Context: We previously reported that sequential teriparatide followed by denosumab substantially increases BMD in premenopausal idiopathic osteoporosis (PremenIOP).

Objective: To determine whether bisphosphonates prevent bone loss after denosumab cessation in PremenIOP

Design: Open-label extension study

Participants: 24 PremenIOP Teriparatide-Denosumab Study participants

Interventions: Oral alendronate (ALN), 70 mg weekly, or IV zoledronic acid (ZOL), 5mg once (patient choice), was administered 7 months (M) after final denosumab dose.

Outcomes: BMD by DXA and serum C-telopeptide (CTX) q6M; vertebral fracture assessment (VFA) and HR-pQCT q12M.

Results: 24 women with PremenIOP (aged 43±8 years), severely affected with low trauma adult fractures (range 0-12; 9 with vertebral fractures) and/or very low BMD, had large BMD increases on sequential teriparatide-denosumab (spine: 25±9%; total hip: 11±6%). During the Bisphosphonate Extension, mean BMD and CTX changes in the entire group were small and not statistically significant at 6 or 12M.

Women choosing ZOL (n=6) versus ALN (n=18) did not differ by baseline age, BMI, fractures, BMD, or CTX. On ZOL, there were small LSBMD declines and CTX increases, particularly between 6M and 12M, while greater stability was observed on ALN.

Changes in BMD and CTX did not differ by duration of denosumab (36M vs <36M) or between 20 women who remained premenopausal and 4 who transitioned into menopause. Higher pre-teriparatide CTX, likely reflecting baseline remodeling status, predicted more spine and hip bone loss. No new vertebral (clinical or VFA screening) or non-vertebral fractures occurred.

Conclusion: Bisphosphonate therapy prevents significant bone loss after sequential teriparatide-denosumab in women with PremenIOP.