in loss of bone density (BMD) gained on-treatment and, in some cases, multiple vertebral fractures following treatment cessation [1]. We found that in women discontinuing long-term treatment with denosumab, zoledronate infusions 6 months after the last dose of denosumab were ineffective in preserving hip BMD and only partially effective at the spine [2]. We hypothesized that this lack of efficacy was contributed to by the very low bone turnover after denosumab treatment, resulting in low skeletal uptake of the bisphosphonate. More recently, we reported data from women followed up for 1 year after the FRAME trial [3]. In that study, osteoporotic women were randomized to romosozumab or placebo for 1 year, and then both groups were provided with open-label denosumab for the subsequent 2 years. Our report demonstrated that zoledronate infusions given to 11 women after a median delay of 65 days from trial-end (i.e., 245 days after the last denosumab injection) substantially preserved BMD, whereas those declining post-trial treatment lost 80–90% of the BMD gained during treatment with romosozumab–denosumab [4]. We have now followed up nine of those zoledronate-treated women for a further year, during which time no further interventions were provided. …