Systemic sclerostin antibody treatment increases osseointegration and biomechanical competence of zoledronic-acid-coated dental implants in a rat osteoporosis model.

Osseointegration of dental implants can be promoted by implant-surface modifications using bisphosphonate coatings. In addition, it is of clinical interest to promote peri-implant bone formation and to restore bony structure in low bone-mass patients. The present study evaluated a combination of an anti-resorptive zoledronic acid (ZOL) implant-coating and a systemically applied sclerostin antibody, a known bone anabolic treatment principle, versus sole sclerostin antibody treatment or ZOL implant-coating in a rat osteoporosis model. Uncoated reference surface implants or ZOL-coated implants (n = 64/group) were inserted into the proximal tibia of aged osteoporotic rats three months following ovariectomy. 32 animals of each group received once weekly sclerostin antibody therapy. Osseointegration was assessed 2 or 4 weeks post-implantation by ex vivo µCT, histology and biomechanical testing. Overall implant survival rate was 97 %. Histomorphology revealed pronounced bone formation along the entire implant length of ZOL-coated implants. At 4 weeks following implant insertion, bone-implant contact, cancellous bone mineral density and bone volume/tissue volume were significantly increased for the combination of ZOL and sclerostin antibody as compared to sclerostin antibody or ZOL implant-coating alone. Removal torque was also significantly increased in the combination therapy group relative to animals receiving only sclerostin antibody therapy or ZOL-coated implants. In an osteoporotic rat model, the combination of anti-resorptive ZOL implant-coating and systemically applied sclerostin antibody led to significantly increased peri-implant bone formation. Therefore, the combination of ZOL and the osteoanabolic sclerostin antibody was more effective than either agent alone.

Characterizing microcrack orientation distribution functions in osteonal bone samples.

Prefailure microdamage in bone tissue is considered to be the most detrimental factor in defining its strength and toughness with respect to age and disease. To understand the influence of microcracks on bone mechanics it is necessary to assess their morphology and three-dimensional distribution. This requirement reaches beyond classic histology and stereology, and methods to obtain such information are currently missing. Therefore, the aim of the study was to develop a methodology that allows to characterize three-dimensional microcrack distributions in bulk bone samples. Four dumbbell-shaped specimens of human cortical bone of a 77-year-old female donor were loaded beyond yield in either tension, compression or torsion (one control). Subsequently, synchrotron radiation micro-computed tomography (SRµCT) was used to obtain phase-contrast images of the damaged samples. A microcrack segmentation algorithm was developed and used to segment microcrack families for which microcrack orientation distribution functions were determined. Distinct microcrack families were observed for each load case that resulted in distinct orientation distribution functions. Microcracks had median areas of approximately 4.7 µm2 , 33.3 µm2 and 64.0 µm2 for tension, compression and torsion. Verifying the segmentation algorithm against a manually segmented ground truth showed good results when comparing the microcrack orientation distribution functions. A size dependence was noted when investigating the orientation distribution functions with respect to the size of the volume of interest used for their determination. Furthermore, a scale separation between tensile, compressive and torsional microcracks was noticeable. Visual comparison to classic histology indicated that microcrack families were successfully distinguished. We propose a methodology to analyse three-dimensional microcrack distributions in overloaded cortical bone. Such information could improve our understanding of bone microdamage and its impact on bone failure in relation to tissue age and disease.

Biomechanical properties of the atlantoaxial joint with naturally-occurring instability in a toy breed dog. A comparative descriptive cadaveric study.

The biomechanical properties of the atlanto-axial joint in a young Yorkshire Terrier dog with spontaneous atlantoaxial instability were compared to those of another young toy breed dog with a healthy atlantoaxial joint. The range-of-motion was increased in flexion and lateral bending in the unstable joint. In addition, lateral bending led to torsion and dorsal dislocation of the axis within the atlas. On gross examination, the dens ligaments were absent and a longitudinal tear of the tectorial membrane was observed. These findings suggest that both ventral and lateral flexion may lead to severe spinal cord compression, and that the tectorial membrane may play a protective role in some cases of atlantoaxial instability.

Influence of two types of self-retaining retractors on multifidus muscle blood flow during dorsolateral thoracolumbar hemilaminectomy in dogs.

OBJECTIVES: To assess the influence of the use of Gelpi and Grevel retractors on multifidus muscle blood flow during hemilaminectomy, using a dorsolateral approach, for acute disc extrusion in dogs as measured by laser speckle contrast imaging (LSCI). METHODS: Blood flow in the multifidus muscles was measured intra-operatively using LSCI prior to insertion of the retractors, immediately after hemilaminectomy and removal of the retractors, and after 10 minutes of lavage of the surgical site. Plasma creatine kinase levels were measured preoperatively and 12-24 hours postoperatively. RESULTS: Muscular blood flow was significantly decreased following retraction and remained lower than initial values 10 minutes after lavage in all dogs. The decrease in blood flow was significantly greater with Gelpi retractors (n = 8) than with Grevel retractors (n = 10). No significant relation was found between the duration of retraction and postoperative changes in creatine kinase levels or blood flow. CLINICAL SIGNIFICANCE: Findings in this study demonstrate a drop in blood flow within the multifidus muscles using the dorsolateral approach regardless of retractor type used. Gelpi retractors seem to have greater influence on muscular blood flow than Grevel retractors. Further studies are warranted to confirm this second finding.

Osseointegration of biochemically modified implants in an osteoporosis rodent model.

The present study examined the impact of implant surface modifications on osseointegration in an osteoporotic rodent model. Sandblasted, acid-etched titanium implants were either used directly (control) or were further modified by surface conditioning with NaOH or by coating with one of the following active agents: collagen/chondroitin sulphate, simvastatin, or zoledronic acid. Control and modified implants were inserted into the proximal tibia of aged ovariectomised (OVX) osteoporotic rats (n = 32/group). In addition, aged oestrogen competent animals received either control or NaOH conditioned implants. Animals were sacrificed 2 and 4 weeks post-implantation. The excised tibiae were utilised for biomechanical and morphometric readouts (n = 8/group/readout). Biomechanical testing revealed at both time points dramatically reduced osseointegration in the tibia of oestrogen deprived osteoporotic animals compared to intact controls irrespective of NaOH exposure. Consistently, histomorphometric and microCT analyses demonstrated diminished bone-implant contact (BIC), peri-implant bone area (BA), bone volume/tissue volume (BV/TV) and bone-mineral density (BMD) in OVX animals. Surface coating with collagen/chondroitin sulphate had no detectable impact on osseointegration. Interestingly, statin coating resulted in a transient increase in BIC 2 weeks post-implantation; which, however, did not correspond to improvement of biomechanical readouts. Local exposure to zoledronic acid increased BIC, BA, BV/TV and BMD at 4 weeks. Yet this translated only into a non-significant improvement of biomechanical properties. In conclusion, this study presents a rodent model mimicking severely osteoporotic bone. Contrary to the other bioactive agents, locally released zoledronic acid had a positive impact on osseointegration albeit to a lesser extent than reported in less challenging models.

Off seasonal and pre-seasonal assessment of circulating energy sources during prolonged running at the anaerobic threshold in competitive triathletes.

OBJECTIVES: To compare changes in circulating energy sources during prolonged exercise in off season (OS) and pre-season (PS) training of triathletes. METHODS: Nine athletes of the Swiss national triathlon team (three female, mean (SD) age 28.7 (4.9) years, height 169.8 (6.0) cm, weight 57.0 (6.2) kg, VO(2)max 66.5 (5.3) ml/min/kg; six male, mean (SD) age 24.0 (4.1) years, height 181.4 (6.9) cm, weight 73.5 (6.0) kg, VO(2)max 75.9 (4.9) ml/min/kg) were tested twice (2.5 months apart) during a 25 km aerobic capacity test run at the end of the OS and just before the season. The average training load during the OS was 9.9 h/week, and this increased to 14.4 h/week in the PS. With heart rates as reference, exercise intensity during the aerobic capacity test was 97.0 (4.9)% of the anaerobic threshold and 91.2 (4.5)% of VO(2)max. Blood samples were collected before, during, and after the aerobic capacity test. Samples were collected every 5 km during three minute rest intervals. RESULTS: Blood was analysed for triglyceride (TG), free fatty acids, cholesterol, high density lipoprotein cholesterol, glucose, insulin, lactate, and changes in plasma volume. A two factor (season by distance) repeated measures analysis of variance revealed an increase in capacity for prolonged exercise in the PS by a decrease in running intensity during the aerobic capacity test (% of speed at 2.0 mmol/l lactate threshold, p = 0.008), an increase in running speed at the anaerobic threshold (p = 0.003) and at 4.0 and 2.0 mmol/l (p<0.001) of the lactate threshold. A significant season by distance interaction was found for TG (p<0.001). TG concentrations peaked at 5 km and decreased logarithmically throughout the OS (1.48 (0.34) to 0.86 (0.20) mmol/l) and PS (1.90 (0.31) to 0.73 (0.18) mmol/l) tests. From the OS to the PS, there was an increase in the difference in TG at 5-15 km with a concomitant increase at 2.0 mmol/l of the lactate threshold. The peak TG concentrations at 5 km followed by a logarithmic decrease suggest that TG may also provide circulating energy. A greater logarithmic decrease in TG occurred in the PS than in the OS, indicating a higher rate of use. There was an increase in the difference in TG at 5-15 km similar to the increase in the speed at 2.0 mmol/l of the lactate threshold between the two seasons. Glucose, insulin, lactate, and free fatty acids were similar in the two seasons. CONCLUSION: Free fatty acid and TG concentrations were much higher than expected, and the two training seasons showed significantly different patterns of TG concentration during prolonged running. These responses may be related to aerobic capacity of prolonged exercise.

Liver ultrasound findings in a low prevalence area of S. japonicum in China: comparison with history, physical examination, parasitological and serological results.

The paper describes a study carried out in a community in Dongdian township, Anhui Province, People's Republic of China. Medical history and the results of a physical examination, ultrasound investigation, parasitological and serological tests for Schistosoma japonicum infection were compared in 661 persons of 169 households. A lack of correlation between parasitological and serological indicators of infection and morbidity was observed in this area of low (6.4%) prevalence and intensity of infection. The prevalence of abnormal ultrasound findings in the liver in this population was high (56%), and was significantly higher than the prevalence of S. japonicum infection. The abnormal ultrasound findings correlated with a history of schistosomiasis, and the correlation increased significantly according to the number of times treated and the time since the last treatment, which suggested that past parenteral treatment has a role in the high rate of abnormal liver ultrasound findings. The significant correlation between the qualitative and quantitative serological results and abnormal ultrasound parenchymal patterns suggests that cross-reactivity between the etiology of the parenchymal disease and these tests is occurring. The presence of HBsAg correlated with the composite presence of ultrasound abnormalities of the liver parenchyma: increased echogenicity, periportal fibrosis and/or nodules and irregular fibrosis, whereas a normal ultrasound pattern was associated with the absence of HBV antigenemia.

Comparison of ultrasonography, intravenous pyelography and cystoscopy in detection of urinary tract lesions due to Schistosoma haematobium.

The use of ultrasound in detecting urinary tract alterations by Schistosoma haematobium such as hydronephrosis and bladder calcifications was studied in 125 patients of the out-patients department of a district hospital in SE Tanzania, in an area highly endemic for this disease. Ultrasound was compared with plain abdominal X-ray (in 33 patients), intravenous pyelography (29), cystoscopy (31) and simple urine examination (125). Except for bladder calcifications which could not be demonstrated other than by X-ray, sonography compared favorably with IVP and cystoscopy and proved therefore to be a valuable tool in assessing S.h. related morbidity. In children moderate and advanced hydronephrosis were always associated with an irregular bladder wall and correlated strongly with the prevalence and intensity of S.h. infections as well as with haematuria and proteinuria. Important congestive pathology was observed in 1 out of 10 infected children and in 1 out of 20 examined adults.

Value of ultrasonography in investigating morbidity due to Schistosoma haematobium infection.

In an area where urinary schistosomiasis was endemic 349 patients were examined by ultrasonography. To evaluate the sensitivity and specificity of this technique, intravenous pyelography and cystoscopies were also done on 29 and 31 patients, respectively. Ultrasonography compared favourably with pyelography and cystoscopy except in demonstrating bladder calcifications. It was a valuable tool for rapid mass detection of Schistosoma haematobium related morbidity. Major renal congestion and irregularity of the bladder wall as seen on ultrasonography correlated strongly with the prevalence and the intensity of S haematobium infection as well as with microhaematuria and proteinuria, thus indicating the usefulness of urine dip sticks for S haematobium case-finding, especially during attempts at morbidity control in endemic areas.