Efficacy and Safety of Denosumab Vs Zoledronic Acid in OI Adults: A Prospective, Open-Label, Randomized Study

Overview

Journal J Clin Endocrinol Metab

Publisher Oxford University Press

Specialty Endocrinology

Date 2024 Jan 5

PMID 38181430

Authors

Xiaoyun Lin

Jing Hu

Bingna Zhou

Xiaojie Wang

Qian Zhang

Yan Jiang

Ou Wang

Weibo Xia

Xiaoping Xing

Mei Li

Affiliations

Soon will be listed here.

Abstract

Context: The comparative effectiveness of denosumab and zoledronic acid for adult patients with osteogenesis imperfecta (OI) has not been established.

Objective: To evaluate the efficacy and safety of denosumab and zoledronic acid in adult patients with OI.

Methods: This was a prospective, open-label study. Patients were randomized to receive denosumab 60 mg every 6 months or zoledronic acid 5 mg once for 12 months. Pathogenic mutations of OI were identified by next-generation sequencing and confirmed by Sanger sequencing. Percentage changes in the areal bone mineral density (aBMD), trabecular bone score (TBS), and bone turnover biomarkers (BTMs) from baseline to 6 and 12 months of treatment, as well as safety, were evaluated.

Results: A total of 51 adults with OI (denosumab: 25, zoledronic acid: 26) were included, of whom 49 patients had identified pathogenic mutations. At 12 months, aBMD at the lumbar spine and total hip significantly increased by 4.34% (P = .005) and 1.45% (P = .023) in the denosumab group and by 4.92% (P = .006) and 2.02% (P = .016) in the zoledronic acid group, respectively. TBS showed an increasing trend by 1.39% and 2.70% in denosumab and zoledronic acid groups, respectively. Serum levels of β-isomerized carboxy-telopeptide of type I collagen and alkaline phosphatase markedly decreased after denosumab treatment. Percentage changes in aBMD, TBS, and BTMs during the treatment were similar between the 2 groups. Patients with OI with milder phenotypes showed a significantly higher increase in the TBS after 12 months of denosumab treatment than those with more severe phenotypes (P = .030). During the study period, the denosumab group had fewer adverse events than the zoledronic acid group.

Conclusion: Denosumab effectively increases aBMD in adults with OI, with similar efficacy to zoledronic acid. Long-term and large-sample studies are needed to confirm the antifracture efficacy and safety of denosumab in adult patients with OI.

References

Song A, Chen R, Guan W, Yu W, Yang Y, Wang J . Trabecular Bone Score as a More Sensitive Tool to Evaluate Bone Involvement in MEN1-related Primary Hyperparathyroidism. J Clin Endocrinol Metab. 2023; 109(1):135-142. DOI: 10.1210/clinem/dgad460. View

Tournis S, Dede A . Osteogenesis imperfecta - A clinical update. Metabolism. 2017; 80:27-37. DOI: 10.1016/j.metabol.2017.06.001. View

Roschger P, Paschalis E, Fratzl P, Klaushofer K . Bone mineralization density distribution in health and disease. Bone. 2007; 42(3):456-66. DOI: 10.1016/j.bone.2007.10.021. View

Seale E, Molina M, Carsen S, Sheffield H, Koujok K, Robinson M . Mitigating the Denosumab-Induced Rebound Phenomenon with Alternating Short- and Long-Acting Anti-resorptive Therapy in a Young Boy with Severe OI Type VI. Calcif Tissue Int. 2023; 112(5):613-620. DOI: 10.1007/s00223-023-01065-4. View

Anastasilakis A, Makras P, Yavropoulou M, Tabacco G, Naciu A, Palermo A . Denosumab Discontinuation and the Rebound Phenomenon: A Narrative Review. J Clin Med. 2021; 10(1). PMC: 7796169. DOI: 10.3390/jcm10010152. View

Cho T, Ko J, Kim H, Shin H, Yoo W, Shin C . Management of Osteogenesis Imperfecta: A Multidisciplinary Comprehensive Approach. Clin Orthop Surg. 2020; 12(4):417-429. PMC: 7683189. DOI: 10.4055/cios20060. View

Hoyer-Kuhn H, Franklin J, Allo G, Kron M, Netzer C, Eysel P . Safety and efficacy of denosumab in children with osteogenesis imperfect--a first prospective trial. J Musculoskelet Neuronal Interact. 2016; 16(1):24-32. PMC: 5089451. View

Tsai J, Jiang L, Lee H, Hans D, Leder B . Effects of Teriparatide, Denosumab, or Both on Spine Trabecular Microarchitecture in DATA-Switch: a Randomized Controlled Trial. J Clin Densitom. 2017; 20(4):507-512. PMC: 5673584. DOI: 10.1016/j.jocd.2017.05.007. View

Pittman K, Antill Y, Goldrick A, Goh J, De Boer R . Denosumab: Prevention and management of hypocalcemia, osteonecrosis of the jaw and atypical fractures. Asia Pac J Clin Oncol. 2016; 13(4):266-276. DOI: 10.1111/ajco.12517. View

10.

Anastasilakis A, Polyzos S, Gkiomisi A, Saridakis Z, Digkas D, Bisbinas I . Denosumab versus zoledronic acid in patients previously treated with zoledronic acid. Osteoporos Int. 2015; 26(10):2521-7. DOI: 10.1007/s00198-015-3174-2. View

11.

Zheng W, Hu J, Zhang J, Yang Z, Wang O, Jiang Y . Specific Characteristic of Hyperplastic Callus in a Larger Cohort of Osteogenesis Imperfecta Type V. Calcif Tissue Int. 2022; 110(4):451-463. DOI: 10.1007/s00223-021-00932-2. View

12.

Hoyer-Kuhn H, Semler O, Schoenau E . Effect of denosumab on the growing skeleton in osteogenesis imperfecta. J Clin Endocrinol Metab. 2014; 99(11):3954-5. DOI: 10.1210/jc.2014-3072. View

13.

Kocijan R, Muschitz C, Haschka J, Hans D, Nia A, Geroldinger A . Bone structure assessed by HR-pQCT, TBS and DXL in adult patients with different types of osteogenesis imperfecta. Osteoporos Int. 2015; 26(10):2431-40. DOI: 10.1007/s00198-015-3156-4. View

14.

Lafage-Proust M, Courtois I . The management of osteogenesis imperfecta in adults: state of the art. Joint Bone Spine. 2019; 86(5):589-593. DOI: 10.1016/j.jbspin.2019.02.001. View

15.

Sillence D, Senn A, Danks D . Genetic heterogeneity in osteogenesis imperfecta. J Med Genet. 1979; 16(2):101-16. PMC: 1012733. DOI: 10.1136/jmg.16.2.101. View

16.

Miller P, Pannacciulli N, Brown J, Czerwinski E, Nedergaard B, Bolognese M . Denosumab or Zoledronic Acid in Postmenopausal Women With Osteoporosis Previously Treated With Oral Bisphosphonates. J Clin Endocrinol Metab. 2016; 101(8):3163-70. PMC: 4971333. DOI: 10.1210/jc.2016-1801. View

17.

Adami S, Gatti D, Colapietro F, Fracassi E, Braga V, Rossini M . Intravenous neridronate in adults with osteogenesis imperfecta. J Bone Miner Res. 2003; 18(1):126-30. DOI: 10.1359/jbmr.2003.18.1.126. View

18.

Chetty M, Roomaney I, Beighton P . The evolution of the nosology of osteogenesis imperfecta. Clin Genet. 2020; 99(1):42-52. DOI: 10.1111/cge.13846. View

19.

Popp A, Guler S, Lamy O, Senn C, Buffat H, Perrelet R . Effects of zoledronate versus placebo on spine bone mineral density and microarchitecture assessed by the trabecular bone score in postmenopausal women with osteoporosis: a three-year study. J Bone Miner Res. 2012; 28(3):449-54. DOI: 10.1002/jbmr.1775. View

20.

Botor M, Fus-Kujawa A, Uroczynska M, Stepien K, Galicka A, Gawron K . Osteogenesis Imperfecta: Current and Prospective Therapies. Biomolecules. 2021; 11(10). PMC: 8533546. DOI: 10.3390/biom11101493. View