Fracture Healing and Bone Mass in Rats Fed on Liquid Diet Containing Ethanol

Elmalı, Nurzat; Ertem, Kadir; Özen, Süleyman; İnan, Muharrem; Baysal, Tamer; Güner, Güntekin; Bora, Arslan

doi:10.1111/j.1530-0277.2002.tb02568.x

Cited by 49 publications

(9 citation statements)

References 24 publications

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“…Up to 40% of orthopedic trauma patients admitted to the emergency department have elevated blood alcohol levels (Levy et al, 1996; Savola et al, 2005), suggesting that alcohol abuse may increase the risk for traumatic orthopedic injury. Clinical studies have found that while alcohol abuse also increases the risk for a non‐healing fracture injury (Chakkalakal, 2005; Elmali et al, 2002; Nyquist et al, 1997), the cellular and molecular mechanisms underlying alcohol consumption‐related fracture nonunion have not been studied extensively.…”

Section: Introductionmentioning

confidence: 99%

Episodic alcohol exposure attenuates mesenchymal stem cell chondrogenic differentiation during bone fracture callus formation

Eby

Sharieh

Azevedo

et al. 2022

Alcoholism Clin & Exp Res

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Background During bone fracture repair, mesenchymal stem cells (MSC) differentiate into chondrocytes and osteoblasts to form a fracture callus. Our laboratory previously reported that alcohol‐exposed rodents with a surgically created tibia fracture display deficient fracture callus formation and diminished signs of endochondral ossification characterized by the absence of chondrocytes and mature hypertrophic chondrocytes, suggesting that alcohol may inhibit MSC differentiation. These findings led to our hypothesis that alcohol exposure inhibits mesenchymal stem cell chondrogenic differentiation within the developing fracture callus. Methods In the present study, we utilized a lineage‐tracing approach to determine which stage(s) of chondrogenic differentiation are affected by alcohol exposure. We utilized lineage‐specific reporter mice to determine the effects of alcohol on MSC and early and late chondrogenic cell frequencies within the fracture callus. In addition, serially sectioned slides were stained immunofluorescently and immunohistochemically and quantified to determine the effect of alcohol on cell proliferation and apoptosis, respectively, within the fracture callus of alcohol‐administered rodents. Results Alcohol‐administered rodents had a reduced fracture callus area at 4, 6, and 9 days postfracture. Alcohol had no effect on apoptosis in the fracture callus at any of the examined timepoints. Alcohol‐administered rodents had significantly fewer proliferative cells in the fracture callus at 9 days postfracture, but no effect on cell proliferation was observed at earlier fracture callus timepoints. Alcohol‐administered rodents had reduced Collagen2a1‐ and Collagen10a1‐expressing cells in the developing fracture callus, suggesting that alcohol inhibits both early chondrogenic differentiation and later chondrocyte maturation during fracture callus development. Conclusion The data suggest that alcohol could affect normal fracture healing through the mitigation of MSC chondrogenic differentiation at the callus site.

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Section: Introductionmentioning

confidence: 99%

Episodic alcohol exposure attenuates mesenchymal stem cell chondrogenic differentiation during bone fracture callus formation

Eby

Sharieh

Azevedo

et al. 2022

Alcoholism Clin & Exp Res

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“…Deregulation of Wnt signaling due to alcohol exposure could be another mechanism of impairment of MSC differentiation, and an incomplete healing process persists up to two weeks post-fracture [127]. Chronic alcohol exposure had an effect on fracture healing with decreased mineralization, as reported in different experimental studies [128][129][130]. Testing the mineralization using alizarin red and perchloric acid staining as well as measuring osteoblast-specific genes, RUNX2, BGLAP and COL1A1, revealed that ethanol-treated MSCs had a significantly lower osteogenic capacity due to downregulation of the SIRT1 gene [131].…”

Section: Pre-clinical Studiesmentioning

confidence: 71%

Bone Marrow Multipotent Mesenchymal Stromal Cells as Autologous Therapy for Osteonecrosis: Effects of Age and Underlying Causes

et al. 2021

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Bone marrow (BM) is a reliable source of multipotent mesenchymal stromal cells (MSCs), which have been successfully used for treating osteonecrosis. Considering the functional advantages of BM-MSCs as bone and cartilage reparatory cells and supporting angiogenesis, several donor-related factors are also essential to consider when autologous BM-MSCs are used for such regenerative therapies. Aging is one of several factors contributing to the donor-related variability and found to be associated with a reduction of BM-MSC numbers. However, even within the same age group, other factors affecting MSC quantity and function remain incompletely understood. For patients with osteonecrosis, several underlying factors have been linked to the decrease of the proliferation of BM-MSCs as well as the impairment of their differentiation, migration, angiogenesis-support and immunoregulatory functions. This review discusses the quality and quantity of BM-MSCs in relation to the etiological conditions of osteonecrosis such as sickle cell disease, Gaucher disease, alcohol, corticosteroids, Systemic Lupus Erythematosus, diabetes, chronic renal disease and chemotherapy. A clear understanding of the regenerative potential of BM-MSCs is essential to optimize the cellular therapy of osteonecrosis and other bone damage conditions.

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“…DWB is commonly prescribed to patients deemed to be at higher risk of complications and the role of selection bias in producing our results must be considered. Factors known to increase rates of complications include older age [ 25 ], smoking [ 26 ], alcohol [ 27 ], diabetes mellitus (DM) [ 28 ], obesity [ 29 ], OTA 42C fractures [ 30 , 31 ] and open fracture [ 32 ]. Furthermore, it is possible that reamed nailing may minimise non-union [ 5 , 33 ], while the effect of dynamic nailing on union time and complication rates has produced mixed results [ 34 – 36 ].…”

Section: Discussionmentioning

confidence: 99%

Outcomes of early versus delayed weight-bearing with intramedullary nailing of tibial shaft fractures: a systematic review and meta-analysis

Bhanushali

Kovoor

Stretton

et al. 2022

Eur J Trauma Emerg Surg

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Purpose Early weight bearing (EWB) is often recommended after intramedullary nailing of tibial shaft fractures, however, the risks and benefits have not been critically evaluated in a systematic review or meta-analysis. Therefore, the aims of this study were to perform a systematic review and meta-analysis comparing EWB and delayed weight-bearing (DWB) after intramedullary nailing of tibial shaft fractures and assess the relationship between weight-bearing, fracture union and healing. Method This review included studies comparing the effects of EWB, defined as weight-bearing before 6 weeks, and DWB on fracture union and healing. PubMed, Embase, CINAHL, and the Cochrane Library were searched from inception to 9 May 2021. Risk of bias was assessed using the Down’s and Black Checklist and Cochrane Risk of Bias Tool 2.0. Data were synthesised in a meta-analysis, as well as narrative and tabular synthesis. Results Eight studies were included for data extraction and meta-analysis. The analysis produced mixed results and found a significant decrease in mean union time (−2.41 weeks, 95% confidence interval: −4.77, −0.05) with EWB and a significant Odd’s Ratio (OR) for complications with DWB (OR: 2.93, 95% CI: 1.40, 6.16). There was no significant difference in rates of delayed union, non-union, re-operation and malunion. Conclusion The included studies were of moderate risk of bias and demonstrated shorter union time and fewer complications with EWB. However, current evidence is minimal and has significant limitations. The role of EWB in high-risk patients is yet to be examined. Further well-designed, randomised studies are required on the topic.

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Fracture Healing and Bone Mass in Rats Fed on Liquid Diet Containing Ethanol

Abstract: This study showed that rats fed on a diet mixed with ethanol have a histologically delayed fracture healing associated with decreased bone density and mineral content. Besides the negative effects of ethanol on bone metabolism, it also interferes with the fracture-healing process.

Cited by 49 publications

References 24 publications

Episodic alcohol exposure attenuates mesenchymal stem cell chondrogenic differentiation during bone fracture callus formation

Episodic alcohol exposure attenuates mesenchymal stem cell chondrogenic differentiation during bone fracture callus formation

Bone Marrow Multipotent Mesenchymal Stromal Cells as Autologous Therapy for Osteonecrosis: Effects of Age and Underlying Causes

Outcomes of early versus delayed weight-bearing with intramedullary nailing of tibial shaft fractures: a systematic review and meta-analysis

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