Objective.Nontraumatic osteonecrosis (ON) is a well-recognized complication causing disability and affecting quality of life in patients with systemic lupus erythematosus (SLE). The aim of this study was to identify the risk factors for ON, and to identify the minimal investigation(s) needed to optimally monitor the risk of ON in patients with SLE.Methods.A systematic review was conducted using MEDLINE and EMBASE. These databases were searched up to January 2016 using the Medical Subject Heading (MeSH) terms “Osteonecrosis,” “Systemic lupus erythematosus,” and synonymous text words. Randomized controlled trials, case control, cohort, and cross-sectional studies were included. Risk factors for ON in patients with SLE were compiled. The quality of each study was assessed using the Newcastle-Ottawa scale for nonrandomized studies. The quality of evidence of each risk factor was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation method.Results.Of the 545 references yielded, 50 met inclusion criteria. Corticosteroid (CS) use may be strongly associated with ON in patients with SLE. Other clinical variables were moderately associated, including hypertension, serositis, renal disease, vasculitis, arthritis, and central nervous system disease. However, the evidence was low to very low in quality.Conclusion.Based on the best evidence available, CS use may be strongly associated with ON in patients with SLE. Results of this review were considered in the development of recommendations for the diagnosis and monitoring of patients with SLE in Canada and will guide clinicians in their assessment of these patients.

R enin-angiotensin system (RAS) is a key component of cardiovascular and renal system homeostasis. RAS activation during development is well described 1 and contributes to organogenesis and growth, especially in the cardiovascular and renal systems. Among RAS components, angiotensin (Ang) II is the major peptide acting during fetal and neonatal life. Both subtypes of Ang receptors are expressed during fetal development 2,3 but have different patterns of expression during the fetal-neonatal transition. In rats, Ang type 2 (AT2) receptors are upregulated in the heart, large vessels, lungs, and kidneys during fetal development and progressively decline after birth, suggesting their contribution to fetal organogenesis. Ang type 1 (AT1) receptors, on the other hand, are detected late in fetal development, increase soon after birth, and are considered to contribute mainly to tissue maturation, growth, and postnatal adaptation. [2][3][4] This switching pattern of Ang receptors suggests that modifications of AT1/AT2 balance play a key role in different developmental stages. A disruption of this balance, depending on the stage of development, may negatively affect cardiovascular and renal homeostasis and contribute to the establishment of cardiovascular diseases.Deleterious perinatal conditions, including preeclampsia, intrauterine growth restriction, and preterm birth can lead to developmental programming of cardiovascular risk factors and diseases. 5,6 Preterm-born individuals in particular, whose numbers are growing in the population because of recent Abstract-Newborn rats exposed to high oxygen (O 2 ), mimicking preterm birth-related neonatal stress, develop later in life cardiac hypertrophy, dysfunction, fibrosis, and activation of the renin-angiotensin system. Cardiac renin-angiotensin system activation in O 2 -exposed adult rats is characterized by an imbalance in angiotensin (Ang) receptors type 1/2 (AT1/2), with prevailing AT1 expression. To study the role of renin-angiotensin system in the developmental programming of cardiac dysfunction, we assessed Ang receptor expression during neonatal high O 2 exposure and whether AT1 receptor blockade prevents cardiac alterations in early adulthood. Sprague-Dawley newborn rats were kept with their mother in 80% O 2 or room air (control) from days 3 to 10 (P3-P10) of life. Losartan or water was administered by gavage from P8 to P10 (n=9/group). Rats were studied at P3 (before O 2 exposure), P5, P10 (end of O 2 ), and P28. Losartan treatment had no impact on growth or kidney development. AT1 and Ang type 2 receptors were upregulated in the left ventricle by high O 2 exposure (P5 and P10), which was prevented by Losartan treatment at P10. Losartan prevented the cardiac AT1/2 imbalance at P28. Losartan decreased cardiac hypertrophy and fibrosis and improved left ventricle fraction of shortening in P28 O 2 -exposed rats, which was associated with decreased oxidation of calcium/calmodulin-dependent protein kinase II, inhibition of the transforming growth factor-β/SMAD3 pathway...

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