Current Opinion in Endocrinology & Diabetes and Obesity最新文献

Purpose of review: The aim of this review was to discuss cardiometabolic risk factors that affect women.

Recent findings: Recent calls to action to address cardiometabolic risk factors specific to women relate to increasing evidence of sex-specific differences in patient-related, drug-related, and socio-demographic factors leading to sub-optimal care of women.

Summary: Certain aspects of common modifiable cardiovascular risk factors (e.g. smoking, hypertension, dyslipidaemia and diabetes) affect female individuals more adversely. Additionally, there are risk factors or enhancers that particularly affect cardiometabolic health in women [e.g. premature menopause, polycystic ovarian syndrome (PCOS), familial partial lipodystrophy, socio-cultural factors]. Understanding these risk factors may provide insight on how to improve cardiometabolic outcomes in women.

Purpose of review: Anabolic therapies have revolutionized the management of patients with osteoporosis, especially those at very high fracture risk. The current review offers valuable insights into the latest evidence and guidelines on the use of anabolic agents, focusing on their comparative efficacy, safety profiles, and optimal implementation in clinical practice.

Recent findings: Romosozumab, abaloparatide, and teriparatide have shown superior efficacy when compared to antiresorptive therapies in increasing bone mineral density and reducing fracture risk. Notably, sequential treatment strategies, commencing with an anabolic agent followed by an antiresorptive, has emerged as an effective approach for both rapid and sustained reduction of fracture risk in patients at high risk. Additionally, anabolics have shown potential in improving outcomes for patients who have a suboptimal response to antiresorptives. Careful patient selection and vigilant monitoring are essential to optimize therapeutic benefits while mitigating the potential risks. As we gain more clinical experience with these agents, we will better understand how to use them effectively, as part of long term, sequential treatment strategies. Ongoing research into novel anabolic therapies and innovative treatment sequences holds promise for expanding our toolkit against fragility fractures.

Summary: Integrating anabolic agents into personalized treatment plans has the potential to significantly improve outcomes and quality of life for patients with severe osteoporosis, highlighting the importance of this therapeutic class in the management of this chronic condition.

Purpose of review: The assessment of fracture risk is playing an ever-increasing role in osteoporosis clinical management and informing international guidelines for osteoporosis. FRAX, a fracture risk calculator that provides individualized 10-year probabilities of hip and major osteoporotic fracture, has been widely used since 2008. In this review, we recap the development and limitations of intervention thresholds and the role of absolute fracture risk.

Recent findings: There is an increasing awareness of disparities and inequities in the setting of intervention thresholds in osteoporosis. The limitations of the simple use of prior fracture or the DXA-derived BMD T -score threshold are increasingly being discussed; one solution is to use fracture risk or probabilities in the setting of such thresholds. This approach also permits more objective assessment of high and very high fracture risk to enable physicians to make choices not just about the need to treat but what agents to use in individual patients.

Summary: Like all clinical tools, FRAX has limitations that need to be considered, but the use of fracture risk in deciding who to treat, when to treat and what agent to use is a mechanism to target treatment equitably to those at an increased risk of fracture.

Purpose of review: Since the release of the 2022 Second International Workshop Evaluation and Management of Hypoparathyroidism Summary Statement and Guidelines, updates and advances are now available in the cause, complications, and treatment of adult chronic hypoparathyroidism (hypoPTH). This review aims to highlight these new findings and implications to patient care.

Recent findings: Postsurgical hypoparathyroidism remains the most common cause, immune-related hypoparathyroidism from checkpoint inhibitors is an emerging autoimmune cause. In a large retrospective cohort study of thyroidectomies, incident fracture was lower, particularly in the vertebra, in the hypoPTH cohort, compared with postthyroidectomy control group. Hypercalciuria increases risk for renal calculi in hypoPTH independent of disease duration and treatment dose. Quality of life is impaired in hypoPTH patients on conventional therapy, improvement was noted post-PTH replacement. TranCon PTH phase 3 RCT reported eucalcemia with reduced renal calcium excretion, normalization of bone turn-over markers, stable BMD and improved quality of life.

Summary: HypoPTH is a chronic disease associated with significant morbidity and poor Quality of Life. Awareness of treatment targets and follow-up investigations can alleviate patient anxiety regarding over-treatment and under-treatment. Progress in long-acting PTH replacement strategies might provide accessible, feasible alternatives to conventional therapy in brittle hypoPTH patients.

Purpose of review: Disturbances in mineral and bone metabolism occurring in osteoporosis and chronic kidney disease-associated osteoporosis place patients at high risk of fracture making these conditions a major public health concern. Due to the limited use of bone histomorphometry in clinical practice, the gold standard for assessing bone turnover, extensive efforts have been made to identify bone turnover markers (BTMs) as noninvasive surrogates. Since the identification of certain commonly used markers several decades ago, considerable experience has been acquired regarding their clinical utility in such bone disorders.

Recent findings: Mounting evidence suggested that BTMs represent a simple, low-risk, rapid and convenient way to obtain data on the skeletal health and that they may be useful in guiding therapeutic choices and monitoring the response to treatment.

Summary: BTMs could provide clinicians with useful information, independent from, and often complementary to bone mineral density (BMD) measurements. They have proven valuable for monitoring the effectiveness of osteoporosis therapy, as well as promising for discriminating low and high turnover states. Improved performance is observed when BTMs are combined, which may be useful for selecting treatments for chronic kidney disease-bone mineral disorders (CKD-MBD).

Purpose of review: Fibroblast growth factor 23 (FGF23) is a hormone to reduce blood phosphate concentration. Excessive actions of FGF23 induce FGF23-related hypophosphatemic disorders, such as X-linked hypophosphatemic rickets (XLH) and tumor-induced osteomalacia (TIO). We will summarize recent advances in the diagnosis and treatment of FGF23-related hypophosphatemic disorders.

Recent findings: The measurement of blood FGF23 is useful to make a diagnosis of FGF23-related hypophosphatemic disorders. It was reported that many patients with FGF23-related hypophosphatemic disorders, especially TIO, were misdiagnosed, therefore, it is necessary to enhance the awareness of these diseases. A novel method to inhibit excessive actions of FGF23 by a human monoclonal antibody for FGF23, burosumab, has been approved in several countries. In more long-term observation than clinical trials, burosumab has also been shown to improve biochemical abnormalities and symptoms of rickets/osteomalacia. Following these advances, several registries and consensus recommendations on FGF23-related hypophosphatemic disorders, especially XLH, have been established in each country or region.

Summary: Further long-term effects of burosumab and the precise mechanism of FGF23 overproduction in patients with FGF23-related hypophosphatemic disorders need to be clarified in the future studies.

Purpose of review: Familial hypercholesterolemia (FH) is an autosomal semi-dominant condition, characterized by excessive circulating low-density lipoprotein cholesterol (LDL-C) from birth that substantially accelerates the onset and progression of atherosclerotic cardiovascular disease (ASCVD), classically coronary artery disease (CAD). Elevated plasma LDL-C integrated over time is unequivocally the major determinant of ASCVD in heterozygous FH (HeFH); however, the wide variation in incidence and progression of ASCVD suggests a role for a wide spectrum of risk modifiers. We reviewed recent evidence describing the features of an ASCVD-free entity referred to as resilient FH among patients with HeFH.

Recent findings: Compared with nonresilient FH patients, resilient patients are more likely to be female, and have a lower prevalence of ASCVD comorbidities, higher levels of HDL-C and larger HDL particles, as well as a lower level of lipoprotein(a). A lower SAFEHEART risk score is also an independent predictor of resilient FH. Gene expression studies also demonstrate that resilient FH patients are associated with a less atherogenic gene expression profile in relation to HDL metabolism and immune responses, as reflected by higher expression of ABCA1 and ABCG1, and lower expression of STAT2 and STAT3, respectively.

Summary: A group of HeFH patients, referred as resilient FH, can survive to advance ages without experiencing any ASCVD events. Several key contributors to the event-fee CAD in HeFH patients have been identified. This could not only improve risk stratification and management for FH but also be of major importance for the general population in primary and secondary prevention. However, resilient FH remains an under-investigated area and requires further research.

Purpose of review: Potassium-competitive acid blockers (PCABs) represent a new class of compounds for the treatment of acid-related disorders. Recent FDA approval of the PCAB vonoprazan for erosive esophagitis has started an important new approach to acid-related disorders.

Recent findings: Compared to conventional proton pump inhibitors (PPIs), PCABs provide more rapid, potent, and sustained suppression of gastric acid with faster and more durable symptom relief. Studies have demonstrated the efficacy of PCABs for erosive esophagitis, nonerosive reflux disease, and peptic ulcer disease including H. pylori. However, the PCAB vonoprazan was only approved in the US as part of combination therapy for eradication of H. pylori. Clinical trials have now demonstrated noninferiority of vonoprazan to lansoprazole for treatment of erosive esophagitis, particularly noting superiority of vonoprazan in patients with severe esophagitis resulting in FDA approval of vonoprazan for treatment of erosive esophagitis. Emerging data suggests a possible utility of vonoprazan for PPI-resistant gastroesophageal reflux disease (GERD) and on-demand therapy for nonerosive reflux disease. Vonoprazan is generally well tolerated but long-term safety data is not well established.

Summary: The PCAB vonoprazan is a newly FDA approved treatment option for erosive esophagitis. Its possible role in PPI-resistant GERD and nonerosive reflux disease warrants further investigation.

Purpose of review: Metabolic and bariatric surgery (MBS) and endoscopic bariatric therapies (EBT) are being increasingly utilized for the management of obesity. They work through multiple mechanisms, including restriction, malabsorption, and changes in the gastrointestinal hormonal and motility.

Recent findings: Roux-en-Y gastric bypass (RYGB) and laparoscopic sleeve gastrectomy (LSG) cause decrease in leptin, increase in GLP-1 and PYY, and variable changes in ghrelin (generally thought to decrease). RYGB and LSG lead to rapid gastric emptying, increase in small bowel motility, and possible decrease in colonic motility. Endoscopic sleeve gastroplasty (ESG) causes decrease in leptin and increase in GLP-1, ghrelin, and PYY; and delayed gastric motility.

Summary: Understanding mechanisms of action for MBS and EBT is critical for optimal care of patients and will help in further refinement of these interventions.

Purpose of review: Various gut hormones interact with the brain through delicate communication, thereby influencing appetite and subsequent changes in body weight. This review summarizes the effects of gut hormones on appetite, with a focus on recent research.

Recent findings: Ghrelin is known as an orexigenic hormone, whereas glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), cholecystokinin (CCK), postprandial peptide YY (PYY), and oxyntomodulin (OXM) are known as anorexigenic hormones. Recent human studies have revealed that gut hormones act differently in various systems, including adipose tissue, beyond appetite and energy intake, and even involve in high-order thinking. Environmental factors including meal schedule, food contents and quality, type of exercise, and sleep deprivation also play a role in the influence of gut hormone on appetite, weight change, and obesity. Recently published studies have shown that retatrutide, a triple-agonist of GLP-1, GIP, and glucagon receptor, and orforglipron, a GLP-1 receptor partial agonist, are effective in weight loss and improving various metabolic parameters associated with obesity.

Summary: Various gut hormones influence appetite, and several drugs targeting these receptors have been reported to exert positive effects on weight loss in humans. Given that diverse dietary and environmental factors affect the actions of gut hormones and appetite, there is a need for integrated and largescale long-term studies in this field.