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

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  • Additional Information
    • Source:
      Publisher: Oxford University Press Country of Publication: United States NLM ID: 0375362 Publication Model: Print Cited Medium: Internet ISSN: 1945-7197 (Electronic) Linking ISSN: 0021972X NLM ISO Abbreviation: J Clin Endocrinol Metab Subsets: MEDLINE
    • Publication Information:
      Publication: 2017- : New York : Oxford University Press
      Original Publication: Springfield, Ill. : Charles C. Thomas
    • Subject Terms:
      Denosumab*/therapeutic use ; Denosumab*/adverse effects ; Denosumab*/administration & dosage ; Zoledronic Acid*/therapeutic use ; Zoledronic Acid*/administration & dosage ; Zoledronic Acid*/adverse effects ; Bone Density Conservation Agents*/therapeutic use ; Bone Density Conservation Agents*/administration & dosage ; Bone Density Conservation Agents*/adverse effects ; Osteogenesis Imperfecta*/drug therapy ; Osteogenesis Imperfecta*/genetics ; Bone Density*/drug effects; Humans ; Female ; Male ; Adult ; Prospective Studies ; Treatment Outcome ; Bone Remodeling/drug effects ; Young Adult ; Middle Aged
    • 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.
      (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)
    • References:
      J Clin Endocrinol Metab. 2023 Dec 21;109(1):135-142. (PMID: 37539859)
      Metabolism. 2018 Mar;80:27-37. (PMID: 28625337)
      Bone. 2008 Mar;42(3):456-66. (PMID: 18096457)
      Calcif Tissue Int. 2023 May;112(5):613-620. (PMID: 36867194)
      J Clin Med. 2021 Jan 04;10(1):. (PMID: 33406802)
      Clin Orthop Surg. 2020 Dec;12(4):417-429. (PMID: 33274017)
      J Musculoskelet Neuronal Interact. 2016 Mar;16(1):24-32. (PMID: 26944820)
      J Clin Densitom. 2017 Oct - Dec;20(4):507-512. (PMID: 28624340)
      Asia Pac J Clin Oncol. 2017 Aug;13(4):266-276. (PMID: 27862983)
      Osteoporos Int. 2015 Oct;26(10):2521-7. (PMID: 25990355)
      Calcif Tissue Int. 2022 Apr;110(4):451-463. (PMID: 34988594)
      J Clin Endocrinol Metab. 2014 Nov;99(11):3954-5. (PMID: 25148238)
      Osteoporos Int. 2015 Oct;26(10):2431-40. (PMID: 25956285)
      Joint Bone Spine. 2019 Oct;86(5):589-593. (PMID: 30742929)
      J Med Genet. 1979 Apr;16(2):101-16. (PMID: 458828)
      J Clin Endocrinol Metab. 2016 Aug;101(8):3163-70. (PMID: 27270237)
      J Bone Miner Res. 2003 Jan;18(1):126-30. (PMID: 12510813)
      Clin Genet. 2021 Jan;99(1):42-52. (PMID: 32901963)
      J Bone Miner Res. 2013 Mar;28(3):449-54. (PMID: 23018784)
      Biomolecules. 2021 Oct 10;11(10):. (PMID: 34680126)
      Lancet. 2022 Mar 12;399(10329):1080-1092. (PMID: 35279261)
      J Bone Miner Res. 1993 Sep;8(9):1137-48. (PMID: 8237484)
      Endocr Rev. 2022 Jan 12;43(1):61-90. (PMID: 34007986)
      Osteoporos Int. 2016 Jan;27(1):81-92. (PMID: 26138583)
      Orphanet J Rare Dis. 2019 Sep 18;14(1):219. (PMID: 31533771)
      Bone Rep. 2021 Nov 13;15:101148. (PMID: 34825020)
      Osteoporos Int. 2023 Sep;34(9):1501-1529. (PMID: 37393412)
      J Clin Endocrinol Metab. 2022 Aug 18;107(9):2571-2579. (PMID: 35727737)
      Orphanet J Rare Dis. 2014 Sep 26;9:145. (PMID: 25257953)
      Osteoporos Int. 2016 Jul;27(7):2383-2386. (PMID: 27098536)
      Tohoku J Exp Med. 2017;242(2):115-120. (PMID: 28626166)
      Endocr Pract. 2016 Nov;22(11):1267-1276. (PMID: 27482615)
      Bone. 2021 Jun;147:115915. (PMID: 33722771)
      Osteoporos Int. 2017 Oct;28(10):2985-2995. (PMID: 28725987)
      J Bone Miner Res. 2023 May;38(5):650-658. (PMID: 36970786)
      J Bone Miner Res. 2017 Jan;32(1):125-134. (PMID: 27448250)
      Osteoporos Int. 2023 Jun;34(6):1075-1084. (PMID: 36862192)
      Arch Endocrinol Metab. 2022 Nov 11;66(5):694-706. (PMID: 36382759)
      J Clin Endocrinol Metab. 2023 Jun 16;108(7):1787-1796. (PMID: 36658750)
      J Clin Densitom. 2019 Apr - Jun;22(2):229-235. (PMID: 30309730)
      Osteoporos Int. 2013 Mar;24(3):1073-8. (PMID: 23052939)
      J Child Orthop. 2019 Feb 1;13(1):1-11. (PMID: 30838070)
      J Bone Miner Res. 2006 Feb;21(2):300-6. (PMID: 16418786)
      J Musculoskelet Neuronal Interact. 2018 Mar 1;18(1):76-80. (PMID: 29504582)
      J Clin Med. 2018 Nov 24;7(12):. (PMID: 30477250)
      J Bone Miner Res. 2022 May;37(5):826-836. (PMID: 35306687)
    • Grant Information:
      2021YFC2501700 National Key R&D Program of China; 82070908 National Natural Science Foundation of China; 2021-I2M-1-051 CAMS Innovation Fund for Medical Sciences; 2022-PUMCH-B-014 National High Level Hospital Clinical Research Funding
    • Contributed Indexing:
      Keywords: adult; bone mineral density; denosumab; osteogenesis imperfecta; trabecular bone score; zoledronic acid
    • Accession Number:
      4EQZ6YO2HI (Denosumab)
      6XC1PAD3KF (Zoledronic Acid)
      0 (Bone Density Conservation Agents)
    • Publication Date:
      Date Created: 20240105 Date Completed: 20240616 Latest Revision: 20240731
    • Publication Date:
      20240801
    • Accession Number:
      PMC11180512
    • Accession Number:
      10.1210/clinem/dgae012
    • Accession Number:
      38181430