Regenerating effect of hyaluronic acid on circumferential bone defects in wistar albino rats / Efecto regenerador del ácido hialurónico en defectos óseos circunferenciales en ratas albinas wistar

Objective: To determine the regenerating effect of hyaluronic acid on circumferential bone defects in albino Wistar rats. Material and Methods: An experimental type study was designed and carried out with 15 albino male Wistar rats, 4 months old and weighing between 250 and 350 grams. Two circumferential bone defects 3mm in diameter and 0.8mm deep were created in the calvaria of the parietal bone (on both sides of the midline). One defect was filled with a demineralized bone matrix (control group); while the other defect was filled with the combination of a demineralized bone matrix plus hyaluronic acid (experimental group). Five experimental rats were euthanized at 30, 60 and 90 days after surgery and they were histologically evaluated following the parameters proposed by Heiple. Results: The experimental group presented a better degree of bone regeneration at 30 and 60 postoperative days. Conclusion: Hyaluronic acid is effective in bone regeneration of circumferential bone defects.

Objetivo: Determinar el efecto regenerador del ácido hialurónico en defectos óseos circunferenciales en ratas albinas Wista. Material y Métodos: Se diseñó un estudio de tipo experimental y se trabajó con 15 ratas albinas Wistar (todas macho) de 4 meses de edad y con un peso entre 250 a 350 gr. Se crearon en todas 2 defectos óseos circunferenciales de 3mm de diámetro y 0.8 mm de profundidad en la calota del hueso parietal (a ambos lados de la línea media). Un defecto fue rellenado con una matriz ósea desmineralizada (grupo control); mientras que el otro defecto fue rellenado con la combinación de una matriz ósea desmineralizada más el ácido hialurónico (grupo experimental). Se realizó la eutanasia a 05 ratas de experimentación a los 30, 60 y 90 días postquirúrgicos y se evaluaron histológicamente siguiendo los parámetros propuestos por Heiple. Resultados: El grupo experimental presentó un mejor grado de regeneración ósea en los 30 y 60 días postoperatorios. Conclusiones: El ácido hialurónico es eficaz en la regeneración ósea de defectos óseos circunferenciales.

Histological comparison between biphasic calcium phosphate and deproteinized bovine bone on critical-size bone defects

Abstract The limited options for bone repair have led to an extensive research of the field and the development of alloplastic and xenogeneic grafts. The purpose of this study was to evaluate bone repair with two bone substitutes: deproteinized bovine bone (DBB) and biphasic calcium phosphate ceramic (BCP) in critical-size defect. A total of 8-mm defects were made in the parietal bones of rabbits (n=12). The animals were divided into three experimental groups: sham (defect filled with a blood clot), DBB (defect filled with DBB), and BCP (defect filled with BCP). After the experimental periods of 15 and 45 days, the animals were euthanized and submitted to histomorphometric analysis. The total defect area, mineralized tissue area, biomaterial area, and soft tissue area were evaluated. A greater amount of immature bone tissue and biomaterial particles were observed in the BCP group compared to DBB and sham at 45 days (p<0.05). There was no difference in the qualitative pattern of bone deposition between DBB and BCP. However, the sham group did not show osteoid islands along with the defect, presenting a greater amount of collagen fibers as well in relation to the DBB and BCP groups. There was a greater number of inflammatory cells in the DBB at 45 days compared to BCP and sham groups. In conclusion, BCP and DBB are options for optimizing the use of bone grafts for maxillofacial rehabilitation. Bone defects treated with BCP showed greater deposition of bone tissue at 45 days.

Resumo As opções limitadas para reparo ósseo levaram ao desenvolvimento de abrangente pesquisa na área de enxertos aloplásticos e xenogênicos. O objetivo deste estudo foi avaliar o reparo ósseo com dois substitutos ósseos: osso bovino desproteinizado (DBB) e cerâmica fosfática de cálcio bifásica (BCP) em defeito de tamanho crítico. Material e métodos: defeitos críticos de 8 mm foram feitos nos ossos parietais de coelhos (n=12). Os animais foram divididos em três grupos experimentais: sham (defeito preenchido com coágulo sanguíneo), DBB (defeito preenchido com DBB) e BCP (defeito preenchido com BCP). Após os períodos experimentais de 15 e 45 dias, os animais foram sacrificados e submetidos à análise histomorfométrica. Foram avaliadas a área total de defeitos, área de tecidos mineralizados, área de biomateriais e área de tecidos moles. Resultados: maior quantidade de tecido ósseo imaturo e de partículas de biomaterial foram observados no grupo BCP em comparação aos grupos DBB e sham aos 45 dias (p<0,05). Não houve diferença no padrão qualitativo de deposição óssea entre DBB e BCP. Ainda, o grupo sham não apresentou ilhas osteóides ao longo do defeito, apresentando maior quantidade de fibras colágenas em relação aos grupos DBB e BCP. Houve maior quantidade de células inflamatórias no DBB aos 45 dias em comparação aos grupos BCP e sham. Conclusões: BCP e DBB são opções para otimizar o uso de enxertos ósseos na reabilitação de pacientes. Defeitos ósseos tratados com BCP mostraram maior deposição de tecido ósseo aos 45 dias.

Integration of heterologous bone matrix associated with polymethylmethacrylate in induced tibial bone defects. An experimental study in rabbits

ABSTRACT Purpose To analyze and compare the reactions at the interface between the composite, composed of fragmented heterologous mineralized bone matrix (MOMHF) and polymethylmethacrylate (PMMA), and the rabbit's tibias, through macroscopic evaluation and scanning electron microscopy (SEM) in different periods. Methods In this study, 12 New Zealand adult rabbits were used (E1: n = 3, E2: n = 3, E3: n = 3 and E4: n = 3). They had the right tibial defects filled with composite and were evaluated immediately after surgery and at 30, 60, 90, and 120 days. Results The composites were incorporated and integrated into the recipient beds in 100% of the cases, defined by the MOMHF osseointegration and the PMMA fibrointegration, with no sign of infection, migration, or rejection. Conclusions The behavior of the composites in the recipient beds demonstrates that these biomaterials have the potential to be used in bone defect repairs, offering, thus, better quality of life to the orthopedic patient.

Caprine demineralized bone matrix (DBMc) in the repair of non-critical bone defects in rabbit tibias. A new bone xenograft

Abstract Purpose To evaluate the use of demineralized bone matrix of caprine origin in experimental bone defects of the tibia in New Zealand rabbits. Methods Fragments of the tibia diaphysis were collected aseptically from clinically healthy goats. The bones were sectioned into 1 cm fragments and stored at -20°C for subsequent hydrochloric acid (HCL) demineralization. A 70 mg portion of DBMc was used to fill the experimental bone defects. Twenty-four female adult New Zealand rabbits were divided into 2 groups: the MG (matrix group, left tibia) and CG (control group, right tibia). Additionally, they were separated into 4 groups with 6 animals, according to the period of analysis (15, 30, 60 and 90 days postoperatively). Using microCT, volumetric parameters were evaluated: bone volume, relationship between bone volume and total volume, bone surface area, relationship between bone surface area and total volume, number of trabeculae, trabecular thickness and trabecular separation. Results There was a statistically significant difference (P<0.05) between groups considering bone volume (BV) and bone:total volume (BV/TV), on 15, 30 and 90 days postoperatively. Control group showed a statistically significant superiority (P < 0.05) considering the mean of the variables bone surface (BS), number of trabeculae (Tb.N) and between bone surface and total volume (BS/TV) at 15 and 90 days. Conclusions Caprine demineralized bone matrix was safe and tolerable. No signs of material rejection were seen macroscopically. It is an alternative for the treatment of bone defects when autologous graft is not available or in insufficient quantities.

Comparison of morphological quantitative characteristics of the newly formed alveolar bone after the application of demineralized bone matrix and cortical bone allografts / Comparación de las características morfológicas cuantitativas del hueso alveolar recién formado después de la aplicación de matriz ósea desmineralizada y aloinjertos de hueso cortical

The allografts were used to obtain sufficient alveolar bone tissue for proper dental implant placement. The objective of the present study was to evaluate the morphological and quantitative characteristics (cellular and collagen densities) of the newly formed alveolar bone with the application of cortical bone (CB) and demineralized bone matrix (DBM) allografts. Six samples of alveolar bone tissue from 5 patients (50 ± 6.3 years) were obtained after 6 months of application of the allografts and immediately before the placement of the dental implants. The samples were fixed (buffered formaldehyde, pH7.2), decalcified (EDTA 10 %) and histologically processed (HE and Picro-Sirius) for histologic analysis. Morphological analysis revealed presence of osteocytes and trabeculae in neoformed bone tissue near the allografts and absence of inflammatory and allergic cells; the remnants of CB were located mainly in the periphery of the bone tissue and the remnants of DBM were more incorporated into the tissue. Osteogenitor cells were observed around the remaining material. The cell density was not modified in newly formed bone tissue with the application of both allografts as compared to mature bone tissue. The density of the type I and III collagens present in the osteoids interspersed with the remainder of the materials showed a tendency to increase in the samples treated with DBM. It was concluded that by the histological characteristics observed both grafts were biocompatible, however the bone treated with DBM presented better incorporation and a tendency of increase of the collagen content in the remnant region of the allografts.

Los aloinjertos son utilizados para obtener tejido óseo alveolar apropiado para la colocación correcta del implante dental. El objetivo de este trabajo fue evaluar las características morfológicas y cuantitativas (densidades celulares y de colágeno) del hueso alveolar recién formado con la aplicación de aloinjertos de hueso cortical (CB) y matriz desmineralizada de hueso (DBM). Seis muestras de tejido óseo alveolar fueron obtenidas de 5 pacientes (50 ± 6,3 años) después de 6 meses de aplicación de los aloinjertos e inmediatamente antes de la colocación de los implantes dentales. Las muestras fueron fijadas (formaldehído tamponado, pH 7,2), descalcificadas (EDTA al 10%) y procesadas histológicamente (HE y Picro-Sirius) para el análisis histológico. El análisis morfológico reveló la presencia de osteocitos y trabéculas en el tejido óseo neoformado cerca de los aloinjertos y la ausencia de células inflamatorias y alérgicas; los remanentes de CB se ubicaron principalmente en la periferia del tejido óseo y los remanentes de DBM se incorporaron más en el tejido. Se observaron células osteogenitoras alrededor del material restante. La densidad celular no se modificó en el tejido óseo recién formado con la aplicación de ambos aloinjertos en comparación con el tejido óseo maduro. La densidad de los colágenos de tipo I y III presentes en los osteoides intercalados con el resto de los materiales mostró una tendencia a aumentar en las muestras tratadas con DBM. Se concluyó que, debido a las características histológicas observadas, ambos injertos fueron biocompatibles, sin embargo, el hueso tratado con DBM presentó una mejor incorporación y una tendencia al aumento del contenido de colágeno en la región remanente de los aloinjertos.

Uso de la Fibrina Rica en Plaquetas Inyectable (i-PRF) en Defectos Infra Óseos en Terapia Periodontal no Quirúrgica. Reporte de Dos Casos / Use of Injectable Platelet-Rich Fibrin (i-PRF) in Infra Osseous Defects in Non-Surgical Periodontal Therapy. Report of Two Cases

RESUMEN: Entre los concentrados plaquetarios de segunda generación, ha suscitado creciente interés, el uso de fibrina rica en plaquetas y leucocitos inyectable (i-PRF); que se obtiene a partir de la centrifugación inmediata de sangre venosa del propio individuo, y que aporta concentraciones elevadas de factor de crecimiento vascular endotelial, factor de crecimiento transformante beta, y factor de crecimiento derivado de plaquetas, entre otras proteínas que inician y coordinan el proceso reparativo. Su nula citotoxicidad y consistencia líquida abren un nuevo campo de estudio y experimentación en el ámbito de la Cirugía Oral y de la Periodoncia, como sustancia para irrigar. El objetivo de este manuscrito fue reportar el uso del i-PRF como irrigador subgingival en el tratamiento periodontal convencional de defectos infra óseos con 6 meses de seguimiento. En ambos casos, se verificó un efecto positivo de irrigación, lo que abre el debate al uso de productos farmacéuticos tradicionales como la clorhexidina versus preparados autólogos sin efectos adversos reportados a la fecha.

ABSTRACT: Second generation platelet concentrates include the use of injectable platelet-rich fibrin (i-PRF), which has generated increasing interest because it is derived from immediate centrifugation of venous blood from the patients themselves. It provides high concentrations of vascular endothelial growth factor, transforming growth factor beta, and platelet-derived growth factor, among other proteins that initiate and coordinate the healing process. Its null cytotoxicity and liquid consistency has opened new research lines in the field of oral surgery and periodontics, as an irrigation substance. The aim of this manuscript was to report the use of i-PRF, as a subgingival irrigator in conventional periodontal treatment of infra osseous defects, with six months follow-up. In both cases, a positive effect of irrigation was confirmed. These findings, open the debate as regards the use of traditional pharmaceutical products (such as chlorhexidine), versus autonomous preparations without adverse effects reported to date.

Fibrin biopolymer as scaffold candidate to treat bone defects in rats

Bone tissue repair remains a challenge in tissue engineering. Currently, new materials are being applied and often integrated with live cells and biological scaffolds. The fibrin biopolymer (FBP) proposed in this study has hemostatic, sealant, adhesive, scaffolding and drug-delivery properties. The regenerative potential of an association of FBP, biphasic calcium phosphate (BCP) and mesenchymal stem cells (MSCs) was evaluated in defects of rat femurs. Methods: Adult male Wistar rats were submitted to a 5-mm defect in the femur. This was filled with the following materials and/or associations: BPC; FBP and BCP; FBP and MSCs; and BCP, FBP and MSCs. Bone defect without filling was defined as the control group. Thirty and sixty days after the procedure, animals were euthanatized and subjected to computed tomography, scanning electron microscopy and qualitative and quantitative histological analysis. Results: It was shown that FBP is a suitable scaffold for bone defects due to the formation of a stable clot that facilitates the handling and optimizes the surgical procedures, allowing also cell adhesion and proliferation. The association between the materials was biocompatible. Progressive deposition of bone matrix was higher in the group treated with FBP and MSCs. Differentiation of mesenchymal stem cells into osteogenic lineage was not necessary to stimulate bone formation. Conclusions: FBP proved to be an excellent scaffold candidate for bone repair therapies due to application ease and biocompatibility with synthetic calcium-based materials. The satisfactory results obtained by the association of FBP with MSCs may provide a more effective and less costly new approach for bone tissue engineering.(AU)

Comparison of Cortical Ring Allograft and Plate Fixation with Autologous Iliac Bone Graft for Anterior Cervical Discectomy and Fusion

STUDY DESIGN: A retrospective cohort study. PURPOSE: To compare the clinical and radiological outcomes of patients who underwent anterior cervical discectomy and fusion (ACDF) supplemented with plate fixation using allograft with those who underwent ACDF using tricortical iliac autograft. OVERVIEW OF LITERATURE: As plate fixation is becoming popular, it is reported that ACDF using allograft may have similar outcomes compared with ACDF using autograft. METHODS: Forty-one patients who underwent ACDF supplemented with plate fixation were included in this study. We evaluated 24 patients who used cortical ring allograft filled with demineralized bone matrix (DBM) (group A) and 17 patients who used tricortical iliac autograft (group B). In radiological evaluations, fusion rate, subsidence of grafted material, cervical lordosis, fused segmental lordosis, and radiological adjacent segment degeneration (ASD) were observed and analyzed with preoperative and postoperative plain radiographs. Clinical outcomes were evaluated using the Neck Disability Index score, Odom criteria, and Visual Analog Scale score of neck and upper extremity pain. Radiological union was determined by dynamic radiographs using cutoff values of 1 mm of interspinous motion as the indication of pseudarthrosis. RESULTS: There was no significant difference in the fusion rate, graft subsidence, cervical lordosis, fused segmental lordosis, and ASD incidence between the groups. Operative time was shorter in group A (136 min) than in group B (141 min), but it was not significant (p>0.05). Blood loss was greater in group B (325 mL) than in group A (210 mL, p=0.013). There was no difference in the clinical outcomes before and after surgery. CONCLUSIONS: In ACDF with plate fixation, cortical ring allograft filled with DBM group showed similar radiological and clinical outcomes compared with those of the autograft group. If the metal plate is reinforced, using cortical ring allograft could be a viable alternative to autograft.

Induction of Chondrogenic Differentiation in Human Mesenchymal Stem Cells Cultured on Human Demineralized Bone Matrix Scaffold under Hydrostatic Pressure

BACKGROUND: Articular cartilage damage is still a troublesome problem. Hence, several researches have been performed for cartilage repair. The aim of this study was to evaluate the chondrogenicity of demineralized bone matrix (DBM) scaffolds under cyclic hydrostatic pressure (CHP) in vitro. METHODS: In this study, CHP was applied to human bone marrow mesenchymal stem cells (hBMSCs) seeded on DBM scaffolds at a pressure of 5 MPa with a frequency of 0.5 Hz and 4 h per day for 1 week. Changes in chondrogenic and osteogenic gene expressions were analyzed by quantifying mRNA signal level of Sox9, collagen type I, collagen type II, aggrecan (ACAN), Osteocalcin, and Runx2. Histological analysis was carried out by hematoxylin and eosin, and Alcian blue staining. Moreover, DMMB and immunofluorescence staining were used for glycosaminoglycan (GAG) and collagen type II detection, respectively. RESULTS: Real-time PCR demonstrated that applying CHP to hBMSCs in DBM scaffolds increased mRNA levels by 1.3-fold, 1.2-fold, and 1.7-fold (p < 0.005) for Sox9, Col2, and ACAN, respectively by day 21, whereas it decreased mRNA levels by 0.7-fold and 0.8-fold (p < 0.05) for Runx2 and osteocalcin, respectively. Additionally, in the presence of TGF-β1 growth factor (10 ng/ml), CHP further increased mRNA levels for the mentioned genes (Sox9, Col2, and ACAN) by 1.4-fold, 1.3-fold and 2.5-fold (p < 0.005), respectively. Furthermore, in histological assessment, it was observed that the extracellular matrix contained GAG and type II collagen in scaffolds under CHP and CHP with TGF-β1, respectively. CONCLUSION: The osteo-inductive DBM scaffolds showed chondrogenic characteristics under hydrostatic pressure. Our study can be a fundamental study for the use of DBM in articular cartilage defects in vivo and lead to production of novel scaffolds with two different characteristics to regenerate both bone and cartilage simultaneously.

The cortical matrix of femur in adult-aged Wistar rats is critically affected by maternal malnutrition during lactation period / La matriz cortical del fémur en ratas Wistar de edad adulta se ve críticamente afectada por la malnutrición materna durante el período de lactancia

Osteoporosis is associated with poor dietary habits. Malnutrition is characterized as a deficit on the intake of necessary nutrients that are essential for optimal health maintenance. It is known that malnutrition during the lactation period can affect the offspring. The present study aims to evaluate the chronic effects caused by maternal energy-protein restriction during lactation period in the offspring. At parturition, Wistar rat dams were divided in three groups: (1) Control group (C) - which received a 23 % protein diet without restrictions; (2) Protein-Energy restriction group (PER)- which received a 8 % protein diet; (3) Energy restriction group (ER) which received a 23 % protein diet in limited amounts, according to the ingestion of the second group. Each group had 12 pups. After weaning, all pups received free access to a 23 % protein diet until 180 days and then were euthanized. Their femur was excised, decalcified, histologically processed and analyzed under a microscope. The measurements of the osteon lacunae on the C, ER and PER groups were, respectively: 2.1 µm, 10.9 µm and 14.7 µm (p<0.05). A poor ingestion of proteins and calories during lactation period provoked critical and permanent changes on the bone matrix of the femur, which simulated osteoporosis.

La osteoporosis se asocia con malos hábitos alimenticios. La desnutrición se caracteriza como un déficit en la ingesta de los nutrientes necesarios que son esenciales para un mantenimiento óptimo de la salud. Se sabe que la malnutrición durante el período de lactancia puede afectar a la descendencia. El presente estudio tiene como objetivo evaluar los efectos crónicos causados por la restricción energética-proteína materna durante el período de lactancia en la descendencia. En el parto, las hijas de rata Wistar se dividieron en tres grupos: (1) grupo control (C) - que recibió una dieta con 23 % de proteína sin restricciones; (2) Grupo restricción de energía de proteína (PER) - que recibió una dieta con 8 % de proteína; (3) Grupo restricción de energía (ER) - que recibió una dieta de 23 % de proteína en cantidades limitadas, de acuerdo con la ingestión del segundo grupo. Cada grupo tenía 12 crías. Después del destete, todas las crías recibieron acceso libre a una dieta con 23 % de proteína hasta 180 días y luego fueron sacrificadas. Su fémur fue extirpado, descalcificado, procesado histológicamente y analizado bajo un microscopio. Las mediciones de las lagunas de osteón en los grupos C, ER y PER fueron, respectivamente: 2,1 mm, 10,9 mm y 14,7 mm (p <0,05). Una mala ingesta de proteínas y calorías durante el período de lactancia provocó cambios críticos y permanentes en la matriz ósea del fémur, que simulaba osteoporosis.

Demineralized bone matrix and calcium-phosphate cement in bone regeneration in rats

Abstract Purpose: To compare bone regeneration in critical-sized defects in rat calvarium using demineralized bone matrix and calcium phosphate cement. Methods: Thirty Wistar rats were divided into 3 groups of 10 animals each. Two defects of 5-mm were made in the parietal bones of each animal. Group I had calcium phosphate cement placed in the experimental defect, Group II had filled with demineralized bone matrix and Group III had with the combination of the matrix and cement in equal parts. All animals had one defect left unfilled to serve as controls. Five animals in each group were sacrificed at 4 and 8 weeks. Histomorphometric analysis was used to quantify the amount of new bone within the defects. Results: The results showed that demineralized bone matrix-treated defects had significantly more new bone at 4 weeks compared to calcium phosphate cement-treated defects (p=0.03) and also had significantly more new bone at 8 weeks compared to unfilled defects (p=0.04). Conclusions: The demineralized bone matrix was superior to calcium phosphate cement in bone regeneration. It seems that calcium phosphate cement acted by inhibiting the osteogenesis when associated with a demineralized bone matrix and this combination should not be recommended.

Combined effect of recombinant human bone morphogenetic protein-2 and low level laser irradiation on bisphosphonate-treated osteoblasts

OBJECTIVES: The purpose of this study was to evaluate the synergic effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) and low-level laser therapy (LLLT) on bisphosphonate-treated osteoblasts. MATERIALS AND METHODS: Human fetal osteoblast cells (hFOB 1.19) were cultured with 100 µM alendronate. Low-level Ga-Al-As laser alone or with 100 ng/mL rhBMP-2 was then applied. Cell viability was measured with MTT assay. The expression levels of receptor activator of nuclear factor kappa-B ligand (RANKL), macrophage colony-stimulating factor (M-CSF), and osteoprotegerin (OPG) were analyzed for osteoblastic activity inducing osteoclastic activity. Collagen type and transforming growth factor beta-1 were also evaluated for bone matrix formation. RESULTS: The results showed that rhBMP-2 and LLLT had a synergic effect on alendronate-treated osteoblasts for enhancing osteoblastic activity and bone matrix formation. Between rhBMP-2 and LLLT, rhBMP-2 exhibited a greater effect, but did not show a significant difference. CONCLUSION: rhBMP-2 and LLLT have synergic effects on bisphosphonate-treated osteoblasts through enhancement of osteoblastic activity and bone formation activity.

An Uncommon Case of Bilateral Pathologic Hip Fractures: Antiviral Drug-induced Osteomalacia in a Patient with Hepatitis B / 대한고관절학회지

The long-term use of adefovir and tenofovir–antiviral medications commonly used to treat chronic hepatitis B–can be associated with proximal renal tubular dysfunction resulting in significant hypophosphatemic osteomalacia. However, there have been few reports about pathological fractures requiring surgical stabilization in cases of antiviral drug-induced hypophosphatemic osteomalacia. We present the case of a 51-year-old man who sustained bilateral pathological hip fractures associated with antiviral drug-induced hypophosphatemic osteomalacia. To treat a lamivudine-resistant hepatitis-B viral infection, the patient received adefovir for 7 years followed by tenofovir for the subsequent 3 years. He had suffered from polyarthralgia and generalized weakness for 2 years prior to presentation at our clinic. Misdiagnosis and inadequate management of his condition accelerated weakness of the bone matrix and ultimately induced pathological fractures. The patient was managed via cementless total hip arthroplasty on the left hip and internal fixation on the right hip. This case highlights that orthopaedic surgeons should consider the possibility of hypophosphatemic osteomalacia if patients receiving antiviral drugs complain of polyarthralgia and generalized weakness.

Outcomes of Anterior Cervical Fusion Using Polyetheretherketone Cage with Demineralized Bone Matrix and Plate for Management of Subaxial Cervical Spine Injuries / 대한신경손상학회지

OBJECTIVE: We evaluated the usefulness of a polyetheretherketone (PEEK) cage filled with demineralized bone matrix (DBM) and plate fixation in anterior interbody fusions for subaxial cervical spine injuries. METHODS: A retrospective review of 98 patients (58 women, 40 men; mean age, 49.7 years; range, 17–78 years) who underwent single-level anterior cervical discectomy and fusion (ACDF) using a PEEK cage filled with DBM and plate fixation for subaxial cervical spine injuries from March 2005 to June 2018 was conducted. Bone fusion, interbody height (IBH), segmental lordosis, and adjacent segment degeneration (ASD) development were assessed with plain radiographs and computed tomography. Clinical outcomes were assessed using a visual analog scale (VAS) for pain and the Frankel grade for neurologic function. RESULTS: The mean follow-up period was 27.6 months (range, 6–142 months). Twenty-one patients (21.4%) had an improvement of at least one Frankel grade. The mean preoperative and final follow-up neck pain VAS scores were 8.3±0.9 and 2.6±1.5 (p < 0.05). All patients showed solid fusion at the final follow-up. The mean preoperative and final Cobb's angles were −3.7±7.9° and 1.9±5.1° (p < 0.05). The mean preoperative and final IBHs were 36.9±1.7 mm and 38.2±1.8 mm (p < 0.05). Five patients (5%) showed ASD. CONCLUSION: ACDF using a PEEK cage filled with DBM and plate fixation yielded high fusion rates and satisfactory clinical outcomes without donor-site morbidity. This procedure is safe and effective for single-level subaxial cervical spine injuries.

Regulation of Osteoblast Metabolism by Wnt Signaling

Wnt/β-catenin signaling plays a critical role in the achievement of peak bone mass, affecting the commitment of mesenchymal progenitors to the osteoblast lineage and the anabolic capacity of osteoblasts depositing bone matrix. Recent studies suggest that this evolutionarily-conserved, developmental pathway exerts its anabolic effects in part by coordinating osteoblast activity with intermediary metabolism. These findings are compatible with the cloning of the gene encoding the low-density lipoprotein related receptor-5 (LRP5) Wnt co-receptor from a diabetes-susceptibility locus and the now well-established linkage between Wnt signaling and metabolism. In this article, we provide an overview of the role of Wnt signaling in whole-body metabolism and review the literature regarding the impact of Wnt signaling on the osteoblast's utilization of three different energy sources: fatty acids, glucose, and glutamine. Special attention is devoted to the net effect of nutrient utilization and the mode of regulation by Wnt signaling. Mechanistic studies indicate that the utilization of each substrate is governed by a unique mechanism of control with β-catenin-dependent signaling regulating fatty acid β-oxidation, while glucose and glutamine utilization are β-catenin-independent and downstream of mammalian target of rapamycin complex 2 (mTORC2) and mammalian target of rapamycin complex 1 (mTORC1) activation, respectively. The emergence of these data has provided a new context for the mechanisms by which Wnt signaling influences bone development.

Oral implant osseointegration model in C57Bl/6 mice: microtomographic, histological, histomorphometric and molecular characterization

Abstract Despite the successful clinical application of titanium (Ti) as a biomaterial, the exact cellular and molecular mechanisms responsible for Ti osseointegration remains unclear, especially because of the limited methodological tools available in this field. Objective: In this study, we present a microscopic and molecular characterization of an oral implant osseointegration model using C57Bl/6 mice. Material and Methods: Forty-eight male wild-type mice received a Ti implant on the edentulous alveolar crest and the peri-implant sites were evaluated through microscopic (μCT, histological and birefringence) and molecular (RealTimePCRarray) analysis in different points in time after surgery (3, 7, 14 and 21 days). Results: The early stages of osseointegration were marked by an increased expression of growth factors and MSC markers. Subsequently, a provisional granulation tissue was formed, with high expression of VEGFb and earlier osteogenic markers (BMPs, ALP and Runx2). The immune/inflammatory phase was evidenced by an increased density of inflammatory cells, and high expression of cytokines (TNF, IL6, IL1) chemokines (CXCL3, CCL2, CCL5 and CXC3CL1) and chemokine receptors (CCR2 and CCR5). Also, iNOS expression remained low, while ARG1 was upregulated, indicating predominance of a M2-type response. At later points in time, the bone matrix density and volume were increased, in agreement with a high expression of Col1a1 and Col21a2. The remodelling process was marked by peaks of MMPs, RANKL and OPG expression at 14 days, and an increased density of osteoclasts. At 21 days, intimate Ti/bone contact was observed, with expression of final osteoblast differentiation markers (PHEX, SOST), as well as red spectrum collagen fibers. Conclusions: This study demonstrated a unique molecular view of oral osseointegration kinetics in C57Bl/6 mice, evidencing potential elements responsible for orchestrating cell migration, proliferation, ECM deposition and maturation, angiogenesis, bone formation and remodeling at the bone-implant interface in parallel with a novel microscopic analysis.

Experimental study of demineralized dentin matrix on osteoinduction and related cells identification / 华西口腔医学杂志

OBJECTIVE@#The aim of this study was to explore the theoretical framework of cells and the forms of osteogenesis in the mechanism by which demineralized dentin matrix (DDM) induces osteogenesis.@*METHODS@#A total of 24 New Zealand rabbits were used in this study. A total of 4 erector spinae bags were created in each animal. A total of 3 erector spinae bags were implanted with DDM by random selection, whereas the remaining one erector spinae bag was not implanted with DDM. The rabbits were sacrificed after 1, 2, 3, 4, 8, 12, 16, and 20 weeks, and the samples were obtained. The samples were examined by hematoxylin-eosin (HE), tartrate-resistant acid phosphatase (TRAP), and immunohistochemical staining to identify the mesenchymal stem cells, osteoblasts, chondrocytes, and osteoclasts.@*RESULTS@#The results of HE staining showed that in the third week, cartilage- and bone-like matrices, as well as the osteoblast-like cells, were observed. The results of immunohistochemical staining showed that the expressions of CD44, alkaline phosphatase (ALP), and collagen Ⅱ were statistically significant 
(P<0.05).@*CONCLUSIONS@#DDM has good histocompatibility and osteoinduction. In addition, induced ectopic osteogenesis mode mainly occurs in the endochondral bone.

Clinical analysis of acellular dermal matrix and acellular bone matrix in oro-antral fistula repair / 华西口腔医学杂志

OBJECTIVE@#This study aimed to investigate the application of acellular dermal matrix and acellular bone matrix in the management of oro-antral fistula.@*METHODS@#Nine patients with oro-antral fistula (with defect greater than 5 mm×5 mm) after maxillary cyst resection or maxillary molar extraction were selected. The defects were repaired by the simultaneous implantation of acellular dermal matrix and acellular bone matrix.@*RESULTS@#The incisions of nine patients were all primary healing. After 6 months of follow-up, the oro-antral communication healed well, and no symptom such as nasal congestion or runny nose was observed. The clinical and CT examinations confirmed wound healing.@*CONCLUSIONS@#The usage of acellular dermal matrix and acellular bone matrix is a reliable repairing method for ora-antral fistula.

Baja masa ósea y osteoporosis en pacientes con lupus eritematoso sistémico / Low bone mass and osteoporosis in patients with systemic lupus erythematosus

RESUMEN Introducción: El lupus eritematoso sistémico es una enfermedad autoinmune, multisistémica y crónica, de etiología desconocida, en la cual la frecuencia de alteraciones en la densidad mineral ósea varía entre 25-74%; si bien su diagnóstico no está estandarizado. Objetivo: Describir las alteraciones densitométricas en pacientes con lupus eritematoso sistémico, así como las características clínicas y demográficas en 2 centros de referencia del noroccidente colombiano. Materiales y métodos: Estudio transversal realizado entre enero de 2013 y diciembre de 2014. Variables incluidas: demográficas, estado de menopausia, consumo de tabaco y alcohol, autoanticuerpos, compromiso orgánico, medicamentos e índices de actividad y cronicidad (SLEDAI, SLICC). Alteraciones densitométricas definidas según la Organización Mundial de la Salud. Análisis estadístico: Frecuencias absolutas y relativas para variables cualitativas; mediana con rango intercuartílico (RIQ) para variables cuantitativas. Resultados: De 302 pacientes evaluados, 65 cumplieron criterios de elegibilidad. Treinta y uno por ciento de las pacientes premenopáusicas tenían baja masa ósea para la edad; un 50% de las mujeres posmenopáusicas tenían osteoporosis y un 27% baja masa ósea. Número de pacientes con alteraciones densitométricas según factores asociados: fracturas 4, consumo de alcohol 2, fumadores activos 3, anticuerpos anti-Ro 8, afección neurológica 7, falla renal crónica 4. Uso de prednisolona: 53,8%; mediana de dosis diaria: 10 mg (RIQ5-52). Medianas de SLEDAI y SLICC: 0 (RIQ= 0-4) y 0,5 (RIQ= 0-1,75), respectivamente. Conclusiones: Se encontraron pocas densitometrías óseas en pacientes con lupus; la frecuencia de las alteraciones minerales óseas fue independiente del estado de menopausia. La mediana de dosis de prednisolona fue alta, en sujetos en remisión y sin daño orgánico.

ABSTRACT Introduction: Systemic lupus erythematosus is a chronic, autoimmune, multisystem disease of unknown aetiology, and in which the frequency of alterations in bone mineral density varies between 25% and 74%, although its diagnosis is not standardised. Objective: To describe the densitometric changes in systemic lupus erythematosus patients, as well as the clinical and demographic characteristics from two reference centres northwestern Colombia. Materials and methods: A cross-sectional study was conducted between January 2013 and December 2014. The data collected included the demographic variables, menopausal status, use of tobacco and alcohol, autoantibodies, organ involvement, medications, as well as the activity and chronicity indices (SLEDAI, SLICC). Densitometric changes were defined according to World Health Organisation criteria. Statistical analyses: Absolute and relative frequencies were calculated for qualitative variables, and medians with interquartile range (IQR) for quantitative variables. Results: Of the total 302 patients evaluated, 65 met eligibility criteria. Thirty-one percent of premenopausal patients had low bone mass for age was observed in 31% of pre-menopausal women, with 50% of post-menopausal women showing osteoporosis, and 27% low bone mass. The number of patients with densitometric alterations according to associated factors was, fractures 4, alcohol consumption 2, active smokers 3, anti-Ro antibodies 8, neurological involvement 7, and chronic renal failure 4. Prednisone was used in 53.8%, with a median daily dose of 10mg (IQR5-52). The median SLEDAI and SLICC was 0 (IQR = 0-4) and 0.5 (IQR = 01.75), respectively. Conclusions: Few bone densitometry results were found in patients with systemic lupus erythematosus. The frequency of mineral bone disorders was independent of menopausal status. The median dose of prednisone was high in subjects in remission, and without organ damage.

Comparison of Clinical and Radiological Outcomes of Lumbar Interbody Fusion Using a Combination of Hydroxyapatite and Demineralized Bone Matrix and Autografts for Lumbar Degenerative Spondylolisthesis

STUDY DESIGN: Prospective, cohort, non-inferiority study. PURPOSE: This study evaluated the clinical and radiological outcomes of interbody fusion using a combination of demineralized bone matrix (DBM) and hydroxyapatite (HA). OVERVIEW OF LITERATURE: The use of autografts remains a gold standard in lumbar interbody fusion, but the limited availability and donor site morbidity encourages the use of bone substitutes. In addition to autografts, a combination of HA and DBM is being increasingly use for lumbar interbody fusion. However, there are no data on the clinical and radiological outcomes of this procedure. METHODS: We examined 35 patients with lumbar degenerative spondylolisthesis who underwent transforaminal interbody fusion. Autografts were used in 18 patients, and 17 patients received a combination of HA and DBM. Clinical outcomes were evaluated using the visual analog scale (VAS) for back and leg pain, Oswestry disability index (ODI), and Japanese Orthopaedic Association (JOA) scores at 3, 6, and 12 months postoperatively. Fusion was evaluated using computed tomography images obtained at 12 months postoperatively. RESULTS: The mean ODI, JOA, and back and leg pain VAS scores increased significantly in both groups. However, the VAS, JOA, and ODI scores did not differ significantly between the two groups (p=0.599, p=0.543, and p=0.780, respectively). The fusion rates at 1 year postoperatively were 77.8% and 76.5% in the autograft and HA+DBM groups, respectively (p=0.99). CONCLUSIONS: The clinical and radiological outcomes of using a combination of HA and DBM in lumbar interbody fusion were not inferior to those of using autografts. A combination of HA and DBM can be considered as an alternative in patients with lumbar degenerative spondylolisthesis requiring surgery.