In premenopausal IOP, BMD gains on teriparatide-denosumab were maintained on bisphosphonate over 1 year. In 19 followed after bisphosphonate, there was a significant bone loss over 6M, leading to retreatment in some. BMD remained significantly above pretreatment baseline. In premenopausal IOP, the optimal duration of bisphosphonate after denosumab requires further study. We have previously reported that sequential teriparatide-denosumab resulted in large BMD increases in premenopausal women with idiopathic osteoporosis (IOP), and that BMD remained stable with bisphosphonate (alendronate or zoledronate) for 1 year after denosumab cessation (Bisphosphonate Extension Study; BES Year 1). To determine the durability of this effect, an observation year (BES Year 2) off therapy was planned.
Participants: 19 women, aged 44 ± 8, with premenopausal IOP.
Measures: BMD by DXA, serum CTX every 6 months (M).
Results: On sequential teriparatide-denosumab, BMD increased by 23 ± 9% at the spine and 12 ± 7% at the total hip. In BES Year 1 on bisphosphonate, BMD and CTX did not change significantly at 6M or 12M. From 12-18M of BES Year 2, BMD declined by 4.2 ± 2.5% at the spine and 1.4 ± 2.1% at the total hip (both p < 0.05); other sites remained stable. CTX increased by 218 ± 210 pg/ml (p < 0.05). At 18M, ten participants resumed bisphosphonates because of bone loss or low BMD and nine continued observation. By the end of BES Year 2, spine BMD stabilized in both groups. BMD at the spine and hip was significantly and substantially higher than before beginning teriparatide.
Conclusion: In premenopausal women with IOP, sequential therapy with teriparatide-denosumab was associated with large gains in bone mass that were maintained by 1 year of bisphosphonate treatment. There was significant bone loss during the first 6 months after discontinuing bisphosphonates, leading to retreatment in about half the participants. Despite this bone loss, BMD remained significantly above pretreatment levels. In premenopausal women with IOP, the optimal duration of bisphosphonate therapy after denosumab cessation requires further study.
Trial registration: ClinicalTrials.gov Identifier: NCT03396315.
Keywords: Alendronate; Bisphosphonate; Bone density; Bone turnover markers; Denosumab; Denosumab cessation; Premenopausal osteoporosis; Teriparatide; Zoledronic acid.
© 2025. The Author(s).