Fracture status in middle-aged individuals with early CKD: cross-sectional analysis of the CARTaGENE survey.

Whether early chronic kidney disease (CKD) is associated with fracture in middle-aged adults is unclear. In a cross-sectional analysis of the CARTaGENE survey, we observed that early CKD was not associated with increased fracture, did not modify the association between calcaneal QUS and fracture, but modified the association between clinical, pharmacological parameters and fracture. INTRODUCTION: The association between advanced CKD and increased fracture risk is well described. However, whether early CKD is associated with increased fractures, especially in middle-aged adults, is unclear. We aimed to assess if early CKD is associated with increased fracture status and whether early CKD status modifies the association between calcaneal quantitative ultrasound parameters, clinical, pharmacological parameters, and fractures. METHODS: Cross-sectional analysis of CARTaGENE, a population-based survey of 40- to 69-year-old individuals. Individuals with CKD (stage 2, estimated glomerular filtration rate [eGFR] 60-89 ml/min/1.73 m2; stage 3, eGFR 30-59) were compared to non-CKD individuals (eGFR > 90). Fracture status (excluding face, toe, hand, and patella) was identified through a questionnaire at baseline. Calcaneal quantitative ultrasound (QUS) was measured in each participant. RESULTS: A total of 17,608 individuals (656 CKD stage 3; 8227 stage 2; 8725 non-CKD) were included. CKD stage 2 and 3 individuals (mean eGFR 78 and 53 ml/min/1.73 m2) were older and had more diabetes, cardiovascular disease, and hypertension. Fracture status prevalence was 14.9% in CKD stage 3, 10.8% in CKD stage 2, and 9.0% in non-CKD individuals. Fracture status prevalence was similar between CKD and non-CKD individuals when stratified by age or after adjustment for demographic and clinical parameters. QUS stiffness index was associated with fracture status in both CKD stage 3 (standardized odds ratio [sOR] = 1.525 [1.200 to 1.939] per 1 SD decrease), stage 2 (sOR = 1.415 [1.310 to 1.530]), and non-CKD individuals (sOR = 1.477 [1.361 to 1.602]). The associations between blood pressure, antihypertensive, and fracture status followed a U-shape throughout the progression of CKD. CONCLUSIONS: CKD stage 3 was not associated with an increase in fracture status. QUS parameters were similarly associated with fracture status in patients with and without CKD.

Prevalence of 5-lipoxygenase expression in canine osteosarcoma and the effects of a dual 5-lipoxygenase/cyclooxygenase inhibitor on osteosarcoma cells in vitro and in vivo.

Canine osteosarcoma is an insidious disease with few effective treatment modalities; therefore, use of pharmacologic intervention to improve mortality or morbidity is constantly sought. The use of cyclooxygenase enzyme inhibitors has been an area of interest with limited efficacy based on retrospective examination of tumor expression and in vivo cell proliferation models. Recently, examination of dual cyclooxygenase and 5-lipoxygenase inhibitors in human and canine oncology suggests that 5-lipoxygenase inhibitors may be an effective approach in vitro and during tumor induction in rodent models. Therefore, the authors decided to examine 5-lipoxygenase expression in primary canine osteosarcoma samples and have shown that approximately 65% of osteosarcomas label positive for cytoplasmic 5-lipoxygenase. Further examination of a cell culture and xenograft model shows similar 5-lipoxygenase expression. Surprisingly, a canine 5-lipoxygenase inhibitor (tepoxalin) significantly reduced cell proliferation at physiologic doses in vitro and diminished xenograft tumor growth in nude mice, suggesting that further investigation is needed. Traditionally, 5-lipoxygense leads to production of lipid mediators, such as leukotriene B(4) and 5-oxo-eicosatetraenoic acid, which, when added back to the media of tepoxalin-treated cells, did not recover cell proliferation. The lack of nuclear staining in primary and xenografted tumors and the lack of response to eicoasanoids suggest that lipid mediator production is not the primary means by which tepoxalin acts to alter proliferation. Regardless of the mechanisms involved in retarding cell proliferation, future investigation is warranted.