Denosumab After Teriparatide in Premenopausal Women With Idiopathic Osteoporosis

Abstract

Context: We have previously reported that teriparatide is associated with substantial increases in bone mineral density (BMD) at the lumbar spine (LS), total hip (TH), and femoral neck (FN) and small declines at the distal radius in 41 premenopausal women with idiopathic osteoporosis (IOP), all severely affected with low trauma fractures and/or very low BMD. Effects of teriparatide dissipate if not followed by antiresorptives.

Objective: To assess the effects of 12 and 24 months of denosumab in premenopausal women with IOP completing 24 months of teriparatide.

Methods: This was a preplanned phase 2B extension study. Premenopausal women with IOP who had completed a course of teriparatide received denosumab 60 mg every 6 months over 24 months. The main outcome measure was within-group change in BMD at the LS at 12 months. Secondary outcomes include change in 12-month BMD at other sites, 24-month BMD at all sites, trabecular bone score (TBS), and bone turnover markers (BTMs).

Results: After completing teriparatide, 32 participants took denosumab for 12 months and 29 for 24 months, with statistically significant increases in BMD at the LS (5.2 ± 2.6% and 6.9 ± 2.6%), TH (2.9 ± 2.4% and 4.6 ± 2.8%), and FN (3.0 ± 3.8% and 4.7 ± 4.9%). Over the entire 24-month teriparatide and 24-month denosumab treatment period, BMD increased by 21.9 ± 7.8% at the LS, 9.8 ± 4.6% at the TH, and 9.5 ± 4.7% at the FN (all P < .0001). TBS increased by 5.8 ± 5.6% (P < .001). Serum BTM decreased by 75% to 85% by 3 months and remained suppressed through 12 months of denosumab. Denosumab was generally well tolerated.

Conclusion: These data support the use of sequential teriparatide and denosumab to increase BMD in premenopausal women with severe osteoporosis.

Trial registration: ClinicalTrials.gov NCT02049866.

Keywords: bone density; bone turnover markers; denosumab; premenopausal osteoporosis; teriparatide.

© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Figures

Figure 1.

Consort diagram.

Figure 2.

Change in BMD by DXA on teriparatide (n = 30 received 24 months, n = 2 received 18 months) followed by denosumab expressed as percent change (±SE) from baseline (prior to teriparatide treatment). a*, P < .001 and a, P < .05 vs baseline (prior to teriparatide treatment); b*, P < .001 and b, P < .05 vs end of teriparatide treatment/denosumab baseline; c*, P < .001 and c, P < .05 vs 12 months of denosumab.

Figure 3.

Mean BMD Z scores (±SE) at the lumbar spine, total hip and femoral neck on teriparatide and after 12 and 24 months of denosumab. a*, P < .001 vs baseline (prior to teriparatide treatment); b*, P < .001 vs end of teriparatide treatment/denosumab baseline; c*, P ≤ .001 vs 12 months of denosumab.

Figure 4.

Change in trabecular bone score (TBS) on teriparatide followed by denosumab expressed as percent change (±SE) from baseline (prior to teriparatide treatment). a, P ≤ .001 vs baseline (prior to teriparatide treatment); b, P < .05 vs end of teriparatide/denosumab study baseline.

Figure 5.

Change in bone turnover markers during the first 12 months of denosumab treatment, expressed as percent change from denosumab baseline (±SE). *PINP, OCN, and CTx vs baseline; all P < .0001.