RESUMEN
Background: Atherosclerotic cardiovascular disease is prevalent among patients with chronic kidney disease (CKD). In this study, we initially aimed to test whether vascular calcification associated with CKD can worsen atherosclerosis. However, a paradoxical finding emerged from attempting to test this hypothesis in a mouse model of adenine-induced CKD. Methods: We combined adenine-induced CKD and diet-induced atherosclerosis in mice with a mutation in the low-density lipoprotein receptor gene. In the first study, mice were co-treated with 0.2% adenine in a western diet for 8 weeks to induce CKD and atherosclerosis simultaneously. In the second study, mice were pre-treated with adenine in a regular diet for 8 weeks, followed by a western diet for another 8 weeks. Results: Co-treatment with adenine and a western diet resulted in a reduction of plasma triglycerides and cholesterol, liver lipid contents, and atherosclerosis in co-treated mice when compared with the western-only group, despite a fully penetrant CKD phenotype developed in response to adenine. In the two-step model, renal tubulointerstitial damage and polyuria persisted after the discontinuation of adenine in the adenine-pre-treated mice. The mice, however, had similar plasma triglycerides, cholesterol, liver lipid contents, and aortic root atherosclerosis after being fed a western diet, irrespective of adenine pre-treatment. Unexpectedly, adenine pre-treated mice consumed twice the calories from the diet as those not pre-treated without showing an increase in body weight. Conclusion: The adenine-induced CKD model does not recapitulate accelerated atherosclerosis, limiting its use in pre-clinical studies. The results indicate that excessive adenine intake impacts lipid metabolism.
RESUMEN
BACKGROUND AND PURPOSE: Due to potential health-related consequences of osteoporosis (OP), health care providers who do not order imaging, such as physical therapists, should be aware of OP screening tools that identify individuals who need medical and rehabilitation care. However, current knowledge and guidance on screening tools is limited. Therefore, we explored OP screening tools that are appropriate and feasible for physical therapy practice, and evaluated tools' effectiveness by examining their clinimetric properties. METHODS: A systematic search of the following databases was performed: PubMed, PEDro, PsycINFO, CINAHL, and Web of Science. Articles were included if the study population was 50 years and older, had a diagnosis of OP, if the screening tool was within the scope of physical therapy practice, and was compared to either a known diagnosis of OP or bone densitometry scan results. Included articles underwent multiple reviews for inclusion and exclusion, with each review round having a different randomly selected pair of reviewers. Data were extracted from included articles for participant demographics, outcome measures, cut-off values, and clinimetric properties. Results were categorized with positive and negative likelihood ratios (+LR/-LR) based on the magnitude of change in the probability of having or not having OP. RESULTS: +LRs ranged from 0.15 to 20.21, with the Fracture Risk Assessment Tool (FRAX) and Study of Osteoporotic Fractures (SOF) having a large shift in posttest probability. -LRs ranged from 0.03 to 1.00, with the FRAX, Male Osteoporosis Risk Estimation Scores, Osteoporosis Self-Assessment Tool (OST), and Simple Calculated Osteoporosis Risk Estimation having a large shift in posttest probability. CONCLUSION: Tools with moderate-large shift for both +LR and -LR recommended for use are: (1) OST; (2) FRAX; and (3) SOF. The variability in cut-off scores and clinimetric properties based on gender, age, and race/ethnicities made it impossible to provide one specific recommendation for an OP screening tool. Future research should focus on OP risk prediction among males and racial and ethnic groups.
