ArticleJournal of orthopaedic research : official publication of the Orthopaedic Research Society2019
Impaired bone healing following treatment of established nonunion correlates with serum cytokine expression.
Article in Journal of orthopaedic research : official publication of the Orthopaedic Research Society, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 25 citations in OpenAlex.
- Article
- Atrophic Long-Bone Non-Union: Current Insights into Pathogenesis and Management-A Narrative Review.Journal of clinical medicine · 2026Review
- The Osteoimmunologic Basis of Biologic and Bioengineered Scaffolds in Fracture Healing.Bioengineering (Basel, Switzerland) · 2026Review
- Systemic administration of all-trans retinoic acid modulated circulating immune cells but failed to improve healing in a preclinical model of musculoskeletal trauma.Frontiers in immunology · 2026Article
- The feasibility of 3D bioprinting for bone regeneration: key challenges and future directions.Regenerative medicine · 2025Review
- Immunomodulation Using BMP-7 and IL-10 to Enhance the Mineralization Capacity of Bone Progenitor Cells in a Fracture Hematoma-Like Environment.Advanced healthcare materials · 2025Article
- Treatment of Bone Defects and Nonunion via Novel Delivery Mechanisms, Growth Factors, and Stem Cells: A Review.ACS biomaterials science & engineering · 2024Review
- Do Not Lose Your Nerve, Be Callus: Insights Into Neural Regulation of Fracture Healing.Current osteoporosis reports · 2024Review
- Role of the Neurologic System in Fracture Healing: An Extensive Review.Current osteoporosis reports · 2024Review
- Segmental defect healing in the presence or absence of recombinant human BMP2: Novel insights from a rat model.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2023Article
- Mesenchymal stromal cells for bone trauma, defects, and disease: Considerations for manufacturing, clinical translation, and effective treatments.Bone reports · 2023Article
- Systemic Immune Modulation Alters Local Bone Regeneration in a Delayed Treatment Composite Model of Non-Union Extremity Trauma.Frontiers in surgery · 2022Article
- BMP-2 delivery strategy modulates local bone regeneration and systemic immune responses to complex extremity trauma.Biomaterials science · 2021Article
- Early systemic immune biomarkers predict bone regeneration after trauma.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Evaluation of global gene expression in regenerate tissues during Masquelet treatment.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2020Article
- Bioinformatic analysis and experimental identification of blood biomarkers for chronic nonunion.Journal of orthopaedic surgery and research · 2020Article
- Epidemiology, Clinical Assessments, and Current Treatments of Nonunions.Current osteoporosis reports · 2020Review
- Heparin-mediated delivery of bone morphogenetic protein-2 improves spatial localization of bone regeneration.Science advances · 2020Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Delayed union and nonunion are a significant concern in long bone fractures and spinal fusions. Treatment of nonunion often entails multiple revision surgeries that further increase the financial, physical, and emotional burden on patients. The optimal treatment strategy for nonunions remains unclear in many cases, and the risk of complications after revision procedures remains high. This is in part due to our limited understanding of the biological mechanisms that inhibit proper bone healing and lead to nonunion. And yet, few preclinical models directly investigate how healing is impacted after establishment of nonunion, with most instead primarily focusing on treatment immediately after a fresh bone injury. Here, we utilized a critical size femoral defect model in rats where treatment was delayed 8 weeks post-injury, at which time nonunion was established. In this study, acute and delayed treatments with bone morphogenetic protein-2 (BMP-2) were assessed. We found that delayed treatment resulted in decreased bone formation and reduced mechanical strength compared to acute treatment, even when BMP-2 dose was increased by 2.5 times the acute treatment dose. Interestingly, serum cytokine analysis at 12 weeks post-treatment revealed signs of chronic immune dysregulation after delayed treatment. In particular, non-responders (rats that did not exhibit defect bridging) demonstrated higher overall expression of inflammatory cytokines, including TNFα and IL-1β, compared to responders. These findings suggest that re-establishing long-term immune homeostasis may be critical for successful bone healing, particularly after nonunion. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:299-307, 2019.
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