Evaluating the Effects of Follow-Up Therapy After Denosumab Discontinuation in Postmenopausal Osteoporosis

Researchers evaluated the effects of follow-up therapy after denosumab discontinuation on bone resorption, bone mineral density (BMD), and clinical fracture risk in postmenopausal osteoporosis in a study published in Modern Rheumatology. Study findings indicated that BMD of the lumbar spine and femoral neck was better maintained in patients who replaced denosumab vs raloxifene with oral bisphosphonates or zoledronate. Compared to other treatment modalities, clinical vertebral fracture incidence was highest among patients who were switched to raloxifene after denosumab discontinuation.

Investigators conducted a nonrandomized retrospective cohort study of patients with postmenopausal osteoporosis who received treatment across 6 medical centers in Japan. Patients who were treated with and subsequently discontinued denosumab were enrolled in the study. To ensure that substantial follow-up data were available, patients who were lost to follow-up prior to 1.5 years after the final denosumab administration were excluded from the study. Clinical and radiographic data were extracted from electronic medical records. Dual-energy x-ray absorptiometry was used to assess BMD of the femoral neck and lumbar spine; spinal radiographs were used to identify vertebral fractures. The primary outcome was change in femoral neck and lumbar spine BMD at 1.5 years after final denosumab administration. The type of treatment initiated after denosumab discontinuation was also recorded. Outcomes were compared across treatment groups using Pearson’s chi-square and Fisher’s exact tests.

The study cohort included 53 participants, with a mean age of 73.1 years at the time of first denosumab administration. Prior to denosumab administration, 49.1% of patients (n=26) had been treated with an oral bisphosphonate and 50.9% (n=27) with teriparatide. Denosumab was administered via subcutaneous injection at a mean of 2.6 times before discontinuation, the primary reason for which was patient preference (20.8%). Following denosumab discontinuation, patients were switched to 1 of the following conditions based on the treating physicians’ recommendations, including daily oral raloxifene; weekly or monthly bisphosphonates administered orally or intravenously; or zoledronate administered intravenously once a year. Mean interval after final denosumab administration was 7.2 months.

At 1.5 years after the final denosumab administration, changes in lumbar spine BMD were -2.7% in the raloxifene group, +0.7% in the bisphosphonates group, and +1.9% in the zoledronate group (P =.31 between groups). A significantly greater BMD loss in the femoral neck (-3.8%) was observed among patients in the raloxifene group compared with those in the bisphosphonate (-0.8%; P =.048) and zoledronate (+1.8%; P =.02) groups. Clinical vertebral fracture incidence rates were 23.1%, 3.4%, and 0.0% in the raloxifene, bisphosphonates (P =.015), and zoledronate groups (P =.048), respectively. No significant differences in BMD loss and clinical fracture incidence were observed between the bisphosphonate and zoledronate group.

Overall, these data suggest that bisphosphonates and zoledronate may better prevent BMD loss in women with postmenopausal osteoporosis who have discontinued denosumab treatment. Clinical fracture incidence was also lower with bisphosphonates and zoledronate compared with raloxifene.

A study limitation included the short study period of 1.5 years. Additional follow-up may be necessary to ascertain the long-term efficacy of bisphosphonates and zoledronate.

“These results may contribute to the selection of adequate follow-on therapy after [denosumab] discontinuation, although further investigations are required,” the investigators concluded.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

Reference

Ebina K, Hashimoto J, Kashii M, et al. Effects of follow-on therapy after denosumab discontinuation in patients with postmenopausal osteoporosis [published online June 8, 2020]. Mod Rheumatol. doi:10.1080/14397595.2020.1769895