Abstract
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.