Volume and density of
Volume and density of
Aims. Impaired fracture repair in patients with type 2 diabetes mellitus (T2DM) is not fully understood. In this study, we aimed to characterize the local changes in gene expression (GE) associated with diabetic fracture. We used an unbiased approach to compare GE in the
Infections regularly complicate orthopaedic procedures loosing implant stability and impairing bone union. Nevertheless, the question whether infection is caused by pathogens transposed intraoperatively, infiltrating the implant with blood stream or lymph, or dwelling in clinically healthy tissues, remains unanswered. The AIM of our study was to validate the hypothesis that pathogens may residue deep tissue. Material and Methods: Skin, subcutaneous fat, muscle and
Aims: The use of vitamin K was proposed in the treatment of osteoporosis. Some experimental studies suggested that vitamin K might promote mesenchymal stem cells (MSCs) differentiation into osteoblasts progenitors and inhibit osteoclasts formation. In the present study we analysed the effects of vitamin K at different concentrations on human mesenchymal stem cells derived from
The multifunctional adhesion molecule CD44 is a major cell-surface receptor for hyaluronic acid (HUA). Recent data suggest that it may also bind the ubiquitous bone-matrix protein, osteopontin (OPN). Because OPN has been shown to be a potentially important protein in bone remodelling, we investigated the hypothesis that OPN interactions with the CD44 receptor on bone cells participate in the regulation of the healing of fractures. We examined the spatial and temporal patterns of expression of OPN and CD44 in healing fractures of rat femora by in situ hybridisation and immunohistochemistry. We also localised HUA in the
1. Autografts, isografts and homografts of fibrocartilaginous callus were observed in the anterior chamber of the eye in rats. Proliferation of cartilage ceased, endochondral ossification followed, and the end-product was a new and complete ossicle with a cortex and a marrow cavity. The size and shape of the ossicle was determined by the size and shape of the sample of callus. Thus the callus in the eye performed the function of a cartilage model like that of the developing epiphysis or a healing fracture of a long bone. 2. Fibrocartilaginous callus, heavily labelled with 3H-thymidine, was transplanted to the eye twenty-four hours after the last injection, when there was little if any radioactive thymidine circulating in the blood. A few small chondrocytes with labelled nuclei persisted in the cores of new bone trabeculae, but the largest part of the labelled callus was resorbed and replaced by unlabelled new bone. 3. Homografts of labelled callus produced the same results as autografts at twenty-five days, but between twenty-five and forty-five days the donor cells were destroyed by the immune response of the host. 4. Isogenous transplants in host rats treated with 3H-thymidine between nine and thirteen days, when the callus was invaded by new blood vessels, produced many osteogenetic cells with labelled nuclei and made it possible to trace the origin of the new bone. The label appeared in the progenitor cells within twenty-four hours. While remaining thereafter in progenitor cells, it appeared also in osteoclasts (or chondroclasts) and osteoblasts in forty-eight to seventy-two hours, and in osteocytes in ninety-six to 120 hours. Chondrocytes did not proliferate and were not labelled in the eye. 5. Homogenous transplants in host rats treated with 3H-thymidine between five and one days before the operation also produced new bone, but contained no labelled osteoprogenitor or bone cells after twenty-five days in the eye. At forty-five days the donor tissue had been destroyed by the immune response of the host. 6. Devitalised callus was encapsulated in inflammatory connective tissue and scar. When the dead callus was absorbed by the capillaries of the host new bone formation by induction produced a scanty deposit as a delayed event in a few instances. 7. Irrespective of whether it originated in the donor or the host, a connective-tissue cell type that proliferated rapidly and became labelled with 3H-thymidine was identified as a progenitor cell. Differentiation and specialisation as osteoprogenitor cells occurred after the growth of blood vessels into the interior of the callus, and developed inside of excavation chambers in cartilage. Except that the interaction of the donor tissue and host cells leading to new bone formation by induction takes place in the interior of the excavation chamber, the biophysico-chemical mechanism is unknown.
The Dkk3-derived cells represent a branch of the periosteal mesenchymal lineage that produces fibrocartilage as well as regenerating the periosteal structures. Mesenchymal progenitor cells are capable of generating a wide variety of mature cells that constitute the connective tissue system. Our Laboratory has been developing SMAA GFP reporter mice to prove to be an effective tool for identifying these cells prior to the expression of markers of differentiation characteristic of bone, fat, muscular blood vessels or fibrocartilage. Dkk3 was chosen as a candidate reporter because microarray of SMAA-sorted cells culture indicated high expression of this non-canonical anti-Wnt factor, which was not anticipated in a culture with strong osteogenic potential.Summary Statement
Introduction
Secondary fracture healing processes are strongly influenced by interfragmentary motion. Shear movement is assumed to be more critical than axial movement, however experimental results are controversial. Numerical fracture healing models allow to simulate the fracture healing process with variation of single input parameters and under comparable normalized mechanical conditions. Therefore, a direct comparison of different in vivo scenarios is possible. The aim of this study was to simulate fracture healing under several axial and shear movement scenarios and compare their respective time to heal. We hypothesize that shear movement is always more critical than axial loading. For the presented study, we used a corroborated numerical model for fracture healing in sheep. Numerous variations of the movement amplitude, the fracture gap size and the musculoskeletal loads were simulated for comparable axial compressive and shear load cases. In all simulated cases, axial compressive load had less inhibitory influences on the healing process than shear load. Therefore, shear loading is more critical for the fracture healing outcome in general. Thus, our findings suggest osteosynthesis implants to be optimized to limit shear movements under musculoskeletal loading.
Virtual mechanical testing is a method for measuring bone healing using finite element models built from computed tomography (CT) scans. Previously, we validated a dual-zone material model for ovine
Integrin α2β1 is one of the major transmembrane receptors for fibrillary collagen. In native bone we could show that the absence of this protein led to a protective effect against age-related osteoporosis. The objective of this study was to elucidate the effects of integrin α2β1 deficiency on fracture repair and its underlying mechanisms. Standardised femoral fractures were stabilised by an intramedullary nail in 12 week old female C57Bl/6J mice (wild type and integrin α2. -/-. ). After 7, 14 and 28 days mice were sacrificed. Dissected femura were subjected to µCT and histological analyses. To evaluate the biomechanical properties, 28-day-healed femura were tested in a torsional testing device. Masson goldner staining, Alizarin blue, IHC and IF staining were performed on paraffin slices. Blood serum of the animals were measured by ELISA for BMP-2. Primary osteoblasts were analysed by in/on-cell western technology and qRT-PCR. Integrin α2β1 deficient animals showed earlier transition from cartilaginous callus to mineralized
Mice are increasingly used for fracture healing research because of the possibility to use transgenic animals to conduct research on the molecular level. Mice from both sexes can be used, however, there is no consensus in the literature if fracture healing differs between female and male mice. Therefore, the aim of the present study was to analyze the similarities and differences in endochondral fracture healing between female and male C57BL/6J mice, since this mouse strain is mainly used in bone research. For that purpose, 12-weeks-old female and male mice received a standardized femur midshaft osteotomy stabilized by an external fixator. Mice were euthanized 10 and 21 days after fracture and bone regeneration was analyzed by biomechanical testing, µCT analysis, histology, immunohistochemistry and gene expression analysis. At day 21, male mice displayed a significantly larger
Objectives. Ubiquitin E3 ligase-mediated protein degradation regulates osteoblast function. Itch, an E3 ligase, affects numerous cell functions by regulating ubiquitination and proteasomal degradation of related proteins. However, the Itch-related cellular and molecular mechanisms by which osteoblast differentiation and function are elevated during bone fracture repair are as yet unknown. Methods. We examined the expression levels of E3 ligases and NF-κB members in callus samples during bone fracture repair by quantitative polymerase chain reaction (qPCR) and the total amount of ubiquitinated proteins by Western blot analysis in wild-type (WT) mice. The expression levels of osteoblast-associated genes in
Secondary bone healing is impacted by the extent of interfragmentary motion at the fracture site. It provides mechanical stimulus that is required for the formation of
Cyclooxygenase-2 (COX-2) activity is necessary for fracture healing to proceed normally. In most cell types, COX-2 is inductively expressed and acts in a coordinated pathway to produce prostaglandins, which affect many physiological processes including inflammation. In the
Summary Statement. This study demonstrated that Sclerostin monoclonal antibody (Scl-Ab) enhanced bone healing in the rat osteotomy model. Scl-Ab increased callus size, callus bone volume fraction, rate of callus bone formation and
Introduction. The fracture healing outcome is often evaluated via ex vivo testing of the
Background and Hypothesis: High-energy fractures associated with severe soft tissue injury have a significant incidence of delayed or non-union. The soft tissue envelope may adversely contribute to the healing of a fracture, not only in stripping of the periosteal blood supply, development of compartment syndrome or tissue interposition between the bone ends but also in its ability to generate an intense acute inflammatory response. Inflammation is the initiator of healing; in clinical scenarios of impaired inflammation (immune deficiency, NSAIDs, corticosteroids) healing is delayed; interestingly, in injury with excess inflammation (CVA, MI) healing is also delayed. Would the inflammatory response following high-energy fractures contribute beneficially or adversely to the healing of the underlying fracture? Using an in-house murine femoral fracture model which reliably demonstrated features of delayed fracture healing when associated with a severe overlying muscle crush injury we proposed these hypotheses:. That
Fracture healing is an issue that has not yet been fully elucidated. It is generally accepted in the literature that head trauma accelerates fracture healing and causes higher volume callus tissue. Recent studies have examined the relationship between head trauma and fracture healing more molecularly. Based on this research; the aim of this study is to show the effect of head trauma on fracture healing radiologically and histologically and to investigate the relationship between serum β-Catenin level and fracture healing with the experiment we performed on rats. A total of 36 Wistar Albino female rats with a mean age of 24 weeks were included in the study with the permission of Mersin University Animal Experiments Local Ethics Committee. Six rats in the first group were not traumatized and their blood samples were collected on the day of the experiment started, end of the third week and end of the sixth week. In the second group, only head trauma was performed and blood samples were collected at the end of the third and sixth weeks. In the third group, only open femoral fracture model was applied, blood samples were collected at the third and sixth weeks and AP and Lateral radiographs of the fractured femurs were taken. After sacrification, femurs were dissected from the surrounding soft tissues and subjected to histological examination. In the fourth group, both head trauma and open femur fracture model were applied, blood samples were collected at the end of third and sixth weeks and AP and Lateral radiographs of the fractured femurs were taken. After sacrification, femurs were dissected from the surrounding soft tissues and subjected to histological examination. The expression level of β-Catenin was measured by PCR from all blood samples. Direct radiographs of the third and fourth groups at 3 and 6 weeks were evaluated by two orthopedists according to Rust and Lane & Sandhu scoring system. The histomorphometric examination was performed by evaluating the Huo scoring and the ratio of
Aims: Cell enlargement or hypertrophy is an intermediate transitional process in the transformation of Òsoft callusÒ into bone. The purpose of this study was to determine whether it is caused by an osmotic phenomenon. Following bone fracture, there is a local increase in tissue ßuid due to inßammation and neovascularisation. According to the osmosis principle, cells bathed in excess tissue ßuid swell. Methods: The specimens examined were 1 and 2-week old closed fractures of the right tibia of 12 NZW rabbits created by a drop tower technique. The specimens were prepared for routine histology. Thin sections were stained for haematoxylin and eosin and examined with the light microscope. Results: Cell enlargement and cell rupture were observed principally in the vicinity of the blood vessels. There was a hierarchy of cell sizes with the larger cells close to the blood vessels and the smaller ones further away from the vessels. Conclusions: According to these þndings, the
Objectives. Bone fracture healing is regulated by a series of complex physicochemical and biochemical processes. One of these processes is bone mineralization, which is vital for normal bone development. Phosphatase, orphan 1 (PHOSPHO1), a skeletal tissue-specific phosphatase, has been shown to be involved in the mineralization of the extracellular matrix and to maintain the structural integrity of bone. In this study, we examined how PHOSPHO1 deficiency might affect the healing and quality of
Previously, we reported impaired biomechanical bone properties and inferior bone matrix quality in tachykinin1 (Tac1)-deficient mice lacking the sensory neuropeptide substance P (SP). Additionally,
Myostatin (GDF-8) is known to play an important role in muscle regeneration, and myostatin is also expressed during the early phases of fracture healing. In this study we used fluorescent immunohistochemistry to define the temporal and spatial localization of myostatin during muscle and bone repair following deep penetrant injury in a mouse model. We then used hydrogel delivery of exogenous myostatin in the same injury model to determine the effects of myostatin exposure on muscle and bone healing. Results show that while myostatin was constitutively expressed in the cytoplasm of intact skeletal muscle fibers, a pool of intense myostatin staining was observed amongst injured skeletal muscle fibers 12-24 hours post-surgery. Myostatin was also expressed in the soft callus chondrocytes 4 days following osteotomy. Hydrogel delivery of 10 or 100 ug/ml recombinant myostatin decreased
We studied the effect of vitamin C on fracture healing in the elderly. A total of 80 elderly Osteogenic Disorder Shionogi rats were divided into four groups with different rates of vitamin C intake. A closed bilateral fracture was made in the middle third of the femur of each rat. Five weeks after fracture the femora were analysed by mechanical and histological testing. The groups with the lower vitamin C intake demonstrated a lower mechanical resistance of the healing callus and a lower histological grade. The vitamin C levels in blood during healing correlated with the torque resistance of the callus formed (r = 0.525). Therefore, the supplementary vitamin C improved the mechanical resistance of the
Endochondral ossification involves a well ordered sequence of cellular events. Chondrocytes change their morphology and functions and are ultimately removed by the process of apoptosis. A variety of apoptotic-related signals have been characterised. These include Fas receptor (FasR)/Fas ligand (FasL), p53 and Bcl family. However, there is little known regarding the activity of these signals in the process of fracture healing. The purpose of this study was to investigate mRNA expression of apoptotic signals using RNase protection assay (RPA) and immunohistochemistry in endochondral bone formation. BALB/C mice aged 8 to 10 weeks were used for this study. First, a transverse fracture was made in the right tibia. Mice were euthanised at 1, 2 and 3 weeks postfracture. The calluses were harvested and studied for the expression of caspase-8, a key enzyme of apoptosis, and apoptosis inducers: tumour necrosis factor-alpha (TNF-α) and its receptor p55, FasL and Fas receptor (FasR), and TNF-related apoptosis-inducing ligand (TRAIL). Four mice at each timepoint were used for immunostaining of
Objectives. As one of the heat-stable enterotoxins, Staphylococcal enterotoxin C2 (SEC2) is synthesized by Staphylococcus aureus, which has been proved to inhibit the growth of tumour cells, and is used as an antitumour agent in cancer immunotherapy. Although SEC2 has been reported to promote osteogenic differentiation of human mesenchymal stem cells (MSCs), the in vivo function of SCE2 in animal model remains elusive. The aim of this study was to further elucidate the in vivo effect of SCE2 on fracture healing. Materials and Methods. Rat MSCs were used to test the effects of SEC2 on their proliferation and osteogenic differentiation potentials. A rat femoral fracture model was used to examine the effect of local administration of SEC2 on fracture healing using radiographic analyses, micro-CT analyses, biomechanical testing, and histological analyses. Results. While SEC2 was found to have no effect on rat MSCs proliferation, it promoted the osteoblast differentiation of rat MSCs. In the rat femoral fracture model, the local administration of SEC2 accelerated fracture healing by increasing
Aim: Antibiotics are currently used during fracture healing for prevention or treatment of infection. Quinolones are well known to delay fracture healing, but little is known about other antibiotics. Cefazolin is the most commonly used drug for antibiotic prophylaxis, but many centres use cefuroxime. When allergy to cephalosporins is present, current recommendations include clindamicin or vancomicin. The purpose of this study is to know if other commonly used antibiotics can delay fracture healing. Methods: 100 male 3-months-old Wistar rats were used. After anaesthesia with ketolar, a closed fracture in the middle third of the femur was carried out. Rats were divided in five groups (20 rats each): one receiving cefazolin (a first generation cephalosporin, CZ), other receiving cefuroxime (a second generation cephalosporine, CF), other vancomicin (group V), other clindamicin (group CL) and the other receiving placebo (P) for 4 weeks. Group CZ received a subcutaneous dose of 50mg/kg/daily, Group CF received a dose of 100 mg/Kg/daily, Group V received a dose of 20 mg/Kg/daily, Group CL received a dose of 25 mg/Kg/daily and group P received water. 4 weeks later rats were killed and femora extracted. A mechanical test (low speed torsion) was performed to evaluate healing. All four groups (CZ, CF, V, CL) were compared to placebo through ANOVA. Results: Six bones were discarded because of technical errors, no infections were found. The maximum torque achieved by the calluses before breaking were 240 mNm in group P (n=18), 238 in group CZ (n=20), 178 in group CF (n=19), 167 in group V (n=19), and 205 in group CL (n=18). When compared to placebo, cefazolin and clindamicin showed no statistical differences (N.S, p>
0,10), vancomicin had lower callus strength (p=0,015), and cefuroxime had also lower callus strength near the significance level (p=0,084). Conclusion: The mechanical strength of
The quantitative measurement is required for fracture healing evaluation in clinical studies approaching toward Evidence Based Medicine. Early detection of fracture healing impairment is demanded to introduce as early as possible the optimal treatment leading to recovery. Clinically validated and tested methods usually utilize X-ray and CT data. The aim of this study was to improve assessment of fracture healing progress or impairment examined with X-ray and computed tomography (CT) and to determine the usefulness of quantitative methods based on newly developed 3D image analyzing software. An original software “3D Reconstructor” was developed. The application operates on medical image data stored in DICOM format. 3D Reconstructor v.2.0 allows 2D reconstruction in custom surface directs through data block and 3D reconstruction as well. The usefulness of the application was evaluated for long bone fracture healing with three-dimensional presentation of
Fracture repair is a complex physiological process during which bone shows the remarkable ability to mount a repair process, restoring its mechanical integrity and anatomical configuration by original osseous tissue. Programmed cell death, or apoptosis, is a naturally occurring cell suicide pathway with a homeostatic function in the maintenance of continuously renewing tissues. The present study investigated the relation between cell proliferation and cell death (apoptosis) during fracture healing in a mouse femoral model. Left femoral osteotomies were performed in 20 male CFLP mice (35–45g), immobilised with uniplanar external fixators. 4 animals were sacrificed on days 2, 4, 8, 16 and 24 post-fracture and
Introduction: Collagen type X is secreted by hypertrophic chondrocytes during fracture repair. Its precise role is uncertain. This study uses a knockout mouse model in which the collagen X gene is removed to examine its function. Method: Bilateral femoral fractures were created in type X collagen knockout mice (mutant) and normal mice (wild type), and were stabilized using an external fixator. The mice were sacrificed 7, 10, 14, 21, 28 and 60 days after fracture. Fracture healing was followed by x-rays, histology, gene expression studies, immuno-histochemistry and mechanical testing. Results: In the mutant mice, bony union was delayed, there was abnormal persistence of aggrecan up to 60 days after fracture. Histology reviewed amorphous acellular areas surrounded by osteoclasts at 21 and 28 days, while mechanical testing revealed that at 14 days after
The February 2024 Wrist & Hand Roundup360 looks at: Occupational therapy for thumb carpometacarpal osteoarthritis?; Age and patient-reported benefits from operative management of intra-articular distal radius fractures: a meta-regression analysis; Long-term outcomes of nonsurgical treatment of thumb carpometacarpal osteoarthritis: a cohort study; Semi-occlusive dressing versus surgery in fingertip injuries: a randomized controlled trial; Re-fracture in partial union of the scaphoid waist?; The WALANT distal radius fracture: a systematic review; Endoscopic carpal tunnel release with or without hand therapy?; Ten-year trends in the level of evidence in hand surgery.
Tobacco, in addition to being one of the greatest public health threats facing our world, is believed to have deleterious effects on bone metabolism and especially on bone healing. It has been described in the literature that patients who smoke are approximately twice as likely to develop a nonunion following a non-specific bone fracture. For clavicle fractures, this risk is unclear, as is the impact that such a complication might have on the initial management of these fractures. A systematic review and meta-analysis were performed for conservatively treated displaced midshaft clavicle fractures. Embase, PubMed, and Cochrane Central Register of Controlled Trials (via Cochrane Library) were searched from inception to 12 May 2022, with supplementary searches in Open Grey, ClinicalTrials.gov, ProQuest Dissertations & Theses, and Google Scholar. The searches were performed without limits for publication date or languages.Aims
Methods
With the ageing population, fragility fractures have become one of the most common conditions. The objective of this study was to investigate whether microbiological outcomes and fracture-healing in osteoporotic bone is worse than normal bone with fracture-related infection (FRI). A total of 120 six-month-old Sprague-Dawley (SD) rats were randomized to six groups: Sham, sham + infection (Sham-Inf), sham with infection + antibiotics (Sham-Inf-A), ovariectomized (OVX), OVX + infection (OVX-Inf), and OVX + infection + antibiotics (OVX-Inf-A). Open femoral diaphysis fractures with Kirschner wire fixation were performed. Aims
Methods
The optimal management of posterior malleolar ankle fractures, a prevalent type of ankle trauma, is essential for improved prognosis. However, there remains a debate over the most effective surgical approach, particularly between screw and plate fixation methods. This study aims to investigate the differences in outcomes associated with these fixation techniques. We conducted a comprehensive review of clinical trials comparing anteroposterior (A-P) screws, posteroanterior (P-A) screws, and plate fixation. Two investigators validated the data sourced from multiple databases (MEDLINE, EMBASE, and Web of Science). Following PRISMA guidelines, we carried out a network meta-analysis (NMA) using visual analogue scale and American Orthopaedic Foot and Ankle Score (AOFAS) as primary outcomes. Secondary outcomes included range of motion limitations, radiological outcomes, and complication rates.Aims
Methods
Alcoholism is a well-known detrimental factor in fracture healing. However, the underlying mechanism of alcohol-inhibited fracture healing remains poorly understood. MicroRNA (miR) sequencing was performed on bone mesenchymal stem cells (BMSCs). The effects of alcohol and miR-19a-3p on vascularization and osteogenic differentiation were analyzed in vitro using BMSCs and human umbilical vein endothelial cells (HUVECs). An in vivo alcohol-fed mouse model of femur fracture healing was also established, and radiological and histomorphometric analyses were used to evaluate the role of miR-19a-3p. The binding of miR-19a-3p to forkhead box F2 (FOXF2) was analyzed using a luciferase reporter assay.Aims
Methods
Objectives. Recent studies have shown that modulating inflammation-related
lipid signalling after a bone fracture can accelerate healing in
animal models. Specifically, decreasing 5-lipoxygenase (5-LO) activity
during fracture healing increases cyclooxygenase-2 (COX-2) expression
in the
Objective. The optimal positioning of the acetabular component is a relevant prognostic factor in total hip arthroplasty (THA). Because of substantial errors of manual technique in cup placement even with experienced surgeon, computer aided navigation system has been developed in recent years. However, existence of the hardware around acetabulum likely deteriorates the accuracy of the navigation system, namely in revision THA case and postoperative status of pelvic fracture. Here we report a case who we successfully performed THA using CT based navigation system although there were multiple hardware around acetabulum due to osteosynthesis for the previous pelvic fracture. Case presentation. A forty-one years old man presented with intolerable hip pain with severe radiographic osteoarthritic findings in left hip joint. He had sustained left pelvic fracture and posterior hip dislocation due to traffic accident and undergone osteosynthesis using multiple plates and screws when he was forty years old. However, progressive collapsing of femoral head and acetabulum occurred. Then, we indicated THA for his situation and planned to apply the CT based navigation system (Stryker CT based hip Ver.1.1 softwear and Cart II system). Preoperative workup revealed incomplete union of posterior and superior acetabular wall and we had to retain plates and screws for the stable fixation of acetabular cup. The existence of the hardware made it complicated to perform three dimensional planning and templating. Meticulous surface editing of pelvis to exclude the metal artifact and fibrocartilagenous tissue was needed to achieve accurate surface registration. In the operation room, we had to use unusual way of registration to complete two steps of registration. In the first step (roughly matching between patient's physical pelvic surface and edited pelvic surface in work station using corresponding 5 points), we utilized head of screw and hole of the plate which we could easily identify intraoperatively, in addition to ASIS and innominate groove. In the second step (strict matching using more than 30 points of pelvic surface), we had to identify the pelvic bony surface, as excluding the metal surface and fibrocartilagenous tissue such as
Clinical evidence that patients with type 2 diabetes mellitus (T2DM) have increased risk of fractures is reported. Furthermore, thiazolidinediones, used to treat T2DM increases the risk of secondary osteoporosis & subsequent fractures. The osteogenic potency of metformin is reported in vitro, few studies have investigated the effects of metformin on bone mass and fracture healing in vivo. We aimed to investigate the effects of metformin on fracture healing in vivo. Method. 20 female Wistar rats aged 3 months were randomly divided in two groups, one group receiving saline, the other group receiving metformin administered orally via the drinking water at a concentration of 2mg/ml. After 4 weeks of metformin treatment, a mid-diaphyseal, open External fixation fracture was performed. Rats were sacrified 4 weeks later. Right contralateral tibia and left osteotomised femora were excised, bone architecture analysed by micro-CT in the right tibia. Results. No significant differences were noted between the two groups.
Introduction. The delay looks radiographically as a
Introduction. Bisphosphonates are among the most commonly prescribed drugs in Osteoporotic Patients. Their mode of action is anti-resorptive. Since remodeling is a key step in fracture healing, there has been concern regarding the effect of bisphosphonates on fracture healing. Objectives. To assess the effect of alendronate on fracture healing in the rabbit ulna osteotomy model. Materials and methods. 16 New Zealand white rabbits were divided into 2 equal groups. Bilateral ulnar osteotomies were performed in the first week. Group 1 was the control group and group 2 was gavaged with alendronate solution (human equivalent dose). 2 rabbits were euthanised at 3 and 6 weeks and the remaining 4 rabbits were euthanised at 8 weeks. Fracture healing was assessed radiologically, with mechanical testing using the Instron 4302 materials testing machine and histologically, in that order. Results. The fractures healed satisfactorily in all the control group animals. However, in the alendronate treated group, there was an abundance of woven bone and little lamellar bone in the callus. However there was no significant difference in mechanical testing. In addition we did not find any evidence of Osteonecrosis in the Bisphosphonate treated group. Conclusion. Bone remodelling in the alendronate treated group is slower but a larger amount of bone callus is formed around the fracture, thus giving the
Background:. In recent times there has been an increasing trend towards surgical intervention in paediatric femoral shaft fractures with widening indications. Titanium elastic nails and external fixation are two widely practiced procedures for such fractures. Materials & Methods:. We report a series of 48 children with 52 fractured femurs, 18 being managed by TENS and 34 in a linear external fixator. Children were aged between 3.5 to 12 years and the fractures were stabilised after an optimal closed reduction on a normal theatre table under image intensifier control. Fracture site distribution was nearly uniform in both the groups. Though most children were assigned to any of the groups at random, external fixators were applied on many younger children and those having financial constraints. Results:. The average age of children in the TENS group was 7.4 years and the average fracture healing time was 9.4 weeks. In the ex-fix group the figures were 5.6 years and 8.6 weeks respectively. Fixators were removed when good callus formation was seen on at least three cortices; average fixator time was 7.5 weeks.
Introduction. Subchondral insufficiency fracture (SIF) needs to be differentiated from osteonecrosis. The purpose of this study was to evaluate the imaging and histopathological findings of patients 60 years or older with radiological evidence of subchondral collapse of the femoral head. Methods. We reviewed 77 consecutive hips in 56 patients aged 60 years or older, which showed subchondral collapse on radiographs. According to the shapes of low-intensity bands on T1-weighted images of magnetic resonance imaging (MRI), the patients were divided into 2 groups. Group A showed a concavity of the articular surface: characteristic appearances of osteonecrosis, and Group B showed an irregular convexity of the articular surface: characteristic appearances of SIF. Results. Thirty-four patients (60.7%) were categorized as Group A and 22 patients (39.3%) as Group B. All the cases in Group A had a history of corticosteroid intake or alcohol abuse. In Group B, the proportion of women as well as unilateral involvement was significantly higher than those in Group A. In 30 cases with histopathological examination, 16 were in Group A and 14 were in Group B. All the cases in Group A demonstrated characteristic features of osteonecrosis. In Group B, the band on T1-weighted images corresponded to viable reparative tissue including granulation tissue and
1. Experimental
1. The bone changes in four autopsied cases of Cushing's syndrome are described. The changes take the form of osteoporosis, which is most marked in the spine and the ribs. 2. The osteoporosis results from impaired osteoblastic bone formation in the presence of a normal degree of osteoclastic bone resorption. 3. Histological abnormalities of
To elucidate the molecular biology of fracture healing, murine models are preferred. We performed a study with the first internal fixation system that allows studying murine fracture healing in a controlled mechanical environment, to characterise the timing of the fracture healing cascade with this model, based on a histological evaluation. Femoral osteotomies were performed in 68 male C57BL/six mice and stabilised with locking internal fixation plates in either stiff, or defined, flexible configurations. Healing progression was studied at 10 time points between 3 and 42 days post- surgery. After surgery, mice were radiographed to confirm the correct implant positioning. After sacrifice, the extracted femora were processed for decalcified histology. Thin sections were taken as serial transverse sections and stained for subsequent histomorphometric analysis and three-dimensional reconstruction of the different
Introduction. Amino acids like arginine and lysine have been suggested to hasten the process of fracture healing by improving the local blood supply, supplementing growth factors, and improving collagen synthesis. We studied the role of lysine and arginine in the fracture repair process with regard to the rate of healing, probable mechanisms involved in the process, and mutual synergism between these agents. Materials and methods. In an experimental study, 40 rabbits were subjected to ulnar osteotomy. They were distributed in control (14) and test groups (26). Twenty-six animals in the test group were fed with a diet rich in lysine and arginine. Both the groups were followed radiologically and histologically till union. Results. Ten weeks postoperatively, there was difference evident radiologically between those supplemented with lysine and arginine, indicating that these components enhance the healing in the later part of bone remodeling, canal restoration, and medullary as well as cortical continuity and repair. X-rays obtained at weeks 9, 10, and 12 in both the groups showed statistical significance. These findings showed that healing is better in the test group in terms of increased vascularity in the early part of healing, i.e., at approx. 2–3 weeks and in terms of bone matrix, Haversian system formation, and cortical repair in the later part of healing, i.e., at approx. 9–12 weeks between the two groups. There was better healing of osteotomy in terms of better vascularization, callus formation, and mineralization in the test group. The time of healing in the test group was reduced by a period of 2 weeks. Discussion. NO is expressed during fracture healing in rats and humans, as after fracture, mRNA, protein, and enzymatic activity iNOS have been identified at the
Fibrinolysis plays a key transition step from haematoma formation to angiogenesis and fracture healing. Low-magnitude high-frequency vibration (LMHFV) is a non-invasive biophysical modality proven to enhance fibrinolytic factors. This study investigates the effect of LMHFV on fibrinolysis in a clinically relevant animal model to accelerate osteoporotic fracture healing. A total of 144 rats were randomized to four groups: sham control; sham and LMHFV; ovariectomized (OVX); and ovariectomized and LMHFV (OVX-VT). Fibrinolytic potential was evaluated by quantifying fibrin, tissue plasminogen activator (tPA), and plasminogen activator inhibitor-1 (PAI-1) along with healing outcomes at three days, one week, two weeks, and six weeks post-fracture.Aims
Methods
This is a clinically based study to assess the reliability of fracture stiffness as a measurement of clinical union and investigate other indicators which may aid the clinician to accurately determine when fracture fixation may be removed. A fracture bending stiffness in the sagittal plane of 15Nm/deg. has been stated as a satisfactory endpoint at which an external fixator may be removed from diaphyseal fractures of the tibia. However using this as a measure to determine when to remove support in a study of 76 patients 4 continued to a malunion.
We describe a new method of biological repair of osteochondral defects. In rabbit knees an osteochondral defect was reconstructed with a callo-osseous graft made of a superficial sheet of medullary
Summary Statement. Parathytorid hormone-related protein (107–111) loaded onto biopolymer-coated nanocrystalline hydroxyapatite (HA. Glu. ) improves the bone repair in a cavitary defect in rat tibiae. Introduction. Biopolymer-coated nanocrystalline hydroxyapatite (HA. Glu. ) made as macroporous foams are promising candidates as scaffolds for bone tissue engineering applications. They exhibit optimal features, promoting internalization, proliferation and differentiation of osteoprogenitors, with an adequate cell colonization over the entire scaffold surface. Parathyroid hormone-related protein (PTHrP) is an important modulator of bone formation. Its 107–111 epitope (osteostatin) exhibits osteogenic properties at least in part by directly acting on osteoblasts. The main aim of this study was to evaluate whether osteostatin loading into HA. Glu. scaffolds might improve their bone regeneration capacity. Materials and Methods. HA. Glu. scaffolds were prepared as previously described (Sánchez-Salcedo S et al. J. Mater. Chem. 2010; 20:6956-61). Osteostatin was adsorbed onto HA. Glu. material by dipping into a solution containing this peptide at 100 nM (in phosphate-buffered saline, pH 7.4), following a standard protocol. We performed a cavitary defect (2 mm in diameter and 3 mm in depth) in both distal tibial metaphysis using a drill under general anesthesia in male Wistar rats (n=8) of 6 months of age. Unloaded HA. Glu. material (7 mg) was implanted into left tibial defects, whereas rigth tibial defects received the osteostatin-loaded material. Animals were sacrificed after 4 weeks for histological, μ-computerised tomography and gene expression analysis of the callus. Our protocol was approved by the Institutional Animal Care and Use Committee at the IIS-FJD. Mouse osteoblastic MC3T3-E1 cells were grown in differentiation medium (α-MEM with 10% fetal bovine serum, 50 µg/ml ascorbic acid, and 10 mM β-glycerolphosphate), in the presence or absence of HA. Glu. material with or without osteostatin. Cell viability (assessed by trypan blue staining), alkaline phosphatase (ALP) activity and mineralization (alizarin red) were analyzed at different culture times. Results. The mean uptake of osteostatin by HA. Glu. scaffolds was about 60 % (representing 0.7 μg/implanted scaffold) after 24 h of loading, and they released a mean of 80 % of loaded peptide to the surrounding medium within 1–24 h. At 4 weeks, this osteostatin-containing HA. Glu. material significantly increased the bone volumen fraction and trabecular thickness of regenerating bone in the tibial methaphysis, compared to those observed with unloaded HAGlu scaffolds. In addition, osteostatin-coated HA. Glu. scaffolds increased (2-fold) the gene expression of osteocalcin and vascular cell adhesion molecule 1, but decreased (2-fold) that of the Wnt inhibitors, SOST and Dickkopf homolog 1 (DKK-1) in the