ctDNA quantification improves estimation of outcomes in patients with high-grade osteosarcoma: a translational study from the OS2006 trial.

BACKGROUND: Osteosarcoma stratification relies on clinical parameters and histological response. We developed a new personalized stratification using less invasive circulating tumor DNA (ctDNA) quantification. PATIENTS AND METHODS: Plasma from patients homogeneously treated in the prospective protocol OS2006, at diagnosis, before surgery and end of treatment, were sequenced using low-passage whole-genome sequencing (lpWGS) for copy number alteration detection. We developed a prediction tool including ctDNA quantification and known clinical parameters to estimate patients' individual risk of event. RESULTS: ctDNA quantification at diagnosis (diagCPA) was evaluated for 183 patients of the protocol OS2006. diagCPA as a continuous variable was a major prognostic factor, independent of other clinical parameters, including metastatic status [diagCPA hazard ratio (HR) = 3.5, P = 0.002 and 3.51, P = 0.012, for progression-free survival (PFS) and overall survival (OS)]. At the time of surgery and until the end of treatment, diagCPA was also a major prognostic factor independent of histological response (diagCPA HR = 9.2, P < 0.001 and 11.6, P < 0.001, for PFS and OS). Therefore, the addition of diagCPA to metastatic status at diagnosis or poor histological response after surgery improved the prognostic stratification of patients with osteosarcoma. We developed the prediction tool PRONOS to generate individual risk estimations, showing great performance ctDNA quantification at the time of surgery and the end of treatment still required improvement to overcome the low sensitivity of lpWGS and to enable the follow-up of disease progression. CONCLUSIONS: The addition of ctDNA quantification to known risk factors improves the estimation of prognosis calculated by our prediction tool PRONOS. To confirm its value, an external validation in the Sarcoma 13 trial is underway.

Geographic variation in bone mineral density and prevalent fractures in the Canadian longitudinal study on aging.

Awareness of the prevalence of osteoporosis and fractures across jurisdictions can guide the development of local preventive programs and healthcare policies. We observed geographical variations in total hip bone mineral density and in the prevalence of major osteoporotic fractures across Canadian provinces, which persisted after adjusting for important covariates. PURPOSE: We aimed to describe sex-specific total hip bone mineral density (aBMD) and prevalent major osteoporotic fractures (MOF) variation between Canadian provinces. METHODS: We used baseline data from 21,227 Canadians (10,716 women, 10,511 men) aged 50-85 years in the Canadian Longitudinal Study on Aging (CLSA; baseline: 2012-2015). Linear and logistic regression models were used to examine associations between province of residence and total hip aBMD and self-reported MOF, stratified by sex. CLSA sampling weights were used to generate the prevalence and regression estimates. RESULTS: The mean (SD) age of participants was 63.9 (9.1) years. The mean body mass index (kg/m2) was lowest in British Columbia (27.4 [5.0]) and highest in Newfoundland and Labrador (28.8 [5.3]). Women and men from British Columbia had the lowest mean total hip aBMD and the lowest prevalence of MOF. Alberta had the highest proportion of participants reporting recent falls (12.0%), and Manitoba (8.4%) the fewest (p-value=0.002). Linear regression analyses demonstrated significant differences in total hip aBMD: women and men from British Columbia and Alberta, and women from Manitoba and Nova Scotia had lower adjusted total hip aBMD than Ontario (p-values<0.02). Adjusted odds ratios (95% confidence intervals, CI) for prevalent MOF were significantly lower in women from British Columbia (0.47 [95% CI: 0.32; 0.69]) and Quebec (0.68 [95% CI: 0.48; 0.97]) and in men from British Columbia (0.40 [95% CI:0.22; 0.71]) compared to Ontario (p-values<0.03). Results were similar when adjusting for physical performance measures and when restricting the analyses to participants who reported White race/ethnicity. CONCLUSION: Geographical variations in total hip aBMD and in the prevalence of MOF between provinces persisted after adjusting for important covariates which suggests an association with unmeasured individual and environmental factors.

Treatment-related fertility impairment in long-term female childhood, adolescent and young adult cancer survivors: investigating dose-effect relationships in a European case-control study (PanCareLIFE).

STUDY QUESTION: Which chemotherapeutic agents and body site-specific radiation fields are dose-dependently associated with an increased risk of fertility impairment in long-term female childhood, adolescent and young adulthood (CAYA) cancer survivors? SUMMARY ANSWER: Busulfan, lower abdominal radiotherapy (RT) and total body irradiation (TBI) seem to be associated with fertility impairment at any dose, whereas gonadotoxicity of melphalan and procarbazine is suggested at medium/high (>140 mg/m2) or high dose (>5600 mg/m2) therapy, respectively. WHAT IS KNOWN ALREADY: Several treatment-related fertility deficits, as assessed by both self-reported outcomes and hormonal markers are known to occur following treatment of CAYA cancer. However, knowledge regarding precise dose-related estimates of these treatment-related risks are scarce. STUDY DESIGN, SIZE, DURATION: The current case-control study was nested within the PanCareLIFE cohort study. In total, 1332 CAYA survivors from 8 countries, 9 institutions and 11 cohorts, participated in and contributed data to the study. PARTICIPANTS/MATERIALS, SETTING, METHODS: All participants were female 5-year CAYA cancer survivors. In total, 450 cases (fertility impaired survivors) and 882 matched controls (not fertility impaired survivors) were included. Fertility impairment was defined using both questionnaire data (primary or secondary amenorrhea; use of artificial reproductive techniques; unfulfilled wish to conceive) and hormonal data (FSH and anti-Müllerian hormone (AMH)). Multivariable logistic regression models were used to investigate the effect of (i) alkylating agent exposure, and (ii) dose categories for individual chemotherapeutic agents and for RT-exposed body sites. MAIN RESULTS AND THE ROLE OF CHANCE: A positive dose-effect relationship between cyclophosphamide equivalent dose (CED) score and fertility impairment was found, with survivors with a CED score > 7121 mg/m2 being at a significantly increased risk of fertility impairment (odds ratio (95% CI) = 2.6 (1.9-3.6) P < 0.001). Moreover, cumulative dose variables of the following treatments were significantly associated with fertility impairment: busulfan, carmustine, cyclophosphamide, melphalan, procarbazine, lower abdominal RT and TBI. Busulfan, lower abdominal RT and TBI seem to be associated with fertility impairment at any dose, whereas gonadotoxicity of melphalan and procarbazine is suggested at medium/high (>140 mg/m2) or high dose (>5600 mg/m2) therapy, respectively. LIMITATIONS, REASONS FOR CAUTION: Our study may have been subject to selection bias since data from about half of the original base cohorts were available for the current study. This could impact the generalizability of our study results. WIDER IMPLICATIONS OF THE FINDINGS: We identified survivors at high risk for fertility impairment and, consequently, for a reduced or even absent reproductive life span. Both girls and young women who are about to start anti-cancer treatment, as well as adult female survivors, should be counselled about future parenthood and referred to a reproductive specialist for fertility preservation, if desired. STUDY FUNDING/COMPETING INTEREST(S): This study has received funding from the European Union's Seventh Framework Programme for research, technological development and demonstration under grant agreement no. 602030. There are no competing interests. TRIAL REGISTRATION NUMBER: n/a.

Perioperative echocardiography-guided hemodynamic therapy in high-risk patients: a practical expert approach of hemodynamically focused echocardiography.

The number of high-risk patients undergoing surgery is growing. To maintain adequate hemodynamic functioning as well as oxygen delivery to the vital organs (DO2) amongst this patient population, a rapid assessment of cardiac functioning is essential for the anesthesiologist. Pinpointing any underlying cardiovascular pathophysiology can be decisive to guide interventions in the intraoperative setting. Various techniques are available to monitor the hemodynamic status of the patient, however due to intrinsic limitations, many of these methods may not be able to directly identify the underlying cause of cardiovascular impairment. Hemodynamic focused echocardiography, as a rapid diagnostic method, offers an excellent opportunity to examine signs of filling impairment, cardiac preload, myocardial contractility and the function of the heart valves. We thus propose a 6-step-echocardiographic approach to assess high-risk patients in order to improve and maintain perioperative DO2. The summary of all echocardiographic based findings allows a differentiated assessment of the patient's cardiovascular function and can thus help guide a (patho)physiological-orientated and individualized hemodynamic therapy.

[Perioperative optimization using hemodynamically focused echocardiography in high-risk patients-A practice guide]. / Perioperative Optimierung mittels auf die Hämodynamik fokussierter Echokardiographie bei Hochrisikopatienten ­ eine Praxisanleitung.

BACKGROUND: The number of high-risk patients undergoing surgery is steadily increasing. In order to maintain and, if necessary, optimize perioperative hemodynamics as well as the oxygen supply to the organs (DO2) in this patient population, a timely assessment of cardiac function and the underlying pathophysiological causes of hemodynamic instability is essential for the anesthesiologist. A variety of hemodynamic monitoring procedures are available for this purpose; however, due to method-immanent limitations they are often not able to directly identify the underlying cause of cardiovascular impairment. OBJECTIVE: To present a stepwise algorithm for a perioperative echocardiography-based hemodynamic optimization in noncardiac surgery high-risk patients. In this context, echocardiography on demand according to international guidelines can be performed under certain conditions (hemodynamic instability, nonresponse to hemodynamic treatment) as well as in the context of a planned intraoperative procedure, mostly as a transesophageal echocardiography. METHODS AND RESULTS: Hemodynamically focused echocardiography as a rapidly available bedside method, enables the timely diagnosis and assessment of cardiac filling obstructions, volume status and volume response, right and left heart function, and the function of the heart valves. CONCLUSION: Integrating all echocardiographic findings in a differentiated assessment of the patient's cardiovascular function enables a (patho)physiologically oriented and individualized hemodynamic treatment.

Testing a theoretical model of imminent fracture risk in elderly women: an observational cohort analysis of the Canadian Multicentre Osteoporosis Study.

We examined the underlying relationship between fracture risk factors and their imminent risk. Results suggested that having past year fracture, worse past year general health, worse past year physical functioning, and lower past year BMD T-score directly predicted higher imminent fracture risk. Past year falls indirectly predicted imminent risk through physical functioning and general health. INTRODUCTION: This study aimed to examine direct and indirect effects of several factors on imminent (1 year) fracture risk. METHODS: Data from women age 65 and older from population-based Canadian Multicentre Osteoporosis Study were used. Predictors were identified from study years 5 and 10, and imminent fracture data (1-year fracture) came from years 6 and 11 (year 5 predicts year 6, year 10 predicts year 11). A structural equation model (SEM) was used to test the theoretical construct. General health and physical functioning were measured as latent variables using items from the 36-Item Short Form Health Survey (SF-36) and bone mineral density (BMD) T-score was a latent variable based on observed site-specific BMD data (spine L1-L4, femoral neck, total hip). Observed variables were fractures and falls. Model fit was evaluated using root mean square error of approximation (RMSEA), Tucker Lewis index (TLI), and comparative fit index (CFI). RESULTS: The analysis included 3298 women. Model fit tests showed that the SEM fit the data well; χ2(172) = 1122.10 < .001, RMSEA = .03, TLI = .99, CFI = .99. Results suggested that having past year fracture, worse past year general health, worse past year physical functioning, and lower past year BMD T-score directly predicted higher risk of fracture in the subsequent year (p < .001). Past year falls had a statistically significant but indirect effect on imminent fracture risk through physical functioning and general health (p < .001). CONCLUSIONS: We found several direct and indirect pathways that predicted imminent fracture risk in elderly women. Future studies should extend this work by developing risk scoring methods and defining imminent risk thresholds.

[Elective tracheostomy in COVID-19 patients: experience with a standardized interdisciplinary approach]. / Elektive Tracheostomie bei COVID-19-Patienten ­ Erfahrungen mit einem standardisierten interdisziplinären Vorgehen.

Experience with an interdisciplinary SOP (standard operating procedure) for tracheostomy (TS) in COVID-19 patients, taking into account the general national and international recommendations, is reported. The operative timing of TS due to prolonged invasive ventilation and frustrating weaning attempts was determined on an interdisciplinary level and involved phases of both high and low disease activity. Five TS were performed in patients with an average age of 70.6 years. In addition to the standard COVID-19 protective measures for medical staff to avoid nosocomial COVID-19 infection, SOP-supported communication during the TS leads to periprocedural safety for all involved. COVID-19 infections among medical staff in the departments involved are not yet known.

Longitudinal assessment of health-related quality of life in osteoporosis: data from the population-based Canadian Multicentre Osteoporosis Study.

Little is known about the association between health-related quality of life (HRQOL) and osteoporosis in the absence of fracture, and how HRQOL may change over time. This study provides evidence of substantially reduced HRQOL in women and men with self-reported and/or BMD-confirmed osteoporosis, even in the absence of fragility fracture. INTRODUCTION: Fragility fractures have a detrimental effect on the health-related quality of life (HRQOL) of those with osteoporosis. Less is known about the association between HRQOL and osteoporosis in the absence of fracture. METHODS: Canadian Multicentre Osteoporosis Study participants completed the SF-36, a detailed health questionnaire and measures of bone mineral density (BMD) at baseline and follow-up. We report the results of participants ≥ 50 years with 10-year follow-up. Self-reported osteoporosis at baseline and BMD-based osteoporosis at follow-up were ascertained. Multivariable linear regression models were developed for baseline SF-36 domains, component summaries, and change over time, adjusting for relevant baseline information. RESULTS: Baseline data were available for 5266 women and 2112 men. Women in the osteoporosis group had substantially lower SF-36 baseline scores, particularly in the physically oriented domains, than those without osteoporosis. A similar but attenuated pattern was evident for the men. After 10-year follow-up (2797 women and 1023 men), most domain scores dropped for women and men regardless of osteoporosis status, with the exception of mentally-oriented ones. In general, a fragility fracture was associated with lower SF-36 scores and larger declines over time. CONCLUSIONS: This study provides evidence of substantially reduced HRQOL in women and men with self-reported and/or BMD-confirmed osteoporosis, even in the absence of fragility fracture. HRQOL should be thoroughly investigated even prior to fracture, to develop appropriate interventions for all stages of the disease.

Mortality risk reduction differs according to bisphosphonate class: a 15-year observational study.

In this prospective cohort of 6120 participants aged 50+, nitrogen-bisphosphonates but not non-nitrogen bisphosphonates were associated with a significant 34% mortality risk reduction compared to non-treated propensity score matched controls. These findings open new avenues for research into mechanistic pathways. INTRODUCTION: Emerging evidence suggests that bisphosphonates (BP), first-line treatment of osteoporosis, are associated with reduced risks for all-cause mortality. This study aimed to determine the association between different BP types and mortality risk in participants with or without a fracture. METHODS: A prospective cohort study of users of different BPs matched to non-users by propensity score (age, gender, co-morbidities, fragility fracture status) and time to starting the BP medication from the population-based Canadian Multicentre Osteoporosis Study from nine Canadian centres followed from 1995 to 2013. Mortality risk for bisphosphonate users vs matched non-users was assessed using pairwise multivariable Cox proportional hazards models. RESULTS: There were 2048 women and 308 men on BP and 1970 women and 1794 men who did not receive medication for osteoporosis. The relationship between BP and mortality risk was explored in three separate 1:1 propensity score-matched cohorts of BP users and no treatment (etidronate, n = 599, alendronate, n = 498, and risedronate n = 213). Nitrogen BP (n-BP) (alendronate and risedronate) was associated with lower mortality risks [pairwise HR, 0.66 (95% CI, 0.48-0.91)] while the less potent non-n-BP, etidronate, was not [pairwise HR: 0.89 (95% CI, 0.66-1.20)]. A direct comparison between n-BP and etidronate (n = 340 pairs) also suggested a better survival for n-BP [paired HR, 0.47 (95%CI, (95% CI, 031-0.70)] for n-BP vs. etidronate]. CONCLUSION: Compared to no treatment, nitrogen but not non-nitrogen bisphosphonates appear to be associated with better survival.

Clostridium difficile infection is associated with graft loss in solid organ transplant recipients.

Clostridium difficile infection (CDI) is a leading cause of infectious diarrhea in solid organ transplant recipients (SOT). We aimed to assess incidence, risk factors, and outcome of CDI within the Swiss Transplant Cohort Study (STCS). We performed a case-control study of SOT recipients in the STCS diagnosed with CDI between May 2008 and August 2013. We matched 2 control subjects per case by age at transplantation, sex, and transplanted organ. A multivariable analysis was performed using conditional logistic regression to identify risk factors and evaluate outcome of CDI. Two thousand one hundred fifty-eight SOT recipients, comprising 87 cases of CDI and 174 matched controls were included. The overall CDI rate per 10 000 patient days was 0.47 (95% confidence interval ([CI] 0.38-0.58), with the highest rate in lung (1.48, 95% CI 0.93-2.24). In multivariable analysis, proven infections (hazard ratio [HR] 2.82, 95% CI 1.29-6.19) and antibiotic treatments (HR 4.51, 95% CI 2.03-10.0) during the preceding 3 months were independently associated with the development of CDI. Despite mild clinical presentations, recipients acquiring CDI posttransplantation had an increased risk of graft loss (HR 2.24, 95% CI 1.15-4.37; P = .02). These findings may help to improve the management of SOT recipients.

Impact of electronic reminder systems on hepatitis C screening in primary care.

Screening for hepatitis C virus (HCV) was recommended in 2012 by the Centers for Disease Control (CDC) for the population born between 1946 and 1965. Reminder systems are effective at promoting HCV screening, but the yield of positive tests among various population subgroups and the linkage to specialty HCV treatment is not well understood. We sought to determine: (i) the effect of the CDC recommendation alone, and the effect of an electronic medical record (EMR) reminder on the proportion of the population screened; (ii) the yield of positive HCV tests as screening strategies have evolved, and according to a patient's history of serum aminotransferase testing; (iii) the proportion of positive cases followed up for HCV treatment. This retrospective cohort study included 60 000 primary care patients at a northeast US academic medical centre serving an urban and rural population in which an EMR reminder was instituted in 2014. Results demonstrated an increase in proportion tested for HCV from 12% prior to the CDC recommendation to 37% after the reminder system. The yield of positive HCV antibody (HCV Ab) tests decreased from 7% in the "case-finding" era to 1.6% after the EMR reminder prompted screening of a lower risk population (P < .001). Patients with a history of abnormal aminotransferase tests had a fivefold higher rate of positive HCV Ab testing (6.7% vs 1.5%, P < .001). Ninety per cent of patients with confirmed HCV infection were seen in specialty care.

Calcium pyrophosphate deposition disease: a frequent finding in patients with long-standing erosive gout.

OBJECTIVE: To characterize patients with both monosodium urate (MSU) and calcium pyrophosphate (CPP) crystals in their synovial fluid (SF). METHOD: Forty-nine gout patients with acute arthritis were included. Those patients with MSU crystals only in their SF were compared to those patients with both MSU and CPP crystals in their SF. RESULTS: A total of 36 out of 49 patients (73.5%) had only MSU crystals, whereas 13 out of 49 (26.5%) had both MSU and CPP crystals in their SF. Co-deposition of CPP crystals was associated with long-standing gout disease (p = 0.022), kidney dysfunction (p = 0.024), and erosive arthritis (p = 0.049), but not with age. CONCLUSION: Long-standing gout may be a risk factor for CPP deposition disease, and the frequency of CPP co-deposition may be higher than expected.

Epidemiology, risk factors and outcomes of invasive aspergillosis in solid organ transplant recipients in the Swiss Transplant Cohort Study.

BACKGROUND: There is lack of recent multicenter epidemiological data on invasive aspergillosis (IA) among solid organ transplant recipient (SOTr) in the mold-acting antifungal era. We describe the epidemiology and outcomes of IA in a contemporary cohort of SOTr using the Swiss Transplant Cohort Study. METHODS: All consecutive SOTr with proven or probable IA between 01.05.2008 and 31.12.2014 were included. A case-control study to identify IA predictors was performed: 1-case was matched with 3-controls based on SOT type, transplant center, and time post-SOT. RESULTS: Among 2868 SOTr, 70 (2.4%) patients were diagnosed with proven (N: 30/70, 42.9%) or probable (N: 40/70, 57.1%) IA. The incidence of IA was 8.3%, 7.1%, 2.6%, 1.3%, and 1.2% in lung, heart, combined, kidney, and liver transplant recipients, respectively, Galactomannan immunoassay was positive in 1/3 of patients tested. Only 33/63 (52.4%) of patients presented with typical pulmonary radiographic findings. Predictors of IA included: renal insufficiency, re-operation, and bacterial and viral infections. 12-week mortality was higher in liver (85.7%, 6/7) compared to other (15.9%, 10/63; P < .001) SOTr. CONCLUSIONS: Invasive aspergillosis remains a rare complication post-SOT, with atypical radiographic presentations and low positivity rates of biomarkers posing significant diagnostic challenges. Although overall mortality has decreased in SOTr, it remains high in liver SOTr.

[Bachmann bundle pacing]. / Bachmann-Bündel-Pacing.

In pacemaker and ICD therapy, atrial leads are usually implanted in the right atrial appendage (RAA). This is easy but associated with a risk of negative hemodynamic and electrophysiological effects. Atrial depolarization, atrial contraction, and atrioventricular conduction can be delayed and desynchronized by RAA pacing leading to atrial fibrillation, pacing-induced long first-degree AV block, right ventricular pacing and the development of heart failure. High-septal atrial pacing near Bachmann's bundle that connects the right and left atrium can prevent the negative effects of RAA pacing and synchronize atrial excitation as demonstrated by the shortening of the PQ time and P wave duration during Bachmann bundle pacing. This review presents techniques to implant atrial leads at Bachmann's bundle. Apart from fluoroscopy in left anterior oblique projection, no additional effort compared to RAA implantation is required. Clinical studies on Bachmann bundle pacing are sparse; our own results suggest beneficial effects in patients with sick sinus syndrome and paroxysmal atrial fibrillation who receive atrial pacing for ≥50% of the time. Bachmann bundle pacing represents an interesting and simple option for atrial pacing. It is desirable to make this technique known to a wider spectrum of implanters and to generate more data on its clinical potential.

A part-declared blind testing program in firearms examination.

In 2015 and 2016 the Central Unit of the Dutch National Police created and submitted 21 cartridge case comparison tests as real cases to the Netherlands Forensic Institute (NFI), under supervision of the University of Twente (UT). A total of 53 conclusions were drawn in these 21 tests. For 31 conclusions the underlying ground truth was "positive", in the sense that it addressed a cluster of cartridge cases that was fired from the same firearm. For 22 conclusions the ground truth was "negative", in the sense that the cartridge cases were fired from different firearms. In none of the conclusions, resulting from examinations under casework conditions, misleading evidence was reported. All conclusions supported the hypothesis reflecting the ground truth. This article discusses the design and results of the tests in more detail.

Low immunoglobulin E flags two distinct types of immune dysregulation.

During the last two decades, hyper-immunoglobulin (Ig)E syndromes have been characterized clinically and molecularly in patients with genetically determined primary immunodeficiencies. However, the detection of low IgE levels, defined here as below detection limit in the routine clinical immunology laboratory, has received little attention. We analysed the association of serum IgA, IgM and IgG levels (including IgG subclasses) with low, normal or high serum IgE levels in patients evaluated in a single-centre out-patient immunodeficiency and allergy clinic. The correlation of serum IgE levels with IgG subclasses depended on the clinical phenotype. In patients with immunodeficiencies, IgE correlated with IgG2 and IgG4 but not with IgG3. In contrast, in patients referred for signs of allergy, IgE correlated with IgG3 but not with IgG2. A low IgE result was associated with low IgG3 and IgG4 in allergy referrals, while immunodeficiency referrals with a low IgE result had significantly lower IgG1, IgG2 and IgG4 levels. Hierarchical clustering of non-IgE immunoglobulin profiles (IgM, IgA, IgG, IgG1-4) validated that non-IgE immunoglobulin levels predict the clinic referral, i.e. phenotype, of low-IgE patients. These results suggesto guide the clinical management of patients with low serum IgE levels.

The association between sclerostin and incident type 2 diabetes risk: a cohort study.

OBJECTIVE: To determine whether sclerostin is associated with fasting glucose, insulin levels, insulin resistance or increased risk of incident type 2 diabetes. BACKGROUND: Type 2 diabetic patients have a higher risk of fractures. Recent studies suggest sclerostin, a regulator of osteoblast activity, is associated with diabetes. MATERIALS AND METHODS: Sclerostin levels were obtained from 1778 individuals with no history of type 2 diabetes participating in the population-based Canadian Multicentre Osteoporosis Study (CaMos) cohort. Participants were followed until diagnosis of type 2 diabetes, death or end of the study period (31 December 2013). The relationship of sclerostin with fasting glucose, insulin levels and homoeostatic model assessment-insulin resistance (HOMA-IR) was studied in linear regression models. Cox proportional hazards models were used to determine the association of sclerostin levels and the risk of incident type 2 diabetes during a mean 7·5 years of follow-up. RESULTS: Fasting glucose, fasting insulin levels and HOMA-IR were weakly correlated with sclerostin levels (Spearman's correlation coefficient: 0·11, P < 0·05; -0·09, P < 0·05; and -0·07, P = 0·02, respectively). Multiple linear regression analyses confirmed a significant association between sclerostin and fasting insulin and HOMA-IR but no significant association with fasting glucose levels. Sclerostin levels were not found to be significantly associated with the risk of incident type 2 diabetes (HR: 1·30; 95% CI: 0·37-4·57). CONCLUSIONS: We observed an association between sclerostin levels with fasting insulin levels and HOMA-IR, but there was no clear association with type 2 diabetes risk. Further studies are needed to understand the role of sclerostin in type 2 diabetes.