Bisphosphonates Maintain BMD After Sequential Teriparatide and Denosumab in Premenopausal Women with Idiopathic Osteoporosis

Context: We previously reported that sequential teriparatide followed by denosumab substantially increases bone mineral density (BMD) in premenopausal idiopathic osteoporosis (PremenIOP). Objective: To determine whether administration of bisphosphonates after denosumab cessation is associated with stable BMD in PremenIOP Design: Open-label extension study. Participants: Twenty-four PremenIOP Teriparatide-Denosumab Study participants. Interventions: Oral alendronate (ALN), 70 mg weekly, or intravenous zoledronic acid (ZOL), 5 mg once (patient choice), was administered 7 months (M) after final denosumab dose. Outcomes: BMD by dual-energy x-ray absorptiometry and serum C-telopeptide (CTX) q6M; Vertebral Fracture Assessment (VFA), and high-resolution peripheral quantitative computed tomography (HR-pQCT) q12 M. Results: Twenty-four 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 12 M. Women choosing ZOL (n = 6) vs ALN (n = 18) did not differ by baseline age, body mass index, fractures, BMD, or CTX. On ZOL, there were small lumbar spine BMD declines and CTX increases, particularly between 6 M and 12 M, while greater stability was observed on ALN. Changes in BMD and CTX did not differ by duration of denosumab (36 M vs <36 M) 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 vertebral fraction assessment screening) or nonvertebral fractures occurred. Conclusion: BMD remained stable in women with PremenIOP who received bisphosphonates after sequential teriparatide-denosumab therapy.