Low Bone Mineral Density Group Research Articles

MRI-based vertebral bone quality score as a novel bone status marker of patients with adolescent idiopathic scoliosis

To investigate the application of MRI-based vertebral bone quality (VBQ) score in assessing bone mineral density (BMD) for patients with adolescent idiopathic scoliosis (AIS). We reviewed the data of AIS patients between January 2021 and October 2023 with MRI, whole-spine plain radiographs, quantitative computed tomography (QCT) and general information. VBQ score was calculated using T1-weighted MRI. Univariate analysis was applied to present the differences between variables of patients with normal BMD group (QCT Z-score > − 2.0) and low BMD group (QCT Z-score ≤ − 2.0). The correlation between VBQ score and QCT Z-score was analyzed with Pearson correlation test. A multivariate logistic regression model was used to determine the independent factors related to low BMD. Receiver operating characteristic curve (ROC) was drawn to analyze the diagnostic performance of VBQ score in distinguishing low BMD. A total of 136 AIS patients (mean age was 14.84 ± 2.10 years) were included, of which 41 had low BMD. The low BMD group had a significantly higher VBQ score than that in normal group (3.48 ± 0.85 vs. 2.62 ± 0.62, P < 0.001). The VBQ score was significantly negative correlated with QCT Z score (r = − 0.454, P < 0.001). On multivariate analysis, VBQ score was independently associated with low BMD (OR: 4.134, 95% CI 2.136–8.000, P < 0.001). The area under the ROC curve indicated that the diagnostic accuracy of the VBQ score for predicting low BMD was 81%. A sensitivity of 65.9% with a specificity of 88.4% could be achieved for distinguishing low BMD by setting the VBQ score cutoff as 3.18. The novel VBQ score was a promising tool in distinguishing low BMD in patients with AIS and could be useful as opportunistic assessment for screening and complementary evaluation to QCT before surgery.

Factors affecting bone mineral density in children and adolescents with systemic lupus erythematosus.

Patients with juvenile-onset systemic lupus erythematosus (JSLE) are at a high risk of entering adulthood with disease-related morbidities like reduced bone mass and osteoporosis. This study aimed to evaluate the clinical characteristics of JSLE and to analyze the factors associated with low bone mineral density (BMD) in these patients. Children and adolescents diagnosed with JSLE at a single institution in Korea were included. Demographic, clinical, and laboratory data as well as details about the use of glucocorticoids (GCs) and disease-modifying antirheumatic drugs were collected. The lumbar spine (LS) BMD z-score was measured using dual energy x-ray absorptiometry, and lateral thoracolumbar spine radiographs were collected. A total of 29 patients with JSLE were included in this study. Of these patients, 7 had a BMD z-score of -2.0 or lower and were designated as the low BMD group. The differences in the clinical parameters and treatment variables between the low BMD and non-low BMD groups were compared. Higher cumulative GC dose, longer GC exposure, and higher cumulative hydroxychloroquine (HCQ) dose were all associated with low BMD; among them, the main factor was the duration of GC exposure. There was no significant correlation between BMD and clinical profile, disease activity, or bone-metabolism markers. The duration of GC exposure, cumulative GC dose, and cumulative HCQ dose were risk factors for low BMD in patients with JSLE, with the main factor being the duration of GC exposure. Thus, patients with JSLE should be routinely monitored for low BMD and potential fracture risks, and GC-sparing treatment regimens should be considered.

Associations among gene polymorphisms, crestal bone loss, and bone mineral density in patients receiving dental implants

ObjectivesInterleukin 1 (IL-1) and interleukin 6 (IL-6) gene polymorphisms have been suggested to be responsible for diminished bone mineral density (BMD) and high crestal bone loss (CBL) in some individuals. However, the effects of systemic BMD on variations in peri-implant CBL are unclear. Hence, this study was aimed at investigating the association of IL-1 and IL-6 gene polymorphisms with systemic BMD and CBL around dental implants. MethodsA total of 190 participants undergoing dental implantation in the mandibular posterior region were selected according to predetermined selection criteria and divided into a normal BMD group (NBD, 93 participants, T-score ≥ −1) and low BMD group (LBD, including both osteoporosis and osteopenia, 97 participants, T-score < −1 standard deviation) according to the BMD of the right femoral neck, measured with dual-energy X-ray absorptiometry. Dental implants were placed through the standard surgical protocol, and CBL was calculated after 6 months with cone beam computed tomography scans before second-stage surgery. Genotyping was performed on all participants for IL-1A-889 A/G, IL-1B-511G/A, IL-1B+3954, and IL-6-572 C/G gene polymorphisms. ResultsThe demographic and clinical characteristics of the participants in both groups were compared with t-test and chi-square test (χ2). The associations of NBD and LBD with the different genotypes and CBL was determined with odds ratios, and p < 0.05 was considered statistically significant. The frequency of IL-1B-511AA and IL-6-572 GG genotypes was significantly higher in LBD than in NBD (p < 0.05). In LBD, the IL-1B-511 AA (AA vs GA + GG; p ≤ 0.001) and IL-6-572 GG (GG vs CC + GC; p = 0.001) genotypes were significantly associated with higher peri-implant CBL. ConclusionsIndividuals with the IL-1B-511 AA or IL-6-572 GG genotype had elevated risk of osteoporosis/osteopenia and were more susceptible to CBL around dental implants.

Persistent low bone mineral density in adolescent idiopathic scoliosis: A longitudinal study

BackgroundSince osteopenia has been reported to potentially associated with the progression of scoliosis, bone mineral density (BMD) might have some influences on adolescent idiopathic scoliosis (AIS). However, little is known about longitudinal BMD changes in AIS patients. This study aimed to investigate whether osteopenia in preoperative AIS patients persist at bone maturity, and to evaluate the association between BMD and AIS severity. MethodsWe reviewed 61 AIS patients who underwent surgery when they were Risser grade 4 or below and less than 20 years old (16.6 ± 1.9 years), were followed until they were at least 18 years old and had a Risser grade of 5, and followed at least 2 years after the surgery (mean follow-up 4.9 ± 1.7 years). We evaluated radiographical parameters and proximal femur BMD before surgery and at the final follow-up. A BMD of less than the mean minus 1SD was considered as low BMD. Based on preoperative BMD, 37 patients were assigned to normal BMD (N) group (1.02 ± 0.08 g/cm2) and 24 patients to low BMD (L) group (0.82 ± 0.06 g/cm2). ResultsAll patients in the N-group had normal BMD at the final follow-up. In the L group, 15 patients (62.5%) had low BMD at the final follow-up (L–L group; preoperative 0.79 ± 0.05 g/cm2 and final follow-up 0.78 ± 0.05 g/cm2). The mean preoperative Cobb angle was significantly larger in the L–L group (67.8 ± 11.2°) than in those with normal BMD at the final follow-up (L–N group, 55.6 ± 11.8°) or the N–N group (50.8 ± 7.6°). Preoperative BMD was significantly negative correlated with the preoperative Cobb angle. The age at surgery and mean preoperative BMI were similar in the L–N and L–L groups. ConclusionsOf AIS patients with low preoperative BMD, 62.5% still had low BMD after reaching bone maturity, and low BMD was associated with the severity of scoliosis.

Prospective assessment of osteoporosis in total shoulder arthroplasty

HypothesisThe risks of shoulder arthroplasty in those with osteopenia and osteoporosis are not fully understood. The purpose of this study was to prospectively evaluate intraoperative complications in those undergoing shoulder arthroplasty with low bone mineral density (BMD). MethodsWe prospectively enrolled consecutive patients undergoing shoulder arthroplasty with a preoperative computed tomography (CT) scan from January to July 2021. Exclusion criteria included age <50 years, revision surgery, fracture, diagnosis of inflammatory arthropathy, or active infection. An intraoperative survey assessing bone quality and complications was collected. A blinded reviewer then measured bone quality based on preoperative CT scan using a previously validated method. Subjects were then divided between normal and low BMD groups with low BMD including both osteopenia and osteoporosis. ResultsWe enrolled 75 consecutive patients who met all inclusion criteria. Nine patients were excluded due to incomplete imaging leaving a final cohort of 66 patients. The average age was 69.2 years (50.4-88.5 years), with 41 males (62.1%) and 25 females (37.9%). There were 33 anatomic total shoulder arthroplasties and 33 reverse shoulder arthroplasties. Surgeons were very accurate in identifying normal bone intraoperatively (95.5% correct) but less accurate in identifying poor bone quality (45.5% correct). Surgeons reported making changes to their plan or technique in 8 cases (12%), with 7 (87.5%) of these changes occurring in those with poor bone quality. The lesser tuberosity was damaged with posterior retraction in 16 cases (24.2%), with 13 (81.3%) of those being in patients with poor bone quality. There was 1 intraoperative glenoid rim fracture, which occurred in a patient with low bone density. ConclusionThe prevalence of osteoporosis in the population undergoing shoulder arthroplasty is high. Performing shoulder arthroplasty on those with poor bone quality presents multiple challenges, which are underappreciated. Being able to better predict bone quality based on preoperative CT imaging can alert the surgeon to potential intraoperative complications.

PERIACETABULAR BONE CHANGES AFTER TOTAL HIP ARTHROPLASTY WITH HIGHLY POROUS TITANIUM CUPS IN PATIENTS WITH LOW BONE MASS.

The aim: To assess the bone remodeling around highly porous titanium cups TTM in patients with low bone mass one year after total hip arthroplasty (THA). Materials and methods: In this prospective study were included 18 patients (18 hips), whom was performed primary THA with the use of TTM cups. According to T-score of Lumbar Spine, patients were divided into 2 groups: normal bone mineral density (BMD) (n=9) if T-score ≥ -1, and low BMD (n=9) if T-score < -1. According to DeLee and Charnley's model BMD in 3 periacetabular regions were evaluated 1 week and 1 year after THA. Results: One year after primary THA, BMD of all 3 periacetabular regions did not differ in patients of both groups comparing with initial data. One week after THA, it was found that BMD R1 and BMD R3 in low BMD group were lower by 1.4 times (p=0.035) and 1.5 times (р=0.001) respectively, BMD R2 did not differ from the normal BMD group. One year after THA it was found that in low BMD group BMD R1 and BMD R2 were lower by 1.5 times (р=0.005) and 1.3 times (р=0.050) respectively, BMD R3 did not differ from the group with normal BMD. Conclusions: The use of highly porous titanium cups TTM in patients with low bone mass did not lead to a bone loss in DeLee and Charnley periacetabular zones one year after THA. Consequently, the use of these cups in patients with low bone mass undergoing THA is a valuable treatment option.

Association between the appendicular lean mass index or handgrip strength and bone mineral density in patients undergoing peritoneal dialysis.

Background: Few studies have investigated the association between muscle mass and bone mineral density (BMD) in patients undergoing peritoneal dialysis (PD). We aimed to investigate the association between muscle mass or strength and BMD in patients undergoing PD.Methods: The data of all prevalent PD cases at a tertiary medical center between September 2017 and November 2020 were collected. Among all patients, 199 patients undergoing PD were finally analyzed. Baseline measurements including handgrip strength (HGS), appendicular lean mass (ALM) index, and BMD were obtained during a peritoneal membrane equilibration test. Patients with a T-score of ≤ -2.5 were categorized into the low BMD group.Results: The number of male patients was 113 (56.8%). Significant differences were observed in various indices, such as BMD, body composition parameters, and laboratory findings, between male and female patients. There was a stronger association between BMD and ALM index than between BMD and HGS in male patients (r = 0.432 and P < 0.001). The association between BMD and HGS was more definitive in female patients than in male patients (r = 0.357 and P = 0.001). Univariate and mutivariate linear regression and AUROC analyses showed similar trends those obtained in correlation analyses.Conclusion: The present study demonstrated that BMD is associated with the ALM index in male patients and with HGS in female patients undergoing PD.

Screening of Important Markers in Peripheral Blood Mononuclear Cells to Predict Female Osteoporosis Risk Using LASSO Regression Algorithm and SVM Method.

Background:Osteoporosis is a bone disease that increases the patient’s risk of fracture. We aimed to identify robust marker genes related to osteoporosis based on different bioinformatic methods and multiple datasets.Methods:Three datasets from Gene Expression Omnibus (GEO) were utilized for analysis separately. Significantly differentially expressed genes (DEGs) from comparing high hip and low hip low bone mineral density (BMD) groups in the first dataset were identified for Gene Ontology (GO), Gene set enrichment analysis (GSEA) and Kyoto encyclopedia of genes and genomes (KEGG) to investigate the discrepantly enriched biological processes between high hip and low hip group. Last absolute shrinkage and selection operator (LASSO), SVM model and protein-protein interaction (PPI) regulatory network were performed and generated robust marker genes for downstream TF-target and miRNA-target prediction.Results:Several DEGs between high hip BMD group and low hip BMD group were obtained. And the metabolism-related pathways such as metabolic pathways, carbon metabolism, glyoxylate and dicarboxylate metabolism shown enrichment in these DEGs. Integration with LASSO regression analysis, 8 differential expression genes (SH3BP1, NARF, ANKRD34B, RNF40, ZNF473, AKT1, SHMT1, and VASH1) in GSE62402 were identified as the optimal differential genes combination. Moreover, the SVM validation analysis in GSE56814 and GSE56815 datasets showed that the characteristic gene combinations presented high diagnostic effects, and the model AUC areas for GSE56814 was 0.899 and for GSE56815 was 0.921. Furthermore, the subcellular localization analysis of the 8 genes revealed that 4 proteins were located in the cytoplasm, 3 proteins were located in the nucleus, and 1 protein was located in the mitochondria. Additionally, the related TFs and miRNAs by performing TF-target and miRNA-target prediction for 5 genes (AKT1, SHMT1, ZNF473, RNF40 and VASH1) were investigated from PPI network.Conclusion:The optimal differential genes combination (SH3BP1, NARF, ANKRD34B, RNF40, ZNF473, AKT1, SHMT1, and VASH1) presented high diagnostic effect for osteoporosis risk.

The association between bone mineral density and postoperative drainage volume following cruciate-substituting primary total knee arthroplasty: a cross-sectional study

BackgroundThe prevalence of osteoporosis in patients who undergo a primary total knee arthroplasty (TKA) is increasing. Low bone mineral density (BMD) is related to unfavorable outcomes following TKA such as migration of uncemented tibial components. Postoperative blood loss in TKA is an important complication. Non-modifying predicting factors for postoperative blood loss in patients undergoing primary TKA need further elucidation. Studies on the association between BMD and blood loss after TKA are limited. We aimed to demonstrate the relationship between BMD and postoperative drainage volume following primary TKA.MethodsA cross-sectional study was conducted between January 2014 and August 2020. A total of 119 primary varus osteoarthritis knees with BMD results were included in the study. Patients with secondary causes of osteoporosis were excluded.ResultsThe median postoperative drainage volume of participants in the normal total hip BMD group and the normal trochanter BMD group was higher than that of patients in the low total hip BMD group and the low trochanter BMD group (285.0 ml vs 230.0 ml, P = 0.003; 282.5 ml vs 240.0 ml, P = 0.013, respectively). Multivariate regression analyses showed that operative time, spinal anesthesia, and normal total hip BMD status were significant predictive factors associated with increased postoperative drainage volume (P = 0.014, 0.022, and 0.013, respectively). No association was identified between the lumbar spine BMD status and postoperative drainage volume.ConclusionsThe relationship between BMD and postoperative blood loss in primary TKA was identified in this study. Normal total hip BMD was found to be associated with an increased postoperative drainage volume after primary TKA compared with low BMD.

Evaluation of the relationship between homocysteine levels and bone mineral density in postmenopausal women

Objective The current study aimed to evaluate the relationship between homocysteine (Hcy) levels and bone mineral density (BMD) in postmenopausal women. Methods The present, cross-sectional study included 760 postmenopausal women. The following variables were recorded: age, age at menopause, body mass index (BMI), BMD (measured by dual-energy X-ray absorptiometry [DXA] scanning and expressed as lumbar, femoral neck and total hip T-scores), smoking status, biochemical parameters (Hcy, creatinine, calcium, phosphorus, vitamin D and parathormone levels) and vitamin D supplementation. Results The mean age of the sample population was 56.4 ± 5.77 years and the mean age at menopause was 49.9 ± 3.62 years. The mean BMI was 25.2 ± 4.49 kg/m2. In the current study, a comparison of the subjects with osteoporosis, osteopenia and normal BMD revealed that the subjects in the low BMD group were significantly older (p < 0.001), had a lower age at menopause (p < 0.001) and had lower BMI (p < 0.001). There was no statistically significant difference among the groups with regard to the plasma levels of Hcy (p = 0.946). The levels of Hcy were positively correlated to the creatinine levels (r = 0.21). The present study did not observe any significant correlations between the Hcy levels and other parameters. Conclusions In the present study, 15.3% of the subjects had hyperhomocysteinemia and 62.11% had low BMD. The current results obtained from a group of postmenopausal women suggest that the plasma levels of Hcy are not related to BMD in the lumbar spine (L1–L4), femoral neck and total hip. In the current study, age, age at menopause and low BMI were observed to be associated with low BMD.

Vitamin D Metabolites and Sex Steroid Indices in Postmenopausal Women with and without Low Bone Mass.

While the independent roles of vitamin D and sex hormones in skeletal health are well established, the associations of vitamin D and its metabolites to sex hormones and their indices are less investigated. In this observational study, clinical information of 189 Saudi postmenopausal women aged ≥50 years old [N = 80 with normal bone mineral density (BMD), aged 53.3 ± 7.7 years with body mass index (BMI)= 34.1kg/m2 ± 5.8, and N = 109 with low BMD (T-score −1.0 to −2.5), aged 57.0 ± 8.2 years, BMI = 32.4kg/m2 ± 6.2] was extracted from an existing capital-wide osteoporosis registry in Riyadh, Saudi Arabia. Data included were BMD scores, serum total 25(OH)D, sex hormones, and bone turnover markers which were measured using commercially available assays. Age- and BMI-adjusted comparisons revealed significantly higher parathyroid hormone (PTH) levels as well as significantly lower testosterone and bioavailable testosterone in the low BMD group than the normal BMD group (p-values 0.04, 0.02, and 0.03, respectively). Stepwise linear regression showed that circulating testosterone levels accounted for 9.7% and 8.9% of the variances perceived in bioavailable 25(OH)D and free 25(OH)D, respectively (p < 0.01), independent of other sex hormones, sex hormone indices, and bone turnover markers. Our study suggests that androgens are significantly associated with non-conventional vitamin D metabolites and these associations may have clinical relevance in assessing risk for low BMD and osteoporosis in Arab postmenopausal women.

Computed tomography-measured bone mineral density as a surrogate marker of survival after resection of colorectal liver metastases.

BackgroundOsteopenia/osteoporosis, characterized by low bone mineral density (BMD), is a potential prognostic factor in cancer patients. We conducted a retrospective single-institution study to evaluate the prognostic impact of preoperative low BMD on colorectal liver metastases (CRLM) in patients undergoing liver resection.MethodsBMD was assessed in 281 patients undergoing initial liver resection for CRLM by analyzing the preoperative computed tomography (CT) images at the level of the eleventh thoracic vertebra as the region of interest. Survival outcomes were compared between the two groups divided by the median BMD value and prognostic factors after surgery were assessed. Propensity score-based inverse probability weighting (IPW) was applied to adjust for between-group differences in baseline characteristics.ResultsThe low BMD group had significantly more older patients (≥75 years) (P=0.01) and a higher incidence of bilobar metastases (P=0.005) than the normal BMD group. After IPW adjustment, overall survival (OS) was significantly poorer (P=0.02) and recurrence-free survival was slightly poorer (P=0.05) in the low BMD group than in the normal BMD group. IPW-adjusted regression analysis revealed that low BMD was independently associated with an adverse OS (hazard ratio, 1.42; 95% CI, 1.04–1.93; P=0.03), in addition to other factors such as tumor number, extrahepatic disease, preoperative carcinoembryonic antigen level (≥5 ng/mL), and right-sided primary tumor location.ConclusionsPreoperative CT-measured low BMD can serve as a surrogate marker of adverse OS in CRLM patients undergoing liver resection. Prevention and early intervention for osteopenia/osteoporosis may be suggested for these patients.

Serum anti-Müllerian hormone levels are associated with low bone mineral density in premenopausal women

Objective To investigate the associations between anti-Müllerian hormone (AMH) and bone mineral density (BMD) induced by ovarian insufficiency in premenopausal women. Methods Subjects were consecutively enrolled from January 2015 to December 2018. Dual energy X-ray absorptiometry (DXA) examination was set as the gold standard, with T-scores less than −2.5/1 as thresholds for the definition of osteoporosis (OP)/osteopenia. Results A total of 87 subjects were included in the low BMD group, and 39 subjects were included in the control group. Serum AMH levels were decreased significantly in the low BMD group (p < 0.05) with a negative correlation between AMH and age. Strong positive correlations between AMH and BMD/T-score existed in all subjects and subjects with low BMD, and remained even after age adjustment. An exploratory multivariate regression model indicated that age and AMH remained predictive and might be independent risk factors with adjusted odds ratios (ORs) of 0.9 (p = 0.009) and 36 (p < 0.001), respectively. The receiver operating characteristic (ROC) curve analysis estimated that the sensitivity and specificity were 78.2 and 76.9%, respectively, for identifying low BMD subjects from controls when the cut-off value for AMH was set to 0.800 ng/mL. Conclusions Serum AMH levels are associated with low BMD in premenopausal women with suspected ovarian insufficiency.

Bone Metabolism Alterations in Patients with Common Variable Immune Deficiency: A Retrospective Cohort Study

Objective: Common variable immunodeficiency (CVID) is a relatively frequent primary immunodeficiency disorder characterized by impaired B cell differentiation with hypogammaglobulinemia in the European Society for Immunodeficiencies (ESID) registry system. Increased inflammatory cytokines, prolonged and/or recurrent infections, gastrointestinal complications, and anti-inflammatory medications are risk factors for diminished bone mineral density (BMD) in CVID patients. Materials and Methods: The study group included 32 patients with CVID (19 males and 13 females; mean age: 37.33 ± 13.70 years, 40.6% female), who had been followed up on a regular basis for a period of four years. The patients were categorized into two groups according to their BMD: low BMD and normal BMD. Results: Seventeen patients (8 females and 9 males) had normal BMD (mean age 34.94 ± 11.41 years, 47.1% female) and fifteen patients (5 females and 10 males) had low BMD (mean age 40.03 ± 15.87 years, 33.3% female). In the low BMD group, three patients had osteoporosis and 12 patients had osteopenia. Univariate regression analysis revealed that lymphopenia (odds ratio, OR:6.562, 95% confidence interval, CI: 1.095-39.324, p=0.039) was significantly associated with low BMD. Multivariate regression analysis showed that higher alkaline phosphatase (ALP) levels (OR:1.017, 95% CI 1.001-1.033, p=0.041), lymphopenia (OR:11.028, 95% CI 1.326-91.709, p=0.026), and lower folic acid levels (OR:1.284, 95% CI 1.007-1.637, p=0.043) were also independent predictors for low BMD. Conclusion: Even with some limitations such as the small number for the study population, a single center experience, and a crosssectional design, we recommend that clinical immunologists should be alert for diminished BMD in CVID patients, especially those with low folic acid and high ALP levels and lymphopenia.

Differences in Physical Activity and Sedentary Behavior Patterns of Postmenopausal Women With Normal vs. Low Total Hip Bone Mineral Density.

Purpose: Recent evidence suggests that sedentary behavior (SB) may be associated with bone health. This study compares free-living physical activity (PA) and SB distribution patterns of postmenopausal women with normal vs. low total hip bone mineral density (BMD).Methods: Sixty nine post-menopausal women [mean (min-max) age: 61 (46–79) years] wore ActiGraph GT3X+ activity monitors on the bilateral ankles for 7 days in free-living. Participants were split into two groups: those with normal hip BMD (T-scores ≥-1.0; N = 34) and those with low hip BMD (T-scores <-1.0; N = 35) as defined by the World Health Organization. Daily active time, step counts, sedentary time, sedentary break number, and median sedentary bout length were estimated from ankle acceleration data. The distribution and accumulation patterns of time spent in sedentary bouts, sedentary breaks, and stepping bouts, and sedentary break and stepping bout lengths' variability were also investigated. Group differences were assessed using two-sampled t-tests and Mann-Whitney U-tests with significance levels of 0.5.Results: Significant between group differences (p < 0.05) were in total daily active time [median (IQR): 257 (209–326) vs. 249 (199–299) min], step count [14,188 (10,938–18,646) vs. 13,204 (10,337–16,630) steps], sedentary time [669 (584–731) vs. 687 (615–753) min], and sedentary break number [93 (68–129) breaks vs. 88 (64–113) breaks], as well as median sedentary bout length [15.1 (11.9–22.1) vs. 15.8 (12.1–24.9) min]. Participants' sedentary bouts were found to be power law distributed with 52% of sedentary time occurring in bouts ≥20 min for the normal BMD group, and 58% for the low BMD group. Significant differences were observed between groups in sedentary bouts' and sedentary breaks' power distribution exponents (p < 0.0001) and patterns of sedentary and stepping time accumulation using the Gini index (p ≤ 0.0014). Variability was significantly lower for sedentary break and stepping bout lengths for the low BMD group (p ≤ 0.0001). Participants with lower hip BMD have longer sedentary bouts with shorter and less complex activity bouts compared to participants with normal hip BMD.Conclusion: The results suggest healthier hip BMD may be associated with PA distributed more evenly throughout the day with shorter sedentary bouts. PA distribution should be considered in exercise-based bone health management programs.

Associations of dietary vitamin K and bone markers in adult Saudi females

ObjectiveOsteoporosis is a bone disease characterized by bone mass reduction with a prevalence of approximately 34–48% in Saudi Arabia. Many risk factors can increase osteoporosis fracture, including low vitamin K levels. However, its exact role on bone mineral density (BMD) remains under investigated. This study aims to determine whether dietary vitamin K is associated with BMD, inflammation, undercarboxylated osteocalcin (ucOC) and other bone markers among adult Saudi females. MethodsA total of 138 Saudi females aged 25 and above were recruited from different primary health care centers in Riyadh, Saudi Arabia, and were divided according to BMD status (N = 53 normal; N = 85 low BMD). Each participant completed a food frequency questionnaire. Anthropometrics were measured and serum 25(OH)D and vitamin K, bone markers (ucOC and CTX) and cytokines (IL-6, TNF-α) were assessed using assays. ResultsLow dietary vitamin K intakes were observed in both groups, ranging only 16–19 µg/day. A positive association was seen between dietary vitamin K and IL-6 in low BMD group and TNF-α in all participants. No significant association was seen between dietary vitamin K and BMD. ConclusionDietary vitamin K is significantly associated with inflammation and not BMD in adult Saudi females. The alarmingly low dietary vitamin K intake is worth investigating further.

Network-based Transcriptome-wide Expression Study for Postmenopausal Osteoporosis.

Menopause is a crucial physiological transition during a woman's life, and it occurs with growing risks of health issues like osteoporosis. To identify postmenopausal osteoporosis-related genes, we performed transcriptome-wide expression analyses for human peripheral blood monocytes (PBMs) using Affymetrix 1.0 ST arrays in 40 Caucasian postmenopausal women with discordant bone mineral density (BMD) levels. We performed multiscale embedded gene coexpression network analysis (MEGENA) to study functionally orchestrating clusters of differentially expressed genes in the form of functional networks. Gene sets net correlations analysis (GSNCA) was applied to assess how the coexpression structure of a predefined gene set differs in high and low BMD groups. Bayesian network (BN) analysis was used to identify important regulation patterns between potential risk genes for osteoporosis. A small interfering ribonucleic acid (siRNA)-based gene silencing in vitro experiment was performed to validate the findings from BN analysis. MEGENA showed that the "T cell receptor signaling pathway" and the "osteoclast differentiation pathway" were significantly enriched in the identified compact network, which is significantly correlated with BMD variation. GSNCA revealed that the coexpression structure of the "Signaling by TGF-beta receptor complex pathway" is significantly different between the 2 BMD discordant groups; the hub genes in the postmenopausal low and high BMD group are FURIN and SMAD3 respectively. With siRNA in vitro experiments, we confirmed the regulation relationship of TGFBR2-SMAD7 and TGFBR1-SMURF2. The present study suggests that biological signals involved in monocyte recruitment, monocyte/macrophage lineage development, osteoclast formation, and osteoclast differentiation might function together in PBMs that contribute to the pathogenesis of postmenopausal osteoporosis.

Mendelian Randomization Identifies CpG Methylation Sites With Mediation Effects for Genetic Influences on BMD in Peripheral Blood Monocytes.

Osteoporosis is mainly characterized by low bone mineral density (BMD) and is an increasingly serious public health concern. DNA methylation is a major epigenetic mechanism that may contribute to the variation in BMD and may mediate the effects of genetic and environmental factors of osteoporosis. In this study, we performed an epigenome-wide DNA methylation analysis in peripheral blood monocytes of 118 Caucasian women with extreme BMD values. Further, we developed and implemented a novel analytical framework that integrates Mendelian randomization with genetic fine mapping and colocalization to evaluate the causal relationships between DNA methylation and BMD phenotype. We identified 2,188 differentially methylated CpGs (DMCs) between the low and high BMD groups and distinguished 30 DMCs that may mediate the genetic effects on BMD. The causal relationship was further confirmed by eliminating the possibility of horizontal pleiotropy, linkage effect and reverse causality. The fine-mapping analysis determined 25 causal variants that are most likely to affect the methylation levels at these mediator DMCs. The majority of the causal methylation quantitative loci and DMCs reside within cell type-specific histone mark peaks, enhancers, promoters, promoter flanking regions and CTCF binding sites, supporting the regulatory potentials of these loci. The established causal pathways from genetic variant to BMD phenotype mediated by DNA methylation provide a gene list to aid in designing future functional studies and lead to a better understanding of the genetic and epigenetic mechanisms underlying the variation of BMD.

Effect of long-term glucocorticoid therapy on bone mineral density of the patients with congenital adrenal hyperplasia.

Congenital adrenal hyperplasia (CAH) is characterized by androgen excess which should be treated with life-long glucocorticoid therapy, thus can affect bone mineralization. We aimed to evaluate the bone mineral density (BMD) and determine the factors affecting bone mineralization in patients with CAH. This prospective case-control study was conducted in children, adolescents and young adults with classical 21-hydroxylase CAH, and age-, sex-, and pubertal stage matched healthy controls. Lumbar1-4 BMD was determined by dual-energy X-ray absorptiometry. BMD z-score was calculated using national standards with respect to height age and was referred as `low BMD` if z-score < -1 SD. Univariate analyses were performed between low BMD and normal BMD groups, and multivariate logistic regression analysis was performed to assess the independent predictors of low BMD. Correlations of Body Mass Index (BMI)-z-score, average serum 17-hydroxyprogesterone level, duration of treatment, average and cumulative glucocorticoid doses with BMD z-score were evaluated with Spearman analyses. Each group included 37 cases. BMD z-score of patients with CAH [0.47 (-0.04 - 1.56)] was higher than control group [-0.43 (-0.82 -0.05)]; p= < 0.001. Number of patients with low BMD was similar in both groups; [CAH: 6(16.2%), control: 5(13.5%); p= 0.744]. BMI- z-score was higher in patients with CAH when compared to control group; p= < 0.001. BMI z-score was lower in low BMD group as comparison to normal BMD group; p= 0.041. Each 1.0 decrease in BMI z-score, risk of having low BMD was found to increase by 1.79 (%95 CI: 1.03- 3.12, p= 0.040). BMI-z-score, average serum 17-hydroxyprogesterone level, duration of treatment, average and cumulative glucocorticoid doses were not found to be correlated with BMD z-score. Long-term glucocorticoid therapy did not have negative effect on BMD of patients with CAH. Higher BMI z-score in patients with CAH may have a positive effect on preserving bone health. Precautions should be taken for increased risk of obesity.

Diagnostic efficacy of routine contrast-enhanced abdominal CT for the assessment of osteoporosis in the Turkish population

Background/aim This study aimed to evaluate the diagnostic efficacy of vertebral Hounsfield unit (HU) values on routine contrast-enhanced abdominal computed tomography (CT) scans for the assessment of osteoporosis using dual-energy X-ray absorptiometry (DXA) T-scores as a reference standard.Materials and methods A total of 111 consecutive patients who underwent contrast-enhanced abdominal CT examination for any indication and DXA within a 6-month period were retrospectively analyzed. The CT attenuation values of trabecular bone in HUs were measured in axial and sagittal planes from lumbar vertebrae 1–4 (L1–L4). The correlation between the DXA T-scores and HU values measured on the CT scans was evaluated by Pearson’s correlation test. Areas under the curves (AUCs) were calculated by receiver operating characteristic analysis for diagnostic proficiency, and threshold values were determined. Paired t-test and Bland–Altman plot test were used to evaluate the correlation between axial and sagittal HU values.Results There was a strong correlation between the DXA T-scores and HU values of all the lumbar vertebrae (P < 0.001). The highest correlation was for the L3 vertebra; L3 was thus chosen for additional analyses. The mean axial and sagittal L3 attenuations were 133.7 HU and 131.9 HU, respectively. The axial measurements were not significantly different from the sagittal measurements, with a mean difference of 1.8 HU (P > 0.05). The L3 axial CT attenuation threshold for 90% sensitivity was 170 HU and that for 90% specificity was 102 HU for distinguishing osteoporosis from osteopenia and normal bone mineral density (BMD). To distinguish the low BMD group from the normal group, the L3 axial CT attenuation threshold for approximately 90% sensitivity was 102 HU and for 90% specificity was 165 HU.Conclusion The HUs derived from routine contrast-enhanced abdominal CT scans can be used for the evaluation of osteoporosis, without additional radiation exposure and cost.