Bone Healing Gone Wrong: Pathological Fracture Healing and Non-Unions—Overview of Basic and Clinical Aspects and Systematic Review of Risk Factors
Abstract
:1. Introduction
2. Materials and Methods
2.1. Search Strategy for Systematic Review
2.2. Eligibility
2.3. Population
2.4. Intervention (Exposure)
2.5. Comparison
2.6. Outcome
2.7. Study Design
2.8. Inclusion Criteria
2.9. Exclusion Criteria
2.10. Search Strategy for Narrative Review
3. Epidemiology
4. Cellular Components Contributing to (Impaired) Bone Healing
4.1. MSCs
4.2. Macrophages
4.3. Osteoprogenitor Cells
4.4. Osteoblasts
4.5. Osteocytes
4.6. Osteoclasts
4.7. Chondrocytes
4.8. Vasculature
5. Risk Factors for Non-Union
6. Therapeutic Options
7. Biomarkers for Non-Union
8. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Factor | Study | Study Design | Bone | Patients (n) | Non-Unions (n) | Follow-Up (yrs) | Result (OR) |
---|---|---|---|---|---|---|---|
Age | [83] | Prospective | Clavicle | 245 | 15 | 9–10 | 1.3 |
[84] | Prospective | Clavicle | 868 | 53 | 0.5 | - | |
[85] | Prospective | Humerus | 110 | 16 | 1 | neg | |
[86] | Retrospective | Clavicle | 337 | 19 | ≥0.5 | 1.07 | |
[87] | Retrospective | Humerus | 1027 | 11 | 1 | neg | |
[88] | Meta-Analysis | Diaphyseal | 38,465 | 3975 | neg | ||
Sex | [88] | Meta-Analysis | Diaphyseal | 38,465 | 3975 | neg | |
Smoking | [89] | Prospective | Tibia | 85 | 9 | 3 | 18.46 |
[90] | Prospective | Long bone | 736 | 124 | 1 | 1.73 | |
[91] | Prospective | Tibia | 647 | 41 | 0.5 | 2.417 | |
[92] | Retrospective | Clavicle | 1196 | 125 | - | 3.76 | |
[93] | Retrospective | Diaphyseal | 114 | 38 | ≥1 | 4.14 | |
[94] | Retrospective | Humerus | 2230 | 231 | n.a. | pos | |
[95] | Retrospective | Humerus | 659 | 24 | 0.75 | 5.34 | |
[96] | Retrospective (case-control) | Femur | 32 | 32 | n.a. | 2.29 | |
[97] | Meta-Analysis | All bones | 6356 | 2.32 | |||
[98] | Meta-Analysis | All bones | 39,920 | 2.5 | |||
[99] | Meta-Analysis | All bones | 7516 | 2.2 | |||
[88] | Meta-Analysis | Diaphyseal | 38,465 | 1.7 | |||
Open fracture | [90] | Prospective | Long bone | 736 | 124 | 1 | 2.49 |
[100] | Retrospective (case-control) | Limb | 446 | 223 | 0.75 | 2.71 | |
[101] | Retrospective | Tibia | 486 | 56 | n.a. | 4.91 | |
[97] | Meta-Analysis | All bones | 6356 | 1.95 | |||
Displacement | [84] | Prospective | Clavicle | 868 | 53 | 0.5 | neg |
[102] | Prospective | Clavicle | 222 | 15 | 2 | - | |
[92] | Prospective | Clavicle | 941 | 125 | - | 1.17 | |
Diabetes | [88] | Meta-Analysis | Diaphyseal | 38,465 | 3975 | 1.6 | |
Obesity | [103] | Retrospective (delayed union) | Extremity | 147 | - | - | 3.39 |
[104] | Retrospective (osteotomy) | Femur | 150 | 7 | 1 | ||
[88] | Meta-Analysis | Diaphyseal | 38,465 | 3975 | 1.5 | ||
Osteoporosis | [105] | Prospective (case-control) | All bones | 1498 | 40 | 1 | neg |
[95] | Retrospective | Humerus | 659 | 24 | pos | ||
[100] | Retrospective (case-control) | Limb | 446 | 223 | 0.75 | 3.16 | |
Alcohol | [106] | Prospective | Femur | 112 | 9 | 4.8 (mean) | neg |
[98] | Meta-Analysis | All bones | 39,920 | 0.97 | |||
Drugs | |||||||
NSAIDs | [107] | Retrospective (case-control) | All bones | 2257 | 401 | 1 | 2.6 |
[96] | Retrospective (case-control) | Femur | 32 | 32 | n.a. | 10.74 | |
[100] | Retrospective (case-control) | Limb | 446 | 223 | 0.75 | 2.04 | |
[95] | Retrospective | Humerus | 659 | 24 | 0.75 | 2.51 | |
Steroids | [91] | Prospective | Tibia | 647 | 41 | 2 | neg |
[108] | Retrospective (pediatric) | All bones | 237,033 | 2003 | 1 | pos | |
PPIs | [109] | Retrospective (case-control) | Femur and tibia | 254 | 12 | n.a. | 4.5 |
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Saul, D.; Menger, M.M.; Ehnert, S.; Nüssler, A.K.; Histing, T.; Laschke, M.W. Bone Healing Gone Wrong: Pathological Fracture Healing and Non-Unions—Overview of Basic and Clinical Aspects and Systematic Review of Risk Factors. Bioengineering 2023, 10, 85. https://doi.org/10.3390/bioengineering10010085
Saul D, Menger MM, Ehnert S, Nüssler AK, Histing T, Laschke MW. Bone Healing Gone Wrong: Pathological Fracture Healing and Non-Unions—Overview of Basic and Clinical Aspects and Systematic Review of Risk Factors. Bioengineering. 2023; 10(1):85. https://doi.org/10.3390/bioengineering10010085
Chicago/Turabian StyleSaul, Dominik, Maximilian M. Menger, Sabrina Ehnert, Andreas K. Nüssler, Tina Histing, and Matthias W. Laschke. 2023. "Bone Healing Gone Wrong: Pathological Fracture Healing and Non-Unions—Overview of Basic and Clinical Aspects and Systematic Review of Risk Factors" Bioengineering 10, no. 1: 85. https://doi.org/10.3390/bioengineering10010085
APA StyleSaul, D., Menger, M. M., Ehnert, S., Nüssler, A. K., Histing, T., & Laschke, M. W. (2023). Bone Healing Gone Wrong: Pathological Fracture Healing and Non-Unions—Overview of Basic and Clinical Aspects and Systematic Review of Risk Factors. Bioengineering, 10(1), 85. https://doi.org/10.3390/bioengineering10010085