A Clinical Trial to Evaluate Efficacy of Once or Twice ZOledronic Acid After Different Duration of denOsumMab Administration in Postmenopausal Women With Osteoporosis (ZOOM Study)

Osteoporosis Clinical Trial

Official title: A Single Center, Open-label, Parallel, Phase IV Clinical Trial to Evaluate Efficacy of Once or Twice ZOledronic Acid After Different Duration of denOsumMab Administration in Postmenopausal Women With Osteoporosis

Status Recruiting

Clinical Trial Summary

Denosumab(Dmab) is a monoclonal antibody that inhibits the receptor-activator of nuclear factor kappa-B ligand. It improves bone density and reduces fractures by inhibiting osteoclast recruitment and differentiation. Although the FREEDOM trial showed Dmab increase bone mineral density for ten years, the effect was reversible. When Dmab is discontinued, the rebound phenomenon, the bone mineral density returns to the pre-treatment value, and multiple vertebral fractures may occur. Recently, a guideline to administer bisphosphonates sequentially when Dmab is discontinued has been published. In several studies, Zoledronic acid prevented bone loss after denosumab discontinuation with a single administration in Dmab short-term(less than 2.5years) users, but in Dmab long-term(more than 2.5years) users, zoledronic acid did not fully prevent loss of BMD. Our study tried to evaluate that ZOL administration twice for six months apart in long-term Dmab users is not inferior to a single administration of ZOL in Dmab short-term users.

Clinical Trial Description

Background Dmab is an osteoporosis treatment that improves bone density and lowers the risk of fractures. However, in a recent study, it is known that cases in which bone density decreases and multiple vertebral fractures occur when Dmab is discontinued. Therefore, the guideline recommends using zoledronic acid sequentially when discontinuing Dmab. However, the effect of preserving bone mineral density in patients who discontinue Dmab after using a long period is still not known.

Aim To investigate the difference in lumbar bone mineral density between the two groups when zoledronic acid was administered differently according to the administration period after discontinuation of denosumab in postmenopausal osteoporosis patients.

Methods A prospective, single-center, open-label, parallel, intervention study in 114 patients investigating the difference in bone mineral density between the short-term denosumab group and long-term denosumab group when zoledronic acid was administered differently. Each group is classified into a short-term group when used for less than 2.5 years and a long-term group when used for more than 2.5 years according to the maintenance period of the denosumab. The short-term group administrates zoledronic acid once six months after the last denosumab injection, and the long-term group administrates zoledronic acid six months and 12 months after the last denosumab injection, respectively. In the long-term group, if the side effect is severe after the first zoledronic acid administration and additional administration is difficult, it can be replaced with risedronic acid and maintained for another six months. The patients will be monitored with DXA at baseline and 12 months. Bone turnover marker (b-crosslap(CTx), P1NP) will be monitored at 6 and 12 months after the infusion of the first zoledronic acid. Whole spine x-rays are taken at baseline and 12 months after the zoledronic acid injection to check for vertebral fractures.

Perspectives Osteoporosis is a disease that requires continuous management in old age. In order to prevent fractures, the order and maintenance of drug administration should be decided from a long-term perspective. Denosumab is a potent inhibitor of bone resorption which can be used in patients with high risk and very high fracture risk. But since it is reversible, additional treatment must be continued to maintain bone mass when the drug is discontinued. This study will show if two injections of zoledronic acid six months apart in long-term denosumab patients can effectively prevent bone loss compared to a single administration of zoledronic acid in the short-term denosumab group. ;

Related Conditions & MeSH terms

• Osteoporosis

• NCT number: NCT05361408
• Study type: Interventional
• Source: Yonsei University
• Contact: Yumie Rhee
• Phone: 82-2-2228-0883
• Email: yumie@yuhs.ac
• Status: Recruiting
• Phase: Phase 4
• Start date: February 28, 2022
• Completion date: September 2023