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Frontiers in Endocrinology 2022To investigate the effects of vibration therapy on fracture healing in diabetic and non-diabetic rats.
OBJECTIVE
To investigate the effects of vibration therapy on fracture healing in diabetic and non-diabetic rats.
METHODS
148 rats underwent fracture surgery and were assigned to four groups: (1) SHAM: weight-matched non-diabetic rats, (2) SHAM+VT: non-diabetic rats treated with vibration therapy (VT), (3) DM: diabetic rats, and (4) DM+VT: diabetic rats treated with VT. Thirty days after diabetes induction with streptozotocin, animals underwent bone fracture, followed by surgical stabilization. Three days after bone fracture, rats began VT. Bone healing was assessed on days 14 and 28 post-fracture by serum bone marker analysis, and femurs collected for dual-energy X-ray absorptiometry, micro-computed tomography, histology, and gene expression.
RESULTS
Our results are based on 88 animals. Diabetes led to a dramatic impairment of bone healing as demonstrated by a 17% reduction in bone mineral density and decreases in formation-related microstructural parameters compared to non-diabetic control rats (81% reduction in bone callus volume, 69% reduction in woven bone fraction, 39% reduction in trabecular thickness, and 45% in trabecular number). These changes were accompanied by a significant decrease in the expression of osteoblast-related genes (), as well as a 92% reduction in serum insulin-like growth factor I (IGF-1) levels. On the other hand, resorption-related parameters were increased in diabetic rats, including a 20% increase in the callus porosity, a 33% increase in trabecular separation, and a 318% increase in serum C terminal telopeptide of type 1 collagen levels. VT augmented osteogenic and chondrogenic cell proliferation at the fracture callus in diabetic rats; increased circulating IGF-1 by 668%, callus volume by 52%, callus bone mineral content by 90%, and callus area by 72%; and was associated with a 19% reduction in circulating receptor activator of nuclear factor kappa beta ligand (RANK-L).
CONCLUSIONS
Diabetes had detrimental effects on bone healing. Vibration therapy was effective at counteracting the significant disruption in bone repair induced by diabetes, but did not improve fracture healing in non-diabetic control rats. The mechanical stimulus not only improved bone callus quality and quantity, but also partially restored the serum levels of IGF-1 and RANK-L, inducing bone formation and mineralization, thus creating conditions for adequate fracture repair in diabetic rats.
Topics: Animals; Bony Callus; Diabetes Mellitus; Fracture Healing; Fractures, Bone; Insulin-Like Growth Factor I; Rats; Vibration; X-Ray Microtomography
PubMed: 36060973
DOI: 10.3389/fendo.2022.909317 -
Injury Jan 2021Long bone fractures typically heal via formation of an external callus, which helps stabilise the bone fragments. Callus composition and morphology influence the...
Long bone fractures typically heal via formation of an external callus, which helps stabilise the bone fragments. Callus composition and morphology influence the mechanical environment, which in turn regulates the progression of healing. Therefore characterising callus development over time is crucial in understanding this mechanobiological regulation. Although bony callus is often assumed to grow towards the fracture from either side, this is not consistent with observations from large animal studies and clinical cases. Therefore, we sought to quantify the morphology of bony callus over time in a large animal model. Sheep tibiae were x-rayed weekly over eight weeks following an osteotomy (n=5), with fixation allowing up to 10% axial displacement under normal weight-bearing. After scaling radiographs by known landmarks and normalising greyscales, bony callus boundaries were defined by manual segmentation. The lateral callus area and coordinates of its centroid were calculated from each image. The external callus initially formed adjacent to the osteotomy site. Over the first four weeks, callus growth from its outer surfaces was characterised by its centre of area moving outwards and away from the osteotomy, on both proximal and distal fragments. Subsequent weeks showed consolidation and resorption from the outer surface of the callus. Our approach allowed bony callus development to be tracked in individuals throughout healing. Contrary to the view that periosteal bone formation originates distant from the fracture, our data showed bony callus adjacent to the defect from early stages, followed by approximately concentric growth. This discrepancy highlights the need for data specific to experimental conditions, and particularly early stages of healing, for evaluating theoretical models of mechanical regulation.
Topics: Animals; Bony Callus; External Fixators; Fracture Healing; Osteotomy; Sheep; Tibial Fractures
PubMed: 33268079
DOI: 10.1016/j.injury.2020.10.083 -
Developmental Cell May 2024Bone is regarded as one of few tissues that heals without fibrous scar. The outer layer of the periosteum is covered with fibrous tissue, whose function in bone...
Bone is regarded as one of few tissues that heals without fibrous scar. The outer layer of the periosteum is covered with fibrous tissue, whose function in bone formation is unknown. We herein developed a system to distinguish the fate of fibrous-layer periosteal cells (FL-PCs) from the skeletal stem/progenitor cells (SSPCs) in the cambium-layer periosteum and bone marrow in mice. We showed that FL-PCs did not participate in steady-state osteogenesis, but formed the main body of fibrocartilaginous callus during fracture healing. Moreover, FL-PCs invaded the cambium-layer periosteum and bone marrow after fracture, forming neo-SSPCs that continued to maintain the healed bones throughout adulthood. The FL-PC-derived neo-SSPCs expressed lower levels of osteogenic signature genes and displayed lower osteogenic differentiation activity than the preexisting SSPCs. Consistent with this, healed bones were thinner and formed more slowly than normal bones. Thus, the fibrous periosteum becomes the cellular origin of bones after fracture and alters bone properties permanently.
Topics: Animals; Periosteum; Mice; Osteogenesis; Fracture Healing; Cell Differentiation; Fractures, Bone; Stem Cells; Mice, Inbred C57BL; Bony Callus; Male
PubMed: 38554700
DOI: 10.1016/j.devcel.2024.03.019 -
Acta Cirurgica Brasileira Nov 2017To evaluate the influence of nandrolone decanoate on fracture healing and bone quality in normal rats.
PURPOSE
To evaluate the influence of nandrolone decanoate on fracture healing and bone quality in normal rats.
METHODS
Male rats were assigned to four groups (n=28/group): Control group consisting of animals without any intervention, Nandrolone decanoate (DN) group consisting of animals that received intramuscular injection of nandrolone decanoate, Fracture group consisting of animals with a fracture at the mid-diaphysis of the femur, and Fracture and nandrolone decanoate group consisting of animals with a femur fracture and treatment with nandrolone decanoate. Fractures were created at the mid-diaphysis of the right femur by a blunt trauma and internally fixed using an intramedullary steel wire. The DN was injected intramuscularly twice per week (10 mg/kg of body mass). The femurs were measured and evaluated by densitometry and mechanical resistance after animal euthanasia. The newly formed bone and collagen type I levels were quantified in the callus.
RESULTS
The treated animals had longer femurs after 28 days. The quality of the intact bone was not significantly different between groups. The bone callus did show a larger mass in the treated rats.
CONCLUSION
The administration of nandrolone decanoate did not affect the quality of the intact bone, but might have enhanced the bone callus formation.
Topics: Anabolic Agents; Animals; Bone Density; Bony Callus; Femoral Fractures; Fracture Healing; Male; Nandrolone; Nandrolone Decanoate; Rats; Rats, Wistar
PubMed: 29236797
DOI: 10.1590/s0102-865020170110000004 -
BMJ Case Reports Feb 2021Fracture healing has four phases: haematoma formation, soft callus, hard callus and remodelling. Often, non-healing fractures have an arrest of one of these phases,...
Fracture healing has four phases: haematoma formation, soft callus, hard callus and remodelling. Often, non-healing fractures have an arrest of one of these phases, which need resurgery. We have repurposed denosumab for impaired fracture healing cases to avoid surgical intervention. Here, we report a series of three cases of impaired fracture healing where denosumab was given 120 mg subcutaneous dosages for 3 months to enhance healing. All the three cases have shown complete bone union at a mean follow-up of 6.7 months (5-9 months) as assessed clinically and radiologically, and have observed no adverse effect of the therapy. Denosumab given in this dose aids fracture healing by increasing callus volume, density and bridges the fracture gap in recalcitrant fracture healing cases where the callus fails to consolidate.
Topics: Adult; Bone Density Conservation Agents; Bony Callus; Denosumab; Femoral Fractures; Fracture Fixation, Internal; Fracture Healing; Fractures, Closed; Fractures, Ununited; Humans; Humeral Fractures; Male; Middle Aged; Reoperation; Young Adult
PubMed: 33558382
DOI: 10.1136/bcr-2020-238460 -
Bulletin of Experimental Biology and... Sep 2020We analyzed biodistribution of Ga-labeled hydroxyethylidenediphosphonic acid (Ga-HEDP) and diethylenetriaminepentakis(methylenephosphonic acid) (Ga-DTPMP) in Wistar rats...
We analyzed biodistribution of Ga-labeled hydroxyethylidenediphosphonic acid (Ga-HEDP) and diethylenetriaminepentakis(methylenephosphonic acid) (Ga-DTPMP) in Wistar rats with experimental model of bone callus. It was shown that the content of Ga-DTPMP and Ga-HEDP in bone callus was ~1.5-fold higher than in intact femur. Ga-DTPMP was characterized by higher stability in vivo, higher uptake in the bone tissue, and lower uptake in others visceral organs in comparison with Ga-HEDP. Thus, Ga-DTPMP had more suitable pharmacokinetic properties than Ga-HEDP.
Topics: Animals; Bone and Bones; Bony Callus; Diphosphonates; Disease Models, Animal; Gallium Radioisotopes; Rats; Rats, Wistar
PubMed: 32986215
DOI: 10.1007/s10517-020-04945-z -
Injury 1997The bony callus was investigated by staining with the PAS and von Gieson techniques. The callus appeared to be composed of two adjoining but distinct types of bone. The...
The bony callus was investigated by staining with the PAS and von Gieson techniques. The callus appeared to be composed of two adjoining but distinct types of bone. The birefringence observed in the periosteum and callus cartilage revealed different sized collagen fibres, each oriented perpendicularly to the long axis of the diaphysis.
Topics: Animals; Bony Callus; Cartilage; Coloring Agents; Fracture Healing; Osteoblasts; Rabbits; Tibial Fractures
PubMed: 9624341
DOI: 10.1016/s0020-1383(97)00126-5 -
Biomechanics and Modeling in... Nov 2013It is proposed that the external asymmetric formation of callus tissues that forms naturally about an oblique bone fracture can be predicted computationally. We present...
It is proposed that the external asymmetric formation of callus tissues that forms naturally about an oblique bone fracture can be predicted computationally. We present an analysis of callus formation for two cases of bone fracture healing: idealised and subject-specific oblique bone fractures. Plane strain finite element (FE) models of the oblique fractures were generated to calculate the compressive strain field experienced by the immature callus tissues due to interfragmentary motion. The external formations of the calluses were phenomenologically simulated using an optimisation style algorithm that iteratively removes tissue that experiences low strains from a large domain. The resultant simulated spatial formation of the healing tissues for the two bone fracture cases showed that the calluses tended to form at an angle equivalent to the angle of the oblique fracture line. The computational results qualitatively correlated with the callus formations found in vivo. Consequently, the proposed methods show potential as a means of predicting callus formation in pre-clinical testing.
Topics: Bony Callus; Compressive Strength; Computer Simulation; Finite Element Analysis; Fracture Healing; Fractures, Bone; Humans; Male; Young Adult
PubMed: 23306603
DOI: 10.1007/s10237-012-0468-6 -
Computer Methods in Biomechanics and... Jan 2018There is lack of further observations on the microstructure and material property of callus during bone defect healing and the relationships between callus properties...
BACKGROUND
There is lack of further observations on the microstructure and material property of callus during bone defect healing and the relationships between callus properties and the mechanical strength.
METHODS
Femur bone defect model was created in rabbits and harvested CT data to reconstruct finite element models at 1 and 2 months. Three types of assumed finite element models were compared to study the callus properties, which assumed the material elastic property as heterogeneous (R-model), homogenous (H-model) or did not change from 1 to 2 months (U-model).
RESULTS
The apparent elastic moduli increased at 2 months (from 355.58 ± 132.67 to 1139.30 ± 967.43 MPa) in R-models. But there was no significant difference in apparent elastic moduli between R-models (355.58 ± 132.67 and 1139.30 ± 967.43 MPa) and H-models (344.79 ± 138.73 and 1001.52 ± 692.12 MPa) in 1 and 2 months. A significant difference of apparent elastic moduli was found between the R-model (1139.30 ± 967.43 MPa) and U-model group (207.15 ± 64.60 MPa) in 2 months.
CONCLUSIONS
This study showed that the callus structure stability remodeled overtime to achieve a more effective structure, while the material quality of callus tissue is a very important factor for callus strength. At the meantime, this study showed an evidence that the material heterogeneity maybe not as important as it is in bone fracture model.
Topics: Animals; Biomechanical Phenomena; Bony Callus; Elastic Modulus; Femur; Finite Element Analysis; Rabbits; Stress, Mechanical; Tomography, X-Ray Computed; Wound Healing
PubMed: 29359598
DOI: 10.1080/10255842.2018.1425404 -
Disease Models & Mechanisms Sep 2019Reduced bone quality or mineral density predict susceptibility to fracture and also attenuate subsequent repair. Bone regrowth is also compromised by bacterial...
Reduced bone quality or mineral density predict susceptibility to fracture and also attenuate subsequent repair. Bone regrowth is also compromised by bacterial infection, which exacerbates fracture site inflammation. Because of the cellular complexity of fracture repair, as well as genetic and environmental influences, there is a need for models that permit visualisation of the fracture repair process under clinically relevant conditions. To characterise the process of fracture repair in zebrafish, we employed a crush fracture of fin rays, coupled with histological and transgenic labelling of cellular responses; the results demonstrate a strong similarity to the phased response in humans. We applied our analysis to a zebrafish model of osteogenesis imperfecta (OI), which shows reduced bone quality, spontaneous fractures and propensity for non-unions. We found deficiencies in the formation of a bone callus during fracture repair in our OI model and showed that clinically employed antiresorptive bisphosphonates can reduce spontaneous fractures in OI fish and also measurably reduce fracture callus remodelling in wild-type fish. The mutant, which has reduced osteoclast numbers, also showed reduced callus remodelling. Exposure to excessive bisphosphonate, however, disrupted callus repair. Intriguingly, neutrophils initially colonised the fracture site, but were later completely excluded. However, when fractures were infected with , neutrophils were retained and compromised repair. This work elevates the zebrafish bone fracture model and indicates its utility in assessing conditions of relevance to an orthopaedic setting with medium throughput.This article has an associated First Person interview with the first author of the paper.
Topics: Alendronate; Animal Fins; Animals; Bony Callus; Diphosphonates; Disease Models, Animal; Fracture Healing; Fractures, Bone; Fractures, Ununited; Osteoclasts; Osteogenesis Imperfecta; Staphylococcus aureus; Zebrafish
PubMed: 31383797
DOI: 10.1242/dmm.037630