Total Body Bone Mineral Density Research Articles

Proteins and pathways involved in inflammation are longitudinally associated with total body bone mineral density among primarily hispanic overweight/obese adolescents and young adults.

Bone mineral density (BMD), an important marker of bone health, is regulated by a complex interaction of proteins. Plasma proteomic analyses can contribute to identification of proteins associated with changes in BMD. This may be especially informative in stages of bone accrual and peak BMD achievement (i.e., adolescence and young adulthood), but existing research has focused on older adults. This analysis in the Study of Latino Adolescents at Risk for Type 2 Diabetes (SOLAR; n = 304; baseline age 8-13, 100% Hispanic) explored associations between baseline proteins (n = 653 proteins) measured with Olink® plasma protein profiling and repeated annual DXA measures of BMD (average of 3.2 visits per participant). Covariate-adjusted linear mixed effect regression models were applied to estimate longitudinal protein-BMD associations using an adjusted p-value cutoff (P < 0.00068). Identified proteins were imported into the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database to determine significantly enriched protein pathways. Forty-four proteins, many of which are involved in inflammatory processes, were associated with longitudinal changes in total body BMD, including several proteins previously linked to bone health such as osteopontin (SPP1) and microfibrillar-associated protein 5 (MFAP5; both P < 0.00068). These 44 proteins were associated with enrichment of pathways including PI3K-Akt Signaling Pathway and Cytokine-Cytokine Receptor Interaction, supporting results from existing proteomics analyses in older adults. To evaluate whether protein associations were consistent into young adulthood, linear mixed effect models were repeated in a young adult cohort (n = 169; baseline age 17-22; 62.1% Hispanic) with 346 available overlapping Olink® protein measures. While there were no significant overlapping longitudinal protein associations between the cohorts, these findings suggest differences in protein regulation at different ages and provide novel insight on longitudinal protein associations with BMD in overweight/obese adolescents and young adults of primarily Hispanic origin, which may inform the development of biomarkers for bone health in youth.

The relationship between non-HDL-C/HDL-C ratio and bone mineral density: an NHANES study

BackgroundThe non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) is a newly developed lipid parameter. However, the current research has only explored the relationship with lumbar spine bone mineral density, lacking studies on bone mineral density at other sites, total body bone mineral density, and an analysis of risk factors. This study aims to determine the potential association between NHHR and lumbar BMD, increase awareness of the impact of lipid levels on bone health.MethodsBy utilizing data from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2018, we conducted univariate and generalized linear models (GLMs) analysis, stratified analysis, threshold effect analysis, smooth curve fitting and stratified analysis to investigate the association between NHHR and BMD. NHHR levels were categorized into tertiles (low, medium, and high) based on their distribution among the study population.ResultsThe study included 8,671participants, studies have shown, the ratio of non-high-density lipoprotein to high-density lipoprotein (NHHR) exhibits a stratified correlation with bone mineral density (BMD). In the BMI subgroup, NHHR is significantly negatively correlated with BMD at multiple sites in the low-to-middle BMI group (BMI &amp;lt;25 kg/m2), while no significant correlation is found in the high BMI group (BMI ≥30 kg/m2). In the gender subgroup, NHHR has a more pronounced effect on male BMD, mainly reflected in the reduction of lumbar spine and total body BMD. In the age subgroup, the negative correlation between NHHR and BMD is strongest in the younger group (18–30 years), gradually weakening in the middle-aged (31–44 years) and older groups (45–59 years). Further analysis suggests that dyslipidemia may influence bone metabolism through pathways such as inflammation and oxidative stress.ConclusionThe effect of NHHR on bone mineral density (BMD) varies by BMI, gender, and age. This study suggests that controlling NHHR levels may be a potential intervention target for bone health management, particularly for individuals with low-to-middle BMI, males, and younger populations. These findings offer a new perspective on the relationship between lipid metabolism and bone metabolism and provide scientific evidence for the development of personalized osteoporosis prevention and treatment strategies.

Don't Sleep on Sleep: A Case Report from a Division I Heptathlete.

A female NCAA Division I track athlete experienced non-localized shin pain midway through her first season, which was diagnosed as medial tibial stress syndrome. Treatments included strengthening and range of motion exercises, reduced training volume, and pain control modalities, but symptoms worsened. It was revealed she had been suffering from severe sleep deprivation (<3 hours/night) contributing to bilateral tibial and fibular stress reactions. Months of trial and error eventually resulted in the implementation of sleep interventions which improved her total body bone mineral density and bilateral stress reactions. Two years after successful sleep interventions this athlete has remained injury-free and continues to set personal bests in her events. Our standard injury screening protocols did not include questioning sleep quality and quantity early in the process and this case highlights the need for these measures to be considered initially and throughout the treatment and recovery phases of sports-related injuries.

Bone Health Determinants in Ambulant Prepubertal Boys With Duchenne Muscular Dystrophy Treated With Deflazacort: Findings From a 3-Year Study.

Duchenne muscular dystrophy (DMD) is complicated by bone fragility. This study aimed to elucidate changes in bone mineral density (BMD) and body composition over time and to explore associations with adiposity measures in DMD. A three-year follow-up analysis was performed of total body (TB) and lumbar spine (LS) dual-energy x-ray absorptiometry (DXA) measurements, anthropometric measures, Tanner stage and bone turnover biomarkers assessments, and the incidence of fragility fractures in 26 ambulant prepubertal DMD patients treated with deflazacort (DFZ). Age at baseline was 7.7 years (interquartile range: 6-9.2). The TB BMD Z-score declined over time and was negatively related to the TB fat mass percentage and fat mass index (p < 0.05), but not to body mass index (BMI) standard deviation score (SDS). In contrast LS bone mineral apparent density (BMAD) Z-score remained stable and normal. The cumulative incidence of fragility fractures was 19.2%; DMD boys with fractures displayed a 1.5-fold higher decline of TB BMD Z-score/year (p < 0.05) and a worse adiposity profile compared to fracture-free patients. No difference was found in DFZ dose or duration between the two groups. We observed a high incidence of fragility fractures, and identified fat tissue as a potential detrimental factor for bone health, suggesting a need for monitoring in DMD patients with excessive adiposity. Fat mass measures assessed by DXA could help to identify those at risk, enabling targeted interventions for better bone health. The co-occurrence of multiple glucocorticoid side effects might characterize patients at higher risk of fractures.

Bone biochemical markers, bone mineral density, and the risk of osteonecrosis of the femoral head: a Mendelian randomization study

BackgroundAlterations in bone metabolism may play a significant role in the early stages of femoral head necrosis, yet the causal relationship remains unclear. This study utilizes a two-sample Mendelian randomization (MR) approach to explore the genetic causal links between biochemical markers of bone metabolism, bone mineral density, and the risk of femoral head necrosis.MethodsThis study utilizes publicly available genome-wide association study (GWAS) datasets, with exposure factors including biochemical bone markers (25OHD, calcium, and alkaline phosphatase) and bone mineral density (measured at the lumbar spine, heel, femoral neck, and total body). The outcome of interest is osteonecrosis of the femoral head. We selected validated single nucleotide polymorphisms that are strongly associated with the exposure factors as instrumental variables. Mendelian randomization analysis was conducted using inverse variance weighting(IVW), MR-Egger regression, and weighted median estimation. Additionally, we performed analyses for horizontal pleiotropy, heterogeneity, and sensitivity.ResultsA total of 934 SNPs were included in this study. The MR analysis results indicate that the IVW analysis of 25OHD, Ca, and ALP did not reach statistical significance (25OHD OR = 1.006, 95%CI: 0.69–1.47, P = 0.975; Ca OR = 0.856, 95%CI: 0.43–1.70, P = 0.657; ALP OR = 1.022, 95%CI: 0.86–1.21, P = 0.801). However, bone density, including heel, lumbar spine, and total body bone density, showed a protective causal relationship with the onset of ONFH, while the results for femoral neck bone density did not reach statistical significance (lumbar spine BMD OR = 0.662, 95%CI: 0.48–0.91, P = 0.010; heel BMD OR = 0.726, 95%CI: 0.62–0.85, P < 0.001; total body BMD OR = 0.726, 95%CI: 0.62–0.85, P < 0.001; femoral neck BMD OR = 0.748, 95%CI: 0.53–1.05, P = 0.096). Cochran’s Q statistic for IVW and MR-Egger methods indicated no intergenic heterogeneity for all exposure outcomes’ SNPs, and the tests for pleiotropy suggested a low likelihood of pleiotropy in all causal analyses.ConclusionsThe results of this study indicate that there is no genetically mediated causal relationship between serum levels of 25-hydroxyvitamin D, calcium, and alkaline phosphatase and osteonecrosis of the femoral head. However, heel, lumbar spine, and total body bone mineral density can be considered protective factors for the occurrence of ONFH. There is no genetic causality between femoral neck bone mineral density and ONFH development.

Paediatric cancer survivors: lean mass attenuates negative impact of watching television on bone.

To investigate the associations of television (TV) watching time with bone parameters and to examine whether high lean mass attenuates the negative impact of watching TV more than one hour per day on bone parameters. This cross-sectional study comprised 116 young paediatric cancer survivors. Dual-energy X-ray Absorptiometry was used to obtain total body and regional areal bone mineral density (g/cm2), and lean mass (kg) outcomes. Hip Structural Analysis was performed at the narrowest point of the femoral neck. Trabecular Bone Score was obtained in the lumbar spine. TV watching time was obtained using the "Youth Activity Profile" questionnaire. Multiple linear regression models showed negative associations of watching TV more than one hour with bone parameters in peri/post pubertal survivors (β = -0.359 to -0.614, P < 0.001 to 0.047). Those survivors watching TV more than one hour per day and with high lean mass presented higher bone parameter Z-score than those with low lean mass. These findings underline the necessity of identifying strategies that promote musculoskeletal development while reducing TV watching time in young paediatric cancer survivors to maximise bone regeneration. The results indicate that watching television (TV) more than one hour (compared to not watching TV) is negatively associated with bone parameters in peri/post pubertal survivors. Survivors with high lean mass counteract these negative associations of watching TV with bone parameters. It is important to promote musculoskeletal development in this vulnerable population to maximise bone regeneration.

La pratique du cyclisme de haut niveau impacte-t-elle la masse osseuse ?

Background : Elite cyclists may be at risk for osteopenia. Many factors can lead to bone loss in cycling, including low energy availability, low grade of inflammation, and a weak mechanical osteogenic stimulus. Thus we wanted to assess bone health in one elite team of professional cyclists, and to identify correlations between BMD and potential risks factors.Methods : Thirty-three adult male cyclists were recruited from one international team. Total body, hip femur and lumbar spine BMD had been measured by DXA and was compared to standard values for a healthy population of same age and sex. Training characteristics, morphometrics, body lean mass, fat mass, history, medication and results of recent blood and stool analysis were collected and compared between the cyclists having low BMD and those with unaltered BMD. Univariate and multivariate correlation analyses were carried out to identify predictive factors for low BMD.Results : Twenty-one (64%) out of 33 cyclists presented a Z score < -1 at one site, and five of them (15%) had densitometric osteoporosis. Lumbar spine was involved every time ‘Z score = -b 1,23 +/- 0,94). Age, history, and training characteristics were significantly and negatively linked to BMD. After multiple regression, no variable had an independent correlation with BMD. No correlation was found with biomarkers or with training characteristics.Conclusion : Our study shows a worrying proposition of low bone mass in our population of young male and otherwise healthy cyclists. Low energy availability, as the missing point of our study, might be the main causal factor. Great attention should be paid in bone status in elite cyclists of any age.

Zoledronate Therapy in Osteogenesis Imperfecta: Perspectives in Indonesia Tertiary Hospital.

Osteogenesis imperfecta (OI) is a rare disease with an estimated incidence of between 1/25,000 and 1/10,000 globally. The main treatment for OI is the administration of bisphosphonate drugs. Research on clinical, radiographic, and biochemical markers to monitor patients with OI treated with zoledronate can be challenging in countries in which patients have limited national health insurance. We aimed to examine patients with OI treated in Indonesia with a minimum follow-up period of 2 years. An observational study was conducted of all patients with OI treated with zoledronate between 2021 and 2023 at a tertiary hospital in Indonesia. We evaluated the paediatric quality of life (PedsQL), bone mineral density (BMD), and alkaline phosphatase (ALP) level before and after zoledronate treatment. To monitor safety, serum creatinine and calcium levels were also measured. Eleven boys (55%) and nine girls (45%), with an average age of 6.9 years (range, 4-17 years), were included. After 2 years of zoledronate treatment, the total PedsQL score increased from 66.7 to 76.9 (P=0.0001) and the mean lumbar and total body BMD increased from 0.467 and 0.501 to 0.599 g/cm2, and 0.626 g/cm2 (P=0.001), respectively. The ALP level decreased from 310.6 to 186.4 mg/mL (P=0.0001). Neither serum creatinine (P=0.586) nor calcium (P=0.53) levels changed from the pre-treatment to 2 years post-treatment time points. Zoledronate was safe and effective for the treatment of OI. There were significant improvements in the quality of life and BMD in patients with OI. The ALP level decreased, but serum creatinine and calcium levels were not affected by zoledronate.

Associations of ethnicity, skin tone, and genome-wide sequencingwith bone mineral density in adolescents.

Dual-energy x-ray absorptiometry reference data designate Black and non-Black categories, as higher BMD has been documented among Black youth. We examined associations of race, skin tone, and genetic factors with bone mineral density (BMD). 557 adolescents were followed longitudinally. Exposures included race, skin tone, and principal components (PC) from genome-wide arrays. Total body BMD Z-score (BMD-Z) was the primary outcome using linear regression. 359 adolescents identified as non-Hispanic White (NHW) and 75, non-Hispanic Black (NHB). BMD-Z was higher in NHB vs. NHW (β: 0.92 units, 95% CI: 0.64, 1.19) or those with darker skin (0.79, 95% CI: 0.49, 1.08 for brown vs. medium). The first genetic PC (PC1) correlated with identification as NHB. PC1 was associated with higher BMD-Z (0.09, 95% CI: 0.06, 0.12), even after including race (0.07, 95% CI: 0.00, 0.14) or skin tone (0.10, 95% CI: 0.05, 0.15); both race (0.26, 95% CI: -0.49, 1.01 for NHB vs. NHW) and skin tone (-0.08, 95% CI: -0.59, 0.44 for brown vs. medium) no longer predicted BMD-Z after adjustment for PC1. Genetic similarity was robustly associated with BMD, prompting a reevaluation of adolescent BMD reference data to exclude the consideration of race. Current bone density reference databases include a binary assignment of patients into "Black" and "non-Black" categories, as a higher BMD has been documented among those identifying as Black compared with individuals of other racial and ethnic backgrounds. This study found genetic similarity to be more strongly associated with bone density by dual-energy x-ray absorptiometry than race or skin tone. These data emphasize a need to reevaluate how bone density measurements are interpreted, including exploring reference data that exclude the consideration of race.

Urinary phthalate metabolites associated with bone mineral density in adults: Data from the NHANES 2011–2018

Phthalates (PAEs) are common environmental endocrine disruptors and environmental bone poisons that can reduce bone mineral density (BMD). The purpose of this study is to investigate whether the concentration of PAE metabolites in urine is related to BMD in many parts of adult bones. We examined a series of cross-sectional data of male (n = 1835) and female (n = 1756) participants aged 18 to 59 years old in the National Health and Nutrition Examination Survey from 2011 to 2018 and measured urine PAE metabolites and dual-energy X-ray absorption to determine BMD (total body, lumbar spine, and pelvis). We used linear regression to test the correlation between a single phthalate biomarker and BMD. After adjusting all confounding variables, MEHP was positively correlated with BMD of total body, lumbar spine and pelvis, and BMD levels of the total body, lumbar spine and pelvis decreased with the increase of MECPP concentration. We used the restricted cubic spline function to test the nonlinear correlation between PAE biomarkers and BMD. The results show that urinary PAE metabolites have a nonlinear relationship with total body BMD, lumbar spine BMD, and pelvic BMD. With the increase in the PAE concentration, the BMD level first increased and then decreased, showing an inverted U-shaped trend (P < 0.05). Gender stratification also shows the same related trend. PAEs may be related to the BMD of adults. When the concentration of PAEs increases to a certain threshold, it will lead to a significant decrease in BMD.

Role of interleukin-18 in mediating the impacts of celiac disease on osteoporosis: a Mendelian randomization study.

Extensive observational data suggest a link between celiac disease (CeD) and osteoporosis, but the causality and mediating mechanism remain undetermined. Herein, we performed a Mendelian randomization (MR) study to address these concerns. We obtained the summary-level statistics for CeD from a large genome-wide association study (GWAS) comprising 4,533 cases and 10,750 controls of European ancestry. The GWAS data for osteoporosis-related traits and inflammatory cytokines were derived from the UK Biobank, FinnGen, IEU OpenGWAS database, or GWAS catalog. Two-sample MR with the inverse variance-weighted methods were employed to evaluate the genetic association between CeD and osteoporosis-related traits. The potential inflammatory mediators from CeD to osteoporosis were explored using two-step mediation analyses. The primary MR analyses demonstrated causal associations between genetically predicted CeD and osteoporosis (odds ratio [OR]: 1.110, 95% confidence interval [CI]: 1.043-1.182, p=0.001), total body bone mineral density (β: -0.025, p=0.039), and osteoporotic fracture (OR: 1.124, 95% CI: 1.009-1.253, p=0.034). Extensive sensitivity analyses consolidated these findings. Among the candidate inflammatory cytokines, only interleukin-18 was observed to mediate the effects of CeD on osteoporosis, with an indirect OR of 1.020 (95% CI: 1.000-1.040, p=0.048) and a mediation proportion of 18.9%. The mediation effects of interleukin-18 could be validated in other datasets (OR: 1.015, 95% CI: 1.001-1.029, p=0.041). Bayesian colocalization analysis supported the role of interleukin-18 in osteoporosis. The present MR study reveals that CeD is associated with an increased risk of developing osteoporosis, which may be partly mediated by upregulation of interleukin-18.

The genetic causal effect of hand grip strength on osteoporosis and falling risk: a Mendelian randomization study.

Patients with osteoporosis (OP) are often associated with decreased hand grip strength and increased risk of falling. It remains unclear whether there is a genetic causal between hand grip strength and OP, falling risk. The Mendelian randomization study was used to investigate the genetic causal effect of low hand grip strength on total body bone mineral density (BMD) at different ages, OP, and falling risk. Genes for low hand grip strength, total body BMD at different ages, OP, and falling risk were obtained from published genome-wide association studies. Inverse variance weighted, MR-Egger, and weighted median were applied to perform the MR analysis. The Cochran's Q test, MR-Egger intercept test, MR-PRESSO global test, and leave-one-out analysis were used to detect the pleiotropy or heterogeneity. The results showed strong evidence that low hand grip strength was positively associated with OP (OR: 1.006, 95% CI: 1.003-1.010; P= 0.0001) and falling risk (OR: 1.069, 95% CI: 1.013-1.129; P= 0.0160), and could not directly affect the different ages of total body BMD (P> 0.05). There was no heterogeneity or horizontal pleiotropy in the sensitivity analysis (all P> 0.05). The study found a positive causal relationship between low hand grip strength and higher risk of OP and falling, which should be taken into account in the development of future prevention and screening strategies for OP and falling.

Bone Health Assessment in Patients with Methylmalonic Acidemia

Abstract Background Methylmalonic acidemia (MMA) is a genetically heterogeneous disorder of methylmalonate and cobalamin metabolism. Isolated MMA is a rare inherited disorder of organic acid metabolism associated with elevated methylmalonic acid concentration in the blood and urine without elevation of homocysteine level or malonic acid. Nutritional intervention for MMA patients includes dietary restriction of proteins along with medical food and dietary supplements. Decreased bone mineral density (BMD) is a widely accepted complication of the life-long protein restricted diet in addition to accumulation of acids and toxic metabolites in those patients. Aim of the Study To investigate the effect of restricted and modified diet on bone health in a sample of patients with MMA. Subject and Methods Clinical, nutritional, selected laboratory parameters of bone health and bone mineral density (BMD) assessment by Dual-energy X-ray absorptiometry (DXA) scan of bones were carried out on Egyptian MMA patients from Genetics Clinic, Medical Genetic Department, Ain Shams University. Bone formation was assessed by measurement of serum osteocalcin level while bone resorption was evaluated by serum carboxy terminal telopeptide of collagen type 1 (S-CTX). Results The study included 24 patients from 14 families (13 males and 11 females). Their ages ranged between 5.2 to 26 years with median age of 10 years (IQR: 6.5-14). Consanguineous marriage was present in 91.67 of families. Median age of symptoms was 140 days (IQR: 3.5-332.5) while median age of diagnosis was 12 months (IQR (2.5-40). History of fractures was present in 5 patients (20.83%). Decreased total body BMD was detected in 14 patients (54.5 %) with mean Z score of -1.31 ± 1.38 SD. Decreased spine BMD was present in 21 patients (79.16%) with mean Z score of -1.9 ± 1.1 SD. This decrease was significantly related to non-compliance, chronic acidosis, low serum copper. There was no significant relation between BMD and creatinine, calcium, vitamin D, zinc, selenium, osteocalcin or S-CTX levels. Conclusion MMA patients have decreased BMD related to copper deficiency, poor compliance and chronic acidosis. This resulted in defective bone formation and increased bone resorption.

Causal relationship between neuroticism and bone mineral density: A univariable and multivariable Mendelian randomization study.

Recent observational studies have indicated that psychiatric disorders were associated with risk of bone mineral density (BMD) reduction. But the causal relationship between neuroticism and BMD remained unclear. By using public genome-wide association study data, a 2-sample bidirectional Mendelian randomization (MR) study was performed to investigate the causal relationship between neuroticism and BMD (heel BMD, forearm BMD, femoral neck BMD, lumbar spine BMD, and total body BMD). Inverse-variance weighted, weighted median, and MR-Egger were used to assess the causal effects. Multiple sensitivity analyses were conducted to assess the potential bias of the causal estimates. Multivariable MR analysis was used to assess the direct causal effects of neuroticism on BMD with adjustment of common risk factors of BMD reduction. Univariable MR analysis indicated that genetically predicted higher neuroticism was significantly associated with an increased risk of heel BMD reduction (inverse-variance weighted β = -0.039; se = 0.01; P = .0001; Bonferroni-corrected P = .0005) but not with other BMD (forearm BMD, femoral neck BMD, lumbar spine BMD, and total body BMD) potentially due to limited statistical power. The causal effects remained significant after accounting for the effects of body mass index, smoking, and drinking. Genetic proxy for higher neuroticism was significantly associated with an increased risk of heel BMD reduction. Further studies were warranted to elucidate the underlying biological mechanisms and explore the potential application in disease early screening and management.

Updated reference values for BMD and lean mass measured by DXA in Thai children.

This study established normative references for total body less head (TBLH) BMD, lumbar spine (L1-L4) BMD, and both total and appendicular lean mass (LM) in Thai children and adolescents (aged 5-18years) using DXA. This work expands upon 2014 normative data for Thai children, which included L2-L4 BMD, total body BMD (head included), and total LM. We reanalyzed total body and lumbar spine DXA scans (Lunar Prodigy Pro, GE Healthcare; enCORE version 7.53) from 174 boys and 193 girls, using upgraded software (enCORE version 17SP2) for TBLH BMD, L1-L4 BMD, and LM analysis. The "enhanced" mode was applied for TBLH BMD and LM. Adjustments for total and appendicular LM were made relative to squared height (m2) to account for body size variability. Normative data stratified by sex and Tanner stage were generated for TBLH BMD, L1-L4 BMD, and LM indices. Weight and Tanner stage significantly determined BMD and LM. Adolescent girls exhibited higher LSBMD values due to earlier pubertal onset. Boys showed higher LM indices with more rapid gains during growth spurts. This study provides updated normative reference values for BMD (TBLH and L1-L4) and LM (total and appendicular) in Thai children and adolescents, measured via DXA. These references will enhance the assessment of low bone mass and LM deficits in Thai pediatric populations, particularly in those with chronic illnesses.

Effects of FGF21 overexpression in osteoporosis and bone mineral density: a two-sample, mediating Mendelian analysis.

Fibroblast growth factor 21 (FGF21) is a secreted protein that regulates body metabolism. In recent years, many observational studies have found that FGF21 is closely related to bone mineral density and osteoporosis, but the causal relationship between them is still unclear. Therefore, this study used two-sample, mediated Mendelian randomization (MR) analysis to explore the causal relationship between FGF21 and osteoporosis and bone mineral density. We conducted a two-sample, mediator MR Analysis using genetic data from publicly available genome-wide association studies (GWAS) that included genetic variants in the inflammatory cytokine FGF21, and Total body bone mineral density, Heel bone mineral density, Forearm bone mineral density, Femoral neck bone mineral density, osteoporosis. The main analysis method used was inverse variance weighting (IVW) to investigate the causal relationship between exposure and outcome. In addition, weighted median, simple median method, weighted median method and MR-Egger regression were used to supplement the explanation, and sensitivity analysis was performed to evaluate the reliability of the results. MR Results showed that FGF21 overexpression reduced bone mineral density: Total body bone mineral density (OR=0.920, 95%CI: 0.876-0.966), P=0.001), Heel bone mineral density (OR=0.971, 95%CI (0.949-0.993); P=0.01), Forearm bone mineral density (OR=0.882, 95%CI(0.799-0.973); P=0.012), Femoral neck bone mineral density (OR=0.952, 95%CI(0.908-0.998), P=0.039); In addition, it also increased the risk of osteoporosis (OR=1.003, 95%CI (1.001-1.005), P=0.004). Sensitivity analysis supported the reliability of these results. The effect of FGF21 overexpression on osteoporosis may be mediated by type 2 diabetes mellitus and basal metabolic rate, with mediating effects of 14.96% and 12.21%, respectively. Our study suggests that the overexpression of FGF21 may lead to a decrease in bone mineral density and increase the risk of osteoporosis, and the effect of FGF21 on osteoporosis may be mediated through type 2 diabetes and basal metabolic rate. This study can provide a reference for analyzing the potential mechanism of osteoporosis and is of great significance for the prevention and treatment of osteoporosis.

Is there a causal relationship between resistin levels and bone mineral density, fracture occurrence? A mendelian randomization study.

In a great many of observational studies, whether there is a relevance of resistin levels on bone mineral density (BMD) and fracture occurrence has been inconsistently reported, and the causality is unclear. We aim to assess the resistin levels on BMD and fracture occurrence within a Mendelian randomization (MR) analysis. Exposure and outcome data were derived from the Integrative Epidemiology Unit (IEU) Open genome wide association studies (GWAS) database. Screening of instrumental variables (IVs) was performed subject to conditions of relevance, exclusivity, and independence. Inverse variance weighting (IVW) was our primary method for MR analysis based on harmonized data. Weighted median and MR-Egger were chosen to evaluate the robustness of the results of IVW. Simultaneously, heterogeneity and horizontal pleiotropy were also assessed and the direction of potential causality was detected by MR Steiger. Multivariable MR (MVMR) analysis was used to identify whether confounding factors affected the reliability of the results. After Bonferroni correction, the results showed a suggestively positive causality between resistin levels and total body BMD (TB-BMD) in European populations over the age of 60 [β(95%CI): 0.093(0.021, 0.165), P = 0.011]. The weighted median [β(95%CI): 0.111(0.067, 0.213), P = 0.035] and MR-Egger [β(95%CI): 0.162(0.025, 0.2983), P = 0.040] results demonstrate the robustness of the IVW results. No presence of pleiotropy or heterogeneity was detected between them. MR Steiger supports the causal inference result and MVMR suggests its direct effect. In European population older than 60 years, genetically predicted higher levels of resistin were associated with higher TB-BMD. A significant causality between resistin levels on BMD at different sites, fracture in certain parts of the body, and BMD in four different age groups between 0-60 years of age was not found in our study.

Acquisition of peak bone mass in a Norwegian youth cohort: longitudinal findings from the Fit Futures study 2010–2022

SummaryIn a Norwegian youth cohort followed from adolescence to young adulthood, bone mineral density (BMD) levels declined at the femoral neck and total hip from 16 to 27 years but continued to increase at the total body indicating a site-specific attainment of peak bone mass.PurposeTo examine longitudinal trends in bone mineral density (BMD) levels in Norwegian adolescents into young adulthood.MethodIn a prospective cohort design, we followed 980 adolescents (473 (48%) females) aged 16–19 years into adulthood (age of 26–29) on three occasions: 2010–2011 (Fit Futures 1 (FF1)), 2012–2013 (FF2), and 2021–2022 (FF3), measuring BMD (g/cm2) at the femoral neck, total hip, and total body with dual x-ray absorptiometry (DXA). We used linear mixed models to examine longitudinal BMD changes from FF1 to FF3.ResultsFrom the median age of 16 years (FF1), femoral neck BMD (mean g/cm2 (95% CI)) slightly increased in females from 1.070 (1.059–1.082) to 1.076 (1.065–1.088, p = 0.015) at the median age of 18 years (FF2) but declined to 1.041 (1.029–1.053, p < 0.001) at the median age of 27 years (FF3). Similar patterns were observed in males: 16 years, 1.104 (1.091–1.116); 27 years, 1.063 (1.050–1.077, p < 0.001); and for the total hip in both sexes (both p < 0.001). Total body BMD increased from age 16 to 27 years in both sexes (females: 16 years, 1.141 (1.133–1.148); 27 years, 1.204 (1.196–1.212), p < 0.001; males: 16 years, 1.179 (1.170–1.188); 27 years, 1.310 (1.296–1.315), p < 0.001).ConclusionBMD levels increased from 16 to 18 years at the femoral and total hip sites in young Norwegian females and males, and a small decline was observed at the femoral sites when the participants were followed up to 27 years. Total body BMD continued to increase from adolescence to young adulthood.

Association between nonalcoholic fatty liver disease and bone mineral density: Mendelian randomization and mediation analysis

BackgroundObservational studies have reported significant association between non-alcoholic fatty liver disease (NAFLD) and bone mineral density (BMD), a critical indicator of bone health. We aimed to investigate whether NAFLD is a cause for changes in BMD. MethodsWe selected 29 independent SNPs as instrumental variables for NAFLD. A range of Mendelian randomization (MR) methods, namely the inverse variance-weighted (IVW) method, weighted-median, weighted-mode, and MR-Egger regression, were utilized to determine the causal effects of NAFLD on BMD. Two-step MR analysis was conducted to determine the mediating effect of fasting glucose, insulin, glycosylated hemoglobin, low-density cholesterol, and body-mass index on the association between NAFLD and BMD. False-discovery-rate (FDR) was used to correct for multiple testing bias. ResultsThe IVW-method indicated a significantly inverse association between genetically predicted NAFLD and total body BMD (β = −0.04, 95 % CI -0.07 to −0.02, FDR = 0.010). Notably, the relationship was more pronounced in participants over 60 years of age (β = −0.06, 95 % CI -0.11 to −0.02, FDR = 0.030). Inverse associations were observed in other subpopulations and in site-specific BMD, though they were not statistically significant after correcting for multiple testing. We observed a significantly positive association between NAFLD and the risk of osteoporosis. Consistency in results was observed across multiple MR methods and in the repeated analysis. Fasting glucose, insulin, and glycosylated hemoglobin mediated 25.4 % (95 % CI 17.6–31.5 %), 18.9 % (12.0–24.9 %), and 27.9 % (19.9–36.7 %) of the effect of NAFLD on BMD, respectively. ConclusionOur findings underscore a probable causal negative link between NAFLD and BMD, indicating that NAFLD might detrimentally affect bone health, especially in older individuals.

Mendelian randomization study on association between grip strength and BMD in different age groups

IntroductionThis study aimed to use the Mendelian randomization study method to verify the causal relationship between grip strength and bone mineral density (BMD) in different ages and different parts of the body.Materials and methodsThe analysis was based on pooled data from genome-wide association studies (GWAS). Hand grip strength (right) was used as the exposure variable and total body bone mineral density (BMD) of different age groups was used as the outcome variable. Single-nucleotide polymorphisms highly correlated with exposure variables were used as instrumental variables. The inverse variance weighted (IVW) method was used as the primary analysis method, and the Mendelian randomization Egger (MR-Egger) regression and weighted median methods were used as supplementary evidence for the IVW results. Horizontal pleiotropy and heterogeneity tests were conducted to ensure the stability of the results.ResultsAnalyzing the GWAS data on osteoporosis as the outcome variable, the IVW analysis showed that osteoporosis risk was associated with decreased grip strength in the 45–60 age group and the risk of declining lumbar spine BMD was associated with decreased grip strength. However, there was no significant correlation between the risk of osteoporosis in other age groups and changes in grip strength.ConclusionA causal relationship exists between decreased grip strength and osteoporosis risk in people aged 45–60 years. The risk of BMD declining in the lumbar spine was associated with reduced grip strength.