Secular Trends in Peak Bone Mineral Density: The National Health and Nutrition Examination Survey 1999-2018.

Peak bone mineral density (BMD) is one of the most important factors influencing the development of osteoporosis. It was predicted that a 10% increase in peak BMD will delay the onset of osteoporosis by 13 years. However, changes in peak BMD over time are unknown. This study aimed to investigate secular trends in peak BMD among young adults in the United States. Based on the National Health and Nutrition Examination Survey from 1999-2018, 3,975 males aged 19-28 years and 2370 females aged 31-40 years were our target population for estimating peak lumbar spine BMD. BMD was measured by dual-energy X-ray absorptiometry. Generalized linear models adjusted for multiple covariates were used to examine the secular trends in peak BMD in males and females, respectively. Secular trends for peak lumbar spine BMD from 1999-2000 to 2017-2018 were not statistically significant in males or females (all Plinear and Pquadratic > 0.05). Similar results were observed in race/ethnicity subgroups (all Plinear and Pquadratic > 0.05). However, in stratified analyses by obesity category, peak lumbar spine BMD in obese males and females increased from 1999-2000 to 2009-2010 and then decreased until 2017-2018, while peak lumbar spine BMD in non-obese females decreased from 1999-2000 to 2005-2006 and then increased until 2017-2018 (all Pquadratic < 0.05). Peak lumbar spine BMD was greater in obese males and females than in non-obese males and females up to 2009-2010, but not from 2011-2012 onwards. Overall, there were no significant secular trends in peak lumbar spine BMD. However, secular trends differed between obese and non-obese groups.

Plasma Fluorescent Oxidation Products and Bone Mineral Density Among Male Veterans: A Cross-Sectional Study.

In vitro and vivo studies indicate that oxidative stress contributes to bone loss. Fluorescent oxidation products (FlOPs) are novel biomarkers of oxidative stress; they reflect global oxidative damage of lipids, proteins, carbohydrates, and DNA. However, whether FlOPs are associated with bone mineral density (BMD) is still unclear. In the present study, we examined the association between FlOPs and BMD among male veterans. This cross-sectional study was conducted among participants recruited from the Department of Medical Examination, The Second Hospital of Jilin University in Jilin, China. We identified male veterans who were at least 50 y old between June and October of 2019. Plasma FlOPs were measured with a fluorescent microplate reader (excitation/emission wavelength: 320/420 nm). BMD were measured by dual-energy X-ray absorptiometry (DXA). The association between FlOPs and BMD was tested by multivariable linear regression models. A total of 164 male veterans were enrolled in the study, the average age was 56.6 y. After adjusting for covariates, veterans who had FlOP levels in the highest tertile had a statistically significant lower femoral neck (ß = -0.044; p = 0.007) and total hip BMD (ß = -0.045; p = 0.020) as compared to those with FlOP levels in the lowest tertile. Similar results were found when FlOPs were treated as a continuous variable (per 1-SD increase, ß = -0.014 and p = 0.033 for femoral neck BMD; ß = -0.016 and p = 0.047 for total hip BMD). Higher FlOP levels were associated with lower BMD among male veterans.

Association between lipid biomarkers and osteoporosis: a cross-sectional study.

BACKGROUND: Osteoporosis and cardiovascular diseases (CVDs) are 2 major public health problems. Osteoporosis and CVDs may be linked but the association between lipid profile and osteoporosis is still controversial. The purpose of this study was to examine the associations of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglyceride (TG) with osteoporosis. METHODS: Using inpatients' and outpatients' electronic medical records (EMR) and dual X-ray absorptiometry (DXA) database stored at The Second Hospital of Jilin University, we included 481 individuals with complete and valid lipid and bone mineral density (BMD) data in 2017. Serum samples were used to measure TC, LDL-C, HDL-C and TG. Femoral neck and total hip BMD were measured by DXA; osteoporosis was defined as femoral neck or total hip T-score ≤ -2.5. Multivariable logistic regression models were used to test the associations of TC, LDL-C, HDL-C and TG with osteoporosis. RESULTS: The mean age for included individuals was 62.7 years (SD = 8.6 years); 60.1 % of them were female. Each standard deviation (SD) increase in TC (Odds Ratio [OR]: 1.48; 95 % Confidence Interval [CI]: 1.06-2.07) and TG (OR: 1.67; 95 % CI: 1.16-2.39) were associated with increased risk of osteoporosis; LDL-C and HDL-C levels were not associated with osteoporosis. Age, sex and body mass index (BMI) did not interact with the relationships of TC and TG with osteoporosis (all P > 0.10). CONCLUSIONS: Higher TC and TG levels were associated with greater risk of osteoporosis in this cross-sectional study.

Associations of Iron Intake, Serum Iron and Serum Ferritin with Bone Mineral Density in Women: The National Health and Nutrition Examination Survey, 2005-2010.

The relationship between iron and bone mineral density (BMD) is still poorly understood. We investigated the associations of iron intake, serum iron and serum ferritin with BMD. This cross-sectional study identified 4000 females aged 12 to 49 years with complete and valid data on iron intake, serum iron, serum ferritin, and femoral neck and lumbar spine BMD from the National Health and Nutrition Examination Survey 2005-2010. Daily iron intake was the mean intake of iron nutrient ascertained from two consecutive 24-h dietary recalls; serum iron and serum ferritin were directly measured with established methods. Femoral neck and lumbar spine BMD were measured by Dual-energy X-ray absorptiometry (DXA). After adjusting for multiple covariates (i.e., age, body mass index and race), we used linear regression and generalized additive models (GAMs) to test the linear and non-linear associations of iron intake, serum iron and serum ferritin with BMD. The mean age of this study was 27.70 years (SD = 11.88 years). Higher serum ferritin was associated with lower femoral neck and lumbar spine BMD (all adjusted P < 0.05); iron intake and serum iron were not associated with femoral neck and lumbar spine BMD. Similar results were found when iron levels were classified as iron deficiency, normal iron and iron overload. There were no obvious non-linear relationships between the above three iron variables and BMD in the GAM analyses. There was a negative and linear association between serum ferritin and BMD; iron intake and serum iron were not associated with BMD. Serum ferritin appeared to be a better iron variable than iron intake and serum iron in relation to BMD.

Awareness of osteoporosis among 368 residents in China: a cross-sectional study.

BACKGROUND: Studies on osteoporosis awareness among the general population in China are still limited. We examined the level of osteoporosis awareness among residents in China, determined the risk factors associated with a lower level of osteoporosis awareness, and assessed the sources of their knowledge about osteoporosis. METHODS: We conducted a cross-sectional study among 368 general residents aged 30 years or older from 19 provinces during January-March 2018 in China. All participants were identified and interviewed face-to-face by medical students in Jilin University using a structured questionnaire. Osteoporosis awareness scores (percent of the correct answer) were determined across several domains, including definition, diagnosis, risk factors, and prevention of osteoporosis. We used multiple linear regression models to test the relationship between risk factors and overall awareness scores. RESULTS: The mean age of included participants was 52.9 ± 10.2 years, and 53% of them were male. Osteoporosis awareness score for definition was 77.7%, diagnosis 49.6%, risk factors 49.2%, treatment 60.5%, and prevention 69.9%. The overall awareness score was 67.8%. Lower family income and education level were significantly associated with lower overall awareness score (all p < 0.05). Television or radio health program was reported to be their main source of knowledge about osteoporosis. CONCLUSION: The awareness level for osteoporosis in our study is moderate; lower family income and education level were risk factors for lower awareness. Television or radio health programs had the greatest contribution to osteoporosis awareness.

Effects of ß-carotene intake on the risk of fracture: a Bayesian meta-analysis.

BACKGROUND: Epidemiological studies examining the association between ß-carotene intake and risk of fracture have reported inconsistent findings. We conducted a meta-analysis to investigate the association between ß-carotene intake and risk of fracture. METHODS: We systematically searched PubMed, EMBASE and Cochrane library databases for relevant articles that were published until December 2019. We also identified studies from reference lists of articles identified from the clinical databases. The frequentist and Bayesian random-effects model was used to synthesize data. RESULTS: Nine studies with a total of 190,545 men and women, with an average age of 59.8 years, were included in this meta-analysis. For ß-carotene intake (1.76-14.30 mg/day), the pooled risk ratio (RR) of any fracture was 0.67 (95% Credible Interval (CrI): 0.51-0.82; heterogeneity: P = 0.66, I2 = 0.00%) and 0.63 (95%CrI: 0.44-0. 82) for hip fracture. By study design, the pooled RRs were 0.55 (95% CrI: 0.14-0.96) for case-control studies and 0.82 (95% CrI: 0.58-0.99) for cohort studies. By geographic region, the pooled RRs were 0.58 (95% CrI: 0.28-0.89), 0.86 (95% CrI: 0.35-0.1.37), and 0.91(95% CrI: 0.75-1.00) for studies conducted in China, the United States, and Europe, respectively. By sex, the pooled RRs were 0.88 (95% CrI: 0.73-0.99) for males and 0.76 (95% CrI, 0.44-1.07) for females. There was a 95% probability that ß-carotene intake reduces risk of hip fracture and any type of fracture by more than 20%. CONCLUSIONS: The present meta-analysis suggests that ß-carotene intake was inversely associated with fracture risk, which was consistently observed for case-control and cohort studies. Randomized controlled trials are warranted to confirm this relationship.

Fracture Risk Indices From DXA-Based Finite Element Analysis Predict Incident Fractures Independently From FRAX: The Manitoba BMD Registry.

OBJECTIVE: Finite element analysis (FEA) is a computational method to predict the behavior of materials under applied loading. We developed a software tool that automatically performs FEA on dual-energy X-ray absorptiometry hip scans to generate site-specific fracture risk indices (FRIs) that reflect the likelihood of hip fracture from a sideways fall. This longitudinal study examined associations between FRIs and incident fractures. METHODS: Using the Manitoba Bone Mineral Density (BMD) Registry, femoral neck (FN), intertrochanter (IT), and subtrochanter (ST) FRIs were automatically derived from 13,978 anonymized dual-energy X-ray absorptiometry scans (Prodigy, GE Healthcare) in women and men aged 50 yr or older (mean age 65 yr). Baseline covariates and incident fractures were assessed from population-based data. We compared c-statistics for FRIs vs FN BMD alone and fracture risk assessment (FRAX) probability computed with BMD. Cox regression was used to estimate hazard ratios and 95% confidence intervals (95% CIs) for incident hip, major osteoporotic fracture (MOF) and non-hip MOF adjusted for relevant covariates including age, sex, FN BMD, FRAX probability, FRAX risk factors, and hip axis length (HAL). RESULTS: During mean follow-up of 6 yr, there were 268 subjects with incident hip fractures, 1003 with incident MOF, and 787 with incident non-hip MOF. All FRIs gave significant stratification for hip fracture (c-statistics FN-FRI: 0.76, 95% CI 0.73-0.79, IT-FRI 0.74, 0.71-0.77; ST-FRI 0.72, 0.69-0.75). FRIs continued to predict hip fracture risk even after adjustment for age and sex (hazard ratio per standard deviation FN-FRI 1.89, 95% CI 1.66-2.16); age, sex, and BMD (1.26, 1.07-1.48); FRAX probability (1.30, 1.11-1.52); FRAX probability with HAL (1.26, 1.05-1.51); and individual FRAX risk factors (1.32, 1.09-1.59). FRIs also predicted MOF and non-hip MOF, but the prediction was not as strong as for hip fracture. SUMMARY: Automatically-derived FN, IT, and ST FRIs are associated with incident hip fracture independent of multiple covariates, including FN BMD, FRAX probability and risk factors, and HAL.

Accuracy of Offspring-Reported Parental Hip Fractures: A Novel Population-Based Parent-Offspring Record Linkage Study.

The objective of this study was to test the validity of offspring-reported parental hip fracture in a unique bone mineral density (BMD) registry linked to administrative databases spanning 4 decades. Population-based data were from Manitoba, Canada, and included hospital abstracts, health insurance registrations, and the provincewide BMD registry. The cohort included individuals aged ≥40 years with BMD tests and self-reports of parental hip fracture between 2006 and 2014. Population registry data for 1966-2014 were used to link offspring with their parents, and hospital records were used to ascertain parental fractures. Overall, 8,112 offspring met the inclusion criteria; 13.6% had a parental hip fracture diagnosis in administrative data during an average of 32.9 years of follow-up. Agreement between parental hip fracture from offspring reports and diagnoses in administrative data was good (κ = 0.68). The sensitivity of offspring reports was 0.70 (95% confidence interval: 0.67, 0.73), and specificity was 0.96 (95% confidence interval: 0.96, 0.97). Offspring characteristics associated with disagreement included male sex, northern rural residence, early BMD test year, and longer interval between BMD test and parental hip fracture diagnosis. This proof-of-concept study focused on hip fractures, but use of record linkage techniques to validate offspring-reported parental information can be extended to other conditions.

The significant effect of chronic intermittent hypoxia on prostaglandin D2 biosynthesis in rat brain.

Obstructive sleep apnea (OSA) is a common disorder characterized by chronic intermittent hypoxia (CIH). Excessive daytime sleepiness (EDS) is one of severe complications frequently associated with OSA. Lipocalin-type prostaglandin synthase (L-PGDS) is potentially responsible for the production of prostaglandin D2 (PGD2) which is an endogenous sleep inducer. To date, whether the content of PGD2 and PGDS is related to intermittent hypoxia has never been reported. The aim of this study was to compare the content of PGD2 and L-PGDS in rats' brains with and without intermittent hypoxia. Adult male Wistar rats (n = 48; 8-10 weeks) were averagely divided into two groups. One was control group, and the other group was exposed to IH (12 h/day for 6 weeks). In each group there are four time-points including 0, 2, 4 and 6 weeks, and six rats were killed and studied at each time-point. At the end of 0, 2, 4 and 6 weeks, the concentrations of PGD2 in brains were measured by LC-MS/MS. In addition, the expressions of L-PGDS protein and mRNA in brains were investigated by western blotting and real-time polymerase chain reaction (RT-PCR), respectively. The results showed the concentrations of PGD2 in CIH rat brains were higher than those in control groups from the second week. At the end of 6 weeks, the concentrations of PGD2 in CIH and control groups were 11.1 and 5.9 ng/g, respectively. The levels of L-PGDS protein and mRNA followed the same trend during the whole 6 weeks. The results will provide a new idea to explore that patients with OSA are always accompanied by excessive daytime sleepiness.

The different metabolism of morusin in various species and its potent inhibition against UDP-glucuronosyltransferase (UGT) and cytochrome p450 (CYP450) enzymes.

1. The aim of this study was to investigate the inhibitory effect of morusin on Glucuronosyltransferase (UGT) isoforms and cytochrome P450 enzymes (CYP450s). We also investigated the metabolism of morusin in human, rat, dog, monkey, and minipig liver microsomes. 2. 100 µM of morusin exhibited strong inhibition on all UGTs and CYP450s. The half inhibition concentration (IC50) values for CYP3A4, CYP1A2, CYP2C9, CYP2E1, UGT1A6, UGT1A7, and UGT1A8 were 2.13, 1.27, 3.18, 9.28, 4.23, 0.98, and 3.00 µM, and the inhibition kinetic parameters (Ki) were 1.34, 1.16, 2.98, 6.23, 4.09, 0.62, and 2.11 µM, respectively. 3. Metabolism of morusin exhibited significant species differences. The quantities of M1 from minipig, monkey, dog, and rat were 7.8, 11.9, 2.0, and 6.3-fold of human levels. The Km values in HLMs, RLMs, MLMs, DLMs, and PLMs were 7.84, 22.77, 14.32, 9.13, and 22.83 µM, and Vmax for these species were 0.09, 1.23, 1.43, 0.15, and 0.75 nmol/min/mg, respectively. CLint (intrinsic clearance) values (Vmax/Km) for morusin obeyed the following order: monkey > rat > minipig > dog > human. CLH (hepatic clearance) values for humans, dogs, and rats were calculated to be 8.28, 17.38, and 35.12 mL/min/kg body weight, respectively. 4. This study provided vital information to understand the inhibitory potential and metabolic behavior of morusin among various species.

Association between plasma fluorescent oxidation products and erectile dysfunction: A prospective study.

BACKGROUND: Existing epidemiological studies of the association between oxidative stress and erectile dysfunction (ED) are sparse and inconclusive, which is likely due to cross-sectional design and small sample size. Therefore, we investigated the association between biomarkers of oxidative stress and ED in prospective setting among a relatively large sample size of men. METHODS: We conducted the prospective study among 917 men ages between 47 and 80 years at the time of blood draw, which is a part of nested prospective case-control study of prostate cancer in the Health Professionals Follow-up Study. Plasma fluorescent oxidation products (FlOPs), a global biomarker for oxidative stress, were measured at three excitation/emission wavelengths (360/420 nm named as FlOP_360; 320/420 nm named as FlOP_320 and 400/475 nm named as FlOP_400). RESULTS: Approximately 35% of men developed ED during follow-up. We did not find an independent association between FlOP_360, FlOP_320, FlOP_400 and risk of ED in the multivariable adjusted model (Tertile 3 vs. tertile 1: odds ratio [OR] = 0.90, 95% confidence interval [CI] = 0.61-1.34, P(trend) = 0.54 for FlOP_360; OR = 0.73, 95% CI = 0.49-1.07, P(trend) = 0.27 for FlOP_320; and OR = 0.98, 95% CI = 0.66-1.45, P(trend) = 0.72 for FlOP_400). Further analysis of the association between FlOPs and ED in the fasting samples or controls only (free of prostate cancer incidence) did not change the results appreciably. CONCLUSIONS: Plasma FlOPs were not associated with the risk of ED, suggesting oxidative stress may not be an independent risk factor for ED.

Association of history of fracture with prehypertension and hypertension: a retrospective case-control study.

BACKGROUND: Hypertension is one of the most common encountered medical comorbidities after hip fracture. Whether fracture is a potential risk factor for hypertension remains poorly understood. The aim of our study was to examine the risk of prehypertension and hypertension in the participants with and without a history of fracture. METHODS: We conducted a retrospective case-control study of 3,515 men and women aged between 20 and 85 years old from the National Health and Nutrition Examination Survey 2005-2006. History of fracture was collected via structured questionnaire. Multiple blood pressure readings (up to 4 times) were performed at interview, and an average of blood pressure readings were used to define prehypertension and hypertension. RESULTS: Among 3,515 participants, 30% (n = 1074), 1.4% (n = 48) and 10% (n = 347) of them had a history of any, hip and wrist fracture, respectively. The positive association between history of any, hip and wrist fracture and prehypertension was similar to the association between history of any, hip and wrist fracture and hypertension in both unadjusted and adjusted model. In the unadjusted model, history of any, hip and wrist fracture was each associated with increased overall risk of prehypertension and hypertension (odds ratio [OR] = 1.61, 95% confidence interval [CI] = 1.38-1.89 for any fracture; OR = 3.57, 95% CI = 1.60-8.00 for hip fracture; and OR = 1.82, 95% CI = 1.41-2.36 for wrist fracture). However, in multivariable adjusted model, only the positive association between history of wrist fracture and overall risk of prehypertension and hypertension remained significant (OR = 1.48, 95% CI = 1.10-1.99). CONCLUSIONS: There was no overall independent association between history of fracture, and risk of prehypertension and hypertension. Although history of fracture overall may not directly cause hypertension, people with a history of wrist fracture can be potentially benefitted from hypertension control at the early stage.

Erythrocyte superoxide dismutase, glutathione peroxidase, and catalase activities and risk of coronary heart disease in generally healthy women: a prospective study.

Erythrocyte antioxidant enzymes are major circulating antioxidant enzymes in the oxidative stress defense system. Few prospective studies have assessed the association between these enzymes and the risk of coronary heart disease (CHD) in generally healthy adults. We conducted a prospective nested case-control study of CHD among 32,826 women at baseline with 15 years of follow-up from 1989 to 2004 in the Nurses' Health Study. We investigated the association of baseline erythrocyte superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) activities with the risk of CHD. A total of 365 cases and 728 controls were included in the analysis. Overall, the relative risks of CHD associated with 1-standard deviation higher SOD, GPx, and CAT activities were 1.07 (95% confidence interval (CI): 0.94, 1.22), 1.04 (95% CI: 0.91, 1.18), and 1.04 (95% CI: 0.92, 1.17), respectively. Multivariable adjustments did not change the associations appreciably. Fasting status did not modify the associations, with the exception that SOD activity was positively associated with the risk of CHD among participants who provided blood samples within 12 hours of fasting. Overall, activities of SOD, GPx, and CAT were not associated with CHD among women who were generally healthy at the time of blood collection.

Tai Chi training as a primary care plan for the prevention and management of hypertension: an opinion and positioning article.

Hypertension is a prevalent chronic condition worldwide that can impact patients' quality of life. Oral antihypertensive drugs are widely used to manage high blood pressure, primarily by regulating the renin-angiotensin-aldosterone system. Nevertheless, limited efficacy and low compliance represent significant obstacles, arising primarily from dose, duration, and medication type restrictions. Furthermore, the prolonged use of antihypertensive medication may result in dependence and adverse effects, without any substantial improvement in achieving targeted blood pressure leves. As a result, research has focused on using exercise therapy to treat hypertension. Tai Chi, a widely-practiced Chinese health exercise, has evolved into a form of exercise therapy that might help alleviate the risk associated with hypertension. Therefore, this article aims to outline the role of Tai Chi in preventing and managing hypertension.

Detection of Cadmium in Human Biospecimens by a Cadmium-Selective Whole-Cell Biosensor Based on Deoxyviolacein.

Cadmium poses a severe health risk, impacting various bodily systems. Monitoring human exposure is vital. Urine and blood cadmium serve as critical biomarkers. However, current urine and blood cadmium detection methods are expensive and complex. Being cost-effective, user-friendly, and efficient, visual biosensing offers a promising complement to existing techniques. Therefore, we constructed a cadmium whole-cell biosensor using CadR10 and deoxyviolacein pigment in this study. We assessed the sensor for time-dose response, specific response to cadmium, sensitivity response to cadmium, and stability response to cadmium. The results showed that (1) the sensor had a preferred signal-to-noise ratio when the incubation time was 4 h; (2) the sensor showed excellent specificity for cadmium compared to the group 12 metals and lead; (3) the sensor was responsive to cadmium down to 1.53 nM under experimental conditions and had good linearity over a wide range from 1.53 nM to 100 µM with good linearity (R2 = 0.979); and (4) the sensor had good stability. Based on the excellent results of the performance tests, we developed a cost-effective, high-throughput method for detecting urinary and blood cadmium. Specifically, this was realized by adding the blood or urine samples into the culture system in a particular proportion. Then, the whole-cell biosensor was subjected to culture, n-butanol extraction, and microplate reading. The results showed that (1) at 20% urine addition ratio, the sensor had an excellent curvilinear relationship (R2 = 0.986) in the range of 3.05 nM to 100 µM, and the detection limit could reach 3.05 nM. (2) At a 10% blood addition ratio, the sensor had an excellent nonlinear relationship (R2 = 0.978) in the range of 0.097-50 µM, and the detection limit reached 0.195 µM. Overall, we developed a sensitive and wide-range method based on a whole-cell biosensor for the detection of cadmium in blood and urine, which has the advantages of being cost-effective, ease of operation, fast response, and low dependence on instrumentation and has the potential to be applied in the monitoring of cadmium exposure in humans as a complementary to the mainstream detection techniques.

Association between amino acids and recent osteoporotic fracture: a matched incident case-control study.

Context: Osteoporotic fracture is a major public health issue globally. Human research on the association between amino acids (AAs) and fracture is still lacking. Objective: To examine the association between AAs and recent osteoporotic fractures. Methods: This age and sex matched incident case-control study identified 44 recent x-ray confirmed fracture cases in the Second Hospital of Jilin University and 88 community-based healthy controls aged 50+ years. Plasma AAs were measured by high performance liquid chromatography coupled with mass spectrometry. After adjusting for covariates (i.e., body mass index, milk intake >1 time/week, falls and physical activity), we conducted conditional logistical regression models to test the association between AAs and fracture. Results: Among cases there were 23 (52.3%) hip fractures and 21 (47.7%) non-hip fractures. Total, essential, and non-essential AAs were significantly lower in cases than in controls. In the multivariable conditional logistic regression models, after adjusting for covariates, each standard deviation increase in the total (odds ratio [OR]: 0.304; 95% confidence interval [CI]: 0.117-0.794), essential (OR: 0.408; 95% CI: 0.181-0.923) and non-essential AAs (OR: 0.290; 95%CI: 0.107-0.782) was negatively associated with recent fracture. These inverse associations were mainly found for hip fracture, rather than non-hip fractures. Among these AAs, lysine, alanine, arginine, glutamine, histidine and piperamide showed the significantly negative associations with fracture. Conclusion: There was a negative relationship between AAs and recent osteoporotic fracture; such relationship appeared to be more obvious for hip fracture.

Associations of global biomarkers of oxidative stress with osteoporosis, bone microstructure and bone turnover: Evidence from human and animal studies.

PURPOSE: Human evidence on the association between oxidative stress and osteoporosis is inconsistent. Fluorescent Oxidation Products (FlOPs) are global biomarkers of oxidative stress. We examined the associations of FlOPs (excitation/emission wavelengths 320/420 nm for FlOP_320, 360/420 nm for FlOP_360, and 400/475 nm for FlOP_400) with osteoporosis, bone microstructure, and bone turnover markers in humans and rats. METHODS: In humans, we conducted a 1:2 age, sex, hospital, and specimen-matched case-control study to test the association between FlOPs and osteoporosis diagnosed from dual-energy X-ray absorptiometry. In eight-week-old male Wistar rats, we administrated D-galactose and 0.9 % saline for 90 days in treatment and control groups (n = 8/group); micro-CT was used to determine bone microstructure. RESULTS: In humans, higher levels of FlOP_320 (OR for per 1 SD increase = 1.49, 95 % CI: 1.01-2.20) and FlOP_360 (OR for per 1 SD increase = 1.59, 95 % CI: 1.07-2.37) were associated with increased odds of osteoporosis. FlOP_400 were not associated with osteoporosis. D-galactose treated rats, as compared with control rats, showed higher levels of FlOP_320 and MDA, and lower P1NP levels during 90 days of experiment (all P < 0.05). The D-galactose group had lower trabecular bone volume fraction (0.07 ± 0.03 vs. 0.13 ± 0.05; P = 0.008) and volumetric BMD (225.4 ± 13.8 vs. 279.1 ± 33.2 mg HA/cm3; P = 0.001) than the control group. CONCLUSION: In conclusion, higher FlOP_320 levels were associated with increased odds of osteoporosis, impaired bone microstructure and decreased bone formation.

Global biomarkers of oxidative stress and fractures: a matched case-control study.

Background: Evidence for a relationship between oxidative stress and osteoporotic fractures in humans is limited. Fluorescent oxidation products (FlOPs, excitation/emission wavelengths 320/420nm denoted FlOP_320; 360/420nm [FlOP_360]; and 400/475nm [FlOP_400]) are global biomarkers of oxidative stress, and reflect oxidative damage to proteins, phospholipids, and nucleic acids. We investigated the association between FlOPs and a recent osteoporotic fracture. Methods: We conducted a case-control study in a Chinese population aged 50 years or older. A recent osteoporotic fracture in the cases was confirmed by x-ray. Cases were matched with community-based non-fracture controls (1:2 ratio) for age (± 4 years) and sex. In addition, we conducted a sensitivity unmatched case-control study which included all fracture cases and all eligible non-fracture controls prior to matching. Plasma FlOPs were measured with a fluorescent microplate reader. We used unconditional logistic regression to analyze the association between FlOPs (per 1-SD increase in logarithmic scale) and fracture; odds ratios (OR) and 95% confidence intervals (95% CI) were reported. Results: Forty-four cases and 88 matched controls (mean age: 68.2 years) were included. After covariate adjustment (i.e., body mass index, physical activity, and smoking), higher FlOP_360 (OR = 1.85; 95% CI = 1.03 - 3.34) and FlOP_400 (OR = 13.29; 95% CI = 3.48 - 50.69) levels, but not FlOP_320 (OR = 0.56; 95% CI = 0.27 - 1.15), were associated with increased fracture risk. Subgroup analyses by fracture site and unmatched case-control study found comparable associations of FlOP_360 and FlOP_400 with hip and non-hip fractures. Conclusions: Higher FlOP_360 and FlOP_400 levels were associated with increased risk of fracture, and this association was comparable for hip and non-hip fractures. Prospective studies are warranted to confirm this finding.

Associations of estrogen therapy and non-estrogen anti-resorptive therapy with diabetes mellitus risk: A classical and Bayesian meta-analysis.

Anti-resorptive therapy (AT) increases insulin resistance and decrease insulin secretion through reduced undercarboxylated osteocalcin in mice. However, there are inconsistent findings regarding the impact of AT use on the risk of diabetes mellitus in humans. We examined the association between AT and incident diabetes mellitus using classical and Bayesian meta-analysis. We searched Pubmed, Medline, Embase, Web of Science, Cochrane, and Google Scholar for studies listed from database inception to 25 February 2022. Randomized controlled trials (RCTs) and cohort studies reporting associations of estrogen therapy (ET) and non-estrogen anti-resorptive therapy (NEAT) with incident diabetes mellitus were included. Two reviewers independently extracted research data such as ET and NEAT, diabetes mellitus, risk ratios (RRs), and 95 % confidence intervals (CIs) for incident diabetes mellitus associated with ET and NEAT from individual studies. This meta-analysis included data from nineteen original studies, consisting of fourteen ET and five NEAT studies. ET was associated with reduced risk of diabetes mellitus in the classical meta-analysis (RR: 0.90; 95 % CI: 0.81-0.99). Slightly stronger results were found in the meta-analysis of RCTs (RR: 0.83; 95 % CI: 0.77-0.89). The probability that RR < 1.0 was 95 % in the overall analysis and 99 % in RCTs under weakly informative prior. Although NEAT was associated with reduced risk of diabetes mellitus overall (RR: 0.80; 95 % CI: 0.67-0.97), this was not found in the RCT meta-analysis (RR: 0.90; 95 % CI: 0.75-1.10). Under weakly informative prior, the probabilities that NEAT reduces diabetes mellitus by >0 % were 99 %, and 73 % in the overall and RCT meta-analysis, respectively. In conclusion, meta-analysis provided consistent evidence against the hypothesis that AT increases diabetes risk. ET may reduce the risk of diabetes mellitus. Whether NEAT reduces the risk of diabetes mellitus is uncertain and requires additional evidence from RCTs.