Angle-stable interlocking nailing in a canine critical-sized femoral defect model for bone regeneration studies: In pursuit of the principle of the 3R's.

Introduction: Critical-sized long bone defects represent a major therapeutic challenge and current treatment strategies are not without complication. Tissue engineering holds much promise for these debilitating injuries; however, these strategies often fail to successfully translate from rodent studies to the clinical setting. The dog represents a strong model for translational orthopedic studies, however such studies should be optimized in pursuit of the Principle of the 3R's of animal research (replace, reduce, refine). The objective of this study was to refine a canine critical-sized femoral defect model using an angle-stable interlocking nail (AS-ILN) and reduce total animal numbers by performing imaging, biomechanics, and histology on the same cohort of dogs. Methods: Six skeletally mature hounds underwent a 4 cm mid-diaphyseal femoral ostectomy followed by stabilization with an AS-ILN. Dogs were assigned to autograft (n = 3) or negative control (n = 3) treatment groups. At 6, 12, and 18 weeks, healing was quantified by ordinal radiographic scoring and quantified CT. After euthanasia, femurs from the autograft group were mechanically evaluated using an established torsional loading protocol. Femurs were subsequently assessed histologically. Results: Surgery was performed without complication and the AS-ILN provided appropriate fixation for the duration of the study. Dogs assigned to the autograft group achieved radiographic union by 12 weeks, whereas the negative control group experienced non-union. At 18 weeks, median bone and soft tissue callus volume were 9,001 mm3 (range: 4,939-10,061) for the autograft group and 3,469 mm3 (range: 3,085-3,854) for the negative control group. Median torsional stiffness for the operated, autograft treatment group was 0.19 Nm/° (range: 0.19-1.67) and torque at failure was 12.0 Nm (range: 1.7-14.0). Histologically, callus formation and associated endochondral ossification were identified in the autograft treatment group, whereas fibrovascular tissue occupied the critical-sized defect in negative controls. Conclusion: In a canine critical-sized defect model, the AS-ILN and described outcome measures allowed refinement and reduction consistent with the Principle of the 3R's of ethical animal research. This model is well-suited for future canine translational bone tissue engineering studies.

Quantifying dog meniscal volume at 1.5T and 3.0T MRI.

The dog has been used extensively as an experimental model to study meniscal treatments such as meniscectomy, meniscal repair and regeneration. Accurate quantification of meniscal size and morphology are a crucial step for developing models of the meniscus. 3.0T magnetic resonance imaging (MRI) has been found to be highly accurate in analyzing the meniscus in both clinical and research fields. However, 3.0T MRI systems are still uncommonly used in veterinary medicine. The goal of the study was to compare meniscal volume measurements from 1.5T MRI system with 3.0T MRI system using proton density sequence, a clinically relevant protocol. The MR images were segmented to reconstruct 3D surface representations of both medial and lateral menisci to compare the meniscal volumes measurements. Average volume differences were 8.8% (P=0.42) and 8.9% (P=0.535) for medial and lateral meniscus, respectively. No significant volume differences were found between 1.5T and 3.0T magnetic resonance (MR) measurements, with high Pearson's correlation coefficient of r > 0.8 and the intraclass correlation coefficient (ICC) of 0.899. For inter- and intra-observer reproducibility, high correlation (ICC = 0.942 and 0.814) was observed, but with high variability for intra-observer reproducibility (lower bound 0.478, upper bound 0.949). We have shown that common clinical MR scanners and pulse sequences can be used to quantify dogs' meniscal volumes with good reproducibility. We believe that repeatable measurements of meniscal volumes using MR may provide a useful capability for assessment of postoperative results following meniscal treatments such as meniscectomy and meniscal regeneration.

Estrogen prescribing practices scrutinized at NIH conference.

PIP: Despite reports of studies linking menopausal estrogen therapy with endometrial cancer in 1975, physicians have persisted in considering menopause a condition needing medication--with estrogens. To assess the risks and benefits, NIH held a conference on estrogen usage in postmenopausal women. A panel of physicians heard the therapeutic, epidemiologic, and sociologic evidence and summarized the findings in a final report. It was agreed that estrogen therapy will be effective in combating vasomotor flushes (hot flashes) and vaginal atrophy and dryness. Evidence to justify estrogen use for coronary vascular disease and depression does not exist. Further evidence is needed to deterine whether estrogen therapy will decrease osteoporosis-related fractures. The risk of endometrial cancer increases 4-8-fold following 2-4 years of continuous estrogen usage. It was concluded that estrogens should be prescribed in the lowest effective dosages and for short terms, not exceedng 2-4 years. Cyclic progestin administration and yearly curettage sampling for endometrial cancer might reduce the risk of developing endometrial cancer while on estrogen therapy.^ieng