Denosumab After Teriparatide in Premenopausal Women with Idiopathic Osteoporosis.

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 (DR) 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. OBJECTIVES To assess the effects of 12 and 24 months (M) of denosumab in premenopausal women with IOP completing 24M of teriparatide. DESIGN Preplanned phase 2B extension study. SETTING Tertiary referral centers. PATIENTS Premenopausal women with IOP. INTERVENTIONS Denosumab 60mg every 6 months for 12 and 24M. MAIN OUTCOME MEASURES Within-group change in BMD at the LS at 12M. Secondary outcomes include change in 12M BMD at other sites, 24M BMD at all sites, trabecular bone score (TBS) and bone turnover markers (BTM). FINDINGS After completing teriparatide, 32 participants took denosumab for 12M and 29 for 24M, 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 24M teriparatide and 24M 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<0.0001). TBS increased by 5.8±5.6% (p<0.001). Serum BTM decreased by 75%-85% by 3M and remained suppressed through 12M of denosumab. Denosumab was generally well-tolerated. CONCLUSIONS These data support the use of sequential teriparatide and denosumab to increase BMD in premenopausal women with severe osteoporosis.