Preclinical therapies to prevent or treat fracture non-union: A systematic review

Bennett, Philippa M.; Stewart, Shona; Dretzke, Janine; Bem, Danai; Penn-Barwell, Jowan G.

doi:10.1371/journal.pone.0201077

Cited by 8 publications

(6 citation statements)

References 113 publications

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“…Although no human trials have yet to evaluate chitosan as a treatment modality for non-union, a number of animal studies have utilised chitosan either alone or in conjunction with another therapy in models of non-union. A recent systematic review examining pre-clinical therapies to prevent or treat non-union identified chitosan as a promising osteogenic agent 74 . Four out of six papers that utilised chitosan as a treatment for an animal model of non-union found that chitosan was superior to a control treatment 75-78 .…”

Section: Future Research Foci and Needsmentioning

confidence: 99%

Fracture Non-Union: A Review of Clinical Challenges and Future Research Needs

2019

Malays Orthop J

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Non-union of bone following fracture is an orthopaedic condition with a high morbidity and clinical burden. Despite its estimated global prevalence of nine million annually, the limit of bone regeneration therapy still results in patients living with pain, a reduced quality of life and associated psychological, social and financial repercussions. This review provides an overview of the current epidemiological and aetiological data, and highlights where the clinical challenges in treating non-union lie. Current treatment strategies are discussed as well as promising future research foci. Development in biotechnologies to treat non-union provides exciting scope for more effective treatment for this debilitating condition.

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Section: Future Research Foci and Needsmentioning

confidence: 99%

Fracture Non-Union: A Review of Clinical Challenges and Future Research Needs

2019

Malays Orthop J

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“…Protected by copyright. 15 This systematic review seeks to identify whether the ability of the military surgeon to achieve union in fractures sustained in the combat environment has improved over a century of conflict.…”

Section: Introductionmentioning

confidence: 99%

Fracture union rates across a century of war: a systematic review of the literature

et al. 2020

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IntroductionFractures have been a common denominator of the injury patterns observed over the past century of warfare. The fractures typified by the blast and ballistic injuries of war lead to high rates of bone loss, soft tissue injury and infection, greatly increasing the likelihood of non-union. Despite this, no reliable treatment strategy for non-union exists. This literature review aims to explore the rates of non-union across a century of conflict, in order to determine whether our ability to heal the fractures of war has improved.MethodsA systematic review of the literature was conducted, evaluating the rates of union in fractures sustained in a combat environment over a 100-year period. Only those fractures sustained through a ballistic or blast mechanism were included. The review was in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Quality and bias assessment was also undertaken.ResultsThirty studies met the inclusion criteria, with a total of 3232 fractures described across 15 different conflicts from the period 1919–2019. Male subjects made up 96% of cases, and tibial fractures predominated (39%). The lowest fracture union rate observed in a series was 50%. Linear regression analysis demonstrated that increasing years had no statistically significant impact on union rate.ConclusionsFailure to improve fracture union rates is likely a result of numerous factors, including greater use of blast weaponry and better survivability of casualties. Finding novel strategies to promote fracture healing is a key defence research priority in order to improve the rates of fractures sustained in a combat environment.

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“…Previous studies discovered the overall relative risk of non-union in long bone fracture to range from 1.9-10%, with observable peaks in young adults. 1,2 Inadequate care of several factors may contribute to the diminution of bone healing, which includes mechanical, biological, and infection. 3,4 Among these, an infection may be present in up to 40% of non-union cases.…”

Section: Introductionmentioning

confidence: 99%

“…However, outcomes from this procedure vary widely and can lead to a series of revision surgeries. 2 Different bone grafts are used in cases where defects are present; these can range from autograft, allograft, or synthetics grafts. After ten years, graft failure is still observed in approximately 60% of cases, leading to recurring non-union.…”

Section: Introductionmentioning

confidence: 99%

Incomplete Eradication of Persistent Infection May Impede Union: Our Experience in Treating Fracture Non-Unions with Allogenic MSC

Dilogo¹,

Hanitya

Pawitan³

et al. 2020

Preprint

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Introduction : Non-union remains a major clinical challenge for orthopaedic surgeons, as the treatments are associated with risks for complications, and sometimes multiple surgeries are required. Mesenchymal stem cells (MSCs) have been found to aid in osteogenesis and fracture healing; however, the number of studies on MSC application for treating non-unions is still sparse. We present a translational study of 8 subjects treated with MSC implantation, along with those considered as standard treatments in treating non-unions. To our knowledge, this is the most extensive clinical study on the use of MSCs to treat fracture non-unions. Methods: We performed 20x10 6 units of MSC implantations derived from adipose tissue, bone marrow, and umbilical cord on subjects diagnosed with fracture non-union of the long bone, along with internal fixation and hydroxyapatite-calcium sulphate (HA-CaSO 4 ) pellets. We excluded pathological fractures, subjects with immunological deficiencies (type II diabetes mellitus, and HIV/AIDS), and subjects with a history of immunosuppressive therapies. All subjects were assessed using the Disabilities of the Arm, Shoulder, and Hand (DASH) or Lower Extremities Functional Scale (LEFS), and visual analog score (VAS). Serial radiological images were also assessed using Tiedeman and Lane-Sandhu scoring to determine union. Follow up assessments were performed every three months for at least 12 months or until clinical and radiological union was achieved. Results: Four (50%) out of eight subjects developed union in a median of five (3-12) months. There was a reduction of VAS, from a median of 1 (0-6) to 0 (0-4), and an increase in mean LEFS/DASH of 56.25 ± 10.71 to 65 ± 22.72. However, the infection was identified in 3 (37.5%) subjects. Methicillin-resistant Staphylococcus aureus (MRSA) was identified in two (25%) subjects, while one was infected with Escherichia coli . No other adverse events occurred during the follow-up period. Conclusion: Allogenic MSC implantation can be used as a potential and safe therapy for fracture non-union. However, the presence of infection may interfere with bone healing; thus, thorough eradication of infection must be ensured to achieve fracture union. Further clinical studies are required to investigate the safety and efficacy of allogeneic MSC implantation.

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Preclinical therapies to prevent or treat fracture non-union: A systematic review

Cited by 8 publications

References 113 publications

Fracture Non-Union: A Review of Clinical Challenges and Future Research Needs

Fracture Non-Union: A Review of Clinical Challenges and Future Research Needs

Fracture union rates across a century of war: a systematic review of the literature

Incomplete Eradication of Persistent Infection May Impede Union: Our Experience in Treating Fracture Non-Unions with Allogenic MSC

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