A single dose of zoledronate preserves bone mineral density for up to 2 years after a second course of romosozumab

Abstract

This phase 2 study evaluated the efficacy and safety of transitioning to zoledronate following romosozumab treatment in postmenopausal women with low bone mass. A single dose of 5 mg zoledronate generally maintained the robust BMD gains accrued with romosozumab treatment and was well tolerated. Introduction Follow-on therapy with an antiresorptive agent is necessary to maintain the skeletal benefits of romosozumab therapy. We evaluated the use of zoledronate following romosozumab treatment. Methods This phase 2, dose-finding study enrolled postmenopausal women with low bone mineral density (BMD). Subjects who received various romosozumab doses or placebo from months 0-24 were rerandomized to denosumab (60 mg SC Q6M) or placebo for 12 months, followed by open-label romosozumab (210 mg QM) for 12 months. At month 48, subjects who had received active treatment for 48 months were assigned to no further active treatment and all other subjects were assigned to zoledronate 5 mg IV. Efficacy (BMD, P1NP, and β-CTX) and safety were evaluated for 24 months, up to month 72. Results A total of 141 subjects entered the month 48-72 period, with 51 in the no further active treatment group and 90 in the zoledronate group. In subjects receiving no further active treatment, lumbar spine (LS) BMD decreased by 10.8% from months 48-72 but remained 4.2% above the original baseline. In subjects receiving zoledronate, LS BMD was maintained (percentage changes: − 0.8% from months 48-72; 12.8% from months 0-72). Similar patterns were observed for proximal femur BMD in both groups. With no further active treatment, P1NP and β-CTX decreased but remained above baseline at month 72. Following zoledronate, P1NP and β-CTX levels initially decreased but approached baseline by month 72. No new safety signals were observed. Conclusion A zoledronate follow-on regimen can maintain robust BMD gains achieved with romosozumab treatment.

Osteoporosis Treatment with Anti-Sclerostin Antibodies—Mechanisms of Action and Clinical Application

“…Similar patterns were seen for BMD changes at the proximal femur in both groups. Regarding bone turnover, there was a decrease in P1NP and CTX concentrations, though remaining above baseline, at month 72, in patients receiving no further active treatment, while in zoledronate recipients, P1NP and CTX levels initially dropped and approached baseline by month 72 [93]. Thus, this study confirmed that romosozumab cessation resulted in bone mass loss, while a single zoledronate infusion preserved BMD for up to two years.…”

“…In the last stage of the extension studies described above [ 91 , 92 ], patients who had received active treatment for 48 months were assigned to no further active treatment, whereas all other women were administered a single intravenous dose of zoledronate 5 mg and evaluated for 24 months, up to month 72 [ 93 ]. In subjects receiving no further active treatment, a BMD decrease of 10.8% was noted at the lumbar spine from months 48–72, thereby remaining 4.2% above the original baseline.…”

Skeletal Aging and Osteoporosis: Mechanisms and Therapeutics

“…Unlike teriparatide, romosozumab had no carcinogenicity concerns in animals or humans [207]. Effects of romosozumab were reversible when discontinued and required a subsequent treatment of denosumab, an an-tiresorptive monoclonal antibody against RANKL [208] and by a single dose of zoledronate, which preserved the anabolic bone accrual initiated by romosozumab, for an additional two years [209].…”

Osteoporose-Update 2021

“…Bei den Wirbelkörperfrakturen ergab sich nach einem und nach 2 Jahren eine Risikoreduktion um mehr als jeweils 70 %. Romosozumab wurde in einem noch immer aktiven großen Studienprogramm inklusive Head-to-Head-Studien untersucht, bereits verfügbare Metaanalysen bestätigen das hohe Potenzial [4][5][6][7][8][9][10].…”

“…Bei Auftreten eines Rezidivs unter laufender Therapie sollte erneut eine anabole Therapiephase erwogen werden. Teriparatid kann nicht wiederholt werden, für Romosozumab gibt es eine erste Studie, die belegt, dass die Knochendichte auch in einer zweiten Anwendungsepisode ansteigt [7,8]. Das Vorgehen muss individuell strukturiert werden, didaktisch schematisch aufbereitete Beispiele finden sich in ▶ Abb.…”