Risk factors for bone loss in patients with rheumatoid arthritis treated with biologic disease-modifying anti-rheumatic drugs

Objective

Osteoporosis is a complication of rheumatoid arthritis. We examined the risk factors for bone loss in rheumatoid arthritis patients receiving biological disease-modifying anti-rheumatic drugs. Lumbar spine and femoral neck bone mineral density was measured at two time points in 153 patients with rheumatoid arthritis managed with biological disease-modifying anti-rheumatic drugs. We examined patients’ variables to identify risk factors for least significant reduction of bone mineral density.

Results

Least significant reduction of lumbar spine bone mineral density (≤ ? 2.4%) was seen in 13.1% of patients. Least significant reduction of femoral neck bone mineral density (≤ ? 1.9%) was seen in 34.0% of patients. Multiple logistic regression analysis showed that a risk factor for least significant reduction of the lumbar spine was high-dose methylprednisolone use. Multiple regression analysis showed that a risk factor for least significant reduction of the femoral neck was short disease duration. Our findings showed that a risk factor for femoral neck bone mineral density reduction was a short disease duration. These findings suggest that rheumatoid arthritis patients receiving treatment with biological disease-modifying anti-rheumatic drugs may benefit from earlier osteoporosis treatments to prevent femoral neck bone loss.

     

Seroprevalence of <Emphasis Type="Italic">Borrelia burgdorferi</Emphasis> sensu lato and <Emphasis Type="Italic">Anaplasma phagocytophilum</Emphasis> in Danish horses

Background

Borrelia burgdorferi sensu lato and Anaplasma phagocytophilum are able to infect horses. However, the extend to which Danish horses are infected and seroconvert due to these two bacteria is unknown. The aim of the present study was to evaluate the seroprevalence of B. burgdorferi sensu lato and A. phagocytophilum in Danish horses.

Methods

A total of 390 blood samples collected from all major regions of Denmark and with a geographical distribution corresponding to the density of the Danish horse population were analyzed. All samples were examined for the presence of antibodies against B. burgdorferi sensu lato and A. phagocytophilum by the use of the SNAP^®4DX ^® ELISA test.

Results

Overall, 29.0% of the horses were seropositive for B. burgdorferi sensu lato whereas 22.3% were seropositive for A. phagocytophilum.

Conclusions

Antibodies against B burgdorferi sensu lato and A. phagocytophilum are commonly found among Danish horses thus showing that Danish horses are frequently infected by these organisms.

     

Gelatin microspheres containing calcitonin gene-related peptide or substance P repair bone defects in osteoporotic rabbits

Objectives

To investigate the therapeutic effect of gelatin microspheres containing different concentrations of calcitonin gene-related peptide (CGRP) or substance P on repairing bone defects in a rabbit osteoporosis model.

Results

Gelatin microspheres containing different concentrations of CGRP or substance P promoted osteogenesis after 3 months in a rabbit osteoporotic bone defective model. From micro-computed tomography imaging results, 10 nM CGRP was optimal for increasing the trabecular number and decreasing the trabecular bone separation degree; similar effects were observed with the microspheres containing 1 µM substance P. Histological analysis showed that the gelatin microspheres containing CGRP or substance P, regardless of the concentration, effectively promoted osteogenesis, and the highest effect was achieved in the groups containing 1 µM CGRP or 1 µM substance P.

Conclusions

Gelatin microspheres containing CGRP or substance P effectively promoted osteogenesis in a rabbit osteoporotic bone defect model dose-dependently, though their effects in repairing human alveolar ridge defects still need further investigation.

     

Weekly oral alendronate in mevalonate kinase deficiency

Background

Mevalonate kinase deficiency (MKD) is caused by mutations in the MVK gene, encoding the second enzyme of mevalonate pathway, which results in subsequent shortage of downstream compounds, and starts in childhood with febrile attacks, skin, joint, and gastrointestinal symptoms, sometimes induced by vaccinations.

Methods

For a history of early-onset corticosteroid-induced reduction of bone mineral density in a 14-year-old boy with MKD, who also had presented three bone fractures, we administered weekly oral alendronate, a drug widely used in the management of osteoporosis and other high bone turnover diseases, which blocks mevalonate and halts the prenylation process.

Results

All of the patient’s MKD clinical and laboratory abnormalities were resolved after starting alendronate treatment.

Conclusions

This observation appears enigmatic, since alendronate should reinforce the metabolic block characterizing MKD, but is crucial because of the ultimate improvement shown by this patient. The anti-inflammatory properties of bisphosphonates are a new question for debate among physicians across various specialties, and requires further biochemical and clinical investigation.

     

Reduced trabecular bone mineral density and cortical thickness accompanied by increased outer bone circumference in metacarpal bone of rheumatoid arthritis patients: a cross-sectional study

Introduction

The objective of this study was to assess three-dimensional bone geometry and density at the epiphysis and shaft of the third meta-carpal bone of rheumatoid arthritis (RA) patients in comparison to healthy controls with the novel method of peripheral quantitative computed tomography (pQCT).

Methods

PQCT scans were performed in 50 female RA patients and 100 healthy female controls at the distal epiphyses and shafts of the third metacarpal bone, the radius and the tibia. Reproducibility was determined by coefficient of varia-tion. Bone densitometric and geometric parameters were compared between the two groups and correlated to disease characteristics.

Results

Reproducibility of different pQCT parameters was between 0.7% and 2.5%. RA patients had 12% to 19% lower trabecular bone mineral density (BMD) (P ≤ 0.001) at the distal epiphyses of radius, tibia and metacarpal bone. At the shafts of these bones RA patients had 7% to 16% thinner cortices (P ≤ 0.03). Total cross-sectional area (CSA) at the metacarpal bone shaft of pa-tients was larger (between 5% and 7%, P < 0.02), and relative cortical area was reduced by 13%. Erosiveness by Ratingen score correlated negatively with tra-becular and total BMD at the epiphyses and shaft cortical thickness of all measured bones (P < 0.04).

Conclusions

Reduced trabecular BMD and thinner cortices at peripheral bones, and a greater bone shaft diameter at the metacarpal bone suggest RA spe-cific bone alterations. The proposed pQCT protocol is reliable and allows measuring juxta-articular trabecular BMD and shaft geometry at the metacarpal bone.     

A genome-wide scan for quantitative trait loci affecting limb bone lengths and areal bone mineral density of the distal femur in a White Duroc × Erhualian F<Subscript>2</Subscript> population

Background

Limb bone lengths and bone mineral density (BMD) have been used to assess the bone growth and the risk of bone fractures in pigs, respectively. It has been suggested that limb bone lengths and BMD are under genetic control. However, the knowledge about the genetic basis of the limb bone lengths and mineralisatinon is limited in pigs. The aim of this study was to identify quantitative trait loci (QTL) affecting limb bone lengths and BMD of the distal femur in a White Duroc × Erhualian resource population.

Results

Limb bone lengths and femoral bone mineral density (fBMD) were measured in a total of 1021 and 116 F₂ animals, respectively. There were strong positive correlations among the lengths of limb bones and medium positive correlations between the lengths of limb bones and fBMD. A whole-genome scan involving 183 microsatellite markers across the pig genome revealed 35 QTL for the limb bone lengths and 2 for femoral BMD. The most significant QTL for the lengths of five limb bones were mapped on two chromosomes affecting all 5 limb bones traits. One was detected around 57 cM on pig chromosome (SSC) 7 with the largest F-value of more than 26 and 95% confidence intervals of less than 5 cM, providing a crucial start point to identify the causal genes for these traits. The Erhualian alleles were associated with longer limb bones. The other was located on SSCX with a peak at 50–53 cM, whereas alleles from the White Duroc breed increased the bone length. Many QTL identified are homologous to the human genomic regions containing QTL for bone-related traits and a list of interesting candidate genes.

Conclusion

This study detected the QTL for the lengths of scapula, ulna, humerus and tibia and fBMD in the pig for the first time. Moreover, several new QTL for the pig femoral length were found. As correlated traits, QTL for the lengths of five limb bones were mainly located in the same genomic regions. The most promising QTL for the lengths of five limb bones on SSC7 merits further investigation.

     

A school-curriculum-based exercise intervention program for two years in pre-pubertal girls does not influence hip structure

Background

It is known that physical activity during growth has a positive influence on bone mineral accrual, and is thus possibly one strategy to prevent osteoporosis. However, as bone geometry, independent of areal bone mineral density (aBMD), influences fracture risk, this study aimed to evaluate whether hip structure in pre-pubertal girls is also affected by a two-year exercise intervention program.

Methods

Forty-two girls aged 7–9 years in a school-curriculum-based exercise intervention program comprising 40 minutes of general physical activity per school day (200 minutes per week) were compared with 43 age-matched girls who participated in the general Swedish physical education curriculum comprising a mean of 60 minutes per week. The hip was scanned by dual energy X-ray absorptiometry (DXA) and the hip structural analysis (HSA) software was applied to evaluate bone mineral content (BMC, g), areal bone mineral density (aBMD, g/cm²), periosteal diameter, cross-sectional area (CSA, cm²), section modulus (Z, cm³) and cross-sectional moment of inertia (CSMI, cm⁴) of the femoral neck (FN). Annual changes were compared. Subjective duration of physical activity was estimated by questionnaire and objective level of everyday physical activity at follow-up by means of accelerometers worn for four consecutive days. All children remained at Tanner stage 1 throughout the study. Group comparisons were made by independent student's t-test between means and analyses of covariance (ANCOVA).

Results

At baseline, the two groups did not differ with regard to age, anthropometrics or bone parameters. No between-group differences were observed for annual changes in the FN variables measured.

Conclusion

A two-year school-based moderately intense general exercise program for 7–9-year-old pre-pubertal girls does not influence structural changes in the FN.

     

Trabecular architecture in the forelimb epiphyses of extant xenarthrans (Mammalia)

Background

Bone structure has a crucial role in the functional adaptations that allow vertebrates to conduct their diverse lifestyles. Much has been documented regarding the diaphyseal structure of long bones of tetrapods. However, the architecture of trabecular bone, which is for instance found within the epiphyses of long bones, and which has been shown experimentally to be extremely plastic, has received little attention in the context of lifestyle adaptations (virtually only in primates). We therefore investigated the forelimb epiphyses of extant xenarthrans, the placental mammals including the sloths, anteaters, and armadillos. They are characterised by several lifestyles and degrees of fossoriality involving distinct uses of their forelimb. We used micro computed tomography data to acquire 3D trabecular parameters at regions of interest (ROIs) for all extant genera of xenarthrans (with replicates). Traditional, spherical, and phylogenetically informed statistics (including the consideration of size effects) were used to characterise the functional signal of these parameters.

Results

Several trabecular parameters yielded functional distinctions. The main direction of the trabeculae distinguished lifestyle categories for one ROI (the radial trochlea). Among the other trabecular parameters, it is the degree of anisotropy (i.e., a preferential alignment of the trabeculae) that yielded the clearest functional signal. For all ROIs, the armadillos, which represent the fully terrestrial and fossorial category, were found as characterised by a greater degree of anisotropy (i.e., more aligned trabeculae). Furthermore, the trabeculae of the humeral head of the most fossorial armadillos were also found to be more anisotropic than in the less fossorial species.

Conclusions

Most parameters were marked by an important intraspecific variability and by a size effect, which could, at least partly, be masking the functional signal. But for some parameters, the degree of anisotropy in particular, a clear functional distinction was recovered. Along with data on primates, our findings suggest that a trabecular architecture characterised by a greater degree of anisotropy is to be expected in species in which the relevant epiphyses withstand a restricted range of load directions. Trabecular architecture therefore is a promising research avenue for the reconstruction of lifestyles in extinct or cryptic species.

     

Ibandronate increases cortical bone density in patients with systemic lupus erythematosus on long-term glucocorticoid

Introduction

The purpose of this research is to assess the effects of oral ibandronate on bone microarchitecture by using high-resolution peripheral quantitative computed tomography (HR-pQCT) in patients with systemic lupus erythematosus (SLE) taking a long-term glucocorticoid.

Methods

In this double-blind placebo-controlled study, 40 Chinese female SLE patients taking prednisolone were randomly assigned to receive either monthly oral ibandronate (150 mg) or placebo with daily 1-hydroxycholecalciferol (Alfacalcidol; 1 μg) and calcium supplement for 12 months. Assessments of bone microarchitecture by using HR-pQCT and area bone mineral density (aBMD) of the lumbar spine and hip with dual-energy x-ray absorptiometry (DXA) were performed at baseline and 12 months.

Results

No differences in baseline characteristics were found between the two groups. After 12 months, no statistical differences were noted in any of the bone densities, microarchitectural parameters, or percentage changes of these parameters, as measured with HR-pQCT or DXA between the two groups. However, within the active group, the percentage improvement was significant in cortical bone density (P = 0.023) which was absent in the placebo group. Improvement was also seen in the aBMD of both the lumbar spine (P < 0.0001) and the hip (P < 0.005). In the placebo group, the percentage increase in trabecular separation was significant (P = 0.04), and the percentage improvement in aBMD in the spine also was significant (P = 0.049).

Conclusions

Oral ibandronate treatment improves microarchitecture in SLE patients taking long-term glucocorticoid assessed with HR-pQCT, and this new technology may have a role in assessing bony changes in future longitudinal studies in SLE patients.

Trial registration

ClinicalTrials.gov identifier: NCT00668330.     

Evaluation of circulating sRAGE in osteoporosis according to BMI,adipokines and fracture risk: a pilot observational study

Background

Osteoporosis is a systemic metabolic disease based on age-dependent imbalance between the rates of bone formation and bone resorption. Recent studies on the pathogenesis of this disease identified that bone remodelling impairment, at the base of osteoporotic bone fragility, could be related to protein glycation, in association to oxidative stress. The glycation reactions lead to the generation of glycation end products (AGEs) which, in turn, accumulates into bone, where they binds to the receptor for AGE (RAGE). The aim of this study is to investigate the potential role of circulating sRAGE in osteoporosis, in particular evaluating the correlation of sRAGE with the fracture risk, in association with bone mineral density, the fracture risk marker FGF23, and lipid metabolism.

Results

Circulating level of soluble RAGE correlate with osteopenia and osteoporosis level. Serum sRAGE resulted clearly associated on the one hand to bone fragility and, on the other hand, with BMI and leptin. sRAGE is particularly informative because serum sRAGE is able to provide, as a single marker, information about both the aspects of osteoporotic disease, represented by bone fragility and lipid metabolism.

Conclusions

The measure serum level of sRAGE could have a potential diagnostic role in the monitoring of osteoporosis progression, in particular in the evaluation of fracture risk, starting from the prevention and screening stage, to the osteopenic level to osteoporosis.

     

Characterization of trotter horses urine metabolome by means of proton nuclear magnetic resonance spectroscopy

Background

Metabolomics has been recognized as a powerful approach for disease screening. In order to highlight potential health issues in subjects, a key factor is the possibility to compare quantitatively the metabolome of their biofluids with reference values from healthy individuals. Such efforts towards the systematic characterization of the metabolome of biofluids in perfect health conditions, far from concluded for humans, have barely begun on horses.

Objectives

The present work attempts, for the first time, to give reference quantitative values for the molecules mostly represented in the urine metabolome of horses at rest and under light training, as observable by ¹H-NMR.

Methods

The metabolome of ten trotter horses, four male and six female, ranging from 3 to 8 years of age, has been observed by ¹H-NMR spectroscopy before and after three training sessions.

Results

We could characterize and quantify 54 molecules in trotter horse urine, originated from diet, protein digestion, energy generation or gut-microbial co-metabolism.

Conclusion

We were able to describe how gender, age and exercise affected their concentration, by means of a two steps protocol based on univariate and robust principal component analysis.

     

A Comparison of Micro-CT and Dental CT in Assessing Cortical Bone Morphology and Trabecular Bone Microarchitecture

Objective

The objective of this study was to evaluate the relationship between the trabecular bone microarchitecture and cortical bone morphology by using micro-computed tomography (micro-CT) and dental cone-beam computed tomography (dental CT).

Materials and Methods

Sixteen femurs and eight fifth lumbar vertebrae were collected from eight male Sprague Dawley rats. Four trabecular bone microarchitecture parameters related to the fifth lumbar vertebral body (percent bone volume [BV/TV], trabecular thickness [TbTh], trabecular separation [TbSp], and trabecular number [TbN]) were calculated using micro-CT. In addition, the volumetric cancellous bone grayscale value (vCanGrayscale) of the fifth lumbar vertebral body was measured using dental CT. Furthermore, four cortical bone morphology parameters of the femoral diaphysis (total cross-sectional area [TtAr], cortical area [CtAr], cortical bone area fraction [CtAr/TtAr], and cortical thickness [CtTh]) were calculated using both micro-CT and dental CT. Pearson analysis was conducted to calculate the correlation coefficients (r) of the micro-CT and dental CT measurements. Paired-sample t tests were used to compare the differences between the measurements of the four cortical bone morphology parameters obtained using micro-CT and dental CT.

Results

High correlations between the vCanGrayscale measured using dental CT and the trabecular bone microarchitecture parameters (BV/TV [r = 0.84] and TbTh [r = 0.84]) measured using micro-CT were observed. The absolute value of the four cortical bone morphology parameters may be different between the dental CT and micro-CT approaches. However, high correlations (r ranged from 0.71 to 0.90) among these four cortical bone morphology parameters measured using the two approaches were obtained.

Conclusion

We observed high correlations between the vCanGrayscale measured using dental CT and the trabecular bone microarchitecture parameters (BV/TV and TbTh) measured using micro-CT, in addition to high correlations between the cortical bone morphology measured using micro-CT and dental CT. Further experiments are necessary to validate the use of dental CT on human bone.     

Effect of flecainide on atrial fibrillatory rate in a large animal model with induced atrial fibrillation

Background

Atrial fibrillatory cycle length has been considered one of the indices of atrial electrical remodelling during atrial fibrillation (AF), which can be assessed from surface ECG by computer-assisted calculation of atrial fibrillatory rate (AFR). Horses have been suggested as a bona fide model for AF studies since horses too, develop lone AF, however data on AF characteristics in horses are extremely sparse and non-invasive characterization of AF complexity using surface ECG processing has not been reported.

Aim

The aim was to study characteristics of induced AF and its modification by flecainide.

Methods

The study group consisted on 3 horses with spontaneous persistent AF and 13 with pace-induced AF. Seven horses were treated with saline (control) and eight with flecainide (2 mg/kg). ECGs were analysed using spatiotemporal cancellation of QRST complexes and calculation of AFR from the residual atrial signal.

Results

At AF onset, AFR was 295?±?52 fibrillations per minute (fpm) in the horses with induced AF treated with flecainide, 269?±?36 fpm in the control group (ns), and 364?±?26 fpm in the horses with spontaneous persistent AF (P?<?0.05 compared to the control group). Flecainide caused a decrease in AFR in all animals and restored sinus rhythm in the animals with induced AF. In the control animals, AFR increased from 269?±?36 fpm to a plateau of 313?±?14 fpm before decreasing to 288?±?28 fpm during the last 10% of the AF episodes preceding spontaneous conversion (P?<?0.05).

Conclusion

AFR in horses with induced AF resembles AFR in humans with paroxysmal AF. Flecainide caused a rapid decrease in AFR in all horses, further supporting the method to be a non-invasive technique to study the effect of antiarrhythmic compounds.

     

Influence of diligent disintegration on anaerobic biomass and performance of microbial fuel cell

Objectives

To enhance the performance of microbial fuel cells (MFC) by increasing the surface area of cathode and diligent mechanical disintegration of anaerobic biomass.

Results

Tannery effluent and anaerobic biomass were used. The increase in surface area of the cathode resulted in 78% COD removal, with the potential, current density, power density and coulombic efficiency of 675 mV, 147 mA m^?2, 33 mW m^?2 and 3.5%, respectively. The work coupled with increased surface area of the cathode with diligent mechanical disintegration of the biomass, led to a further increase in COD removal of 82% with the potential, current density, power density and coulombic efficiency of 748 mV, 229 mA m^?2, 78 mW m^?2 and 6% respectively.

Conclusions

Mechanical disintegration of the biomass along with increased surface area of cathode enhances power generation in vertical MFC reactors using tannery effluent as fuel.

     

The effect of colloid formulation on colloid osmotic pressure in horses with naturally occurring gastrointestinal disease

Background

Naturally occurring gastrointestinal disease is an important cause of acute hypoproteinemia in adult horses and hydroxyethyl starch colloid fluid treatment is a component of supportive care in these cases to improve plasma volume and maintain colloid osmotic pressure (COP). The objectives of the present study were to compare 2 formulations of high molecular weight hydroxyethyl starch and their relative effect on COP, acid-base status, and survival of horses with acute hypoproteinemia secondary to gastrointestinal disease.

Methods

Twenty adult horses, ≥ 1 year of age, were prospectively enrolled, with informed client consent, if they developed acute hypoproteinemia, defined as a plasma total protein <5.0 g/dL or albumin <2.2 g/dL during hospitalization while undergoing treatment for gastrointestinal disease. Horses were randomly assigned to receive a rapid infusion of either 6% hydroxyethyl starch in 0.9% saline or 6% hydroxyethyl starch in lactated ringers solution at a dose of 10ml/kg. Venous blood gas analysis, COP, and PCV were evaluated before and after colloid administration.

Results

For both groups, average COP prior to treatment was 11.0 mmHg (9.7 – 12.2 mmHg) and post colloid treatment was 13.2 mmHg (12.0 -14.7 mmHg) [Normal range 18 – 22 mmHg]. COP was significantly increased with colloid treatment (p<0.001) but this increase was not significantly different between treatment groups. Venous pH did not change significantly with treatment. Twelve horses survived to hospital discharge and survival did not differ significantly between treatment groups.

Conclusions

Post-treatment COP improved approximately 20% regardless of the formulation used, however, values did not reach the normal range of COP observed in healthy horses. Acid-base parameters were not significantly impacted by either treatment. Further study is needed to determine how these two products compare with regards to other outcome measures. Evaluation of the relative effects of colloid formulation in horses with clinical disease is a future area of interest.

     

Prevalence of and risk factors for colic in horses that display crib-biting behaviour

Background

Crib-biting and windsucking (CBWS) behaviour in horses has been associated with increased risk of colic in general, recurrence of colic and specific forms of colic. The aims of the present study were to determine the prevalence of colic within a population of horses that display CBWS behaviour and to identify risk factors for colic.

Methods

Owners/carers of horses in the general UK equine population that display CBWS behaviour were invited to participate in a questionnaire-based survey about the management and health of these horses. Data were obtained for a number of variables considered to be possible risk factors for colic. The prevalence of colic was calculated and multivariable logistic regression was used to identify associations between horse- and management-level variables for two outcomes of interest: a history of colic ever and a history of colic in the previous 12 months.

Results

Data were obtained for 367 horses. One or more episodes of colic had been observed in 130 horses (35.4%). A total of 672 colic episodes were reported and 13 colic episodes required surgical intervention in 12 horses. Where the horse/pony had been in that persons care over the previous 12 months (n=331), colic had been observed in 67 horses (20.2%) during that time. A total of 126 colic episodes were reported in the preceding 12 months of which veterinary attendance was required in 69 (54.8%) episodes. Increased duration of ownership, increased duration of stabling in the Autumn months (September-November), crib-biting/windsucking behaviour associated with eating forage and horses that were fed haylage were associated with increased risk of colic (ever). Increasing severity (frequency) of CBWS behaviour and increased duration of stabling in the Autumn were associated with increased risk of colic in the previous 12 months.

Conclusions

The prevalence of colic in a population of horses that display CBWS appeared to be relatively high. The results of this study can be used to identify horses that display CBWS who are at increased risk of colic and identifies areas for further research to determine if there are ways in which this risk might be reduced.

     

Long-term potentiation in bone – a role for glutamate in strain-induced cellular memory?

Background

The adaptive response of bone cells to mechanical strain is a primary determinant of skeletal architecture and bone mass. In vivo mechanical loading induces new bone formation and increases bone mineral density whereas disuse, immobilisation and weightlessness induce bone loss. The potency of mechanical strain is such that a single brief period of loading at physiological strain magnitude is able to induce a long-lasting osteogenic response that lasts for days. Although the process of mechanotransduction in bone is incompletely understood, observations that responses to mechanical strain outlast the duration of stimulation necessitate the existence of a form of cellular memory through which transient strain episodes are recorded, interpreted and remembered by bone cells. Recent evidence supports the existence of a complex multicellular glutamate-signalling network in bone that shares functional similarities to glutamatergic neurotransmission in the central nervous system. In neurones, these signalling molecules coordinate synaptic communication required to support learning and memory formation, through a complex process of long-term potentiation.

Presentation of the hypothesis

We hypothesise that osteoblasts use a cellular mechanism similar or identical to neuronal long-term potentiation in the central nervous system to mediate long-lasting changes in osteogenesis following brief periods of mechanical strain.

Testing the hypothesis

N-methyl-D-aspartate (NMDA) receptor antagonism should inhibit the saturating response of mechanical strain and reduce the enhanced osteogenicity of segregated loading to that of an equivalent period of uninterrupted loading. Changes in α-amino-3-hydroxy-5-methyl-isoxazole propionate (AMPA) receptor expression, localisation and electrophysiological responses should be induced by mechanical strain and inhibited by modulators of neuronal long-term potentiation.

Implications of the hypothesis

If true, this hypothesis would provide a mechanism through which the skeleton could be pharmacologically primed to enhance or retrieve the normal osteogenic response to exercise. This would form a basis through which novel therapies could be developed to target osteoporosis and other prevalent bone disorders associated with low bone mass.

     

Neutrophil extracellular traps are downregulated by glucocorticosteroids in lungs in an equine model of asthma

Background

Severe neutrophilic asthma is poorly responsive to glucocorticosteroids (GC). Neutrophil extracellular traps (NETs) within the lungs have been associated with the severity of airway obstruction and inflammation in asthma, and were found to be unaffected by GC in vitro. As IL-17 is overexpressed in neutrophilic asthma and contributes to steroid insensitivity in different cell types, we hypothesized that NETs formation in asthmatic airways would be resistant to GC through an IL-17 mediated pathway.

Methods

Six neutrophilic severe asthmatic horses and six healthy controls were studied while being treated with dexamethasone. Lung function, bronchoalveolar lavage fluid (BALF) cytology and NETs formation, as well as the expression of CD11b and CD13 by blood and airway neutrophils were evaluated. The expression of IL-17 and its role in NETs formation were also studied.

Results

Airway neutrophils from asthmatic horses, as opposed to blood neutrophils, enhanced NETs formation, which was then decreased by GC. GC also tended to decrease the expression of CD11b in blood neutrophils, but not in airway neutrophils. IL-17 mRNA was increased in BALF cells of asthmatic horses and was unaffected by GC. However, both GC and IL-17 inhibited NETs formation in vitro.

Conclusion

GC decreased NETs formation in vitro and also in vivo in the lungs of asthmatic horses. However, airway neutrophil activation during asthmatic inflammation was otherwise relatively insensitive to GC. The contribution of IL-17 to these responses requires further study.

     

<Emphasis Type="Italic">In vitro</Emphasis> description of a new technique for stapled side-to-side jejunocecal anastomosis in horses and CT scan anatomical comparison with other techniques

Background

Stapled jejunocecal anastomoses are commonly performed in equine abdominal surgery. They carry higher complication rates compared to handsewn techniques. In human surgery various causes likely to lead to failure of stapled techniques have been evaluated, including staple line failure. Recently Freeman proposed a technique to perform a stapled jejunocecal anastomosis in horses while avoiding blind pouch formation. The aim of this study is to describe a method for stapled side-to-side jejunocecal anastomosis in horses and to compare it with other techniques with computed tomography to assess stomal area, shape and blind pouch size.

Methods

Intestinal specimens comprising the cecum, ileum and jejunum from 18 horses were collected and were divided into three groups. In Group S a standard stapled side-to-side jejunocecal anastomosis was performed. In Group F the anastomosis was performed using a modified technique proposed by Freeman. In Group G the anastomosis was performed with a modified technique proposed by the authors. Inflated bowel segments were CT scanned to obtain a MultiPlanar Reconstruction of the stoma and afferent small intestine before calculating the cross-sectional area of each of these regions. The ratio of the measured areas was compared between the three techniques. The volume of the blind-end pouch was measured and its ratio with the intestinal area compared between techniques. The cecum was opened and the length of the stoma measured with a caliper and compared to the intended initial length.

Results

The stomal/intestinal area ratio was not significantly different between techniques.No statistically significant difference was found in the stomal ideal/real perimeter ratio.There was no statistically significant difference in the intended/real stomal length ratio, and all techniques featured an increase in stomal length ranging from 2 to 12 %. Blind pouch formation was a consistent finding in Group S and was virtually absent in Groups F and G.

Conclusions

Both the Freeman and the new (G) technique were comparable to the standard technique in terms of stomal area, stomal shape and difference in stomal elongation. They consistently produced a smaller blind pouch and allowed easier placement of the staplers.

     

Significance of ossificated ungular cartilages regarding the performance of cold-blooded trotters

Background

Ossification of the ungular cartilages (OUC) in the foot of horses has been studied for more than 100 years. There is a high heritability of this condition but its clinical relevance has remained questionable. Nevertheless, modern equine orthopedic literature ranks OUC as one of top 10 causes of lameness in cold-blooded trotters and stallions of these breeds are excluded from breeding if they have more than mild levels of side bones. Cold-blooded trotters have been used for racing for many decades and official sports data have been available since 1923. A decreased performance is often the only obvious clinical sign noticed by trainers and owners motivating them to seek professional help from veterinarians and farriers. By comparing various performance parameters in Swedish-Norwegian cold-blooded trotters without and with different grades of OUC, we aimed to determine the clinical relevance of ossified hoof cartilages in a population of high-performance horses.Front hooves from 649 Swedish-Norwegian cold-blooded trotters were evaluated radiologically regarding OUC. Breeding index and official sports data originating from strict protocols kept by groups of officials in trotting associations was used for comparison of performance of these horses that together had competed in more than 23,000 races between 1973 and 2009. Generalized linear mixed models were used for the statistical analyses. The response variable was modeled using ordinal logistic models with a multinomial distribution and a cumulative logit link function. The horse was used as a random factor.

Results

Significant effects of gender on performance were demonstrated, but no correlations were found between different positions nor grades of ossified ungular cartilage and number of starts, running pace, race winnings, number of races completed in a regular gait.

Conclusions

Ossification of the ungular cartilages does not cause decreased performance in cold-blooded trotters and is therefore most likely not a cause of clinical or subclinical lameness in this breed. Results from this study can assist equine professionals in evaluating and interpreting the clinical relevance of radiological findings on ossified hoof cartilage among heavy and high-performing horses.