scholarly journals The Effects of TMP Treatment and High Fat Diet on Bone Fracture Healing

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Samuel Zike ◽  
Jeffery Nielsen ◽  
Caio De Andrade Staut ◽  
Vincent Alentado ◽  
Ushashi Dadwal ◽  
...  
Keyword(s):  
Fracture Healing ◽  
Bone Healing ◽  
Bone Fracture ◽  
High Fat Diet ◽  
Saline Control ◽  
Diabetic Patients ◽  
High Fat ◽  
Bone Fracture Healing ◽  
Orthopaedic Surgeons

Delayed and impaired bone fracture healing are associated with diabetic populations. This is a challenging problem for orthopaedic surgeons especially in the US where the percentage of type 2 diabetic patients continues to climb at an alarming rate. Limited treatment options exist for orthopaedic surgeons to improve fracture healing, and the most commonly used therapies involve placement of proteins (bone morphogenetic protein), graft tissue, or demineralized bone matrix at the fracture site. We have previously demonstrated that local administration of the main megakaryocyte growth factor, thrombopoietin, enhances bone healing. Here we demonstrate the utility of systemically administering thrombopoietin mimetic peptides (TMPs) to improve impaired fracture healing in a mouse model of type 2 diabetes. Briefly, 120 male mice on a C57BL/6 background were placed on a low fat diet (LFD) or high fat diet (HFD) for 12 weeks prior to undergoing a surgically created femoral fracture. Mice were treated with 33 nmol/kg of TMP or saline immediately after surgery and daily for the following week. Mice were euthanized at 1, 2, and 4 weeks post-surgery (n=10/group). Here, we confirmed that HFD resulted in impaired fracture healing. We also showed accelerated bone union and increased callus formation in TMP treated mice compared to saline groups, irrespective of diet (p<0.05). Among TMP groups that were fed either a HFD or LFD, the HFD TMP group showed greater improvements in bone healing compared to the HFD saline control mice. Further study on TMP should include alternative routes of administration and providing treatment when a surgical repair appears to be deteriorating. Although there is more to be understood about the clinical importance and mechanism by which systemic TMP treatment enhances fracture healing, these data appear promising.

scholarly journals Long-Lasting Exendin-4 Fusion Protein Improves Memory Deficits in High-Fat Diet/Streptozotocin-Induced Diabetic Mice

Pharmaceutics ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 159 ◽  
Author(s):  
Kyung-Ah Park ◽  
Zhen Jin ◽  
Jong Youl Lee ◽  
Hyeong Seok An ◽  
Eun Bee Choi ◽  
...  
Keyword(s):  
Glycemic Control ◽  
Fusion Protein ◽  
High Fat Diet ◽  
Memory Deficits ◽  
Receptor Expression ◽  
Diabetic Patients ◽  
Diabetic Mice ◽  
High Fat ◽  
Type 2 Diabetic

Glucagon-like peptide 1 (GLP-1) mimetics have been approved as an adjunct therapy for glycemic control in type 2 diabetic patients for the increased insulin secretion under hyperglycemic conditions. Recently, it is reported that such agents elicit neuroprotective effects against diabetes-associated cognitive decline. However, there is an issue of poor compliance by multiple daily subcutaneous injections for sufficient glycemic control due to their short duration, and neuroprotective actions were not fully studied, yet. In this study, using the prepared exendin-4 fusion protein agent, we investigated the pharmacokinetic profile and the role of this GLP-1 mimetics on memory deficits in a high-fat diet (HFD)/streptozotocin (STZ) mouse model of type 2 diabetic mellitus. After induction of diabetes, mice were administered weekly by intraperitoneal injection of GLP-1 mimetics for 6 weeks. This treatment reversed HFD/STZ-induced metabolic symptoms of increased body weight, hyperglycemia, and hepatic steatosis. Furthermore, the impaired cognitive performance of diabetic mice was significantly reversed by GLP-1 mimetics. GLP-1 mimetic treatment also reversed decreases in GLP-1/GLP-1 receptor expression levels in both the pancreas and hippocampus of diabetic mice; increases in hippocampal inflammation, mitochondrial fission, and calcium-binding protein levels were also reversed. These findings suggest that GLP-1 mimetics are promising agents for both diabetes and neurodegenerative diseases that are associated with increased GLP-1 expression in the brain.

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 Role of TNF-α and FGF-2 in the Fracture Healing Disorder of Type 2 Diabetes Model Induced by High Fat Diet Followed by Streptozotocin

2020 ◽  
Vol Volume 13 ◽  
pp. 2279-2288
Author(s):  
Heqing Huang ◽  
Ling Luo ◽  
Zhitao Liu ◽  
Yan Li ◽  
Zhaochen Tong ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Fracture Healing ◽  
High Fat Diet ◽  
High Fat ◽  
Diabetes Model ◽  
Tnf Α

scholarly journals Management of impaired fracture healing: Historical aspects

2005 ◽  
Vol 58 (9-10) ◽  
pp. 507-512
Author(s):  
Djordje Gajdobranski ◽  
Ivan Micic ◽  
Milorad Mitkovic ◽  
Desimir Mladenovic ◽  
Miroslav Milankov
Keyword(s):  
Fracture Healing ◽  
Bone Healing ◽  
Bone Fracture ◽  
Human Life ◽  
Historical Review ◽  
Treatment Modalities ◽  
Bone Fracture Healing ◽  
Ancient Medicine ◽  
Adequate Treatment ◽  
Orthopedic Surgeons

Introduction Establishing continuity of long bones in cases of impaired bone healing and pseudo-arthrosis is one of the most complex problems in orthopedics. Impaired bone healing The problem of impaired fracture healing is not new. As in other areas of human life, the roots of modern treatment of impaired bone healing lie in ancient medicine. A relatively high percentage of impaired bone healing, as well as unsatisfactory results of standard therapies of impaired bone healing and pseudoarthrosis demonstrate the actuality of this problem. This paper represents an attempt to pay respect to some of those who have dedicated their work to this problem in orthopedic surgery, and it is a historical review on impaired bone fracture healing. At the same time it should be an additional stimulus and challenge for orthopedic surgeons to further study impaired bone fracture healing, improve the existing and find new methods for their adequate treatment. Conclusion The authors are certain that the number of researchers throughout the world who have contributed to treatment modalities of impaired bone healing, is much higher, but not all are mentioned in this paper. However, it does not lessen their contributions to orthopedics.

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.

scholarly journals Akkermansia muciniphila promotes type H vessel formation and bone fracture healing by reducing gut permeability and inflammation

2020 ◽  
Vol 13 (11) ◽  
pp. dmm043620 ◽  
Author(s):  
Jiang-Hua Liu ◽  
Tao Yue ◽  
Zhong-Wei Luo ◽  
Jia Cao ◽  
Zi-Qi Yan ◽  
...  
Keyword(s):  
Fracture Healing ◽  
Systemic Inflammation ◽  
Bone Healing ◽  
Bone Fracture ◽  
Early Stage ◽  
Gut Permeability ◽  
Bone Fracture Healing ◽  
Gut Barrier ◽  
Vessel Formation ◽  
Akkermansia Muciniphila

ABSTRACTImproving revascularization is one of the major measures in fracture treatment. Moderate local inflammation triggers angiogenesis, whereas systemic inflammation hampers angiogenesis. Previous studies showed that Akkermansia muciniphila, a gut probiotic, ameliorates systemic inflammation by tightening the intestinal barrier. In this study, fractured mice intragastrically administrated with A. muciniphila were found to display better fracture healing than mice treated with vehicle. Notably, more preosteclasts positive for platelet-derived growth factor-BB (PDGF-BB) were induced by A. muciniphila at 2 weeks post fracture, coinciding with increased formation of type H vessels, a specific vessel subtype that couples angiogenesis and osteogenesis, and can be stimulated by PDGF-BB. Moreover, A. muciniphila treatment significantly reduced gut permeability and inflammation at the early stage. Dextran sulfate sodium (DSS) was used to disrupt the gut barrier to determine its role in fracture healing and whether A. muciniphila still can stimulate bone fracture healing. As expected, A. muciniphila evidently improved gut barrier, reduced inflammation and restored the impaired bone healing and angiogenesis in DSS-treated mice. Our results suggest that A. muciniphila reduces intestinal permeability and alleviates inflammation, which probably induces more PDGF-BB+ preosteoclasts and type H vessel formation in callus, thereby promoting fracture healing. This study provides the evidence for the involvement of type H vessels in fracture healing and suggests the potential of A. muciniphila as a promising strategy for bone healing.This article has an associated First Person interview with the first author of the paper.

scholarly journals Impaired Muscle Regeneration in Ob/ob and Db/db Mice

2011 ◽  
Vol 11 ◽  
pp. 1525-1535 ◽  
Author(s):  
Mai-Huong Nguyen ◽  
Ming Cheng ◽  
Timothy J. Koh
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Muscle Regeneration ◽  
High Fat Diet ◽  
Diabetic Patients ◽  
High Fat ◽  
Type 2 Diabetic Patients ◽  
Macrophage Accumulation

In obesity and type 2 diabetes, efficient skeletal muscle repair following injury may be required, not only for restoring muscle structure and function, but also for maintaining exercise capacity and insulin sensitivity. The hypothesis of this study was that muscle regeneration would be impaired in ob/ob and db/db mice, which are common mouse models of obesity and type 2 diabetes. Muscle injury was produced by cardiotoxin injection, and regeneration was assessed by morphological and immunostaining techniques. Muscle regeneration was delayed in ob/ob and db/db mice, but not in a less severe model of insulin resistance – feeding a high-fat diet to wild-type mice. Angiogenesis, cell proliferation, and myoblast accumulation were also impaired in ob/ob and db/db mice, but not the high-fat diet mice. The impairments in muscle regeneration were associated with impaired macrophage accumulation; macrophages have been shown previously to be required for efficient muscle regeneration. Impaired regeneration in ob/ob and db/db mice could be due partly to the lack of leptin signaling, since leptin is expressed both in damaged muscle and in cultured muscle cells. In summary, impaired muscle regeneration in ob/ob and db/db mice was associated with reduced macrophage accumulation, angiogenesis, and myoblast activity, and could have implications for insulin sensitivity in the skeletal muscle of obese and type 2 diabetic patients.

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.

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