High-dose romosozumab promoted bone regeneration of critical-size ulnar defect filled with demineralized bone matrix in nonhuman primates
(2025) In Journal of Orthopaedic Translation 54. p.1-7- Abstract
Background: Large bone defects are challenging to manage clinically and usually require treatment with bone graft or bone graft substitute. This study evaluated the effect of romosozumab, a sclerostin antibody, in combination with demineralized bone matrix (DBM) on bone regeneration in a critical-size ulnar defect model in nonhuman primates. Methods: In cynomolgus monkeys (N = 22, male, 10–12 years old), a full-cortex bone defect (0.5 cm long) was created in the left ulnar shaft and filled with DBM. Animals were randomized to receive vehicle (n = 10) or romosozumab (n = 12; 30 mg/kg) subcutaneously, every 2 weeks for 28 weeks. Radiographs of the left ulna were taken every 2 weeks for 28 weeks to monitor bone regeneration response. Ulnae... (More)
Background: Large bone defects are challenging to manage clinically and usually require treatment with bone graft or bone graft substitute. This study evaluated the effect of romosozumab, a sclerostin antibody, in combination with demineralized bone matrix (DBM) on bone regeneration in a critical-size ulnar defect model in nonhuman primates. Methods: In cynomolgus monkeys (N = 22, male, 10–12 years old), a full-cortex bone defect (0.5 cm long) was created in the left ulnar shaft and filled with DBM. Animals were randomized to receive vehicle (n = 10) or romosozumab (n = 12; 30 mg/kg) subcutaneously, every 2 weeks for 28 weeks. Radiographs of the left ulna were taken every 2 weeks for 28 weeks to monitor bone regeneration response. Ulnae were excised and analyzed by ex-vivo x-ray and micro-computed tomography (micro-CT) to evaluate bone repair, and lumbar vertebrae were excised for bone histomorphometric analysis to evaluate the systemic anabolic response. Results: In-vivo and ex-vivo x-ray images of surgical ulnae demonstrated that the critical-size ulnar defect fully bridged in 3 romosozumab-treated monkeys at week 28 but not in any vehicle-treated monkey. Micro-CT analysis demonstrated that average new bone volume and new bone area within the defect region were 118 % and 105 % greater, respectively, with romosozumab versus vehicle. Trabecular bone volume per tissue volume and trabecular thickness of lumbar vertebral body were 72 % and 92 % greater, and eroded surface was significantly lower with romosozumab versus vehicle. Conclusion: High-dose romosozumab in combination with DBM improved bone regeneration in a critical-size ulnar defect model and increased bone mass in non-surgical bone in nonhuman primates. The translational potential of this article: Clinical management of large bone defect is complex and challenging. More effective management is needed. This paper reports the first nonhuman primate study that evaluated high-dose romosozumab in combination with demineralized bone matrix in a critical-size defect model and provides perspective for the future research evaluating the combination of romosozumab and bone graft or bone graft substitutes in various relevant clinical conditions.
(Less)
- author
- Li, Xiaodong ; Asuncion, Frank ; Ominsky, Michael ; Niu, Qing Tian ; Akesson, Kristina E. LU ; Wang, Jeffrey ; Lieberman, Jay and Ke, Hua Zhu
- organization
- publishing date
- 2025-09
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Bone regeneration, Critical-size bone defect, Demineralized bone matrix, Nonhuman primates, Romosozumab
- in
- Journal of Orthopaedic Translation
- volume
- 54
- pages
- 7 pages
- publisher
- Elsevier
- external identifiers
-
- scopus:105010250697
- pmid:40809811
- ISSN
- 2214-031X
- DOI
- 10.1016/j.jot.2025.06.019
- language
- English
- LU publication?
- yes
- additional info
- Publisher Copyright: © 2025 The Authors
- id
- ad8ea15f-78c2-4d94-b125-b632e8170688
- date added to LUP
- 2025-11-27 14:46:23
- date last changed
- 2025-11-28 03:00:05
@article{ad8ea15f-78c2-4d94-b125-b632e8170688,
abstract = {{<p>Background: Large bone defects are challenging to manage clinically and usually require treatment with bone graft or bone graft substitute. This study evaluated the effect of romosozumab, a sclerostin antibody, in combination with demineralized bone matrix (DBM) on bone regeneration in a critical-size ulnar defect model in nonhuman primates. Methods: In cynomolgus monkeys (N = 22, male, 10–12 years old), a full-cortex bone defect (0.5 cm long) was created in the left ulnar shaft and filled with DBM. Animals were randomized to receive vehicle (n = 10) or romosozumab (n = 12; 30 mg/kg) subcutaneously, every 2 weeks for 28 weeks. Radiographs of the left ulna were taken every 2 weeks for 28 weeks to monitor bone regeneration response. Ulnae were excised and analyzed by ex-vivo x-ray and micro-computed tomography (micro-CT) to evaluate bone repair, and lumbar vertebrae were excised for bone histomorphometric analysis to evaluate the systemic anabolic response. Results: In-vivo and ex-vivo x-ray images of surgical ulnae demonstrated that the critical-size ulnar defect fully bridged in 3 romosozumab-treated monkeys at week 28 but not in any vehicle-treated monkey. Micro-CT analysis demonstrated that average new bone volume and new bone area within the defect region were 118 % and 105 % greater, respectively, with romosozumab versus vehicle. Trabecular bone volume per tissue volume and trabecular thickness of lumbar vertebral body were 72 % and 92 % greater, and eroded surface was significantly lower with romosozumab versus vehicle. Conclusion: High-dose romosozumab in combination with DBM improved bone regeneration in a critical-size ulnar defect model and increased bone mass in non-surgical bone in nonhuman primates. The translational potential of this article: Clinical management of large bone defect is complex and challenging. More effective management is needed. This paper reports the first nonhuman primate study that evaluated high-dose romosozumab in combination with demineralized bone matrix in a critical-size defect model and provides perspective for the future research evaluating the combination of romosozumab and bone graft or bone graft substitutes in various relevant clinical conditions.</p>}},
author = {{Li, Xiaodong and Asuncion, Frank and Ominsky, Michael and Niu, Qing Tian and Akesson, Kristina E. and Wang, Jeffrey and Lieberman, Jay and Ke, Hua Zhu}},
issn = {{2214-031X}},
keywords = {{Bone regeneration; Critical-size bone defect; Demineralized bone matrix; Nonhuman primates; Romosozumab}},
language = {{eng}},
pages = {{1--7}},
publisher = {{Elsevier}},
series = {{Journal of Orthopaedic Translation}},
title = {{High-dose romosozumab promoted bone regeneration of critical-size ulnar defect filled with demineralized bone matrix in nonhuman primates}},
url = {{http://dx.doi.org/10.1016/j.jot.2025.06.019}},
doi = {{10.1016/j.jot.2025.06.019}},
volume = {{54}},
year = {{2025}},
}