Endothelial Dysfunction, Inflammation, and Apoptosis in Diabetes Mellitus

Endothelial dysfunction is regarded as an important factor in the pathogenesis of vascular disease in obesity-related type 2 diabetes. The imbalance in repair and injury (hyperglycemia, hypertension, dyslipidemia) results in microvascular changes, including apoptosis of microvascular cells, ultimately leading to diabetes related complications. This review summarizes the mechanisms by which the interplay between endothelial dysfunction, inflammation, and apoptosis may cause (micro)vascular damage in patients with diabetes mellitus

Common mechanisms and holistic care in atherosclerosis and osteoporosis

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Osteopenia: A Diagnostic and Therapeutic Challenge

We discussed whether we are able to select a subgroup of patients with osteopenia having a high fracture risk, in which anti-osteoporotic drug treatment can be advocated. We concluded that in individuals in whom, based on clinical risk factors, a dual-energy x-ray absorptiometry (DXA) was performed in which osteopenia was diagnosed, anti-osteoporotic treatment should be prescribed in those patients with prevalent vertebral fractures, and in patients chronically using glucocorticoids, in a dosage of 7.5 mg per day or more. Although recent developments with regard to high-resolution imaging techniques (eg, peripheral quantitative computed tomography) seem to be promising, until now they do not provide substantial more reliable information than DXA in the prediction of fractures. We think that more data are urgently needed, since safe and effective drugs are available, but there is uncertainty to which patients with osteopenia these drugs should be prescribed

Critical issues and current challenges in osteoporosis and fracture prevention. An overview of unmet needs

Osteoporosis is a silent disease with increasing prevalence due to the global ageing population. Decreased bone strength and bone quality is the hallmark of osteoporosis which leads to an increased risk of fragility fractures in elderly. It has been estimated that approximately ~50% of women will suffer during their lifetime from an osteoporotic fracture. This must be considered as a major health concern, as it has previously been established that fragility fracture has been associated with decreased quality of life due to increased disability, more frequent hospital admission and most importantly, osteoporotic fractures have been related to an augmented mortality risk. Anti-osteoporotic drugs are available for improving bone quality. Although there is access to these therapeutic options, there remain multiple unmet needs in the field of osteoporosis and fracture care, for example, the primary prevention of osteoporosis in young individuals (to reach a high peak bone mass), the optimization of the use of imaging techniques [dual-energy X-ray absorptiometry (DXA), vertebral fracture assessment (VFA) and new techniques measuring bone quality], the use of nonmedical treatment options and surgical techniques of fracture healing. In this review, we will discuss topics that play a role in the occurrence and prevention of fractures, and we give an overview of and insight into the critical issues and challenges around osteoporosis and fracture prevention

Pharmacological Management of Osteoporosis in Rheumatoid Arthritis Patients: A Review of the Literature and Practical Guide

Rheumatoid arthritis (RA) is a chronic disabling disease that is associated with increased localized and generalized osteoporosis (OP). Previous studies estimated that approximately one-third of the RA population experience bone loss. Moreover, RA patients suffer from a doubled fracture incidence depending on several clinical factors, such as disease severity, age, glucocorticoid (GC) use, and immobility. As OP fractures are related to impaired quality of life and increased mortality rates, OP has an enormous impact on global health status. Therefore, there is an urgent need for a holistic approach in daily clinical practice. In other words, both OP- and RA-related factors should be taken into account in treatment guidelines for OP in RA. First, to determine the actual fracture risk, dual-energy X-ray absorptiometry (DXA), including vertebral fracture assessment (VFA) and calculation of the 10-year fracture risk with FRAX®, should be performed. In case of high fracture risk, calcium and vitamin D should be supplemented alongside anti-osteoporotic treatment. Importantly, RA treatment should be optimal, aiming at low disease activity or remission. Moreover, GC treatment should be at the lowest possible dose. In this way, good fracture risk management will lead to fracture risk reduction in RA patients. This review provides a practical guide for clinicians regarding pharmacological treatment options in RA patients with OP, taking into account both osteoporotic-related factors and factors related to RA

Osteoporosis in patients with rheumatoid arthritis: an update in epidemiology, pathogenesis, and fracture prevention

Introduction: Rheumatoid arthritis (RA) is a chronic disabling disease characterized by a symmetrical articular involvement due to ongoing joint inflammation, if left insufficiently treated. Local and generalized bone loss is one of the main extra-articular complications of RA and leads to an increased risk for fragility fractures, which further impair functional ability, quality of life, and life expectancy. Therefore, there is an urgent need for good fracture risk management in the vulnerable RA patient. Areas covered: The authors review: the epidemiology and pathophysiology (i.e. risk factors) of osteoporosis (OP), fracture, and vertebral fracture risk assessment, the effects of anti-rheumatic drugs on bone loss, pharmacological treatment of OP in RA including both bisphosphonates (BP) and newer drugs including anti-resorptives and osteoanabolic treatment options. Expert opinion: Patients with active RA have elevated bone resorption and local bone loss. Moreover, these patients are at increased risk for generalized bone loss, vertebral and non-vertebral fractures. Since general risk factors (such as low BMI, fall risk) and RA-related factors play a role, optimal fracture prevention in RA patients is based on optimal diagnostics based on both of these factors, and on the use of adequate non-medical and medical treatment options