Biological and molecular profile of fracture non‐union tissue: A systematic review and an update on current insights

Panteli, Michalis; Vun, Shen Hwa; Pountos, Ippokratis; Howard, Anthony; Jones, Elena; Giannoudis, Peter V.

doi:10.1111/jcmm.17096

Cited by 29 publications

(23 citation statements)

References 60 publications

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“…Giannoudis and his team are widely known for the “diamond concept” (the basic therapeutic concept of bone healing). Their recent study comprehensively analyzed the biological, molecular, and genetic profiles associated with fracture nonunion that provide evidence for macroscopic appearances of nonunion and potential biomarkers in clinical practice [ 57 ]. In the clinic, they constructed a nonunion risk model that reliably identified high-risk patients early [ 58 ].…”

Section: Discussionmentioning

confidence: 99%

Efficacy of adjuvant treatment for fracture nonunion/delayed union: a network meta-analysis of randomized controlled trials

Yang

Zhang

Liang

et al. 2022

BMC Musculoskelet Disord

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Background Fracture nonunion/delayed union seriously affects physical and mental health and quality of life. The aim of this study was to evaluate the relative efficacy of different adjuvant treatments for nonunion/delayed union by network meta-analysis. Methods A comprehensive search was performed to identify randomized controlled trials (RCTs) evaluating adjuvant treatment in the management of nonunion/delayed union. A network meta-analysis reporting on healing rate, healing time, and adverse effect (AE) outcomes was conducted to assess and compare different interventions. Results Thirty studies were included in the analysis. For the healing rate outcome, bone marrow aspirate (BMA) + autologous cancellous bone (ACB) was found to be significantly better than ACB alone (odds ratio: 0.12; 95% confidence interval: 0.03, 0.59). In the ranking results, BMA+ platelet-rich plasma (PRP) (96%), BMA + ACB (90%), and BMA alone (82%) showed relative advantages in the healing rate. Low-intensity pulsed ultrasonography (LIUS) intervention significantly shortened the healing time compared with ACB (SMD: -9.26; 95% CI: − 14.64, − 3.87). LIUS (100%), BMA + PRP (74%), and bone morphogenetic proteins (BMPs) (69%) have relative advantages. Compared with the control, electromagnetic field (EMF) (OR: 13.21; 95% CI: 1.58, 110.40) and extracorporeal shock wave (ESWT) (OR: 4.90; 95% CI: 1.38, 17.43) had a higher AE risk. Conclusions Among the current intervention strategies, BMA in combination with PRP and ACB can improve the healing rate of nonunion/delayed union. LIUS can significantly shorten the healing time. EMF and ESWT may have a high risk of AE. However, large-scale, well-designed studies are still needed to confirm the results. Trial registration Retrospectively registered.

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Section: Discussionmentioning

confidence: 99%

Efficacy of adjuvant treatment for fracture nonunion/delayed union: a network meta-analysis of randomized controlled trials

Yang

Zhang

Liang

et al. 2022

BMC Musculoskelet Disord

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“…Research in animal models suggests that the conversion of cartilage to bone is altered as large numbers of chondrocytes appear to undergo apoptosis in diabetic models due to increased production of Tnfα (Kayal et al 2010). Similarly, persistent cartilage in hypertrophic nonunions (Panteli et al 2022) suggests a failure of the conversion of chondrocytes to osteoblasts, indicating a mechanism that could be targeted to stimulate repair. In fact, a large area of research focuses on therapies designed to enhance bone formation.…”

Section: Clinical Implications Of Mechanisms Of Bone Regenerationmentioning

confidence: 99%

A Shifting Paradigm: Transformation of Cartilage to Bone during Bone Repair

2022

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While formation and regeneration of the skeleton have been studied for a long period of time, significant scientific advances in this field continue to emerge based on an unmet clinical need to improve options to promote bone repair. In this review, we discuss the relationship between mechanisms of bone formation and bone regeneration. Data clearly show that regeneration is not simply a reinduction of the molecular and cellular programs that were used for development. Instead, the mechanical environment exerts a strong influence on the mode of repair, while during development, cell-intrinsic processes drive the mode of skeletal formation. A major advance in the field has shown that cell fate is flexible, rather than terminal, and that chondrocytes are able to differentiate into osteoblasts and other cell types during development and regeneration. This is discussed in a larger context of regeneration in vertebrates as well as the clinical implication that this shift in understanding presents.

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“…In advanced stages (> 3 months), the persistent vascularization of the fracture site can be related to a delayed union of the bony segments [ 53 ]. In the latter case, dynamic sonographic assessment can also be performed to mechanically stress the fracture and check the eventual instability of the “immature” callus mainly composed of fibrocartilaginous tissue [ 15 , 54 ]. The type of dynamic maneuver is highly variable depending on the anatomical site of fracture.…”

Section: Ultrasound Assessment Of Fracture Healingmentioning

confidence: 99%

“…We recommend firmly holding the probe over the fracture line with one hand and using the other one to passively move the target joint or apply stress forces over the fractured bone [ 55 ]. An unstable callus can progressively develop a cystic degeneration of its inner portion leading to pseudoarthrosis [ 54 ].…”

Section: Ultrasound Assessment Of Fracture Healingmentioning

confidence: 99%

Ultrasound imaging of bone fractures

et al. 2022

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Ultrasound imaging is widely used to evaluate the neuromusculoskeletal system, and recently, a particular interest is mounting in assessing the bone tissue and fractures. Ultrasound can be considered a valuable diagnostic tool to perform a first-line evaluation of bone tissue, especially in particular settings without direct access to X-ray imaging and/or in emergency conditions. Moreover, different healing phases of bone fractures can be accurately assessed by combining the B-mode modality and (high-sensitive) color/power Doppler optimizing the management of patients—e.g., planning of progressive loads and rehabilitation procedures. In this review, we summarized the role of ultrasound imaging in the management of bone fractures and described the most common sonographic signs encountered in the daily practice by assessing different types of bone fractures and the progressive phases of the healing process.

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Biological and molecular profile of fracture non‐union tissue: A systematic review and an update on current insights

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 29 publications

References 60 publications

Efficacy of adjuvant treatment for fracture nonunion/delayed union: a network meta-analysis of randomized controlled trials

Efficacy of adjuvant treatment for fracture nonunion/delayed union: a network meta-analysis of randomized controlled trials

A Shifting Paradigm: Transformation of Cartilage to Bone during Bone Repair

Ultrasound imaging of bone fractures

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