Intrauterine alcohol exposure disturbs trabecular morphology in the Sprague Dawley rat humerus epiphysis up to 3- weeks postnatally / La exposición al alcohol intrauterino altera la morfología trabecular en la epífisis del húmero de la rata Sprague Dawley hasta 3 semanas después del nacimiento

SUMMARY: Gestational alcohol exposure inhibits neurological as well as bone growth and development both in fetal and postnatal life. Stunted stature, osteoporosis and fractures in adult life are some of the adverse effects. While the impact of intrauterine alcohol on the brain has been extensively investigated, studies on the effects on bone are relatively few. Therefore, our study aimed to examine the impact of prenatal alcohol exposure on bone microarchitecture in 3-week-old rats using Micro-focus X-Ray Computed Tomography (Micro CT). Time mated pregnant Sprague Dawley dams (13) were randomly placed into 3 groups: ethanol (n=5), saline control (n=5) and untreated control (n=3). The former 2 groups received treatment with 0.015ml/g of 25.2 % ethanol and 0.9 % saline, respectively, for the first 19 days of gestation. The untreated group received no treatment. The pups remained with their dams until termination at 21 days of age. From each dam, 2 pups were collected resulting in: ethanol (n=10), saline controls (n= 10) and untreated controls (n = 6). The humeri of the pups were dissected and scanned using a 3D-μCT scanner (Nikon XTH 225L) at 15μm resolution. Trabecular and cortical parameters were analysed using Volume Graphics Studio® software following reconstruction. Results showed a decrease in trabecular size, spaces, thickness, and volume. There was a decrease in cortical bone area in the ethanol group compared to the controls. These findings may suggest that osteoporosis and fractures seen as gestational alcohol effects may be due to compromised trabecular structure.

RESUMEN: La exposición al alcohol durante la gestación inhibe el crecimiento y desarrollo neurológico y óseo tanto en la vida fetal como posnatal. Algunos de los efectos adversos incluyen la estatura atrofiada, osteoporosis y fracturas en la vida adulta. Si bien se ha estudiado el impacto del alcohol intrauterino en el cerebro, los estudios sobre los efectos en los huesos son escasos. Por lo tanto, nuestro estudio tuvo como objetivo examinar el impacto de la exposición prenatal al alcohol en la microarquitectura ósea en ratas de 3 semanas de edad utilizando Tomografía Computarizada de Rayos X Micro-focus (Micro CT). Las hembras de Sprague Dawley preñadas con apareamiento temporal (13) se colocaron aleatoriamente en 3 grupos: etanol (n = 5), control de solución salina (n = 5) y control sin tratar (n = 3). Los primeros 2 grupos recibieron tratamiento con 0,015 ml /g de etanol al 25,2 % y solución salina al 0,9 %, respectivamente, durante los primeros 19 días de gestación. El grupo no tratado no recibió tratamiento. Las crías permanecieron con sus madres hasta la terminación a los 21 días de edad. De cada madre, se recolectaron 2 crías que dieron como resultado: etanol (n = 10), controles salinos (n = 10) y controles no tratados (n = 6). Se diseccionaron y escanearon los húmero de las crías usando un escáner 3D-μCT (Nikon XTH 225L) a una resolución de 15 μm. Los parámetros trabeculares y corticales se analizaron utilizando el software Volume Graphics Studio® después de la reconstrucción. Los resultados mostraron una disminución en el tamaño trabecular, los espacios, el grosor y el volumen. Hubo una disminución en el área del hueso cortical en el grupo de etanol en comparación con los controles. Estos hallazgos pueden sugerir que la osteoporosis y las fracturas por causa de los efectos del alcohol gestacional se pueden deber a una estructura trabecular comprometida.

The effect of maternal HMB supplementation on bone mechanical and geometrical properties, as well as histomorphometry and immunolocalization of VEGF, TIMP2, MMP13, BMP2 in the bone and cartilage tissue of the humerus of their newborn piglets.

The presented experiment focuses on assessing the impact of HMB (hydroxy-ß-methobutyrate) supplementation of mothers during pregnancy on the development of the skeletal system of their offspring. For this purpose, an experiment was carried out on 12 clinically healthy sows of the Great White Poland breed, which were divided randomly into two groups the control and the HMB group. All animals were kept under standard conditions and received the same feed for pregnant females. In contrast, females from the HMB group between 70 and 90 days were supplemented with 3-hydroxy-3-methylbutyle in the amount of 0.2g/kg b.w/day. Immediately after birth, the piglets were also divided into groups based on: sex, and presence or lack HMB supplementation, and subsequently were euthanized and humerus bones from all piglets were collected. Mother's HMB supplementation during pregnancy affected the multiple index of their offspring. The higher humerus mass and length was observed with the greater effect in males. Maternal supplementation also influenced on the geometrical and mechanical properties of the humerus as in the case of mass, this effect was higher in males. Also, the collagen structure of the compacted and trabecular bone changed under the HMB addition. Maternal supplementation also affected the expression of selected proteins in growth cartilage and trabecular bone. The obtained results show that the administration to the mother during pregnancy by the HMB significantly affects the development of the humerus in many ways. The obtained results also confirm the utility of such experiments in understanding of the importance of the pregnancy diet as an develop and adaptable factor of offspring organisms and are the base for further research in that area as well as in the protein markers expression area.

Chronic Nicotine Exposure Minimally Affects Rat Supraspinatus Tendon Properties and Bone Microstructure.

Cigarette smoking is the largest cause of preventable deaths, and a known risk factor for musculoskeletal issues including rotator cuff tendon tears. Tendon degeneration is believed to be due in part to changes in tendon cell health and collagen structure. Several studies have demonstrated that exposure to nicotine negatively impacts tendon healing, but surprisingly, nicotine exposure was shown to increase rat supraspinatus tendon stiffness. In order to address this seeming contradiction, the objective of this study was to comprehensively investigate the effects of long-term (18 weeks) exposure of nicotine on tendon-to-bone microstructural properties in a rat model. We hypothesized that long term subcutaneous nicotine delivery would lead to diminished tendon mechanical properties, decreased bone microstructure in the humeral head, and altered tendon cell morphology compared to age-matched control rats receiving saline. Results demonstrated a small decrease in tendon size and stiffness, with decreased cell density in the tendon midsubstance. However, no differences were found in the enthesis fibrocartilage or in the underlying subchondral or trabecular bone. In conclusion, our study revealed limited effects of nicotine on the homeostatic condition of the supraspinatus tendon, enthesis, and underlying bone. Future studies are needed to ascertain effects of other components of tobacco products.

Cartilage Homeostasis Affects Femoral Head Necrosis Induced by Methylprednisolone in Broilers.

(1) Background: Since the large-scale poultry industry has been established, femoral head necrosis (FHN) has always been a major leg disease in fast-growing broilers worldwide. Previous research suggested that cartilage homeostasis could be taken into consideration in the cause of FHN, but the evidence is insufficient. (2) Methods: One-day-old broiler chickens were randomly divided into three groups, 16 broilers per group. The birds in group L were injected intramuscularly with methylprednisolone (MP) twice a week for four weeks (12.5 mg·kg-1). The birds in group H were injected intramuscularly with MP (20 mg·kg-1·d-1) for 7 d (impulse treatment). The birds in group C were treated with sterile saline as a control group. Broilers were sacrificed at 42 and 56 d. Blood samples were collected from the jugular vein for ELISA and biochemical analysis. Bone samples, including femur, tibia, and humerus, were collected for histopathological analysis, bone parameters detection, and real-time quantitative PCR detection. (3) Results: The FHN broilers in group L and H both showed lower body weight (BW) and reduced bone parameters. In addition, the MP treatment resulted in reduced extracellular matrix (ECM) anabolism and enhanced ECM catabolism. Meanwhile, the autophagy and apoptosis of chondrocytes were enhanced, which led to the destruction of cartilage homeostasis. Moreover, the impulse MP injection increased the portion of birds with severer FHN, whereas the MP injection over a long period caused a more evident change in serum cytokine concentrations and bone metabolism indicators. (4) Conclusions: The imbalance of cartilage homeostasis may play a critical role in the development of FHN in broilers. FHN broilers induced by MP showed a more pronounced production of catabolic factors and suppressed the anabolic factors, which might activate the genes of the WNT signal pathway and hypoxia-inducible factors (HIFs), and then upregulate the transcription expression of ECM to restore homeostasis.

Treatment of simple bone cysts of the humerus by intramedullary nailing and steroid injection.

BACKGROUND: Simple bone cysts (SBCs) are common benign lytic bone lesions in children. This study focused on exploring a clinical treatment method, minimally invasive intramedullary decompression and drainage with elastic stable intramedullary nailing (ESIN) combined with intralesional injections of steroids, and evaluated its effectiveness, complications and morbidity through functional and radiographic outcomes. METHODS: The postoperative recovery of 18 children who suffered from SBCs of humerus was evaluated (mean follow-up, 40 months) from January 2009 to December 2016. These patients (11 males, 7 females; 8 in the left, 10 in the right; mean age, 10.9 years old) were treated with minimally invasive intramedullary decompression and drainage with ESIN combined with intralesional injections of steroids. The diagnosis was based on not only pre-operative typical medical images (X-rays/CT/MRI) but also surgical findings and pathological diagnosis. Radiological and functional outcomes were evaluated according to Capanna and Musculoskeletal Tumor Society (MSTS) score. The interclass differences were analyzed by t-test. RESULTS: According to Capanna and MSTS criteria, after treatment, 14 patients made full recoveries which was presented by all the cysts filled with bone tissue, and 4 patients made partially recoveries, which were presented by cystic spaces partially filled with low density bone. All the cysts responded to treatment method, and there was no cyst recurrence. All except 2 patients had good functional results. One of the two patients had irritation of the end of the nail and one patient had a valgus deformity. CONCLUSIONS: Treatment for SBCs of humerus by minimally invasive intramedullary decompression and drainage with ESIN combined with intralesional injections of steroids is safe, effective and convenient. The clinical effect is satisfactory and worth popularizing.

On the influence of surface coating on tissue biomechanics - effects on rat bones under routine conditions with implications for image-based deformation detection.

BACKGROUND: Biomechanical testing using image-based deformation detection techniques such as digital image correlation (DIC) offer optical contactless methods for strain and displacement measurements of biological tissues. However, given the need of most samples to be speckled for image correlation using sprays, chemical alterations with impact on tissue mechanicals may result. The aim of this study was to assess the impact of such surface coating on the mechanical properties of rat bones, under routine laboratory conditions including multiple freeze-thaw cycles. METHODS: Two groups of rat bones, highly-uniform and mixed-effects, were assigned to six subgroups consisting of three types of surface coating (uncoated, commercially-available water- and solvent-based sprays) and two types of bone conditions (periosteum attached and removed). The mixed-effects group had undergone an additional freeze-thaw cycle at - 20 degrees. All bones underwent a three-point bending test ranging until material failure. RESULTS: Coating resulted in similar and non-significantly different mechanical properties of rat bones, indicated by elastic moduli, maximum force and bending stress. Scanning electron microscopy showed more pronounced mechanical alterations related to the additional freeze-thaw cycle, with fewer cracks being present in a bone from the highly-uniform group. CONCLUSIONS: This study has concluded that surface coating with water- or solvent-based sprays for enhancing image correlation for DIC and having an additional freeze-thaw cycle do not significantly alter mechanical properties of rat bones. Therefore, this method may be recommended as an effective way of obtaining a speckled pattern.

Local application of a gentamicin-loaded thermo-responsive hydrogel allows for fracture healing upon clearance of a high Staphylococcus aureus load in a rabbit model.

Antibiotic-loaded biomaterials (ALBs) have emerged as a potential useful adjunctive antimicrobial measure for the prevention of infection in open fracture care. A biodegradable thermo-responsive poly(N-isopropylacrylamide) grafted hyaluronic acid (HApN) hydrogel loaded with gentamicin has recently been shown to prevent implant-related infection in a rabbit osteosynthesis model. The primary aim of this study was to determine the influence of this HApN hydrogel on bone healing at an early stage (4 weeks). A rabbit humeral osteotomy model with plating osteosynthesis was used to compare fracture healing in rabbits receiving the hydrogel as compared with control animals. The secondary aim was to observe fracture healing in groups treated with and without antibiotic-loaded hydrogel in the presence of bacterial contamination. In all groups, outcome measures were mechanical stability and histological score, with additional quantitative bacteriology in the inoculated groups. Application of the HApN hydrogel in non-inoculated rabbits did not significantly influence humeral stiffness or histological scores for fracture healing in comparison to controls. In the inoculated groups, animals receiving the bacterial inoculum without hydrogel were culture-positive at euthanasia and found to display lower humeral stiffness values and higher histopathological scores for bacterial presence in comparison with equivalents receiving the gentamicin-loaded HApN hydrogel, which were also infection-free. In summary, our data showed that HApN was an effective antibiotic carrier that did not affect fracture healing. This data supported its suitability for application in fracture care. Addition of osteopromotive compounds could provide further support for accelerating fracture healing in addition to successful infection prophylaxis.

Dietary 2-oxoglutarate prevents bone loss caused by neonatal treatment with maximal dexamethasone dose.

Synthetic glucocorticoids (GCs) are widely used in the variety of dosages for treatment of premature infants with chronic lung disease, respiratory distress syndrome, allergies, asthma, and other inflammatory and autoimmune conditions. Yet, adverse effects such as glucocorticoid-induced osteoporosis and growth retardation are recognized. Conversely, 2-oxoglutarate (2-Ox), a precursor of glutamine, glutamate, and collagen amino acids, exerts protective effects on bone development. Our aim was to elucidate the effect of dietary administered 2-Ox on bone loss caused by neonatal treatment with clinically relevant maximal therapeutic dexamethasone (Dex) dose. Long bones of neonatal female piglets receiving Dex, Dex+2-Ox, or untreated were examined through measurements of mechanical properties, density, mineralization, geometry, histomorphometry, and histology. Selected hormones, bone turnover, and growth markers were also analyzed. Neonatal administration of clinically relevant maximal dose of Dex alone led to over 30% decrease in bone mass and the ultimate strength ( P < 0.001 for all). The length (13 and 7% for femur and humerus, respectively) and other geometrical parameters (13-45%) decreased compared to the control ( P < 0.001 for all). Dex impaired bone growth and caused hormonal imbalance. Dietary 2-Ox prevented Dex influence and vast majority of assessed bone parameters were restored almost to the control level. Piglets receiving 2-Ox had heavier, denser, and stronger bones; higher levels of growth hormone and osteocalcin concentration; and preserved microarchitecture of trabecular bone compared to the Dex group. 2-Ox administered postnatally had a potential to maintain bone structure of animals simultaneously treated with maximal therapeutic doses of Dex, which, in our opinion, may open up a new opportunity in developing combined treatment for children treated with GCs. Impact statement The present study has showed, for the first time, that dietary 2-oxoglutarate (2-Ox) administered postnatally has a potential to improve/maintain bone structure of animals simultaneously treated with maximal therapeutic doses of dexamethasone (Dex). It may open the new direction in searching and developing combined treatment for children treated with glucocorticoids (GCs) since growing group of children is exposed to synthetic GCs and adverse effects such as glucocorticoid-induced osteoporosis and growth retardation are recognized. Currently proposed combined therapies have numerous side effects. Thus, this study proposed a new direction in combined therapies utilizing dietary supplementation with glutamine derivative. Impairment caused by Dex in presented long bones animal model was prevented by dietary supplementation with 2-Ox and vast majority of assessed bone parameters were restored almost to the control level. These results support previous thesis on the regulatory mechanism of nutrient utilization regulated by glutamine derivatives and enrich the nutritional science.

Bone-site-specific responses to zoledronic acid.

OBJECTIVES: Bisphosphonates are widely used to treat bone diseases such as osteoporosis. However, they may cause osteonecrosis of the jaw. Here, we investigated whether in vivo exposure to bisphosphonates has a different effect on long bone and jaw osteoclasts, and on the turnover of these different bones. MATERIALS AND METHODS: Zoledronic acid (0.5 mg kg-1 weekly) was administered intraperitoneally to 3-month-old female mice for up to 6 months. The effects on the number of osteoclasts, bone mineralization and bone formation were measured in the long bones and in the jaw. RESULTS: Long-term treatment with zoledronic acid reduced the number of jaw bone marrow cells, without affecting the number of long bone marrow cells. Zoledronic acid treatment did not affect the number of osteoclasts in vivo. Yet, the bisphosphonate increased bone volume and mineral density of both long bone and jaw. Interestingly, 6 months of treatment suppressed bone formation in the long bones without affecting the jaw. Unexpectedly, we showed that bisphosphonates can cause molar root resorption, mediated by active osteoclasts. CONCLUSIONS: Our findings provide more insight into bone-site-specific effects of bisphosphonates and into the aetiology of osteonecrosis of the jaw. We demonstrated that bisphosphonates can stimulate osteoclast activity at the molar roots.

Ovarian hormone depletion affects cortical bone quality differently on different skeletal envelopes.

The physical properties of bone tissue are determined by the organic and mineral matrix, and are one aspect of bone quality. As such, the properties of mineral and matrix are a major contributor to bone strength, independent of bone mass. Cortical bone quality may differ regionally on the three skeletal envelopes that compose it. Each of these envelopes may be affected differently by ovarian hormone depletion. Identifying how these regions vary in their tissue adaptive response to ovarian hormones can inform our understanding of how tissue quality contributes to overall bone strength in postmenopausal women. We analyzed humeri from monkeys that were either SHAM-operated or ovariectomized. Raman microspectroscopic analysis was performed as a function of tissue age based on the presence of multiple fluorescent double labels, to determine whether bone compositional properties (mineral/matrix ratio, tissue water, glycosaminoglycan, lipid, and pyridinoline contents, and mineral maturity/crystallinity) are similar between periosteal, osteonal, and endosteal surfaces, as well as to determine the effects of ovarian hormone depletion on them. The results indicate that mineral and organic matrix characteristics, and kinetics of mineral and organic matrix modifications as a function of tissue age are different at periosteal vs. osteonal and endosteal surfaces. Ovarian hormone depletion affects the three cortical surfaces (periosteal, osteonal, endosteal) differently. While ovarian hormone depletion does not significantly affect the quality of either the osteoid or the most recently mineralized tissue, it significantly affects the rate of subsequent mineral accumulation, as well as the kinetics of organic matrix modifications, culminating in significant differences within interstitial bone. These results highlight the complexity of the cortical bone compartments, add to existing knowledge on the effects of ovarian hormone depletion on local cortical bone properties, and may contribute to a better understanding of the location specific action of drugs used in the management of postmenopausal osteoporosis.

The utility of bone scintigraphy in the assessment of mandibular metabolism during long-term bisphosphonate administration.

The duration of antiresorptive therapy is an important risk factor for medication-related osteonecrosis of the jaw. We performed a pilot study using quantitative analysis by bone scintigraphy to test the hypothesis that mandibular metabolism is affected by long-term bisphosphonate (BP) therapy. Our primary objectives were to assess changes in bone metabolism of the mandible in response to long-term BP therapy and compare the bone metabolism changes of the mandible with other bone sites. We compared the metabolic difference at the site in the mandible unaffected by disease, the humerus and the femur between 14 osteoporosis patients who were being treated with BP (BP group) and 14 patients who were not being treated with BP (control group) using a quantitative analysis and bone scintigraphy. Study endpoints were the mean and maximum bone uptake values (BUVs) quantified using bone scintigraphy images of the mandible, humerus and femur. Quantified images of the site in the mandible unaffected by disease had significantly higher mean and maximum BUVs compared to the controls (mean, 0.74 vs. 0.49, p = 0.019; max., 1.29 vs. 0.85, p = 0.009, respectively). The mean and maximum BUV of femur ROIs in the BP group were significantly lower than those in control patients (mean BUV, 0.23 vs. 0.30, p = 0.039; max. BUV, 0.43 vs. 0.53, p = 0.024, respectively). This is the first report of mandible changes in response to long-term BP treatment, using bone scintigraphy. The results using bone scintigraphy demonstrated that the bone metabolism of the intact mandible is affected by a long-term administration of BP.

Injectable gentamicin-loaded thermo-responsive hyaluronic acid derivative prevents infection in a rabbit model.

UNLABELLED: Despite the use of systemic antibiotic prophylaxis, the surgical fixation of open fractures with osteosynthesis implants is associated with high infection rates. Antibiotic-loaded biomaterials (ALBs) are increasingly used in implant surgeries across medical specialties to deliver high concentrations of antibiotics to the surgical site and reduce the risk of implant-associated infection. ALBs which are either less or not restricted in terms of spatial distribution and which may be applied throughout complex wounds could offer improved protection against infection in open fracture care. A thermo-responsive hyaluronic acid derivative (hyaluronic acid-poly(N-isopropylacrylamide) (HApN)) was prepared by a direct amidation reaction between the tetrabutyl ammonium (TBA) salt of hyaluronic acid and amine-terminated poly(N-isopropylacrylamide) (pN). The degree of grafting, and gelation properties of this gel were characterized, and the composition was loaded with gentamicin. The rheological- and release properties of this gentamicin-loaded HApN composition were tested in vitro and its efficacy in preventing infection was tested in a rabbit model of osteosynthesis contaminated with Staphylococcus aureus. The gentamicin-loaded HApN composition was able to prevent bacterial colonization of the implant site as shown by quantitative bacteriology. This finding was supported by histopathological evaluation of the humeri samples where no bacteria were found in the stained sections. In conclusion, this gentamicin-loaded HApN hydrogel effectively prevents infection in a complex wound, simulating a contaminated fracture treated with plating osteosynthesis. STATEMENT OF SIGNIFICANCE: Fracture fixation after trauma is associated with high infection rates. Antibiotic loaded biomaterials (ALBs) can provide high local concentrations without systemic side effects. However, the currently available ALBs have limited accessibility to contaminated tissues in open fractures because of predetermined shape. Thus, a novel thermo-responsive hyaluronan based hydrogel with control over gelation temperature is reported. The efficacy of this gentamicin loaded hyaluronan derivative is demonstrated in an in vivo fracture model in the presence of fracture fixation hardware. The bacterial burden is cleared in all of the inoculated rabbits in the presence of the ALB. Thus, the proposed injectable thermo-responsive hyaluronan presents an effective ALB for the prevention of infection.

In Utero Tenofovir Exposure Is not Associated With Fetal Long Bone Growth.

BACKGROUND: Despite widespread use of tenofovir disoproxil fumarate (TDF) in pregnant and breastfeeding women, few data exist on fetal bone development after in utero TDF exposure. We evaluated fetal long bone growth in human immunodeficiency virus (HIV)-infected pregnant woman/fetus dyads in Cape Town, South Africa. METHODS: Women were recruited from primary care antenatal services and underwent ultrasonography to determine femur (FLZ) and humerus (HLZ) length z scores. The duration of in utero TDF exposure was calculated in weeks. Linear regression models were applied to assess the associations between the duration of in utero TDF exposure and change in FLZ and HLZ. RESULTS: A total of 646 woman/fetus dyads contributed 1376 ultrasonographic scans to this analysis: 132 dyads with ≥25 weeks, 326 with 10-24 weeks, and 188 with <10 weeks of TDF exposure. Women receiving TDF for ≥25 weeks were older than those receiving TDF for 10-24 or <10 weeks (median age, 31 vs 28 and 28 years, respectively; P < .01), and had lower HIV RNA levels (median log10 HIV RNA level, 1.59 vs 4.08 and 3.83, respectively; P < .01). Throughout gestation, overall median FLZ and HLZ were 0.30 (interquartile range, -0.03 to 0.63) and 0.22 (-0.26 to 0.59) respectively. In multivariate analysis, there was no association between duration of in utero TDF exposure per 1-week increment and change in FLZ (ß = .00; P = .51) or change in HLZ (ß = .00; P = .40). Results were similar using mixed-effects models. CONCLUSIONS: Although longer follow-up is needed, these in utero data are reassuring and support the continued use of TDF in pregnancy.

Safety and efficacy of additive and subtractive surface modification of Ti6Al4V endosseous implant in goat bone.

Growing interest of endosseous implant research is focused on surface modification to achieve early and strong osseointegration. The present study compared the behaviour of hydroxyapatite coated, zinc doped hydroxyapatite coated and hydrothermally treated titanium (Ti6Al4V) with machined Ti6Al4V implants (control) on osseointegration. The surface characterization and bacterial affinity test for implants were performed. Forty eight (48) cylinders (4 types in each animal) were placed in the humerus bone of 12 black Bengal goats. Bone-implant interface was examined with histological, radiological parameters and scanning electron microscopy on 42nd, 90th, and 180th day post-implantation. Surface roughness alterations of bone-detached implants with time were analyzed by non-contact profilometer. Push-out test (90th day) was performed to assess the strength of bony integration of implants. The coated implants revealed direct and early bone-implant contact but high bacterial affinity and coating resorption/cracks. Low bacterial affinity and strongest osseointegration was observed with hydrothermally treated implants. Poor bacterial affinity and delayed but strong fixation were evident with control implant. Based on the results of laboratory and animal experiments, we conclude that the hydrothermal modification of titanium implant is the more suitable way to achieve safe and effective osseointegration than the other three implant types for endosseous application.

Lycopene treatment against loss of bone mass, microarchitecture and strength in relation to regulatory mechanisms in a postmenopausal osteoporosis model.

Lycopene supplementation decreases oxidative stress and exhibits beneficial effects on bone health, but the mechanisms through which it alters bone metabolism in vivo remain unclear. The present study aims to evaluate the effects of lycopene treatment on postmenopausal osteoporosis. Six-month-old female Wistar rats (n=264) were sham-operated (SHAM) or ovariectomized (OVX). The SHAM group received oral vehicle only and the OVX rats were randomized into five groups receiving oral daily lycopene treatment (mg/kg body weight per day): 0 OVX (control), 15 OVX, 30 OVX, and 45 OVX, and one group receiving alendronate (ALN) (2µg/kg body weight per day), for 12weeks. Bone densitometry measurements, bone turnover markers, biomechanical testing, and histomorphometric analysis were conducted. Micro computed tomography was also used to evaluate changes in microarchitecture. Lycopene treatment suppressed the OVX-induced increase in bone turnover, as indicated by changes in biomarkers of bone metabolism: serum osteocalcin (s-OC), serum N-terminal propeptide of type 1 collagen (s-PINP), serum crosslinked carboxyterminal telopeptides (s-CTX-1), and urinary deoxypyridinoline (u-DPD). Significant improvement in OVX-induced loss of bone mass, bone strength, and microarchitectural deterioration was observed in lycopene-treated OVX animals. These effects were observed mainly at sites rich in trabecular bone, with less effect in cortical bone. Lycopene treatment down-regulated osteoclast differentiation concurrent with up-regulating osteoblast together with glutathione peroxidase (GPx) catalase (CAT) and superoxide dismutase (SOD) activities. These findings demonstrate that lycopene treatment in OVX rats primarily suppressed bone turnover to restore bone strength and microarchitecture.

Does the use of Testosterone Enanthate as a Form of Doping in Sports Cause Early Closure of Epiphyseal in Bones? / ¿El Uso de Enantato de Testosterona como Forma de Dopaje en el Deporte Causa Cierre Epifisiario Temprano de los Huesos?

The purpose of this research is to investigate the morphometric effects of short term usage of testosterone enanthate among the anabolic androgenic steroids used as doping by athletes on humerus bones of male rats. 30 rats (35 days) were utilized in this research. The rats were divided into three equal groups. For the experimental group (n= 10), testosterone enanthate at 10 mg/kg dose in 100 µl peanut oil diluents, for the peanut oil group (n= 10), peanut oil of testosterone enanthate' diluent (100 µl) was executed intraperitoneally 5 days in a week for 3 weeks. The control group (n= 10) was nourished without any practice for 3 weeks. All rats were euthanized end of the research. Humerus bones were exposed by the dissection of rats' front extremite bones and measurements and the averages were taken. When the length of rats' humerus bones were analyzed, the growth of humerus bones of rats testosterone enanthate applied in the experimental group stopped significantly and the difference was significant (p<0.05). It was observed that among anabolic androgenic steroids, testosterone enathate's usage on male rats in puberty period caused early epiphyseal closure and stopped the growth of humerus bones significantly.

El objetivo de esta investigación fue estudiar en el húmero de ratas macho, los efectos morfométricos del uso a corto plazo de Enantato de testosterona entre los esteroides anabólicos usados como dopaje por atletas. En esta investigación se utilizaron 30 ratas divididas en tres grupos iguales. Un grupo experimental (n= 10), que se le administró Enantato de testosterona en dosis de 10 mg/kg en 100 µl diluido en aceite de maní, a otro grupo sólo se le administró aceite de maní (n= 10). La administración fue realizada por vía intraperitoneal 5 días a la semana durante 3 semanas. El grupo control (n= 10) fue alimentado durante 3 semanas. Todas las ratas fueron sacrificadas al término de la investigación. Los húmeros fueron expuestos por disección, se realizaron las mediciones y se tomaron los promedios. Cuando se analizó la longitud de los húmeros se observó que su crecimiento en las ratas del grupo experimental que recibieron Enantato de testosterona, se detuvo de manera significativa (p<0,05). Se observó que entre los esteroides anabólicos androgénicos, el uso de testosterona en ratas macho en el periodo de la pubertad causó el cierre epifisario temprano y detuvo el crecimiento del húmero de manera significativa.

Bone and bone marrow involvement in sarcoidosis.

Bone and bone marrow involvement in sarcoidosis have been infrequently reported. We aimed to describe the clinical features, radiological descriptions, pathological examinations, and outcomes of three patients with osseous sarcoidosis and one patient with bone marrow sarcoidosis seen at our institution. Our case series included fluorodeoxyglucose positron emission tomography descriptions in assessing the whole-body extent of sarcoidosis. In the era of advanced imaging, large bone and axial skeleton sarcoidosis lesions are more common than previously reported.

Coating cortical bone allografts with periosteum-mimetic scaffolds made of chitosan, trimethyl chitosan, and heparin.

Bone allografts have very limited healing leading to high rates of failure from non-union, fracture, and infection. The limited healing of bone allografts is due in large part to devitalization and removal of the periosteum, which removes osteogenic cells and osteoinductive signals. Here we report techniques for directly coating cortical bone with tissue scaffolds, and evaluate the scaffolds' capacity to support osteoprogenitor cells. Three types of coatings are investigated: N,N,N-trimethyl chitosan-heparin polyelectrolyte multilayers, freeze-dried porous chitosan foam coatings, and electrospun chitosan nanofibers. The freeze-dried and electrospun scaffolds are also further modified with polyelectrolyte multilayers. All of the scaffolds are durable to subsequent aqueous processing, and are cytocompatible with adipose-derived stem cells. Alkaline phosphatase and receptor activator of nuclear factor kappa-B ligand expression at days 7 and 21 suggest that these scaffolds support an osteoprogenitor phenotype. These scaffolds could serve as periosteum mimics, deliver osteoprogenitor cells, and improve bone allograft healing.

Changes of elastic constants and anisotropy patterns in trabecular bone during disuse-induced bone loss assessed by poroelastic ultrasound.

Currently, the approach most widely used to examine bone loss is the measurement of bone mineral density (BMD) using dual X-ray absorptiometry (DXA). However, bone loss due to immobilization creates changes in bone microarchitecture, which in turn are related to changes in bone mechanical function and competence to resist fracture.Unfortunately, the relationship between microarchitecture and mechanical function within the framework of immobilization and antiresorptive therapy has not being fully investigated. The goal of the present study was to investigate the structure­function relationship in trabecular bone in the real-world situations of a rapidly evolving osteoporosis(disuse), both with and without antiresorptive treatment. We evaluated the structure­function relationship in trabecular bone after bone loss (disuse-induced osteoporosis)and bisphosphonate treatment (antiresorptive therapy using risedronate) in canine trabecular bone using lCT and ultrasound wave propagation. Microstructure values determined from lCT images were used into the anisotropic poroelastic model of wave propagation in order to compute the apparent elastic constants (EC) and elastic anisotropy pattern of bone. Immobilization resulted in a significant reduction in trabecular thickness (Tb.Th) and bone volume fraction (BV/TV), while risedronate treatment combined with immobilization exhibited a lesser reduction in Tb.Th and BV/TV, suggesting that risedronate treatment decelerates bone loss, but it was unable to fully stop it. Risedronate treatment also increased the tissue mineral density (TMD), which when combined with the decrease in Tb.Th and BV/TV may explain the lack of significant differences invBMD in both immobilization and risedronate treated groups. Interestingly, changes inapparent EC were much stronger in the superior­inferior (SI) direction than in the medial­lateral (ML) and anterior­posterior (AP) anatomical directions, producing changes in elastic anisotropy patterns. When data were pooled together, vBMD was able to explain 58% of ultrasound measurements variability, a poroelastic wave propagation analytical model (i.e., BMD modulated by fabric directionality) was able to predict 81%of experimental wave velocity variability, and also explained 91% of apparent EC and changes in elastic anisotropy patterns. Overall, measurements of vBMD were unable to distinguish changes in apparent EC due to immobilization or risedronate treatment.However, anisotropic poroelastic ultrasound (PEUS) wave propagation was able to distinguish functional changes in apparent EC and elastic anisotropy patterns due to immobilization and antiresorptive therapy, providing an enhanced discrimination of anisotropic bone loss and the structure­function relationship in immobilized and risedronate-treated bone, beyond vBMD.