Metabolic Syndrome and its Correlates among Hypertensive Patients in Abuja, North Central Nigeria.

BACKGROUND: Metabolic syndrome is a constellation of abnormalities which includes central obesity, dyslipidaemia, elevated blood pressure and hyperglycemia. Hypertension, (which is a very common component of metabolic syndrome), and diabetes mellitus, are independently associated. Also, studies examining metabolic syndrome inAbuja, a city with affluence-driven lifestyle, are not available. This study aimed to investigate the prevalence of metabolic syndrome among hypertensive patients in Abuja, Nigeria, as well as to examine the associations between metabolic syndrome and certain factors in that cohort of hypertensive patients. METHODS: This was a retrospective study that used data from hypertensive patients who attended clinic over a period of five years. Eight hundred and fifty-eight, (858-combined), case files of pre-treated, (previously known hypertensive patients) and newly diagnosed hypertensive participants were used for the study. The student t-tests were used to compare continuous variables, while Chi-square (χ2) tests were used for relationship between qualitative variables. The likelihood ratio test was employed to further confirm the statistical significance of certain independent variables relating with metabolic syndrome. A P-value of < 0.05 was considered statistically significant. RESULTS: The mean ages were 48.70±12.18, 49.19±11.06 and 48.2±13.3 years for combined group, the pre-treated and the newly-diagnosed groups respectively. The pre-treated, group consists of those previously known hypertensive patients, while the new group consists of those who were newly diagnosed hypertensive patients and were treatment naïve. The prevalence of metabolic syndrome in this study was 45.5% in the combined group, 47.23% in the pre-treated group and 37.3% in the newly diagnosed group. The commonest component of metabolic syndrome was reduced high density lipoprotein cholesterol, HDL-C. CONCLUSION: Metabolic syndrome is prevalent among hypertensive patients in Abuja, Nigeria. Some correlates of metabolic syndrome include; elevated BMI, truncal obesity, elevated total cholesterol, the use of thiazide diuretics and beta blockers as antihypertensives.

CONTEXTE: Le syndrome métabolique est une constellation d'anomalies qui comprend l'obésité centrale, la dyslipidémie, l'élévation de la pression artérielle et l'hyperglycémie. L'hypertension, qui est un composant très courant du syndrome métabolique, et le diabète sucré sont indépendamment associés. De plus, des études examinant le syndrome métabolique à Abuja, une ville au mode de vie axé sur l'aisance, ne sont pas disponibles. Cette étude visait à enquêter sur la prévalence du syndrome métabolique parmi les patients hypertendus à Abuja, au Nigeria, ainsi qu'à examiner les associations entre le syndrome métabolique et certains facteurs dans cette cohorte de patients hypertendus. MÉTHODES: Il s'agissait d'une étude rétrospective utilisant des données de patients hypertendus ayant fréquenté la clinique sur une période de cinq ans. Huit cent cinquante-huit (858 - combinés) dossiers de cas de patients hypertendus préalablement traités (patients hypertendus connus) et nouvellement diagnostiqués ont été utilisés pour l'étude. Les tests t de Student ont été utilisés pour comparer les variables continues, tandis que les tests du chi-carré (χ2) ont été utilisés pour examiner la relation entre les variables qualitatives. Le test du rapport de vraisemblance a été utilisé pour confirmer davantage la signification statistique de certaines variables indépendantes liées au syndrome métabolique. Une valeur P < 0,05 était considérée comme statistiquement significative. RÉSULTATS: Les âges moyens étaient de 48,70 ± 12,18, 49,19 ± 11,06 et 48,21 ± 13,3 ans pour le groupe combiné, le groupe prétraité et le groupe nouvellement diagnostiqué, respectivement. La prévalence du syndrome métabolique dans cette étude était de 45,5% dans le groupe combiné, 47,23% dans le groupe prétraité et 37,3% dans le groupe nouvellement diagnostiqué. Le composant le plus courant du syndrome métabolique était une diminution du cholestérol lipoprotéique de haute densité, le HDL-C. CONCLUSION: Le syndrome métabolique est prévalent parmi les patients hypertendus àAbuja, au Nigeria. Certains corrélats du syndrome métabolique comprennent un IMC élevé, une obésité tronculaire, une augmentation du cholestérol total, l'utilisation de diurétiques thiazidiques et de bêta-bloquants comme antihypertenseurs. Mots-clés: Syndrome métabolique, corrélats, patients hypertendus, Abuja Nigeria.

Clinical practice guidelines for perioperative care in bariatric surgery 2023: Adapted ERAS (enhanced recovery after surgery) guidelines with consensual voting of the working group of the Joint Bariatric and Metabolic Surgery Section of the Czech Surgery .

INTRODUCTION: Currently, bariatric surgery is the most effective treatment for the morbid obesity. It provides sustained weight loss as well as demonstrated positive effects on obesity-related comorbidities. The number of procedures performed worldwide has seen a sharp increase in the past twenty years. Therefore, an effort has been developed to establish a consensus in perioperative care based on best evidence. METHODS: The working group of the Joint Bariatric and Metabolic Surgery Section of the Czech Surgery Society and Czech Society of Obesitology prepared clinical practice guidelines for the ERAS (enhanced recovery after surgery) concept in perioperative care in bariatric surgery. The working group based its guidelines on ERAS guidelines published in 2021. The working group adopted the original text and then adapted the text and added its comments to specific items as appropriate. Electronic voting of all members of the working group was the final phase, by which the strength of consensus was expressed with respect to individual elements of the guidelines. RESULTS: The Czech working group reached a consensus with ERABS (enhanced recovery after bariatric surgery) guidelines for most elements. The quality of evidence is low for some interventions of the ERAS protocol for bariatric surgery. Therefore, extrapolation from other surgeries and fields is needed for evidence-based practice. CONCLUSION: The guidelines are intended for clinical practice in bariatric surgery with the ERAS protocol based on updated evidence and guidelines. It is based on recent and comprehensive ERAS guidelines adopted and adapted by the Czech working group of the Joint Bariatric and Metabolic Surgery Section of the Czech Surgery Society and Czech Society of Obesitology. Some supplementations and specifications are reflected in comments added to the Czech version.

Baseline bone turnover marker levels can predict change in bone mineral density during antiresorptive treatment in osteoporotic patients: the Copenhagen bone turnover marker study.

Anti-resorptive osteoporosis treatment might be more effective in patients with high bone turnover. In this registry study including clinical data, high pre-treatment bone turnover measured with biochemical markers was correlated with higher bone mineral density increases. Bone turnover markers may be useful tools to identify patients benefitting most from anti-resorptive treatment. INTRODUCTION: In randomized, controlled trials of bisphosphonates, high pre-treatment levels of bone turnover markers (BTM) were associated with a larger increase in bone mineral density (BMD). The purpose of this study was to examine this correlation in a real-world setting. METHODS: In this registry-based cohort study of osteoporosis patients (n = 158) receiving antiresorptive therapy, the association between pre-treatment levels of plasma C-telopeptide of type I Collagen (CTX) and/or N-terminal propeptide of type I procollagen (PINP) and change in bone mineral density (BMD) at lumbar spine, total hip, and femoral neck upon treatment was examined. Patients were grouped according to their pre-treatment BTM levels, defined as values above and below the geometric mean for premenopausal women. RESULTS: Pre-treatment CTX correlated with annual increase in total hip BMD, where patients with CTX above the geometric mean experienced a larger annual increase in BMD (p = 0.008) than patients with CTX below the geometric mean. The numerical pre-treatment level of CTX showed a similar correlation at all three skeletal sites (total hip (p = 0.03), femoral neck (p = 0.04), and lumbar spine (p = 0.0003)). A similar association was found for PINP where pre-treatment levels of PINP above the geometric mean correlated with a larger annual increase in BMD for total hip (p = 0.02) and lumbar spine (p = 0.006). CONCLUSION: Measurement of pre-treatment BTM levels predicts osteoporosis patients' response to antiresorptive treatment. Patients with high pre-treatment levels of CTX and/or PINP benefit more from antiresorptive treatment with larger increases in BMD than patients with lower pre-treatment levels.

New options for surgeons to improve malnutrition in the outpatient setting.

Malnutrition is a significant negative factor for surgical patients in the entire perioperative period. However, this factor can be controlled and is easy to detect in the outpatient setting. Starting from May 1, 2020, surgeons have the possibility to prescribe sipping under certain conditions for a limited period of 4 weeks. Thereby they have become able to strongly impact any altered nutritional status both preoperatively and postoperatively. The authors describe scoring questionnaires used for the detection of malnutrition and required by health insurance companies. Additionally, prescribing conditions and potential mistakes in the outpatient setting are analysed.

Vertebral fracture assessment by DXA is inferior to X-ray in clinical severe osteoporosis.

UNLABELLED: Spine fractures are diagnosed by X-ray or vertebral fracture assessment (VFA) by dual-energy X-ray absorptiometry (DXA) scanning. The use of VFA evaluation by DXA is still debated. We demonstrate that VFA is inferior relative to X-ray in visualizing vertebrae properly in the upper spine and therefore with a reduced diagnostic performance in detecting fractures. INTRODUCTION: Vertebral fracture assessment (VFA) by DXA has been evaluated for many years, and its use in clinical practice is still debated. In a cross-sectional setting, we aimed to compare VFA with traditional radiography in vertebral fracture (VF) diagnosis in severe osteoporotic patient. METHODS: A total of 207 patients referred to the outpatient clinic for teriparatide treatment were screened, out of whom 35 (16.9 %) severe osteoporotic patients were identified (mean age 67.5 ± 11.3 years and median T-score -3.2 interquartile range (IQR) (-1.9 to -3.7). VF diagnosis was performed independently using VFA and X-ray in accordance with the semiquantitative (SQ) approach. The same technician performed the primary interpretation on both sets of images, after which a radiologist and an endocrinologist reviewed the evaluation for a conclusive judgement. RESULTS: In total, 180 radiographic fractures were detected, corresponding to 5.1 fractures per individual. Using VFA, 18.5 % of vertebrae were considered unreadable, compared to 2.0 % on X-ray. The accuracy of VFA in VF detection using X-ray as a reference resulted in sensitivity and specificity of 75.5 and 86.7 %, respectively. Sensitivity decreased from the lumbar to thoracic level. Nevertheless, VFA only identified fractures consistently between Th11 and L3. CONCLUSION: Our data, based on a severe osteoporotic population, demonstrate that VFA is inferior relative to X-ray in visualizing vertebrae properly in the upper spine, resulting in vertebrae not being assessable for analysis and a reduced diagnostic performance in detecting fractures. Improvements in DXA techniques are needed for it to be comparable with X-ray in VF diagnosis.

Epidemiology of forearm fractures in adults in Denmark: national age- and gender-specific incidence rates, ratio of forearm to hip fractures, and extent of surgical fracture repair in inpatients and outpatients.

UNLABELLED: National epidemiological studies of forearm fractures are scarce. We examined in- and outpatient rates in Denmark, including anatomical location, surgery, hospitalization ratio, recurrent fractures, and ratio of forearm to hip fractures. This may be useful for triangulation in countries with less detailed information. Rates were higher than previously estimated. INTRODUCTION: Despite a significant contribution to the overall burden of osteoporotic, nonvertebral fractures, relatively little information is available about age- and gender-specific incidence rates for many countries including Denmark. METHODS: We used national individual patient data on inpatient and outpatient treatment to calculate rates of forearm fractures, taking readmissions into account, with subtables for distal and proximal fractures. We also calculated ratios of forearm to hip fractures that may be useful when imputing forearm fracture rates from other administrative sources. In addition, we report the rates of hospital admission and the rates of surgical treatment, allowing readers to extrapolate from the number of admissions or surgical procedures to incidence rates, should their data sources be less comprehensive. RESULTS: Forearm fracture rates were 278 per 100,000 patient years in men aged 50+ and 1,110 per 100,000 in women aged 50+. The female to male incidence rate ratio was 4.0 for the age group 50+ but close to unity in persons aged 40 or under. Two thirds of patients were treated on an outpatient basis with little difference across age and gender strata. Four out of five fractures were treated conservatively. The rate of forearm fractures in Denmark was somewhat higher in both genders than recently imputed from hip fracture rates and were close to the rates previously reported in studies from Norway and Sweden. CONCLUSION: The rates of forearm fracture in Denmark are higher than previously estimated and very similar to the high risk reported from studies in Norway and Sweden.

[Cardiac and metabolic risk factors in severe mental disorders. Task of a prevention manager]. / Kardiale und metabolische Risikofaktoren bei schweren psychischen Erkrankungen. Aufgaben eines Präventionsmanagers.

People with severe mental disorders have a reduction in life expectancy of 13-30 % compared with the general population. This severe disadvantage is primarily due to an increased prevalence of cardiac and metabolic disorders, especially coronary heart disease (CHD) and type 2 diabetes mellitus and are the result of untoward health behavior characterized by smoking, low levels of physical activity and unhealthy dietary habits. Obesity, arterial hypertension and lipid disorders are also associated with this behavior and further increase the risk of CHD and type 2 diabetes. Thus, people with mental disorders constitute a population with a high risk of cardiovascular events. Appropriate measures for prevention and therapy are urgently indicated but rarely applied. This article presents new organizational structures to overcome this deficit with a prevention manager playing a central role in organizing and applying preventive and therapeutic care. Results from cardiology and diabetic medicine have shown the effectiveness of pooling this responsibility. The measure has the potential to reduce the increased mortality of people with severe mental disorders.

[Screening and prevention of diabetes]. / Diabetesscreening und -vorsorge.

A valid and efficient screening for individual diabetes risk is a highly welcomed tool in primary care and specialist medical practice. It is needed to detect early stages of diabetes risk and prediabetes and to start interventions that have the aim to prevent diabetes and also other chronic diseases from developing. The oral glucose tolerance test is the gold standard, but it is difficult to perform in an evidence-based manner in primary care. Furthermore, measuring fasting and 2-h postprandial glucose values detects only late stages of the pathophysiological development of type 2 diabetes. Interestingly, the 1-h glucose value is highly predictive of future diabetes risk, but is rarely used in primary care. Therefore, risk scores are commonly used to evaluate diabetes risk, but unfortunately, they generally do not mirror the relevance of increased risk due to the person's own lifestyle. Measuring waist circumference is another possibility, because the waist is directly associated with the amount of visceral fat, which again directly correlates with the pathophysiology of diabetes development. A further possibility is the EZSCAN™ technology. The EZSCAN™ is based on reverse iontophoresis, a new technology to detect very early forms of peripheral neuropathies, which are commonly associated with early diabetes risk stages. It is important to perform diabetes screening in a targeted manner, in both medical and paramedical environments, and it is mandatory to add targeted interventions, based on the screening evaluated diabetes risk.

Lipidomic profiling before and after Roux-en-Y gastric bypass in obese patients with diabetes.

Bariatric surgery is a well-established approach to improve metabolic disease in morbidly obese patients with high cardiovascular risk. The post-operative normalization of lipid metabolism has a central role in the prevention of future cardiovascular events. The aim of the present study therefore was to characterize changes of plasma lipidomic patterns, consisting of 229 lipid species of 13 lipid classes, 3 months after Roux-en-Y gastric bypass (RYGB) in morbidly obese patients with and without diabetes. RYGB resulted in a 15-32% decrease of body mass index, which was associated with a significant reduction of total cholesterol (TC, -28.3%; P=0.02), LDL-cholesterol (LDL-C, -26.8%; P=0.03) and triglycerides (TGs, -63.0%; P=0.05) measured by routine clinical chemistry. HDL-cholesterol remained unchanged. The effect of RYGB on the plasma lipidomic profile was characterized by significant decreases of 87 lipid species from triacylglycerides (TAGs), cholesterol esters (CholEs), lysophosphatidylcholines (LPCs), phosphatidylcholines (PCs), phosphatidylethanolamine ethers (PEOs), phosphatidylinositols (PIs) and ceramides (Cers). The total of plasma lipid components exhibited a substantial decline of 32.6% and 66 lipid species showed a decrease by over 50%. A direct correlation with HbA1C values could be demonstrated for 24 individual lipid species (10 TAG, three CholE, two LPC, one lysophosphatidylcholine ethers (LPCO) (LPC ether), one PC, two phosphatidylcholine ethers (PCO) and five Cer). Notably, two lipid species (TAG 58:5 and PEO 40:5) were inversely correlated with HbA1C. LPCO, as single whole lipid class, was directly related to HbA1C. These data indicate that RYGB-induced modulation of lipidomic profiles provides important information about post-operative metabolic adaptations and might substantially contribute to improvements of glycemic control. These striking changes in the human plasma lipidome may explain acute, weight independent and long-term effects of RYGB on the cardiovascular system, mental status and immune regulation.

Assessment of small C-fiber status for screening of oxidative stress in patients at risk of diabetes.

Oxidized LDL (oxLDL), anti-oxLDL antibody (anti-oxLDL) and paraoxonase (PON1) are increasingly being reported to be associated with diabetic atherosclerosis. Oxidative stress could affect also small C-fibers innervating the sweat glands even in prediabetes. Hence it could be hypothesized that sweat dysfunction may be a predictor of oxidative stress status for early detection of diabetes. Ezscan, a new device, has recently been developed to measure the sweat function. Therefore, this study was aimed to determine the relevance of this Ezscan method to identify impairment in oxidative stress parameters. Plasma levels of oxLDL and anti-oxLDL were measured by enzyme immunoassay and ELISA respectively. Small C-fiber status was assessed by measurement of hand and foot sweat function with the help of Ezscan device and subsequent calculation of a risk score. Out of 82 subjects recruited in this study, 38 had impaired glucose tolerance and 6 had newly diagnosed diabetes mellitus. Ezscan risk score was significantly (p=0.004) correlated with oxLDL/anti-oxLDL ratio (0.32). Area under the curve (AUC) of receiver operating characteristics (ROC) analysis for detection of oxLDL/anti-oxLDL ratio (>0.12) was 0.76. For an Ezscan risk score of 50%, the sensitivity and specificity were 68% and 71% respectively. After adjustment for age and BMI, PON1 activity showed significant difference among the 3 risk groups defined by Ezscan risk score. Based on these results it may be concluded that Ezscan could be a useful screening tool in daily practice to assess alterations in oxidative stress parameters in individuals at risk of developing diabetes.

Enhancing the effectiveness of diabetes self-management education: the diabetes literacy project.

Patient empowerment through self-management education is central to improving the quality of diabetes care and preventing Type 2 Diabetes. Although national programs exist, there is no EU-wide strategy for diabetes self-management education, and patients with limited literacy face barriers to effective self-management. The Diabetes Literacy project, initiated with the support of the European Commission, aims to fill this gap. The project investigates the effectiveness of diabetes self-management education, targeting people with or at risk of Type 2 Diabetes in the 28 EU Member States, as part of a comprehensive EU-wide diabetes strategy. National diabetes strategies in the EU, US, Taiwan, and Israel are compared, and diabetes self-management programs inventorized. The costs of the diabetes care pathway are assessed on a per person basis at national level. A comparison is made of the (cost)-effectiveness of different methods for diabetes self-management support, and the moderating role of health literacy, organization of the health services, and implementation fidelity of education programs are considered. Web-based materials are developed and evaluated by randomized trials to evaluate if interactive internet delivery can enhance self-management support for people with lower levels of health literacy. The 3-year project started in December 2012. Several literature reviews have been produced and protocol development and research design are in the final stages. Primary and secondary data collection and analysis take place in 2014. The results will inform policy decisions on improving the prevention, treatment, and care for persons with diabetes across literacy levels.

Association of P2X7 receptor polymorphisms with bone mineral density and osteoporosis risk in a cohort of Dutch fracture patients.

UNLABELLED: The P2X7 receptor is thought to be involved in bone physiology in a pro-osteogenic manner. Therefore, we examined associations between genetic variations in the P2X7 receptor gene and bone mineral density (BMD). We found an association between four non-synonymous polymorphism of the human P2X7 receptor and the risk of osteoporosis. INTRODUCTION: The purpose of this study was to determine whether genetic variation in the P2X7 receptor gene (P2RX7) is associated with decreased BMD and risk of osteoporosis in fracture patients. METHODS: Six hundred ninety women and 231 men aged≥50 years were genotyped for 15 non-synonymous P2RX7 SNPs. BMD was measured at the total hip, lumbar spine and femoral neck. RESULTS: Four non-synonymous SNPs were associated with BMD. The Ala348Thr gain-of-function polymorphism was associated with increased BMD values at the lumbar spine (p=0.012). Decreased hip BMD values were associated with two loss-of-function SNPs in the P2RX7, i.e., in subjects homozygous for the Glu496Ala polymorphism as well as in subjects carrying at least one variant allele of the Gly150Arg polymorphism (p=0.018 and p=0.011; respectively). In men, we showed that subjects either heterozygous or homozygous for the Gln460Arg gain-of-function polymorphism in the P2RX7 had a significantly 40% decrease in risk of a lower T-score value (OR=0.58 [95%CI, 0.33-1.00]). CONCLUSION: Thus, genetic aberrations of P2X7R function are associated with lower BMD and increased osteoporosis risk. Therefore, detection of non-synonymous SNPs within the P2RX7 might be useful for osteoporosis risk estimation at an early stage, potentially enabling better osteoporosis prevention and treatment.

Circulating very-low-density lipoprotein from subjects with impaired glucose tolerance accelerates adrenocortical cortisol and aldosterone synthesis.

Apart from their role in cardiovascular homeostasis and immunomodulation, aldosterone and cortisol are also implicated in the pathogenesis of insulin resistance and type 2 diabetes mellitus (T2DM). Furthermore, glycoxidative modifications of lipoproteins are increasingly recognized as an etiological factor for increased cardiovascular morbidity and mortality in prediabetic individuals. The causative relationship between in vivo lipoprotein modifications and steroidogenesis in subjects with impaired glucose tolerance (IGT), however, is not well defined. Therefore, we aimed to investigate the impact of in vivo modified lipoproteins on aldosterone and cortisol release from human adrenocortical H295R cells. Following an oral glucose tolerance test, 20 individuals with normal glucose tolerance (NGT) and 20 IGT subjects were randomly selected from the ongoing PRAEDIAS prevention study in our department. Cells were incubated for 24 h with lipoproteins isolated from NGT and IGT individuals and aldosterone and cortisol release was measured in the supernatants. VLDL induced a greater stimulating effect on adrenocortical aldosterone and cortisol release compared to HDL and LDL. Moreover, IGT-VLDL evoked a significantly higher effect (p<0.05) on hormone release than NGT-VLDL. Incubation of cells with in vitro modified lipoproteins and specific pharmacological inhibitors suggests that VLDL presumably recruits ERK1/2 as one of the downstream effectors of Jak-2. In summary, in vivo modified VLDL are able to promote prediabetic hormonal dysregulation by modulating adrenocortical steroidogenesis via Jak-2-ERK dependent pathway.

The European perspective of diabetes prevention: the need for individualization of diabetes prevention.

Over the last decade the situation for people with diabetes mellitus in Europe has changed significantly. The number of patients increases continuously, the age of diagnosis decreases and effective management grows to become a burden for European healthcare systems. In this situation numerous stakeholders try to develop concepts for innovative chronic care management as well as individualized and personalized diabetes management. A major focus is set to activities for early screening and prevention of the diabetes and associated diseases. The present article will give an overview about current achievements in European projects addressing the unmet needs in diabetes management and also to introduce undergoing projects in the field of diabetes prevention and care. Furthermore, the SweetSmart concept will be presented, which is the initiation of a strategy to individualize interventions for the prevention of diabetes and care management. In the current discussion about the management of health care resources it is important to have a strategic vision about a realistic future of innovative chronic care management.

Genetic variation in the gene encoding calpain-10 is associated with type 2 diabetes mellitus.

Type 2 or non-insulin-dependent diabetes mellitus (NIDDM) is the most common form of diabetes worldwide, affecting approximately 4% of the world's adult population. It is multifactorial in origin with both genetic and environmental factors contributing to its development. A genome-wide screen for type 2 diabetes genes carried out in Mexican Americans localized a susceptibility gene, designated NIDDM1, to chromosome 2. Here we describe the positional cloning of a gene located in the NIDDM1 region that shows association with type 2 diabetes in Mexican Americans and a Northern European population from the Botnia region of Finland. This putative diabetes-susceptibility gene encodes a ubiquitously expressed member of the calpain-like cysteine protease family, calpain-10 (CAPN10). This finding suggests a novel pathway that may contribute to the development of type 2 diabetes.

Clopidogrel and the risk of osteoporotic fractures: a nationwide cohort study.

OBJECTIVES: The P2Y(12) inhibitor clopidogrel inhibits platelet aggregation and is used in the treatment and prevention of coronary artery disease. It is widely used and, in combination with acetylsalicylic acid, is the standard of care for acute coronary syndrome and percutaneous coronary intervention. The mode of action of clopidogrel involves pathways that are important to the metabolic activity in bone cells, although to our knowledge whether P2Y(12) receptors are involved in the regulation of bone metabolism has not yet been investigated. Therefore, the objective of the present study was to investigate the association between clopidogrel use and risk of fractures. METHODS: We investigated the association between clopidogrel use and fracture incidence in a nationwide cohort study within the Danish population of approximately 5.3 million individuals. All patients who were prescribed clopidogrel during the years 1996-2008 were included in the study (n = 77 503), and three nonusers were randomly selected, matched for age and gender (n = 232 510), for each clopidogrel-treated subject. RESULTS: Treatment with clopidogrel was associated with both increased overall fracture risk and increased risk of osteoporotic fractures, especially in subjects with a treatment duration of more than 1 year. However, individuals with low exposure to clopidogrel (<0.01 defined daily dose) had a lower risk of fracture than never users. CONCLUSIONS: Use of the P2Y(12) inhibitor clopidogrel is associated with risk of fractures. There seems to be a biphasic relation so that lower doses are associated with decreased fracture risk, whereas higher doses (recommended dose range) are associated with increased risk. More studies are warranted to determine the potential in vivo effect of platelet aggregation inhibitors on bone metabolism.