Effects of ergosteroside combined risedronate on fracture healing and BMP-2, BMP-7 and VEGF expression in rats

Purpose To evaluate the effect of ergosterol combined with risedronate on fracture healing. Methods Sixty male Sprague Dawley fracture model rats were assigned into group A (n=20), group B (n=20), and group C (n=20) at random. All rats were fed by gavage until their sacrifice as it follows: group A with ergosteroside and risedronate, group B with risedronate, and group C with saline solution. At weeks 2 and 4, 10 rats of each group were sacrificed. Healing effect and bone tissue changes in the fractures site were assessed by using hematoxylin and eosin stain histology. Enzyme-linked immunosorbent assay was used to detect the expression of serum bone morphogenetic protein-2 (BMP-2), bone morphogenetic protein-7 (BMP-7), and vascular endothelial growth factor (VEGF). Reverse transcriptase polymerase chain reaction was applied to detect the expression of osteoprotegerin (OPG) mRNA, osteocalcin (OCN) mRNA and core-binding factor subunit-?1 (CBF-?1) mRNA. Results In terms of serum BMP-2, BMP-7, and VEGF expression at weeks 2 and 4 after gavage, group A < group B < group C (P<0.05). At week 4 after gavage, serum VEGF expression in the three groups harbored positive relationship with serum BMP-2 and BMP-7 expression (P<0.05). Regarding serum OPG, OCN and CBF-?1 mRNA expression at weeks 2 and 4 after gavage, group A

The effectiveness and safety of parathyroid hormone in fracture healing: A meta-analysis

The very large economic and social burdens of fracture-related complications make rapid fracture healing a major public health goal. The role of parathyroid hormone (PTH) in treating osteoporosis is generally accepted, but the effect of PTH on fracture healing is controversial. This meta-analysis was designed to investigate the efficacy and safety of PTH in fracture healing. The EMBASE, PubMed, and Cochrane Library databases were systematically searched from the inception dates to April 26, 2018. The primary randomized clinical trials comparing PTH treatment for fracture healing with placebo or no treatment were identified. We did not gain additional information by contacting the authors of the primary studies. Two reviewers independently extracted the data and evaluated study quality. This meta-analysis was executed to determine the odds ratio, mean difference, standardized mean difference, and 95% confidence intervals with random-effects models. In total, 8 randomized trials including 524 patients met the inclusion criteria. There were significant differences in fracture healing time, pain relief and function improvement. There were no significant differences in the fracture healing rate or adverse events, including light-headedness, hypercalcemia, nausea, sweating and headache, except for slight bruising at the injection site. We determined that the effectiveness and safety of PTH in fracture healing is reasonably well established and credible.

Alendronato administrado en el foco de fractura: Estudio experimental en conejos / Alendronate administered at the fracture site. Experimental study in rabbits

Introducción: El objetivo de este estudio experimental fue evaluar el resultado radiológico e histológico del empleo de alendronato colocado localmente en el foco de fracturas de fémur en conejos. Materiales y Métodos: Se utilizaron 30 conejos a los cuales se les fracturó el fémur derecho y se los dividió en tres grupos de 10 animales cada uno. A los conejos del grupo 1 se les colocó una solución con alendronato en el foco de fractura; los del grupo 2 fueron sometidos al mismo procedimiento a los siete días de la fractura y el grupo 3 era de control. Se realizó la evaluación radiográfica en el momento de la fractura y a los 42 días del procedimiento. Se evaluaron las características del callo óseo mediante anatomía patológica, radiología y tomografía computarizada. Resultados: Se evaluaron 24 conejos (2 conejos del grupo 2 y 4 del grupo 3 murieron). El análisis histológico reveló moderada formación ósea en los tres grupos, sin diferencias estadísticamente significativas (p = 0,8336). Según los resultados de los estudios por imágenes, no existieron diferencias estadísticamente significativas en el tamaño del callo óseo entre los grupos para los dos estudios (radiografía: p = 0,777 y tomografía: p = 0,349). Conclusión: El alendronato colocado localmente en el foco de fractura, en la etapa aguda y luego de una semana, no alteró, de manera estadísticamente significativa, el proceso normal de consolidación, determinado por anatomía patológica y radiología, a las seis semanas de la fractura de fémur en conejos. Nivel de Evidencia: II

Introduction: The aim of this experimental study was to evaluate the radiologic and histological results of the use of alendronate administered locally at the fractures site in rabbits. Methods: The fractured right femur of 30 rabbits was used for evaluation. The animals were distributed in three groups of 10 rabbits each. A solution with alendronate was placed at the fracture site in group 1; the same procedure was performed 7 days after the fracture in group 2, and group 3 functioned as control. Radiographic evaluation was performed at the time of the fracture and at day 42. Radiological, PA and CT-scan evaluations of bone callus characteristics in each rabbit were performed. Results: Twenty-four rabbits were evaluated (2 rabbits in group 2 and 4 in group 3 died). Histological evaluation evidenced moderate bone formation in the three groups without statistically significant differences (p=0.8336). Concerning imaging studies, there were no statistically significant differences in the size of bone callus among groups for both studies (X-rays: p=0.777 and CT: p=0.349). Conclusion: The use of alendronate administered locally at the fracture site, in the acute period and after one week, did not alter the normal consolidation process determined by PA and radiology, six weeks after femur fracture in rabbits. Level of Evidence: II

Nandrolone decanoate appears to increase bone callus formation in young adult rats after a complete femoral fracture

Abstract 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.

Effects of local alendronate administration on bone defect healing. Histomorphometric and radiological evaluation in a rabbit model

Abstract Purpose: To performed a histomorphometric and radiological study to evaluate the effects of alendronate sodium administered locally in mandibular bone defects created in rabbits. Methods: Two circular defects 5 mm in diameter were created bilaterally in the mandibular corpus of 20 New Zealand rabbits (i.e., four defects per animal). Each defect received one of four treatments: no treatment (EC group), alendronate irrigation (AL group), autogenous bone grafting (AG group), or alendronate irrigation with autogenous bone grafting (AL+AG group). Histomorphometric and radiological assessments were conducted at 4 and 8 weeks after surgery. Results: Between-group comparisons of the new bone area, the value of the AL+AG group was significantly lower thanthe remaining three groups at 4 weeks postoperatively. In all groups, the new bone area was significantly larger at 8 weeks than at 4 weeks. The residual graft area at 4 and 8 weeks was significantly higher in the AL+AG group than in the AG group, although it was significantly smaller at 8 weeks than at 4 weeks in both these groups. Conclusion: The use of alendronate sodium in conjunction with autogenous bone grafting improves the osteoconductive properties of the graft, enhances graft retention in the defect, and improves ossification.

The effects of supplemental melatonin administration on the healing of bone defects in streptozotocin-induced diabetic rats

ABSTRACT Diabetes mellitus (DM) causes an increased production of free radicals that can impair bone healing. Melatonin is a hormone secreted mainly by the pineal gland, which participates in the neutralization process of free radicals. Objective The aim of this study was to investigate histologic and biochemical effects of supplemental melatonin administration on bone healing and antioxidant defense mechanism in diabetic rats. Material and Methods Eighty-six Sprague-Dawley male rats were used in this study. Diabetes mellitus was induced by intraperitoneal (i.p.) administration of 65 mg/kg streptozotocin (STZ). Surgical bone defects were prepared in the tibia of each animal. Diabetic animals and those in control groups were treated either with daily melatonin (250 μg/animal/day/i.p.) diluted in ethanol, only ethanol, or sterile saline solution. Rats were humanely killed at the 10th and 30th postoperative days. Plasma levels of Advanced Oxidation Protein Products (AOPP), Malondialdehyde (MDA), and Superoxide Dismutase (SOD) were measured. The number of osteoblasts, blood vessels and the area of new mineralized tissue formation were calculated in histologic sections. Results At the 10th day, DM+MEL (rats receiving both STZ and melatonin) group had significantly higher number of osteoblasts and blood vessels as well as larger new mineralized tissue surfaces (p<0.05 for each) when compared with DM group. At the 30th day, DM group treated with melatonin had significantly lower levels of AOPP and MDA than those of DM group (p<0.05). Conclusion Melatonin administration in STZ induced diabetic rats reduced oxidative stress related biomarkers and showed beneficial effects on bone healing at short term.

Impact of micronutrients supplementation on bone repair around implants: microCT and counter-torque analysis in rats

ABSTRACT The use of natural substances and micronutritional approaches has been suggested as a therapeutic alternative to benefit the bone healing associated with no side effects. Nevertheless, the influence of micronutritional interventions with therapeutic proprieties on the bone repair has yet to be intensely evaluated, and no evidence is available exploring the impact of micronutrient supplementation on the peri-implant bone healing. Objective This study investigated the effect of micronutrients supplementation on the bone repair around implants. Material and Methods One screw-shaped titanium implant was inserted in each tibia of each rat, which were assigned to: daily administration, for 30 d, of the placebo solution (Placebo group-n:18) or micronutrients supplementation (Micronutrients group-n:18), based on calcium, magnesium, zinc, and vitamin D3 intake. After, the animals were sacrificed. One of the implants was removed by applying a counter-torque force to evaluate the force to rupture the bone-implant interface. The other implant was evaluated by microcomputed tomography (CT) examination to determine the bone-to-implant contact (BIC) and the bone volume (BV/TV). Results No statistically significant differences were observed between the groups for both counter-torque values and microCT parameters (p>0.05). Conclusion Within the limits of this study, micronutrients supplementation did not provide additional benefits to the bone healing around dental implants.

Effect of collagen sponge and fibrin glue on bone repair

ABSTRACT The ability of hemostatic agents to promote bone repair has been investigated using in vitro and in vivo models but, up to now, the results are inconclusive. Objective In this context, the aim of this study was to compare the potential of bone repair of collagen sponge with fibrin glue in a rat calvarial defect model. Material and Methods Defects of 5 mm in diameter were created in rat calvariae and treated with either collagen sponge or fibrin glue; untreated defects were used as control. At 4 and 8 weeks, histological analysis and micro-CT-based histomorphometry were carried out and data were compared by two-way ANOVA followed by Student-Newman-Keuls test when appropriated (p≤0.05). Results Three-dimensional reconstructions showed increased bone formation in defects treated with either collagen sponge or fibrin glue compared with untreated defects, which was confirmed by the histological analysis. Morphometric parameters indicated the progression of bone formation from 4 to 8 weeks. Additionally, fibrin glue displayed slightly higher bone formation rate when compared with collagen sponge. Conclusion Our results have shown the benefits of using collagen sponge and fibrin glue to promote new bone formation in rat calvarial bone defects, the latter being discreetly more advantageous.

Bisphosphonate associated osteomyelitis of the jaw in patients with bony exposure: prevention, a new way of thinking

Objective There is strong evidence of a link between the use of systemic bisphosphonates (BPs) and osteonecrosis of the jaw, especially in cancer patients. Among risk factors for BRONJ, tooth extraction and immune suppressive drugs seem to have significant role on bone healing. Therefore, the importance of these parameters in development of BRONJ was reviewed in this retrospective study in two maxillofacial surgery units. Material and Methods From 2007 to 2012, 46 patients on bisphosphonate who had developed oral bony lesions participated in this study. The pharmacological exposure, comorbidities, maxillofacial findings, types of treatment and outcome data were collected from clinical and radiological records. Results The most frequently used BP was alendronate (67%). Tooth extraction was reported in 61% of patients with BRONJ. Systemic corticosteroids were prescribed in 35 cases (76%) as an adjuvant for BP. Patients on corticosteroids had a lower probability of bony lesion healing (p<0.05) than patients without corticosteroids. Of the 46 patients who underwent conservative treatments, only ten were completely healed (21%). Conclusions Beside tooth extraction, corticosteroids were shown to be an implant risk factor for low rate of bone healing and hence the development of BRONJ. The outcome of conservative treatment was uncertain and this emphasizes the importance of prevention. .

Hard tissue regeneration using bone substitutes: an update on innovations in materials

Bone is a unique organ composed of mineralized hard tissue, unlike any other body part. The unique manner in which bone can constantly undergo self-remodeling has created interesting clinical approaches to the healing of damaged bone. Healing of large bone defects is achieved using implant materials that gradually integrate with the body after healing is completed. Such strategies require a multidisciplinary approach by material scientists, biological scientists, and clinicians. Development of materials for bone healing and exploration of the interactions thereof with the body are active research areas. In this review, we explore ongoing developments in the creation of materials for regenerating hard tissues.

Accelerated fracture healing with teriparatide / Consolidação de fratura acelerada com teriparatida

Satisfactory healing of the osteoporotic fracture is critically important to functional recovery, morbidity, and quality of life. Some therapies for osteoporosis may affect the processes associated with bone repair. For example, bisphosphonates in experimental models are associated with increased callus size and mineralization, reduced callus remodeling, and improved mechanical strength. Local and systemic bisphosphonate treatment may improve implant fixation. No negative impact on fracture healing has been observed, even after major surgery or when administered immediately after fracture. For the osteoanabolic agent teriparatide, case reports and a randomized trial have produced mixed results, but they are consistent with a positive impact of teriparatide on fracture healing. Some of the agents currently being developed for osteoporosis, notably sclerostin and DKK1 antibodies have shown a beneficial effect on fracture healing. At this point, therefore, there is no evidence that osteoporosis therapies are detrimental to fracture healing with some promising experimental evidence for positive effects on healing, notably for those agents whose actions are primarily anabolic.

A consolidação adequada da fratura osteoporótica é essencial para recuperação funcional, morbidade e qualidade de vida. Alguns tratamentos para osteoporose podem afetar os processos associados ao reparo ósseo. Por exemplo, os bisfosfonatos, em modelos experimentais, estão associados com aumento do tamanho do calo e a mineralização, reduzindo o remodelamento do calo e melhorando a força mecânica. Tratamento com bisfosfonato, local ou sistêmico, pode melhorar a fixação de implantes. Não foi observado impacto negativo na consolidação da fratura, mesmo após uma cirurgia maior ou quando administrado imediatamente após a fratura. Relatos e um estudo randomizado com o osteoanabólico teriparatida produziram resultados mistos, mas que são consistentes com o impacto positivo da teriparatida na consolidação da fratura. Algumas das drogas que estão sendo desenvolvidas no momento para osteoporose, como anticorpos para esclerotina e DKK1, têm mostrado efeito benéfico na consolidação da fratura. No estágio atual, portanto, não há evidência de que terapias para osteoporose impeçam a consolidação da fratura, mas existem algumas evidências experimentais promissoras de efeito positivo na consolidação, especialmente daqueles agentes cuja ação é primariamente anabólica.

The effects of alpha-tocopherol supplementation on fracture healing in a postmenopausal osteoporotic rat model

OBJECTIVE: Osteoporosis increases the risk of bone fractures and may impair fracture healing. The aim of this study was to investigate whether alpha-tocopherol can improve the late-phase fracture healing of osteoporotic bones in ovariectomized rats. METHOD: In total, 24 female Sprague-Dawley rats were divided into three groups. The first group was sham-operated, and the other two groups were ovariectomized. After two months, the right femora of the rats were fractured under anesthesia and internally repaired with K-wires. The sham-operated and ovariectomized control rat groups were administered olive oil (a vehicle), whereas 60 mg/kg of alpha-tocopherol was administered via oral gavage to the alpha-tocopherol group for six days per week over the course of 8 weeks. The rats were sacrificed, and the femora were dissected out. Computed tomography scans and X-rays were performed to assess fracture healing and callus staging, followed by the assessment of callus strengths through the biomechanical testing of the bones. RESULTS: Significantly higher callus volume and callus staging were observed in the ovariectomized control group compared with the sham-operated and alpha-tocopherol groups. The ovariectomized control group also had significantly lower fracture healing scores than the sham-operated group. There were no differences between the alpha-tocopherol and sham-operated groups with respect to the above parameters. The healed femora of the ovariectomized control group demonstrated significantly lower load and strain parameters than the healed femora of the sham-operated group. Alpha-tocopherol supplementation was not able to restore these biomechanical properties. CONCLUSION: Alpha-tocopherol supplementation appeared to promote bone fracture healing in osteoporotic rats but failed to restore the strength of the fractured bone.

Mechanical properties of radial bone defects treated with autogenous graft covered with hydroxyapatite in rabbit / Propriedades mecânicas de defeito de osso radial tratado com enxerto autógeno coberto com nano-hydroxyapatite em coelho

PURPOSE: To determine biomechanical property of autogenous bone graft covered with hydroxyapatite in the defect of radial bone in rabbit. METHODS: Eighteen adult male New Zealand white rabbits were used which were divided into three groups (I, II, III) of six rabbits each. A segmental bone defect of 10 mm in length was created in the middle of the right radial shaft under general effective anesthesia in all rabbits and were stabilized using mini-plate with four screws. The defects In group I were left as such without filler, whereas in group II the defect were filled up with harvested 10 mm rib bone and in group III the defect were packed with rib bone covered with nano-hydroxyapatite. All rabbits in three groups were divided into two subgroups (one month and three months duration with three rabbits in each one). RESULTS: The mechanical property and the mean load for fracturing normal radial bone was recorded 388.2±6 N whereas it was 72.4±12.8 N for group I in 1 month duration which was recorded 182.4±14.2 N for group II and 211.6±10.4 N for group III at the end of 1 month. These values were 97.6±10.2 N for group I and 324.6±8.2 N for group II and 372.6±17.4 N for group III at the end of three months after implantation. CONCLUSION: Implantation of autologous graft covered with hydroxyapatite indicated to have positive effect in integral formation of qualitative callus at the site of fracture and early re-organization of callus to regain mechanical strength too.

OBJETIVO: Determinar as propriedades biomecânicas de enxerto ósseo autógeno coberto com hidroxiapatita em defeito do osso radial em coelhos. MÉTODOS: Foram utilizados 18 coelhos adultos, machos, brancos, Nova Zelândia, distribuídos em três grupos (I, II, III) de seis coelhos cada. Um defeito segmentar de 10 mm de comprimento foi criado no meio do eixo radial direito sob anestesia geral efetiva em todos os coelhos e foram fixados usando mini-placa com quatro parafusos. Os defeitos no grupo I foram deixados sem preenchimento, enquanto no grupo II o defeito foi preenchido com 10 mm de costela recoberta com nano-hidroxiapatita. Os coelhos nos três grupos foram distribuídos em dois subgrupos (Um e três meses, com três coelhos cada um). RESULTADOS: A propriedade mecânica e a média do peso para fraturar o osso radial normal foi 388,2±6 N, enquanto para o Grupo I, com um mês foi 72,4±12,8 N, para o grupo II 182,4±14,2 N e para o Grupo III 211,6±10,4 N. Após três meses de implantação, os valores foram 97,6±10,2 N para o Grupo I, 324,6±8,2 N para o Grupo II e 372,6±17,4 N para o Grupo III. CONCLUSÃO: A implantação de enxerto autólogo recoberto com hidroxiapatita indicou ter um efeito positivo na formação integral qualitativa do calo ósseo no local da fratura e precoce reorganização do calo com recuperação da força mecânica.

Value of color Doppler ultrasonography and radiography for the assessment of the cancellous bone scaffold coated with nano-hydroxyapatite in repair of radial bone in rabbit / Valor da ultrassonografia Doppler em cores e da radiografia na avaliação da capacidade osteo-regenerativa da nano-hidroxiapatita no reparo de osso radial em coelho

PURPOSE: To evaluate the osteo-regenerative capacity of proprietary bone grafting material as a bone defect filler and osteogenetic stimulation to speed up bone healing too. METHODS: Eighteen adult male New Zealand white rabbits were anesthetized and a segmental full thickness bone defect of 10 mm in length was created in the middle of the right radial shaft in all rabbits. They were divided into two groups of 9 rabbits. Group I was considered as control and the fractured site was fixed using finger bone plate with 4 screws, whereas the cancellous bone scaffold coated with Nano-Hydroxyapatite was used to fill the gap after fracture fixation in Group II. Radiography, two dimensional and color Doppler ultrasonography were done before and after creating defects and on 0, 15, 30, 60 and 90 days to evaluate local reaction as far as new blood vessels network and callus formation are observed. RESULTS: On the radiographs during the whole process, bone repair in Group I was not as perfect as those in Group II samples and trace of internal callus filled the gap incompletely in 60 days in Group I, whereas in Group II internal callus almost was formed on 30 days and in addition intercortical callus was seen supporting to cover and filled the gap completely in this group in 60 day; Sonographic findings confirmed the protrusion of newly formed blood vascular network in 30 days in Group I and from 15 days in Group II and remarkably increased till end of observation period. CONCLUSIONS: The nano-hydroxyapatite with more features and shorter in time, made possible the reconstruction of bone tissue and alternative techniques as well as previous bone graft, also radiography and ultrasonography are reliable techniques to trace local reaction at proper time.

OBJETIVO: Avaliar a capacidade osteo-regenerativa de biomaterial no preenchimento de defeito ósseo e como estímulo osteogênico para acelerar a cicatrização óssea. ÉTODOS: Dezoito coelhos brancos, Nova Zelandia, adultos, machos foram anestesiados e um defeito ósseo segmentar de toda a espessura e 10 mm de comprimento foi criado no meio do eixo do osso radial direito de todos os coelhos. Os animais foram distribuídos em dois grupos de nove: Grupo I foi considerado como controle e o local da fratura foi fixado usando placa de dedo de osso com quatro parafusos, enquanto o molde de osso esponjoso revestido com nano-hidroxiapatita foi usado para preencher o espaço após fixação da fratura no Grupo II. Radiografia, bidimensional e ultrassonografia Doppler colorida foi feita antes e após criar os defeitos e nos dias 0, 15, 30, 60 e 90 para avaliar a reação local tais como nova rede vascular e formação do calo ósseo. RESULTADOS: Nas radiografias durante todo o processo, o reparo ósseo no Grupo I não foi perfeito como no Grupo II; amostras e traços de calo ósseo preencheram o espaço de forma incompleta em 60 dias no Grupo I, enquanto no Grupo II o calo ósseo interno foi quase formado em 30 dias e, além disso, calo intercortical foi visto apoiar para revestir e preencher o espaço completamente em 60 dias; nos achados ultrassonográficos a protrusão da rede vascular neoformada em 30 dias no Grupo I e a partir de 15 dias no Grupo II e acentuado aumento até o fim do período de observação. CONCLUSÕES: A nano-hidroxiapatita, com mais propriedade e menor período de tempo, tornou possível a reconstrução de tecido ósseo e técnicas alternativas como o enxerto ósseo prévio, assim como a radiografia e a ultrassonografia são técnicas confiáveis para traçar a reação local em tempo adequado.

Spontaneous Non-Traumatic Stress Fractures in Bilateral Femoral Shafts in a Patient Treated with Bisphosphonates

Bisphosphonates are potent inhibitors of bone resorption and widely used to treat osteoporosis. Extensive studies have shown that therapy with bisphosphonates improves bone density and decreases fracture risk. However, concerns have been raised about potential over-suppression of bone turnover during long-term use of bisphosphonates, resulting in increased susceptibility to and delayed healing of non-spinal fractures. We report a patient who sustained non-traumatic stress fractures in bilateral femoral shafts with delayed healing after long-term bisphosphonate therapy. She underwent open reduction and surgical internal fixation. Although bisphosphonates effectively prevent vertebral fractures, and their safety has been tested in randomized trials, we must emphasize the need for awareness of the possibility that long-term suppression of bone turnover with bisphosphonates may eventually lead to an accumulation of fatigue-induced damage and adverse skeletal effects such as delayed fracture healing.

Histomorphometric analysis of the repair process of autogenous bone grafts fixed at rat calvaria with cyanoacrylate

OBJECTIVE: The purpose of this study was to perform histological and histometric analyses of the repair process of autogenous bone grafts fixed at rat calvaria with ethyl-cyanoacrylate adhesive. MATERIAL AND METHODS: Thirty-two rats were divided into two groups (n=16), Group I - Control and Group II - Adhesive. Osteotomies were made at the right parietal bone for graft obtainment using a 4-mm-diameter trephine drill. Then, the bone segments were fixed with the adhesive in the parietal region of the opposite side to the donor site. After 10 and 30 days, 8 animals of each group were euthanized and the calvarias were laboratorially processed for obtaining hematoxylin and eosin-stained slides for histological and histometric analyses. RESULTS: An intense inflammatory reaction was observed at the 10-day period. At 30 days, this reaction was less intense, despite the presence of adhesive at the recipient-site/graft interface. Graft incorporation to the recipient site was observed only at the control group, which maintained the highest graft size at 10 and 30 days. CONCLUSIONS: Although the fragment was stable, the presence of adhesive in Group II did not allow graft incorporation to the recipient site, determining a localized, discrete and persistent inflammatory reaction.

Expression of TGF-β1 in the blood during fracture repair in an estrogen-deficient rat model

OBJECTIVES: Previous studies have reported that osteoporosis due to estrogen deficiency influences fracture healing. Transforming growth factor (TGF-b) has been found to be involved in fracture healing via the regulation of the differentiation and activation of osteoblasts and osteoclasts. The current study aimed to determine the effects of estrogen on the expression of TGF-β1 during fracture healing in ovariectomized rats. METHODS: Thirty female Sprague-Dawley rats weighing 200-250 g were assigned to: (i) a sham-operated group that was given a normal saline; (ii) an ovariectomized control group that was given a normal saline; or (iii) an ovariectomized + estrogen (100 mg/kg/day) group that was treated with conjugated equine estrogen. The right femur of all rats was fractured, and a Kirschner wire was inserted six weeks post-ovariectomy. Treatment with estrogen was given for another six weeks post-fracture. At the end of the study, blood samples were taken, and the right femur was harvested and subjected to biomechanical strength testing. RESULTS: The percentage change in the plasma TGF-β1 level before treatment was significantly lower in the ovariectomized control and estrogen groups when compared with the sham group (p<0.001). After six weeks of treatment, the percentage change in the plasma TGF-β1 level in the estrogen group was significantly higher compared with the level in the ovariectomized control group (p = 0.001). The mean ultimate force was significantly increased in the ovariectomized rats treated with estrogen when compared with the ovariectomized control group (p = 0.02). CONCLUSION: These data suggest that treatment with conjugated equine estrogen enhanced the strength of the healed bone in estrogen-deficient rats by most likely inducing the expression of TGF-β1.

Piper sarmentosum enhances fracture healing in ovariectomized osteoporotic rats: a radiological study

INTRODUCTION: Osteoporotic fractures are common during osteoporotic states. Piper sarmentosum extract is known to possess antioxidant and anti-inflammatory properties. OBJECTIVES: To observe the radiological changes in fracture calluses following administration of a Piper sarmentosum extract during an estrogen-deficient state. METHODS: A total of 24 female Sprague-Dawley rats (200-250 g) were randomly divided into 4 groups: (i) the sham-operated group; (ii) the ovariectomized-control group; (iii) the ovariectomized + estrogen-replacement therapy (ovariectomized-control + estrogen replacement therapy) group, which was supplemented with estrogen (100 μg/kg/day); and (iv) the ovariectomized + Piper sarmentosum (ovariectomized + Piper sarmentosum) group, which was supplemented with a water-based Piper sarmentosum extract (125 mg/kg). Six weeks after an ovariectomy, the right femora were fractured at the mid-diaphysis, and a K-wire was inserted. Each group of rats received their respective treatment for 6 weeks. Following sacrifice, the right femora were subjected to radiological assessment. RESULTS: The mean axial callus volume was significantly higher in the ovariectomized-control group (68.2 + 11.74 mm³) than in the sham-operated, estrogen-replacement-therapy and Piper sarmentosum groups (20.4 + 4.05, 22.4 + 4.14 and 17.5 + 3.68 mm³, respectively). The median callus scores for the sham-operated, estrogen-replacement-therapy and Piper sarmentosum groups had median (range, minimum - maximum value) as 1.0 (0 - 2), 1.0 (1 - 2) and 1.0 (1 - 2), respectively, which were significantly lower than the ovariectomized-control group score of 2.0 (2 - 3). The median fracture scores for the sham-operated, estrogen-replacement-therapy and Piper sarmentosum groups were 3.0 (3 - 4), 3.0 (2 - 3) and 3.0 (2 - 3), respectively, which were significantly higher than the ovariectomized-control group score of 2.0 (1 - 2) (p<0.05). CONCLUSION: The Piper sarmentosum extract improved fracture healing, as assessed by the reduced callus volumes and reduced callus scores. This extract is beneficial for fractures in osteoporotic states.

Comparison between the effects of platelet-rich plasma and bone marrow concentrate on defect consolidation in the rabbit tibia

OBJECTIVE: To perform a comparative analysis of the effects of platelet-rich plasma and centrifuged bone marrow aspirate on the induction of bone healing in rabbits. METHOD: Twenty adult, male New Zealand rabbits were randomly separated into two equal groups, and surgery was performed to create a bone defect (a cortical orifice 3.3 mm in diameter) in the proximal metaphysis of each rabbit's right tibia. In the first group, platelet-rich plasma was implanted in combination with β-tricalcium phosphate (platelet-rich plasma group), and in the second group, centrifuged bone marrow in combination with β-tricalcium phosphate (centrifuged bone marrow group) was implanted. After a period of four weeks, the animals were euthanized, and the tibias were evaluated using digital radiography, computed tomography, and histomorphometry. RESULTS: Seven samples from each group were evaluated. The radiographic evaluation confirmed the absence of fractures in the postoperative limb and identified whether bone consolidation had occurred. The tomographic evaluation revealed a greater amount of consolidation and the formation of a greater cortical bone thickness in the platelet-rich plasma group. The histomorphometry revealed a greater bone density in the platelet-rich plasma group compared with the centrifuged bone marrow group. CONCLUSION: After four weeks, the platelet-rich plasma promoted a greater amount of bone consolidation than the bone marrow aspirate concentrate.