scholarly journals Short-Term Bone Healing Response to Mechanical Stimulation—A Case Series Conducted on Sheep

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 988
Author(s):  
Jan Barcik ◽  
Manuela Ernst ◽  
Marc Balligand ◽  
Constantin Edmond Dlaska ◽  
Ludmil Drenchev ◽  
...  
Keyword(s):  
Fracture Healing ◽  
Bone Healing ◽  
Mechanical Stimulation ◽  
Callus Formation ◽  
Case Series ◽  
Tibial Osteotomy ◽  
Tissue Stiffness ◽  
Short Term ◽  
Custom Made ◽  
Post Operation

It is well known that mechanical stimulation promotes indirect fracture healing by triggering callus formation. We investigated the short-term response of healing tissue to mechanical stimulation to compare the changes in tissue stiffness during stimulation and resting phases in a preclinical case-series. Four sheep underwent a tibial osteotomy and were instrumented with a custom-made active fixator which applied a mechanical stimulation protocol of 1000 cycles/day, equally distributed over 12 h, followed by 12 h of rest. During each cycle, a surrogate metric for tissue stiffness was measured, enabling a continuous real-time monitoring of the healing progression. A daily stiffness increase during stimulation and an increase during resting were evaluated for each animal. One animal had to be excluded from the evaluation due to technical reasons. For all included animals, the stiffness began to increase within the second week post-op. A characteristic pattern was observed during daily measurements: the stiffness dropped considerably within the first stimulation cycles followed by a steady rise throughout the rest of the stimulation phase. However, for all included animals, the average daily stiffness increase within the first three weeks post operation was larger during resting than during stimulation (Sheep I: 16.9% vs. −5.7%; Sheep II: 14.7% vs. −1.8%; Sheep III: 8.9% vs. 1.6%). A continuous measurement of tissue stiffness together with a controlled fracture stimulation enabled the investigation of the short-term effects of specific stimulatory parameters, such as resting periods. Resting was identified as a potentially determining factor for bone healing progression. Optimizing the ratio between stimulation and resting may contribute to more robust fracture healing in the future.

scholarly journals Can Optimizing the Mechanical Environment Deliver a Clinically Significant Reduction in Fracture Healing Time?

Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 691
Author(s):  
Jan Barcik ◽  
Devakara R. Epari
Keyword(s):  
Fracture Healing ◽  
Bone Healing ◽  
Mechanical Stimulation ◽  
Callus Formation ◽  
Weight Bearing ◽  
Healing Process ◽  
Healing Time ◽  
Mechanical Environment ◽  
Clinically Significant ◽  
The Impact

The impact of the local mechanical environment in the fracture gap on the bone healing process has been extensively investigated. Whilst it is widely accepted that mechanical stimulation is integral to callus formation and secondary bone healing, treatment strategies that aim to harness that potential are rare. In fact, the current clinical practice with an initially partial or non-weight-bearing approach appears to contradict the findings from animal experiments that early mechanical stimulation is critical. Therefore, we posed the question as to whether optimizing the mechanical environment over the course of healing can deliver a clinically significant reduction in fracture healing time. In reviewing the evidence from pre-clinical studies that investigate the influence of mechanics on bone healing, we formulate a hypothesis for the stimulation protocol which has the potential to shorten healing time. The protocol involves confining stimulation predominantly to the proliferative phase of healing and including adequate rest periods between applications of stimulation.

scholarly journals Analysis of low-dose estrogen on callus BMD as measured by pQCT in postmenopausal women

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
K. Jäckle ◽  
J. P. Kolb ◽  
A. F. Schilling ◽  
C. Schlickewei ◽  
M. Amling ◽  
...  
Keyword(s):  
Bone Density ◽  
Beneficial Effect ◽  
Fracture Healing ◽  
Postmenopausal Women ◽  
Bone Healing ◽  
Bone Fracture ◽  
Low Dose ◽  
Callus Formation ◽  
Trial Registration ◽  
Bone Fracture Healing

Abstract Background Osteoporosis affects elderly patients of both sexes. It is characterized by an increased fracture risk due to defective remodeling of the bone microarchitecture. It affects in particular postmenopausal women due to their decreased levels of estrogen. Preclinical studies with animals demonstrated that loss of estrogen had a negative effect on bone healing and that increasing the estrogen level led to a better bone healing. We asked whether increasing the estrogen level in menopausal patients has a beneficial effect on bone mineral density (BMD) during callus formation after a bone fracture. Methods To investigate whether estrogen has a beneficial effect on callus BMD of postmenopausal patients, we performed a prospective double-blinded randomized study with 76 patients suffering from distal radius fractures. A total of 31 patients (71.13 years ±11.99) were treated with estrogen and 45 patients (75.62 years ±10.47) served as untreated controls. Calculated bone density as well as cortical bone density were determined by peripheral quantitative computed tomography (pQCT) prior to and 6 weeks after the surgery. Comparative measurements were performed at the fractured site and at the corresponding position of the non-fractured arm. Results We found that unlike with preclinical models, bone fracture healing of human patients was not improved in response to estrogen treatment. Furthermore, we observed no dependence between age-dependent bone tissue loss and constant callus formation in the patients. Conclusions Transdermally applied estrogen to postmenopausal women, which results in estrogen levels similar to the systemic level of premenopausal women, has no significant beneficial effect on callus BMD as measured by pQCT, as recently shown in preclinical animal models. Trial registration Low dose estrogen has no significant effect on bone fracture healing measured by pQCT in postmenopausal women, DRKS00019858. Registered 25th November 2019 - Retrospectively registered. Trial registration number DRKS00019858.

scholarly journals Influence of high-frequency cyclical stimulation on the bone fracture-healing process: mathematical and experimental models

2011 ◽  
Vol 369 (1954) ◽  
pp. 4278-4294 ◽  
Author(s):  
María José Gómez-Benito ◽  
Libardo Andrés González-Torres ◽  
Esther Reina-Romo ◽  
Jorge Grasa ◽  
Belén Seral ◽  
...  
Keyword(s):  
Fracture Healing ◽  
Bone Healing ◽  
Mechanical Stimulation ◽  
Bone Fracture ◽  
High Frequency ◽  
Endochondral Ossification ◽  
Healing Process ◽  
Bone Fracture Healing ◽  
Bone Healing Process ◽  
Low Magnitude

Mechanical stimulation affects the evolution of healthy and fractured bone. However, the effect of applying cyclical mechanical stimuli on bone healing has not yet been fully clarified. The aim of the present study was to determine the influence of a high-frequency and low-magnitude cyclical displacement of the fractured fragments on the bone-healing process. This subject is studied experimentally and computationally for a sheep long bone. On the one hand, the mathematical computational study indicates that mechanical stimulation at high frequencies can stimulate and accelerate the process of chondrogenesis and endochondral ossification and consequently the bony union of the fracture. This is probably achieved by the interstitial fluid flow, which can move nutrients and waste from one place to another in the callus. This movement of fluid modifies the mechanical stimulus on the cells attached to the extracellular matrix. On the other hand, the experimental study was carried out using two sheep groups. In the first group, static fixators were implanted, while, in the second one, identical devices were used, but with an additional vibrator. This vibrator allowed a cyclic displacement with low magnitude and high frequency (LMHF) to be applied to the fractured zone every day; the frequency of stimulation was chosen from mechano-biological model predictions. Analysing the results obtained for the control and stimulated groups, we observed improvements in the bone-healing process in the stimulated group. Therefore, in this study, we show the potential of computer mechano-biological models to guide and define better mechanical conditions for experiments in order to improve bone fracture healing. In fact, both experimental and computational studies indicated improvements in the healing process in the LMHF mechanically stimulated fractures. In both studies, these improvements could be associated with the promotion of endochondral ossification and an increase in the rate of cell proliferation and tissue synthesis.

Controlled Cyclic Compression of an Open Tibial Fracture Using an External Fixator Affects Fracture Healing in Mice

2015 ◽  
Vol 137 (5) ◽  
Author(s):  
Jennifer A. Currey ◽  
Megan Mancuso ◽  
Sylvie Kalikoff ◽  
Erin Miller ◽  
Sean Day
Keyword(s):  
Fracture Healing ◽  
Mechanical Stimulation ◽  
External Fixator ◽  
Qualitative Assessment ◽  
Control Group ◽  
External Fixators ◽  
Tibial Osteotomy ◽  
Micro Computed Tomography ◽  
Trabecular Thickness ◽  
Significant Difference

Fractures resulting in impaired healing can be treated with mechanical stimulation via external fixators. To examine the effect of mechanical stimulation on fracture healing, we developed an external fixator for use in a mouse model. A 0.5 mm tibial osteotomy was stabilized with the external fixator in C57BL/6 mice. Osteotomies in the treatment group (nt = 41) were subjected to daily sessions of 150 μm of controlled displacement with the aim to create a more mineralized callus at 21 days compared with the control group (nc = 39). Qualitative assessment of the histology found no notable difference in healing patterns between groups at 7, 12, 17, and 21 days. At 21 days, micro-computed tomography (CT) analysis showed that the control group had a significantly higher bone volume (BV) fraction and trabecular number compared with treatment; however there was no significant difference in the total volume (TV) of the callus or trabecular thickness between groups. In summary, the external fixator was used with a motion application system to apply controlled displacement to a healing fracture; however, this treatment did not result in a more mineralized callus at 21 days.

scholarly journals The Effects of Autologous Platelet-Rich Plasma on the Bone Fracture Healing in Rabbits

2019 ◽  
Vol 12 (2) ◽  
Keyword(s):  
Fracture Healing ◽  
Callus Formation ◽  
Platelet Rich Plasma ◽  
Histological Finding ◽  
Control Group ◽  
Post Operation ◽  
Group A ◽  
Autologous Platelet Rich Plasma ◽  
Group B ◽  
Autologous Platelet

The purpose of this study was to evaluate the effects of an autologous platelet rich-plasma on femoral fracture healing in experimentally induced rabbits’ model. In this study, 34 local breed rabbits, around 2-2.5 kg body weight, were divided into two equal groups randomly; Group A: platelet-rich plasma (PRP) and Groups B: Control group. Rabbits in both groups underwent a complete mid-shaft transverse osteotomy of the femur by a fine electrical saw. After fracture induction, the rabbits in group A (PRP group) were treated by application of 0.5 ml of autologous PRP at the site of the fractured bone, while in group B (control), rabbits were injected with distilled water. Samples from the fractured femur were collected at 10th, 20th, 30th days post operation for radiological evaluation and at 10th, 14th, 20th, and 30th days for histopathological evaluation. In radiological study, it was found that the rate of callus formation in rabbits treated with PRP (Group A) were faster than the control group (Group B) at different periods. Similarly, in histological finding it found that the stages of healing were faster in Group A when compared with Group B. It was concluded that using autologous PRP has beneficial effect to enhance the process of bone healing in the rabbit’s model.

scholarly journals Flunixin Meglumine Enhanced Bone Fracture Healing in  Rabbits Associated with Activation of Early Collagen Deposition and Enhancement of Vascular Endothelial Growth Factor Expression

Animals ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 2834
Author(s):  
Mohamed Elgendy ◽  
Gamal Elsayad ◽  
Magdi Seleim ◽  
Walied Abdo ◽  
Roua S. Baty ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Fracture Healing ◽  
Bone Healing ◽  
Callus Formation ◽  
Control Group ◽  
Vascular Endothelial ◽  
Collagen Deposition ◽  
Flunixin Meglumine ◽  
Endothelial Growth Factor

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly used postoperative analgesics, antipyretics, and anti-inflammatories, and they help prevent blood clotting. However, most NSAIDs delay bone healing. This study was aimed to investigate bone healing in a rabbit animal model by assessing the ability of flunixin meglumine (FM) and ketoprofen to induce fracture healing by examining histology, radiological changes, and vascular endothelial growth factor (VEGF) immunostaining during bone healing. For this purpose, 24 New Zealand rabbits were assigned to three groups: the control group, the FM group, and the ketoprofen group. Our results revealed that there were no intraoperative complications, and all surviving rabbits achieved full-weight bearing. Significant periosteal reaction and callus formation were confirmed at 2 postoperative weeks. Interestingly, FM enhanced callus formation, bone union, and remodeling in the FM group compared to the control and ketoprofen groups. FM enhanced bone healing through early collagen deposition and marked angiogenesis process activation by increasing the expression of VEGF. Our findings demonstrated, for the first time, the potential imperative action of FM in the bone healing process rather than other NSAIDs in animals.

scholarly journals Analysis of low-dose estrogen on callus BMD as measured by pQCT in postmenopausal women

2020 ◽  
Author(s):  
Katharina Blanka Dr. Jäckle ◽  
Jan Philipp Kolb ◽  
Arndt F Schilling ◽  
Carsten Schlickewei ◽  
Michael Amling ◽  
...  
Keyword(s):  
Bone Density ◽  
Beneficial Effect ◽  
Fracture Healing ◽  
Postmenopausal Women ◽  
Bone Healing ◽  
Bone Fracture ◽  
Low Dose ◽  
Callus Formation ◽  
Trial Registration ◽  
Bone Fracture Healing

Abstract Background: Osteoporosis affects elderly patients of both sexes. It is characterized by an increased fracture risk due to defective remodeling of the bone microarchitecture. It affects in particular postmenopausal women due to their decreased levels of estrogen. Preclinical studies with animals demonstrated that loss of estrogen had a negative effect on bone healing and that increasing the estrogen level led to a better bone healing. We asked whether increasing the estrogen level in menopausal patients has a beneficial effect on bone mineral density (BMD) during callus formation after a bone fracture.Methods: To investigate whether estrogen has a beneficial effect on callus BMD of postmenopausal patients, we performed a prospective double-blinded randomized study with 76 patients suffering from distal radius fractures. A total of 31 patients (71.13 years ± 11.99) were treated with estrogen and 45 patients (75.62 years ± 10.47) served as untreated controls. Calculated bone density as well as cortical bone density were determined by peripheral quantitative computed tomography (pQCT) prior to and six weeks after the surgery. Comparative measurements were performed at the fractured site and at the corresponding position of the non-fractured arm.Results: We found that unlike with preclinical models, bone fracture healing of human patients was not improved in response to estrogen treatment. Furthermore, we observed no dependence between age-dependent bone tissue loss and constant callus formation in the patients.Conclusions: Transdermally applied estrogen to postmenopausal women, which results in estrogen levels similar to the systemic level of premenopausal women, has no significant beneficial effect on callus BMD as measured by pQCT, as recently shown in preclinical animal models.Trial registration: Low dose estrogen has no significant effect on bone fracture healing measured by pQCT in postmenopausal women, DRKS00019858. Registered 25th November 2019 - Retrospectively registered. Trial registration number DRKS00019858.

scholarly journals Accelerated Lower Leg Fracture Healing in Traumatic Brain Injury in Accordance With Increased Hematoma Formation

2021 ◽  
Author(s):  
Dong Woo Shim ◽  
Hyunjoo Hong ◽  
Kwang-Chun Cho ◽  
Se Hwa Kim ◽  
Jin Woo Lee ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Fracture Healing ◽  
Bone Healing ◽  
Open Fracture ◽  
Callus Formation ◽  
Lower Leg ◽  
Hematoma Formation ◽  
Lower Leg Fracture ◽  
Group 1

Abstract BackgroundTraumatic brain injury (TBI) has been known to accelerate bone healing. Many cells and molecules have been investigated but the exact mechanism is still unknown. We aimed to investigate the effect of TBI on fracture healing regarding accelerated hematoma formation.MethodsWe retrospectively investigated patients who were surgically treated for lower leg fractures and who showed secondary bone healing. Patients with and without TBI were divided for comparative analyses. Radiological parameters were time to bridging callus formation and the largest callus ratio during follow-up. Preoperative levels of complete blood count and chemical battery within 3 days from trauma were measured in all patients. Subgroup division regarding age, gender, open fracture, concomitant fracture and severity of TBI were compared.ResultsWe included 48 patients with a mean age of 44.9 (range, 17 – 78), of whom 35 patients (72.9%) were male. There were 12 patients with TBI (Group 1) and 36 patients without TBI (Group 2). Group 1 showed shorter time to callus formation (P < 0.001), thicker callus ratio (P = 0.015), leukocytosis and lymphocytosis (P ≤ 0.028), and lower red blood cell counts (RBCs), hemoglobin, and hematocrit (P < 0.001). Aging and severity of TBI were correlated with time to callus formation and callus ratio (P ≤ 0.003) while gender, open fracture, and concomitant fracture were unremarkable.ConclusionLower leg fractures with TBI showed accelerated bone healing and superior measurements associated with hematoma formation (lymphocytes, RBCs, hemoglobin, hematocrit). Promoted fracture healing in TBI was correlated with the enhanced proinflammatory state.Level of Evidence: Case control study; III

scholarly journals Evaluation of Bone Healing Using Contrast-Enhanced Ultrasonography in Non-Operative Treatment of Tibial Fracture in a Puppy Dog

Animals ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 284
Author(s):  
Francesco Macrì ◽  
Vito Angileri ◽  
Teresa Russo ◽  
Maria Tomiko Russo ◽  
Marco Tabbì ◽  
...  
Keyword(s):  
Fracture Healing ◽  
Bone Healing ◽  
Tibial Fracture ◽  
Callus Formation ◽  
Color Doppler ◽  
Healing Process ◽  
Power Doppler ◽  
Low Velocity ◽  
Blood Flows ◽  
Contrast Enhanced

A 10-month-old mixed-breed male dog was presented with an oblique tibial fracture. The dog was treated with a Robert Jones-like bandage as a conservative approach, and was subjected to X-ray, B-mode, Color Doppler and contrast-enhanced ultrasound (CEUS) examinations during the fracture healing, in order to assess bone hemodynamic changes. B-mode, Power Doppler and CEUS examinations of the fracture gap were performed at 7, 20, 35, and 50 days post-trauma. Quantitative analysis of CEUS and perfusion parameters were obtained. On CEUS, a steep incline in signal numbers was visible in fracture gap at 7 days with peaks at 35 days, after which the vascularization decreases gradually over the next days. In this study, CEUS provided important information on the early stages of the callus formation and on the healing of neighboring tissues, allowing recognition of a correct bone healing. Moreover, the number of vascular signals on CEUS was greater than that on Doppler images on the same day. This report showed the application of CEUS in controlling the fracture healing process. CEUS could be a method of monitoring the remedial processes, assessing the tibial fracture perfusion characterized by low-velocity, small-volume blood flows.

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