Stevioside Ameliorates Palmitic Acid-Induced Abnormal Glucose Uptake via the PDK4/AMPK/TBC1D1 Pathway in C2C12 Myotubes.

BACKGROUND: Stevioside (SV) with minimal calories is widely used as a natural sweetener in beverages due to its high sweetness and safety. However, the effects of SV on glucose uptake and the pyruvate dehydrogenase kinase isoenzyme (PDK4) as an important protein in the regulation of glucose metabolism, remain largely unexplored. In this study, we used C2C12 skeletal muscle cells that was induced by palmitic acid (PA) to assess the effects and mechanisms of SV on glucose uptake and PDK4. METHODS: The glucose uptake of C2C12 cells was determined by 2-NBDG; expression of the Pdk4 gene was measured by quantitative real-time PCR; and expression of the proteins PDK4, p-AMPK, TBC1D1 and GLUT4 was assessed by Western blotting. RESULTS: In PA-induced C2C12 myotubes, SV could significantly promote cellular glucose uptake by decreasing PDK4 levels and increasing p-AMPK and TBC1D1 levels. SV could promote the translocation of GLUT4 from the cytoplasm to the cell membrane in cells. Moreover, in Pdk4-overexpressing C2C12 myotubes, SV decreased the level of PDK4 and increased the levels of p-AMPK and TBC1D1. CONCLUSION: SV was found to ameliorate PA-induced abnormal glucose uptake via the PDK4/AMPK/TBC1D1 pathway in C2C12 myotubes. Although these results warranted further investigation for validation, they may provide some evidence of SV as a safe natural sweetener for its use in sugar-free beverages to prevent and control T2DM.

Effect of steviol glycosides as natural sweeteners on glucose metabolism in adult participants.

Steviol glycosides (SGs) are recognized as safe natural sweeteners; however, evidence from randomized controlled trials (RCTs) showed an inconclusive effect of SGs on glucose metabolism in adult participants. We aimed to conduct a systematic review and meta-analysis of RCTs to assess the effect of SGs on glucose metabolism. We systematically searched PubMed, Web of Science and EMBASE to include eligible RCTs. Our primary outcomes were differences between SGs and the control group with respect to changes in blood glucose from the baseline to the end of intervention (including fasting blood glucose [FBG], and HbA1c measurements). A random-effects meta-analysis was conducted for data synthesis to calculate the pooled mean difference (MD). There were twelve RCTs included for analyses with a total of 871 participants (48% females). A significant effect of SGs on FBG (MD = -4.10 mg dl-1, 95% CI -6.55 to -1.65) was found, while no significant difference in HbA1c (MD = 0.01%, 95% CI -0.12% to 0.13%) was observed between SGs and controls. The whole quality of evidence was rated as low. Subgroup analyses demonstrated favorable effects of SGs on FBG in participants aged ≤50 years, those without diabetes mellitus (DM) or hypertension at the baseline, and overweight and obese adults. Sensitivity analyses yielded results largely similar to the main findings. To conclude, SGs are found to produce significant improvement in glucose metabolism in adult participants when compared with the control. More evidence is required to further clarify and support the benefit of SGs as a sugar substitute for glucose metabolism.

Relationship between trajectories of dietary iron intake and risk of type 2 diabetes mellitus: evidence from a prospective cohort study.

BACKGROUND: The association between dietary iron intake and the risk of type 2 diabetes mellitus (T2DM) remains inconsistent. In this study, we aimed to investigate the relationship between trajectories of dietary iron intake and risk of T2DM. METHODS: This study comprised a total of 61,115 participants without a prior T2DM from the UK Biobank database. We used the group-based trajectory model (GBTM) to identify different dietary iron intake trajectories. Cox proportional hazards models were used to evaluate the relationship between trajectories of dietary iron intake and risk of T2DM. RESULTS: During a mean follow-up of 4.8 years, a total of 677 T2DM events were observed. Four trajectory groups of dietary iron intake were characterized by the GBTM: trajectory group 1 (with a mean dietary iron intake of 10.9 mg/day), 2 (12.3 mg/day), 3 (14.1 mg/day) and 4 (17.6 mg/day). Trajectory group 3 was significantly associated with a 38% decreased risk of T2DM when compared with trajectory group 1 (hazard ratio [HR] = 0.62, 95% confidence interval [CI]: 0.49-0.79), while group 4 was significantly related with a 30% risk reduction (HR = 0.70, 95% CI: 0.54-0.91). Significant effect modifications by obesity (p = 0.04) and history of cardiovascular disease (p < 0.01) were found to the relationship between trajectories of dietary iron intake and the risk of T2DM. CONCLUSIONS: We found that trajectories of dietary iron intake were significantly associated with the risk of T2DM, where the lowest T2DM risk was observed in trajectory group 3 with a mean iron intake of 14.1 mg/day. These findings may highlight the importance of adequate dietary iron intake to the T2DM prevention from a public health perspective. Further studies to assess the relationship between dietary iron intake and risk of T2DM are needed, as well as intervention studies to mitigate the risks of T2DM associated with dietary iron changes.

Remnant cholesterol and risk of premature mortality: An analysis from a nationwide prospective cohort study.

AIMS: To explore the relationship between remnant cholesterol (RC) and risk of premature mortality as well as life expectancy in the general population. METHODS: We included a total of 428,804 participants from the UK Biobank for analyses. Equivalent population percentiles approach based on the low-density lipoprotein cholesterol (LDL-C) cut-off points was performed to categorize participants into three RC groups: low (with a mean RC of 0.34 mmol/L), moderate (0.53 mmol/L), and high (1.02 mmol/L). We used multivariable Cox proportional hazards models to evaluate the relationship between RC groups and risk of premature mortality (defined as death before age 75 years). Life table methods were used to estimate life expectancy by RC groups. RESULTS: During a median follow-up of 12.1 years (Q1 - Q3: 11.0 - 13.0), there were 23,693 all-cause premature deaths documented with an incidence of 4.83 events per 1,000 person-years (95% confidence interval [CI]: 4.77 - 4.89). Compared with low RC group, the moderate RC group was associated with a 9% increased risk of all-cause premature mortality (hazard ratio [HR] = 1.09, 95% CI: 1.05 - 1.14), while the high RC group had an 11% higher risk (HR = 1.11, 95% CI: 1.07 - 1.16). At the age of 50 years, high RC group was associated with an average 2.2 lower years of life expectancy for females, and an average 0.1 lower years of life expectancy for males when compared to their counterparts in low RC group. CONCLUSIONS: Elevated RC was significantly related to increased risk of premature mortality and reduced life expectancy. Premature death in the general population would benefit from measurement to aid risk stratification and proactive management of RC to improved cardiovascular risk prevention efforts.

Effects of glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors on cardiovascular and kidney outcomes in Asian versus White patients with type 2 diabetes mellitus.

BACKGROUND: The study aimed to assess the treatment effects of the two medications on cardiovascular and kidney outcomes in Asian compared with White patients with type 2 diabetes mellitus (T2DM). METHODS: MEDLINE, EMBASE, and CENTRAL were searched up to October 31, 2022. We included the trials that assessed the effects of glucagon-like peptide-1 receptor agonists (GLP-1 RA) or sodium-glucose cotransporter-2 inhibitors (SGLT2i) versus placebo in Asian and White patients with T2DM on major adverse cardiovascular events (MACE) and kidney outcomes. The Bucher method was used to perform an indirect comparison for estimating the differences in treatment effects of GLP-1 RA and SGLT2i between Asian versus White patients. Interaction tests were also performed for treatment-by-race to assess the potential effect modification by race. RESULTS: We included 22 publications from 13 randomized trials. For MACE, there were no differences in treatment effects of GLP-1 RA (HR = 0.84, 95% CI: 0.68-1.04) or SGLT2i (HR = 0.90, 95% CI: 0.72-1.13) in Asian versus White patients. No differences in treatment effects of SGLT2i on kidney outcomes in Asian versus White patients were found (HR = 1.01, 95% CI: 0.75-1.36). There was no significant effect modification by race on cardiovascular and kidney outcomes. CONCLUSIONS: There were no significant differences in treatment effects of GLP-1 RA or SGLT2i for MACE between Asian and White patients with T2DM. Likewise, no significant differences in treatment effects of SGLT2i on kidney outcomes were found between Asian and White patients.

Relationship between obesity severity, metabolic status and cardiovascular disease in obese adults.

BACKGROUND: Evidence about the associations between obesity severity, metabolic status and risk of incident cardiovascular disease (CVD) in adults with obesity remains limited. METHODS: The study included 109,301 adults with obesity free of prior CVD based on the UK Biobank cohort. Metabolic status was categorized into metabolically healthy obesity (MHO; free of hypertension, hypercholesterolemia and diabetes) and metabolically unhealthy obesity (MUO). Obesity severity was classified into three levels: class I (body mass index of 30.0-34.9 kg/m2 ), II (35.0-39.9) and III (≥40.0). Cox proportional hazards models were used for analyses. RESULTS: There were 8059 incident CVD events during a median follow-up of 8.1 years. MUO was significantly associated with a 74% increased CVD risk compared with MHO (HR = 1.74, 95% CI: 1.62-1.83). There was a significant interaction between obesity severity and metabolic status on an additive scale regarding CVD risk. When taking class I obesity as reference, class II was nonsignificantly associated with an increased risk of CVD in the MHO group (HR = 1.07, 95% CI: 0.90-1.27), while class III was significantly related to increased risks of CVD (HR = 1.48, 95% CI: 1.12-1.96). In the MUO group, both classes II and III were significantly related to increased risks of CVD. Significant subgroup effects of age (p = .009) and sex (p = .047) were observed among participants with MUO but not in the MHO group. CONCLUSIONS: Both elevated obesity severity and MUO were significantly associated with increased risks of CVD in adults with obesity, while metabolic status could modify the relationship between obesity severity and CVD risk. More research is needed to further clarify the relationship.

Racial and ethnic subgroup reporting in diabetes randomized controlled trials published from 2000 to 2020: A survey.

BACKGROUND: It remained unknown about the status of and trends in racial/ethnic subgroup reporting in the diabetes trials over the past two decades. OBJECTIVES: In this survey, we aimed to evaluate the current state of and temporal trends in subgroup reporting by race/ethnicity regarding the effects of interventions in diabetes randomized controlled trials (RCTs) from year 2000-2020 and to explore the potential trial factors in relation to racial/ethnic subgroup reporting. METHODS: We searched electronic databases for eligible diabetes RCTs. The outcome was whether the trials had the event of racial/ethnic subgroup reporting regarding the intervention effects on trial primary outcomes. Poisson regression was used to assess the temporal trends in racial/ethnic subgroup reporting, and univariable logistic regression models were employed for evaluating trial factors related to racial/ethnic subgroup reporting. RESULTS: A total of 405 diabetes RCTs were eligible for inclusion. There were 26 (6.42%) trials with racial/ethnic subgroup reporting. A chronological trend towards increased rates of racial/ethnic subgroup reporting was observed; however, the trend was not statistically significant (p = 0.07). Advanced patients' age (Odds ratio [OR] = 2.92, 95% confidence interval [CI]: 1.24-6.88), follow-up duration (OR = 3.53, 95% CI: 1.13-11.00), and BIPOC (Black, Indigenous, and People of Colour) enrolment (OR = 2.39, 95% CI: 1.01-5.62) were found to positively relate with racial/ethnic subgroup reporting, while the industrial funding was associated with decreased reporting (OR = 0.43, 95% CI: 0.19-0.97). Less than one fourth of the trials with racial/ethnic subgroup reporting predefined the subgroup analysis. CONCLUSIONS: The majority of diabetes RCTs did not report intervention effects by racial/ethnic subgroup, which was not temporally improved over the past two decades. More efforts and strategies are needed to improve the racial/ethnic subgroup consideration and reporting in diabetes trials.

Consumption of Non-Nutritive Sweetener during Pregnancy and Weight Gain in Offspring: Evidence from Human Studies.

The relationship between the consumption of maternal non-nutritive sweeteners (NNS) during pregnancy and the risk of obesity in offspring remains inconsistent. We aimed to systematically evaluate and clarify the relationship between NNS intake during pregnancy and weight gain in offspring based on evidence from population and clinical research. Databases including PubMed (via Medline), EMBASE, and the Cochrane Library were systematically searched for eligible human studies. The primary outcome was the differences in body mass index (BMI) z-scores between offspring at 1 year of age who were with and without NNS intake during pregnancy or between offspring with different NNS intake levels during pregnancy. A random-effects meta-analysis was conducted for data synthesis to calculate the weighted mean difference (WMD). A total of six prospective cohort studies were eligible for inclusion, among which three were used for pooled analysis of the BMI z-score. A significant increase was found in an offspring's weight at 1 year of age in the NNS group when compared with the control group: WMD in BMI z-score = 0.19 (95% CI: 0.07, 0.31), p-value = 0.002. Results from the dose-response analysis showed a linear relationship between NNS intake during pregnancy and WMD at 1 year of age: beta = 0.02 (95% CI: 0.001, 0.04) for per serving/week increase in NNS consumption. The whole body of evidence for the review was rated as low quality. In summary, maternal NNS intake during pregnancy was found to be associated with increased weight gain in offspring based on evidence from human studies. Further well-designed and adequately powered studies are needed to confirm this relationship.

Sleep pattern in relation to recurrent osteoporotic fracture in the elderly.

Background: Previous studies assessed the relationship between individual sleep behavior and fracture risk, rather than taking into account the joint complexity of the sleep behaviors. We aimed to explore the association between sleep pattern and risk of imminent recurrent osteoporotic fracture in older hospitalized patients due to an index osteoporotic fracture, where sleep pattern was evaluated as a combination incorporating five common sleep behaviors (i.e., insomnia, snoring, nocturnal sleep duration, daytime napping, and midnight waking up). Methods: We used data from a prospective cohort study for analyses. Patients who aged not < 55 years and were admitted to the hospital due to an index osteoporotic fracture were recruited. Sleep pattern was grouped as healthy, intermediate, and poor pattern, based on the categorization of overall sleep scores. We used Cox proportional hazard models to explore sleep pattern in relation to imminent recurrent fracture. Results: We included a total of 185 elderly hospitalized patients for analyses with mean (± standard deviation) age = 71.5 ± 10.3 years and 87.0% female. During a mean follow-up of 14.7 months, there were 10 (5.4%) recurrent osteoporotic fractures observed. A significantly higher overall sleep score was found in patients with recurrent fractures when compared with those without fractures (3.20 vs. 2.36, p = 0.038). Both intermediate (p = 0.76) and poor sleep patterns (p = 0.093) were non-significantly associated with an elevated risk of fracture when compared with a healthy pattern. Per-one-increase in the overall sleep score was significantly related to an increased risk of fracture: hazard ratio = 1.60 (95% confidence interval: 1.00--2.55) from the multivariable model. Conclusion: Per-one-increase in the overall sleep score was found to be significantly associated with a 60% higher risk of imminent recurrent osteoporotic fracture in the elderly, and intermediate and poor sleep patterns were non-significantly related to an increased risk of recurrent fracture. More high-quality evidence is required to further evaluate the relationship between the sleep pattern and the risk of recurrent osteoporotic fracture in the elderly.

Associations between glycated hemoglobin and the risks of incident cardiovascular diseases in patients with gout.

BACKGROUND: Evidence for the relationship between glycated hemoglobin (HbA1c) levels and risk of cardiovascular diseases (CVD) in patients with gout remained sparse and limited. This study aims to explore the associations between HbA1c levels and risks of incident CVD in patients with gout. METHODS: We included patients with gout who had an HbA1c measurement at baseline from the UK Biobank. CVD events were identified from through medical and death records. We used multivariable Cox proportional hazards model with a restricted cubic spline to assess the potential non-linear effect of HbA1c on CVD risk. RESULTS: We included a total of 6,685 patients (mean age 59.7; 8.1% females) with gout for analyses. During a mean follow-up of 7.3 years, there were 1,095 CVD events documented with an incidence of 2.26 events per 100 person-years (95% confidence interval [CI]: 2.13-2.40). A quasi J-shaped association between HbA1c and risk of CVD was observed, with the potentially lowest risk found at the HbA1c of approximately 5.0% (hazard ratio [HR] = 0.65, 95% CI: 0.53-0.81). When compared with the HbAlc level of 7%, a significantly decreased risk of CVD was found from 5.0 to 6.5%, while an increased risk was observed at 7.5% (HR = 1.05) and 8.0% (HR = 1.09). Subgroup analyses yielded similar results to the main findings in general. CONCLUSIONS: Based on data from a nationwide, prospective, population-based cohort, we found a quasi J-shaped relationship between HbA1c and risk of CVD in patients with gout. More high-quality evidence is needed to further clarify the relationship between HbA1c and CVD risk in patients with gout.

Relationship between sleep pattern and bone mineral density in patients with osteoporotic fracture.

Background: Evidence investigating sleep pattern in relation to bone health in elderly participants with osteoporosis remains sparse. We aimed to assess the relationship between sleep pattern incorporating five sleep characteristics (snoring, midnight waking up, insomnia, sleep duration, and daytime napping) and bone mineral density (BMD) in elderly participants with osteoporotic fracture. Methods: A cross-sectional study was conducted to include eligible elderly patients from the Department of Orthopedics who were admitted to hospital due to an osteoporotic fracture. Sleep pattern was constructed based on total sleep scores and categorized into healthy, intermediate, and poor pattern groups. Multivariable logistic regression model was used to assess sleep pattern in relation to risk of low BMD. Results: A total of 169 elderly patients with osteoporotic fracture were included in this study (mean age: 71.91 years; 87.57% females). There were 36 (21.30%), 107 (63.31%), and 26 (15.38%) patients with healthy, intermediate, and poor sleep pattern, respectively. Compared with healthy sleep pattern, no significant relationship between intermediate sleep pattern and BMD was detected [odds ratio (OR) = 1.72, 95% confidence interval (CI): 0.74, 3.97, p = 0.21), while poor pattern was significantly associated with decreased BMD (OR = 3.50, 95% CI: 1.10, 11.14, p = 0.034). Conclusion: The majority of elderly patients with osteoporotic fracture had unhealthy sleep pattern; poor sleep pattern was significantly related to reduced BMD when compared with healthy pattern. Further high-quality evidence is needed to assess and validate the relationship between sleep pattern and risk of low BMD in the elderly.

Relationship between Serum 25-Hydroxyvitamin D Level and Risk of Recurrent Stroke.

Evidence for the association between vitamin D and risk of recurrent stroke remains sparse and limited. We aimed to assess the relationship between serum circulating 25-hydroxyvitamin D (25(OH)D) level and risk of recurrent stroke in patients with a stroke history, and to identify the optimal 25(OH)D level in relation to lowest recurrent stroke risk. Data from the nationwide prospective United Kingdom Biobank were used for analyses. Primary outcome was time to first stroke recurrence requiring a hospital visit during follow-up. We used Cox proportional hazards regression model with restricted cubic splines to explore 25(OH)D level in relation to recurrent stroke. The dose-response relationship between 25(OH)D and recurrent stroke risk was also estimated, taking the level of 10 nmol/L as reference. A total of 6824 participants (mean age: 60.6 years, 40.8% females) with a baseline stroke were included for analyses. There were 388 (5.7%) recurrent stroke events documented during a mean follow-up of 7.6 years. Using Cox proportional hazards regression model with restricted cubic splines, a quasi J-shaped relationship between 25(OH)D and risk of recurrent stroke was found, where the lowest recurrent stroke risk lay at the 25(OH)D level of approximate 60 nmol/L. When compared with 10 nmol/L, a 25(OH)D level of 60 nmol/L was related with a 48% reduction in the recurrent stroke risk (hazard ratio = 0.52, 95% confidence interval: 0.33-0.83). Based on data from a large-scale prospective cohort, we found a quasi J-shaped relationship between 25(OH)D and risk of recurrent stroke in patients with a stroke history. Given a lack of exploring the cause-effect relationship in this observational study, more high-quality evidence is needed to further clarify the vitamin D status in relation to recurrent stroke risk.

Trends in risk factor control in patients with gout: data from the National Health and Nutrition Examination Survey, 2007-2018.

OBJECTIVES: To explore trends in risk factor control (hypertension, diabetes mellitus, hyperlipidaemia) in patients with gout and medication use among those whose risk factor control targets were not achieved. METHODS: We used the data from National Health and Nutrition Examination Survey (NHANES) between 2007-2008 and 2017-2018 for analyses. The study samples were weighted so that they could be representative of the non-institutionalized US population. We conducted a cross-sectional analysis to assess trends in risk factor control and medication use, and employed logistic regression analyses to explore patient characteristics associated with risk factor control. RESULTS: The prevalence of participants in whom blood pressure control target was achieved decreased from 64.6% in 2007-2008 to 55.3% in 2017-2018 (P-value for trend = 0.03). The percentage of participants whose glycaemic, lipid or all three risk factor control targets were achieved remained stable temporally (P > 0.05). Some patient characteristics were significantly related to risk factor control, including age 45-64, age ≥65, Asian Americans, non-Hispanic Blacks, higher family income, and being overweight and obese. A trend towards increased use of glucose-lowering medication was found (from 71.0% in 2007-2008 to 94.7% in 2017-2018, P < 0.01), while the prevalence of taking blood pressure-lowering and lipid-lowering medications remained stable (P > 0.05). CONCLUSION: Based on NHANES data, a significant trend towards decreased blood pressure control was observed in patients with gout, while glycaemic and lipid control levelled off. These findings emphasize that more endeavours are needed to improve management of cardiovascular risk factors in patients with gout.

Relationship between diurnal temperature range and emergency ambulance dispatches due to stroke in Guangzhou, China.

BACKGROUND: The evidence between diurnal temperature range (DTR) and stroke remains controversial and sparse. We aimed to assess the relationship between DTR and emergency ambulance dispatches (EADs) due to stroke, and to explore whether there were effect modifications to the relationship. METHODS: A Quasi-Poisson generalized linear regression combined with a distributed lag non-linear model was used to examine the relationship between DTR and EADs for stroke between January 1st 2011 and June 30th 2018 in Guangzhou, China. We estimated the effects of the low DTR and high DTR (defined as DTR below and above 10 °C respectively) on EADs. The effects of minimum, maximum, 5th, 25th, 50th, 75th, and 95th percentiles of DTR compared with the DTR of 10 °C were also analyzed. RESULTS: A total of 20,275 EADs for stroke were included for analyses, among which 17,556 EADs were used in the model further adjusted for age and sex. A quasi-U-shaped relationship between DTR and EADs over lag0-2 days was observed. For the low DTR, per 1 °C decrease in DTR was significantly associated with an increase of 2.64% (RR = 1.03, 95% CI: 1.01-1.04) for EADs, while per 1 °C increase for the high DTR was non-significantly related with an increased risk of EADs (RR = 1.01, 95% CI: 0.90-1.13). Significant effects of the 5th and 25th percentiles of DTR on EADs were found when compared with the DTR of 10 °C. No significant effect modifications by age, sex or season were found to the association between DTR and EADs. CONCLUSIONS: We found a quasi-U-shaped relationship between DTR and EADs due to stroke in this study, while age, sex or season did not significantly modify the association between DTR and EADs. More high-quality evidence is needed to further explore and validate the relationship between DTR and stroke.

Relationship between glucosamine use and the risk of lung cancer: data from a nationwide prospective cohort study.

BACKGROUND: Research on glucosamine shows anti-inflammatory and anti-cancer benefits with minimal adverse effects. We aimed to explore the relationship between use of glucosamine and risk of lung cancer and lung cancer mortality based on data from the large-scale nationwide prospective UK Biobank cohort study. METHODS: Participants were enrolled between 2006 and 2010 and followed-up to 2020. The Cox proportional hazards model was used to assess the relationship between glucosamine use and risk of lung cancer and lung cancer mortality. Subgroup analyses and sensitivity analyses were performed to explore the potential effect modifications and the robustness of the main findings. RESULTS: 439 393 participants (mean age 56 years; 53% females) with a mean follow-up of 11 years were included for analyses. 82 603 (18.80%) participants reported regular use of glucosamine at baseline. During follow-up, 1971 (0.45%) lung cancer events were documented. Glucosamine use was significantly associated with a decreased risk of lung cancer (hazard ratio (HR) 0.84, 95% CI 0.75-0.92; p<0.001) and lung cancer mortality (HR 0.88, 95% CI 0.81-0.96; p=0.002) in fully adjusted models. A stronger association between glucosamine use and decreased lung cancer risk was observed in participants with a family history of lung cancer when compared with those without a family history. CONCLUSION: Regular use of glucosamine was significantly related with decreased risk of lung cancer and lung cancer mortality, based on data from this nationwide prospective cohort study.

Association between bone turnover markers and the risk of imminent recurrent osteoporotic fracture.

The association between bone turnover markers (BTMs) and the risk of imminent recurrent osteoporotic fracture (ROF) in the elderly remains unclear. The present study thus aimed to explore BTMs in relation to imminent ROF in the elderly with an index OF. For this purpose, data from a prospective cohort study were used for analysis. Elderly patients hospitalized due to an index OF were included and followed-up. The BTMs included bone resorption marker (C-terminal telopeptide of type I collagen) and the bone formation markers, procollagen type I N propeptide, osteocalcin (OC) and total alkaline phosphatase. The outcome was the time to the first ROF following their index fracture. Cox regression analysis was used to assess the association between BTMs and ROF. Model discrimination was calculated to explore whether the BTMs had potential to improve fracture risk prediction. There were 169 eligible patients included in the analysis (median age, 72 years; 87.6% females). During a median follow-up period of 10.5 months, there were seven ROFs (4.1%) observed. Serum OC levels were found to be significantly associated with the risk of ROF [hazard ratio, 0.13; 95% confidence interval (CI) 0.018-0.90; P=0.039] for per-SD increase in OC from multivariable analysis. After incorporating OC into the model, a C-index of 0.83 (95% CI, 0.70-0.96; P<0.001) was observed, which outperformed the model with bone mineral density alone (improvement for C-index, 0.29; 95% CI, 0.028-0.55). On the whole, the present study demonstrates a significant association between serum OC and the decreased risk of imminent ROF in the elderly with index fractures. However, further high-quality evidence is required to further clarify and validate the BTMs in relation to the imminent risk of ROFs among the elderly.