Disuse rescues the age-impaired adaptive response to external loading in mice.

UNLABELLED: We aimed to determine whether aged bone's diminished response to mechanical loading could be rescued by modulating habitual activity. By reducing background loading, aged bone's response to loading increased to a level no different to young mice. This suggests, given the right stimulus, that ageing bone can respond to mechanical loading. INTRODUCTION: Age-related decline in bone mass has been suggested to represent an impaired ability of bone to adapt to its mechanical environment. In young mice, the tibia's response to external mechanical loading has been shown to increase when habitual activity is reduced by sciatic neurectomy. Here we investigate if neurectomy can rescue bone's response to loading in old mice. METHODS: The effect of tibial disuse, induced by unilateral sciatic neurectomy (SN), on the adaptive response to a single peak magnitude of dynamic load-engendered mechanical strain was assessed in 19-month-old (aged) mice. In a second experiment, a range of peak loads was used to assess the load magnitude-related effects of loading on a background of disuse in young adult and aged mice. Bone architecture was analysed using micro-computed tomography (µCT) and dynamic histomorphometry. RESULTS: In the first experiment, SN in aged mice was associated with a significant periosteal osteogenic response to loading not observed in sham-operated mice (7.98 ± 1.7 vs 1.02 ± 2.2 % increase in periosteally enclosed area, p < 0.05). In the second experiment, SN abrogated the expected age-related difference in the bones' osteogenic response to peak strain magnitude (p > 0.05). CONCLUSIONS: These data suggest that bones' age-related decline in osteogenic responsiveness to loading does not originate in bone cells to either assess, or appropriately respond to strain, but rather is likely to be due to inhibitory "averaging" effects derived from the habitual strains to which the bone is already adapted. If such "strain averaging" is applicable to humans, it suggests that gentle exercise may degrade the beneficially osteogenic effects of short periods of more vigorous activity.

The cyclooxygenase-2 selective inhibitor NS-398 does not influence trabecular or cortical bone gain resulting from repeated mechanical loading in female mice.

UNLABELLED: A single injection of the cyclooxygenase-2 (COX-2) selective inhibitor NS-398 reduces bone's osteogenic response to a single period of mechanical loading in female rats, while women taking COX-2 selective inhibitors do not have lower bone mass. We show that daily NS-398 injection does not influence bone gain from repeated loading in female mice. INTRODUCTION: Prostaglandins are mediators of bone cells' early response to mechanical stimulation. COX-2 expression is up-regulated by exposure of these cells to mechanical strain or fluid flow, and the osteogenic response to a single loading period is reduced by COX-2 inhibition. This study determined, in female mice in vivo, the effect of longer term COX-2 inhibition on adaptive (re)modelling of cortical and trabecular bone in response to repeated loading. METHODS: Nineteen-week-old female C57BL/6 mice were injected with vehicle or NS-398 (5 mg/kg/day) 5 days a week for 2 weeks. On three alternate days each week, the right tibiae/fibulae were axially loaded [40 cycles (7 min)/day] three hours after injection. Left limbs acted as internal controls. Changes in three-dimensional bone architecture were analysed by high-resolution micro-computed tomography. RESULTS: In control limbs NS-398 was associated with reduced trabecular number but had no influence on cortical bone. In loaded limbs trabecular thickness and cortical periosteally enclosed volume increased. NS-398 showed no effect on this response. CONCLUSION: Pharmacological inhibition of COX-2 by NS-398 does not affect trabecular or cortical bone's response to repeated mechanical loading in female mice and thus would not be expected to impair the functional adaptation of bone to physical activity in women.

Computed tomographic staging of dogs with anal sac adenocarcinoma.

OBJECTIVES: To describe the CT appearance of anal sac adenocarcinoma lesions in a population of dogs including the relations between primary tumour, and locoregional and distant metastasis. MATERIALS AND METHODS: Retrospective review of dogs with confirmed anal sac adenocarcinoma and available CT images of the thorax, abdomen and pelvis. RESULTS: A population of 70 dogs were included in the study. No association was found between anal sac mass size and presence or absence of iliosacral lymph node enlargement. The prevalence of local metastatic disease characterised by iliosacral lymphadenomegaly in this study was 71%, with pulmonary metastases identified in 11% of cases. There were no cases of distant pulmonary metastasis without concurrent locoregional lymphadenomegaly. CLINICAL SIGNIFICANCE: In our population of dogs local metastatic spread of anal sac adenocarcinoma was common, with a relatively low prevalence of pulmonary metastasis. The study demonstrates the importance of thorough rectal examination and/or imaging to assess the iliosacral lymph centre in this disease irrespective of the size of the anal sac mass.

Prevalence, outcome and risk factors for postoperative pyothorax in 232 dogs undergoing thoracic surgery.

OBJECTIVE: To determine the prevalence, outcome and risk factors for postoperative pyothorax in dogs undergoing thoracic surgery. METHODS: Case records were reviewed retrospectively to identify dogs with post thoracic surgery pyothorax, defined as septic neutrophilic inflammation within the pleural space based on cytology and/or a positive bacterial culture of pleural fluid. Those identified were reviewed for potential risk factors for postoperative pyothorax based on biological plausibility and previously published data. These potential risk factors were explored by multivariable logistic regression. RESULTS: Of 232 dogs undergoing thoracic surgery, 15 (6.5%) dogs developed pyothorax. Bacteria cultured included methicillin-resistant Staphylococcus aureus and multi-resistant Escherichia coli. Of these dogs, six died, four were euthanased and five were treated successfully. A diagnosis of idiopathic chylothorax [Odds Ratio (OR)=12.5, 95% Confidence Interval (CI)=2.7-58.5, P=0.001], preoperative intrathoracic biopsy (OR=14.3, 95% CI=1.7-118.7, P=0.014) and preoperative thoracocentesis (OR=11.2, 95% CI=1.6-78.2, P=0.015) were identified as independent risk factors for development of postoperative pyothorax. CLINICAL SIGNIFICANCE: Idiopathic chylothorax, intrathoracic biopsy and prior thoracocentesis are independent risk factors for postoperative pyothorax, which was associated with a 67% mortality rate.