scholarly journals Lithium for Fracture Treatment (LiFT): a double-blind randomised control trial protocol

BMJ Open ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. e031545 ◽  
Author(s):  
Diane Nam ◽  
Phumeena Balasuberamaniam ◽  
Katrine Milner ◽  
Monica Kunz ◽  
Kathak Vachhani ◽  
...  
Keyword(s):  
Fracture Healing ◽  
Bone Fractures ◽  
Fracture Site ◽  
Long Bone ◽  
Randomised Control Trial ◽  
Secondary Outcome ◽  
Double Blind ◽  
Carbonate Group ◽  
Main Trial ◽  
Radiographic Union

IntroductionFracture healing can fail in up to 10% of cases despite appropriate treatment. While lithium has been the standard treatment for bipolar disorder, it may also have a significant impact to increase bone healing in patients with long bone fractures. To translate this knowledge into clinical practice, a randomised clinical trial (RCT) is proposed.Methods and analysisA multicentre double blind, placebo-controlled RCT is proposed to evaluate the efficacy of lithium to increase the rate and predictability of long bone fracture healing in healthy adults compared to lactose placebo treatment. 160 healthy individuals from 18 to 55 years of age presenting with shaft fractures of the femur, tibia/fibula, humerus or clavicle will be eligible. Fractures will be randomised to placebo (lactose) or treatment (300 mg lithium carbonate) group within 2 weeks of the injury. The primary outcome measure will be radiographic union defined as visible callus bridging on three of the four cortices at the fracture site using a validated radiographic union score. Secondary outcome measures will include functional assessment and pain scoring.Ethics and disseminationParticipant confidentiality will be maintained with publication of results. Research Ethics Board Approval: Sunnybrook Research Institute (REB # 356–2016). Health Canada Approval (HC6-24-C201560). Results of the main trial and secondary endpoints will be submitted for publication in a peer-reviewed journal and presented at conferences.Trial registration numberNCT02999022.

Effect of Intramedullary Nailing Patterns On Interfragmentary Strain in a Mouse Femur Fracture: a Parametric Finite Element Analysis

2021 ◽  
Author(s):  
Gregory Lowen ◽  
Katherine Garrett ◽  
Moore-Lotridge Stephanie ◽  
Sasidhar Uppuganti ◽  
Scott A. Guelcher ◽  
...  
Keyword(s):  
Finite Element Analysis ◽  
Finite Element ◽  
Fracture Healing ◽  
Bone Repair ◽  
Bone Fractures ◽  
Fracture Site ◽  
Fracture Repair ◽  
Long Bone ◽  
Design Parameters ◽  
Element Analysis

Abstract Delayed long bone fracture healing and nonunion continue to be a significant socioeconomic burden. While mechanical stimulation is known to be an important determinant of the bone repair process, understanding how the magnitude, mode, and commencement of interfragmentary strain (IFS) affect fracture healing can guide new therapeutic strategies to prevent delayed healing or non-union. Mouse models provide a means to investigate the molecular and cellular aspects of fracture repair, yet there is only one commercially available, clinically-relevant, locking intramedullary nail (IMN) currently available for studying long bone fractures in rodents. Having access to alternative IMNs would allow a variety of mechanical environments at the fracture site to be evaluated, and the purpose of this proof-of-concept finite element analysis study is to identify which IMN design parameters have the largest impact on IFS in a murine transverse femoral osteotomy model. Using the dimensions of the clinically relevant IMN as a guide, the nail material, distance between interlocking screws, and clearance between the nail and endosteal surface were varied between simulations. Of these parameters, changing the nail material from stainless steel (SS) to polyetheretherketone (PEEK) had the largest impact on IFS. Reducing the distance between the proximal and distal interlocking screws substantially affected IFS only when nail modulus was low. Therefore, IMNs with low modulus (e.g., PEEK) can be used alongside commercially available SS nails to investigate the effect of initial IFS or stability on fracture healing with respect to different biological conditions of repair in rodents.

scholarly journals Percutaneous administration of allogeneic bone-forming cells for the treatment of delayed unions of fractures: a pilot study

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Marc Jayankura ◽  
Arndt Peter Schulz ◽  
Olivier Delahaut ◽  
Richard Witvrouw ◽  
Lothar Seefried ◽  
...  
Keyword(s):  
Pilot Study ◽  
Adverse Events ◽  
Phase I ◽  
Bone Fractures ◽  
Fracture Site ◽  
Post Treatment ◽  
Long Bone ◽  
Allogeneic Bone ◽  
Hla Antibodies ◽  
Long Bone Fractures

Abstract Background Overall, 5–10% of fractures result in delayed unions or non-unions, causing major disabilities and a huge socioeconomic burden. Since rescue surgery with autologous bone grafts can cause additional challenges, alternative treatment options have been developed to stimulate a deficient healing process. This study assessed the technical feasibility, safety and preliminary efficacy of local percutaneous implantation of allogeneic bone-forming cells in delayed unions of long bone fractures. Methods In this phase I/IIA open-label pilot trial, 22 adult patients with non-infected delayed unions of long bone fractures, which failed to consolidate after 3 to 7 months, received a percutaneous implantation of allogeneic bone-forming cells derived from bone marrow mesenchymal stem cells (ALLOB; Bone Therapeutics) into the fracture site (50 × 106 to 100 × 106 cells). Patients were monitored for adverse events and need for rescue surgery for 30 months. Fracture healing was monitored by Tomographic Union Score (TUS) and modified Radiographic Union Score. The health status was evaluated using the Global Disease Evaluation (GDE) score and pain at palpation using a visual analogue scale. The presence of reactive anti-human leukocyte antigen (HLA) antibodies was evaluated. Results During the 6-month follow-up, three serious treatment-emergent adverse events were reported in two patients, of which two were considered as possibly treatment-related. None of the 21 patients in the per-protocol efficacy population needed rescue surgery within 6 months, but 2/21 (9.5%) patients had rescue surgery within 30 months post-treatment. At 6 months post-treatment, an improvement of at least 2 points in TUS was reached in 76.2% of patients, the GDE score improved by a mean of 48%, and pain at palpation at the fracture site was reduced by an average of 61% compared to baseline. The proportion of blood samples containing donor-specific anti-HLA antibodies increased from 8/22 (36.4%) before treatment to 13/22 (59.1%) at 6 months post-treatment, but no treatment-mediated allogeneic immune reactions were observed. Conclusion This pilot study showed that the percutaneous implantation of allogeneic bone-forming cells was technically feasible and well tolerated in patients with delayed unions of long bone fractures. Preliminary efficacy evidence is supporting the further development of this treatment. Trial registration NCT02020590. Registered on 25 December 2013. ALLOB-DU1, A pilot Phase I/IIa, multicentre, open proof-of-concept study on the efficacy and safetyof allogeneic osteoblastic cells (ALLOB®) implantation in non-infected delayed-union fractures.

scholarly journals Mechanical flexural ex vivo study of osteotomized swine femurs stabilized with two types of polyamide 12 rods

2017 ◽  
Vol 47 (8) ◽  
Author(s):  
Juliana Scarpa da Silveira Almeida ◽  
Débora de Oliveira Garcia ◽  
Renato Camargo Bortholin ◽  
Carlos Amaral Razzino ◽  
Cristiane dos Santos Honsho ◽  
...  
Keyword(s):  
Bone Fractures ◽  
Ex Vivo ◽  
Polymeric Materials ◽  
Fracture Site ◽  
Medullary Canal ◽  
Modulus Of Rupture ◽  
Long Bone ◽  
Bone Implant ◽  
Polyamide 12 ◽  
Implant System

ABSTRACT: Long bone fractures are commonly in surgery routine and several bone imobilization techniques are currently available. Technological progress has enabled to use low cost materials in surgical procedures. Thus, the aim of this study was to evaluate the applicability of polyamide 12 rods, solid and hollow in swine femurs, comparing them through flexion strength. This study had as second aim to fix the locking errors, commom place in interlocking nails, once polyamide 12 allows perforation in any direction by orthopaedic screw. Six groups were used: G1 - eight whole swine femurs; G2 - eight whole swine femurs with drilled medullary canal; G3 - two solid polyamide 12 rods; G4 - two hollow polyamide 12 rods; G5 - eight osteotomized drilled swine femurs with a solid polyamide 12 rod implanted in the medullary canal and locked by four 316L stainless steel screws; and G6 - similar to G5 but using hollow rods instead of solid ones. No significant differences were observed for the modulus of rupture between solid and hollow rods, demonstrating that both rods had similar performances. These results led to the speculation that the addition of other polymers to the hollow rods could increase their strength and thus the bone-implant system. Furthermore, the comparison between G1, G5 and G6 could be analyzed using the finite element method in future. New polymeric materials may be developed based on the data from this study, strengthening the bone-implant system and making possible screws to be placed in any direction, nullifying the detrimental forces on the fracture site.

scholarly journals Development and Biocompatibility Characterization of a BioMEMS Sensor for Monitoring the Progression of Fracture Healing

2009 ◽  
Author(s):  
Brandon G. Santoni ◽  
Rohat Melik ◽  
Emre Unal ◽  
Nihan Kosku Perkgoz ◽  
Debra A. Kamstock ◽  
...  
Keyword(s):  
United States ◽  
Fracture Healing ◽  
Bone Fractures ◽  
Financial Burden ◽  
Early Period ◽  
The United States ◽  
Long Bone ◽  
Extremity Injuries ◽  
Manual Manipulation

Orthopaedic extremity injuries present a large medical and financial burden to the United States and world-wide communities [1]. Approximately six million long bone fractures are reported annually in the United States and approximately 10% of these fractures do not heal properly. Though the exact mechanism of impaired healing is poorly understood, many of these non-unions result when there is a communited condition that does not proceed through a stabilized healing pathway [2]. Currently, clinicians may monitor healing visually by radiographs, or via manual manipulation of the bone at the fracture [3]. Unfortunately, the course of aberrant fracture healing is not easily diagnosed in the early period when standard radiographic information of the fracture is not capable of discriminating the healing pathway. Manual assessment of fracture healing is also an inadequate diagnostic tool in the early stages of healing [4].

scholarly journals Gukang Capsule Promotes Fracture Healing by Activating BMP/SMAD and Wnt/β-Catenin Signaling Pathways

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Xue Ma ◽  
Jian Yang ◽  
Ting Liu ◽  
Jing Li ◽  
Yanyu Lan ◽  
...  
Keyword(s):  
Fracture Healing ◽  
Signaling Pathways ◽  
Bone Fractures ◽  
Glycogen Synthase ◽  
Fracture Site ◽  
Bone Morphogenetic Protein 2 ◽  
Radius Fracture ◽  
Smad Signaling ◽  
Alp Activity ◽  
Human Osteosarcoma Cells

Background. Gukang capsule (GKC) is a traditional Chinese medicine formulation which has been used extensively in the clinical treatment of bone fractures. However, the mechanisms underlying its effects on fracture healing remain unclear. Methods. In this study we used a rabbit radius fracture model, and we measured the serum content of bone alkaline phosphatase (ALP), calcium, and phosphorus and examined pathology of the fracture site as indicators of the fracture healing effects of GKC. SaOS-2 human osteosarcoma cells were used to measure (i) ALP activity, (ii) ornithine transcarbamylase (OTC), calcium, and mineralization levels, (iii) the expression of osteogenic-related genes, that is, runt-related transcription factor 2 (RUNX2), bone morphogenetic protein 2 (BMP2), collagen I (COL-I), osteopontin (OPN), OTC, and osterix (Osx), and (iv) the expression of key proteins in the Wnt/β-catenin and BMP/SMAD signaling pathways to study the mechanisms by which GKC promotes fracture healing. Results. We found that GKC effectively promotes radius fracture healing in rabbits and enhances ALP activity, increases OTC and calcium levels, and stimulates the formation of mineralized nodules in SaOS-2 cells. Moreover, COL-I, OTC, Osx, BMP2, and OPN expression levels were higher in SaOS-2 cells treated with GKC than control cells. GKC upregulates glycogen synthase kinase 3β (GSK3β) phosphorylation and Smad1/5 and β-catenin protein levels, thereby activating Wnt/β-catenin and BMP/Smad signaling pathways. Inhibitors of the Wnt/β-catenin and BMP/Smad signaling pathways (DKK1 and Noggin, respectively) suppress the osteogenic effects of GKC. Conclusions. GKC promotes fracture healing by activating the Wnt/β-catenin and BMP/Smad signaling pathways and increasing osteoprotegerin (OPG) secretion by osteoblasts (OBs), which prevents receptor activator of nuclear factor kappa B ligand (RANKL) binding to RANK.

scholarly journals What is the role of ultrasound in fracture management?

2019 ◽  
Vol 8 (7) ◽  
pp. 304-312 ◽  
Author(s):  
J. A. Nicholson ◽  
S. T. J. Tsang ◽  
T. J. MacGillivray ◽  
F. Perks ◽  
A. H. R. W. Simpson
Keyword(s):  
Image Processing ◽  
Fracture Healing ◽  
Bone Fractures ◽  
Therapeutic Ultrasound ◽  
Long Bone ◽  
Future Application ◽  
Current Evidence ◽  
Potential Clinical Benefit ◽  
Fracture Management

Objectives The aim of this study was to review the current evidence and future application for the role of diagnostic and therapeutic ultrasound in fracture management. Methods A review of relevant literature was undertaken, including articles indexed in PubMed with keywords “ultrasound” or “sonography” combined with “diagnosis”, “fracture healing”, “impaired fracture healing”, “nonunion”, “microbiology”, and “fracture-related infection”. Results The use of ultrasound in musculoskeletal medicine has expanded rapidly over the last two decades, but the diagnostic use in fracture management is not routinely practised. Early studies have shown the potential of ultrasound as a valid alternative to radiographs to diagnose common paediatric fractures, to detect occult injuries in adults, and for rapid detection of long bone fractures in the resuscitation setting. Ultrasound has also been shown to be advantageous in the early identification of impaired fracture healing; with the advent of 3D image processing, there is potential for wider adoption. Detection of implant-related infection can be improved by ultrasound mediated sonication of microbiology samples. The use of therapeutic ultrasound to promote union in the management of acute fractures is currently a controversial topic. However, there is strong in vitro evidence that ultrasound can stimulate a biological effect with potential clinical benefit in established nonunions, which supports the need for further investigation. Conclusion Modern ultrasound image processing has the potential to replace traditional imaging modalities in several areas of trauma practice, particularly in the early prediction of impaired fracture healing. Further understanding of the therapeutic application of ultrasound is required to understand and identify the use in promoting fracture healing. Cite this article: J. A. Nicholson, S. T. J. Tsang, T. J. MacGillivray, F. Perks, A. H. R. W. Simpson. What is the role of ultrasound in fracture management? Diagnosis and therapeutic potential for fractures, delayed unions, and fracture-related infection. Bone Joint Res 2019;8:304–312. DOI: 10.1302/2046-3758.87.BJR-2018-0215.R2.

Development of a Bioabsorbable Glass-Reinforced-Glass Intra-Osseous Scaffold for Fracture Healing

2011 ◽  
Vol 9 ◽  
pp. 81-91
Author(s):  
Philip Boughton ◽  
Y. Chen ◽  
C. Thompson ◽  
G. Roger ◽  
Jari Hyvarinen ◽  
...  
Keyword(s):  
Fracture Healing ◽  
Bone Fractures ◽  
Stress Shielding ◽  
Long Bone ◽  
Hematopoietic Tissue ◽  
Shear Tests ◽  
Intramedullary Canal ◽  
Long Bone Fracture ◽  
Torsional Loads ◽  
Mechanically Stabilized

Intramedullary (IM) nails are routinely used to stabilize long bone fractures. They can however lead to stress shielding, pain, migration, obstruct hematopoietic tissue, become a loci for infection, and require subsequent surgical retrieval. Novel intra-osseous scaffold (IOS™) prototypes for fracture healing have been developed to function as a regenerative scaffold to enhance callous formation under mechanically stabilized conditions then resorb. Prototype fixation pins and rod systems were formed from glass-reinforced-glass. Flexion, torsion and shear tests were performed to evaluate the composite pins and rods. A modular rod design was successfully deployed and dilated while in a deformable state. When fitted and gripping the intramedullary canal then set in a rigid state. An obliquely sectioned ovine femur was used as a long bone fracture model for deployment and mechanical verification. Flexural support provided by the intramedullary scaffold was superior to multiple k-wire fixation, while the k-wire approach was more stabilizing under torsional loads. Glass reinforced glass samples were mechanically tested after soaking for up to 4 weeks in saline. Strength and modulus of the composite was reduced to approximately 25% of initial values after 2 weeks.

Enhancement of Long Bone Fracture Healing by Local Soft Tissue Compression1

2014 ◽  
Vol 8 (2) ◽  
Author(s):  
Ernest C. Chisena ◽  
Jahangir S. Rastegar ◽  
Robert S. Chisena
Keyword(s):  
Blood Flow ◽  
Fracture Healing ◽  
Soft Tissues ◽  
Fracture Site ◽  
Long Bone ◽  
Bony Union ◽  
Bone Fracture Healing ◽  
Mechanical Pressure ◽  
Long Bone Fracture ◽  
Local Oxygen

Endochondral fracture healing, the process in which callus bridges a fracture, can be enhanced using a brace with a deforming element. This deforming element acts to locally increase pressure at the fracture site. In this paper, we describe a bracing device, which has the capability of controlling blood flow in targeted regions of an extremity. Controlling the blood flow around a fracture site induces a mechanism that enhances fracture healing. We hypothesize that, since local oxygen tension is lowered by means of controlling the blood flow at the fracture site, fracture healing is accelerated and bony union is more likely. Using the results of several previous studies, we will show that increased mechanical pressure in the soft tissues over the fracture site enhances fracture healing.

BOSENTAN, A NON-SPECIFIC ENDOTHELIN ANTAGONIST, STIMULATES FRACTURE HEALING

2007 ◽  
Vol 19 (01) ◽  
pp. 37-46 ◽  
Author(s):  
Hasan H. Muratli ◽  
Feza Korkusuz ◽  
Petek Korkusuz ◽  
Ali Bicimoglu ◽  
Z. Sevim Ercan
Keyword(s):  
Fracture Healing ◽  
Bone Fractures ◽  
Fracture Site ◽  
Controlled Study ◽  
Prostaglandin E ◽  
Matrix Mineralization ◽  
Hind Limbs ◽  
Diaphyseal Bone ◽  
Activity Measurements ◽  
Intramedullary Rod

It is assumed that bosentan, a non-selective ET-1 receptor antagonist, will enhance fracture healing. The aim of this prospective randomized controlled study was to investigate the effects of transcutaneous bosentan administration into diaphyseal bone fractures using radiology, histology, prostaglandin E2 (PGE2) and leukotrien C 4 (LTC4) activity measurements. A closed diaphyseal fracture was created in the hind limbs following intramedullary rod fixation of Guinea pigs. Bosentan was administred by repetitive weekly 0.1 μg transcutaneous injections into the fracture site. The effects of bosentan were evaluated by radiology and histology on weeks 1, 2 and 4, whereas prostaglandin E2 (PGE2)-like and leukotrien C 4 (LTC4)-like activity was assessed on weeks 1 and 2. The radiological degree of union (p = 0.001) at the fracture site and cortex-callus ratio (p = 0.02) was significantly better in the bosentan administered site at week 1 when compared to the control. Histology presented an initial stimulation of bone formation on weeks 1 and 2 in the experimental group. PGE2-like activity was significantly higher (p = 0.002) on week 1 and 2 in the bosentan-administered side. LTC4-like activity remained constant on week one and decreased on week two. Transcutaneous repetitive bosentan administration into the fracture site initially stimulated periosteal bone healing that resulted with extracellular matrix mineralization. The inflammatory mediators PGE2/LTC4 played a significant role in this process.

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