Bone Mass Gains After One Denosumab Injection Followed by Zoledronate

Abstract

Denosumab discontinuation can lead to bone loss despite subsequent bisphosphonate therapy. This bone loss is more severe in patients treated with denosumab for longer than 3 years. We aimed to evaluate the bone mass changes after only a single denosumab injection followed by zoledronate administration. We screened all of our patients who received a single denosumab injection and who were included in the osteoporosis register from the Swiss Society of Rheumatology between August 1, 2010, and January 31, 2022. This case series assessed the outcome of patients who were consecutively treated with one denosumab injection followed by a single infusion of zoledronate 6 months later. Bone mineral density (BMD) and bone turnover markers (BTM) changes were analysed before therapy and 18 months later. Percentage BMD changes and T-scores were compared with those of registered patients who received 2.5 years of denosumab treatment and one subsequent infusion of zoledronate. Thirty-two patients (31 female, 1 male) received a single denosumab injection and one zoledronate infusion 6 months later. BTM decreased significantly in this period (p = 0.035). Percentage BMD changes from baseline to 1 year after zoledronate treatment were 7.6% [IQR 3.2, 9.4] at the lumbar spine, 3.5% [1.8, 5.9] at the total hip and 4.6% [1.3, 6.0] at the femoral neck. In contrast, percentage changes from baseline in 110 patients with 2.5 years of denosumab treatment and one zoledronate infusion were 5.6% [3.0, 9.1], 2.3% [0.2, 4.9] and 2.3% [-0.9, 4.7], respectively. Differences between the 2 groups were significant at the lumbar spine (p = 0.014), total hip (p = 0.010) and femoral neck (p = 0.010). A single denosumab injection followed by zoledronate led to a remarkable gain of BMD at the lumbar spine and hip within a short time. This observation could help to identify a new short treatment sequence for patients with osteoporosis.

Keywords: Bisphosphonates; denosumab; discontinuation; osteoporosis; treat-to-target.