Osteoporosis Cohort Research Articles

Disulfidptosis-related Protein RPN1 may be a Novel Anti-osteoporosis Target of Kaempferol.

Osteoporosis (OP) is an age-related skeletal disease. Kaempferol can regulate bone mesenchymal stem cells (BMSCs) osteogenesis to improve OP, but its mechanism related to disulfidptosis, a newly discovered cell death mechanism, remains unclear. The study aimed to investigate the biological function and immune mechanism of disulfidptosis- related ribophorin I (RPN1) in OP and to experimentally confirm that RPN1 is the target for the treatment of OP with kaempferol. Differential expression analysis was conducted on disulfide-related genes extracted from the GSE56815 and GSE7158 datasets. Four machine learning algorithms identified disease signature genes, with RPN1 identified as a significant risk factor for OP through the nomogram. Validation of RPN1 differential expression in OP patients was performed using the GSE56116 dataset. The impact of RPN1 on immune alterations and biological processes was explored. Predictive ceRNA regulatory networks associated with RPN1 were generated via miRanda, miRDB, and TargetScan databases. Molecular docking estimated the binding model between kaempferol and RPN1. The targeting mechanism of kaempferol on RPN1 was confirmed through pathological HE staining and immunohistochemistry in ovariectomized (OVX) rats. RPN1 was abnormally overexpressed in the OP cohort, associated with TNF signaling, hematopoietic cell lineage, and NF-kappa B pathway. Immune infiltration analysis showed a positive correlation between RPN1 expression and CD8+ T cells and resting NK cells, while a negative correlation with CD4+ naive T cells, macrophage M1, T cell gamma delta, T cell follicular helper cells, activated mast cells, NK cells, and dendritic cells, was found. Four miRNAs and 17 lncRNAs associated with RPN1 were identified. Kaempferol exhibited high binding affinity (-7.2 kcal/mol) and good stability towards the RPN1. The experimental results verified that kaempferol could improve bone microstructure destruction and reverse the abnormally high expression of RPN1 in the femur of ovariectomized rats. RPN1 may be a new diagnostic biomarker in patients with OP, and may serve as a new target for kaempferol to improve OP.

Serum metabolomics analyses reveal biomarkers of osteoporosis and the mechanism of Quanduzhong capsules

With the aging of the population, the prevalence of osteoporosis (OP) is rising rapidly, making it an important public health concern. Early screening and effective treatment of OP are the primary challenges facing the management of OP today. Quanduzhong capsule (QDZ) is a single preparation composed of Eucommia ulmoides Oliv., which is included in the Pharmacopoeia of the People's Republic of China. It is used to treat OP in clinical practice, but its mechanisms are unclear. This study involved 30 patients with OP, 30 healthy controls (HC), and 28 OP patients treated with QDZ to identify potential biomarkers for the early diagnosis of OP and to investigate the potential mechanism of QDZ in treating OP. The serum samples were analyzed using targeted amino acid metabolomics. Significant differences in amino acid metabolism were identified between the OP cohort and the HC group, as well as between OP patients before and after QDZ treatment. Compared with HC, the serum levels of 14 amino acids in OP patients changed significantly. Kynurenine, arginine, citrulline, methionine, and their combinations are expected to be potential biomarkers for OP diagnosis. Notably, QDZ reversed the changes in levels of 10 amino acids in the serum of OP patients and significantly impacted numerous metabolic pathways during the treatment of OP. This study focuses on screening potential biomarkers for the early detection of OP, which offers a new insight into the mechanism study of QDZ in treating OP.

Multi-modal molecular determinants of clinically relevant osteoporosis subtypes

Due to a rapidly aging global population, osteoporosis and the associated risk of bone fractures have become a wide-spread public health problem. However, osteoporosis is very heterogeneous, and the existing standard diagnostic measure is not sufficient to accurately identify all patients at risk of osteoporotic fractures and to guide therapy. Here, we constructed the first prospective multi-omics atlas of the largest osteoporosis cohort to date (longitudinal data from 366 participants at three time points), and also implemented an explainable data-intensive analysis framework (DLSF: Deep Latent Space Fusion) for an omnigenic model based on a multi-modal approach that can capture the multi-modal molecular signatures (M3S) as explicit functional representations of hidden genotypes. Accordingly, through DLSF, we identified two subtypes of the osteoporosis population in Chinese individuals with corresponding molecular phenotypes, i.e., clinical intervention relevant subtypes (CISs), in which bone mineral density benefits response to calcium supplements in 2-year follow-up samples. Many snpGenes associated with these molecular phenotypes reveal diverse candidate biological mechanisms underlying osteoporosis, with xQTL preferences of osteoporosis and its subtypes indicating an omnigenic effect on different biological domains. Finally, these two subtypes were found to have different relevance to prior fracture and different fracture risk according to 4-year follow-up data. Thus, in clinical application, M3S could help us further develop improved diagnostic and treatment strategies for osteoporosis and identify a new composite index for fracture prediction, which were remarkably validated in an independent cohort (166 participants).

Telomere Length among Chinese Aged 75+ Years

Introduction: Telomere length (TL) is generally regarded as a biomarker of aging. TL, which is influenced by sociodemographic factors, has been shown to be inversely associated with morbidity. However, most studies examined the youngest, and whether the findings can be extended to older individuals is less clear. Further, few studies have examined these questions in Chinese older adults. This cross-sectional study examined TL and its associated factors in Chinese aged 75+ years in Hong Kong. Methods: Participants were from the Mr. and Ms. Osteoporosis cohort. A structured interview on sociodemographic factors and physical measurement was conducted. Frailty and sarcopenia status were respectively determined by Fried’s criteria and the Asian Working Group for Sarcopenia definition. TL was measured by a molecular inversion probe-quantitative PCR assay and expressed as a novel telomere/a single copy reference gene (T/S) ratio. Adjusted binary logistic regressions were used to examine the associations between TL and the presence of multimorbidity, age-related diseases, frailty, and sarcopenia. Results: Among 555 participants (mean age 83.6 ± 3.8 years, 41.3% females), the mean T/S ratio was 1.01 ± 0.20. Males had a lower T/S ratio (0.97 ± 0.20) compared with females (1.07 ± 0.18) (p < 0.001). A lower education level was related to a longer TL (p = 0.016). Being a current smoker was related to a shorter TL (p = 0.007). TL was not significantly different across categories of age, subjective socioeconomic status, drinking status, physical activity level, and body mass index (p > 0.05). There were no associations between TL and the presence of multimorbidity, diabetes, stroke, cardiovascular diseases, cognitive impairment, frailty, and sarcopenia. Conclusion: Among Chinese aged 75+ years, males had shorter TL compared with females. TL was not associated with age-related diseases, frailty, and sarcopenia in this age group. TL may not be a biological marker of aging among older individuals.

Preoperative glenoid bone density is associated with systemic osteoporosis in primary shoulder arthroplasty

BackgroundIn shoulder arthroplasty, poor bone mineral density can impact humeral and glenoid fixation, as well as increase the risk of periprosthetic fracture. The purposes of this study were to (1) determine the association between preoperative glenoid and humeral Hounsfield units (HUs) with systemic bone density in primary shoulder arthroplasty, (2) determine a threshold for HU on preoperative shoulder computed tomography (CT) to classify patients as osteoporotic, and (3) identify which anatomic T-score locations were significantly associated with glenoid and/or humeral HU measurements. MethodsConsecutive patients who had both a preoperative shoulder CT and a dual-energy x-ray absorptiometry (DEXA) scan were included. HU measurements of the glenoid vault and proximal humerus were recorded. DEXA T-scores from the spine, hip, and femoral neck were recorded, and osteoporosis was defined as a T-score of −2.5 or lower in any of the anatomic sites. Patients were grouped into osteoporosis and nonosteoporosis cohorts and these cohorts were compared using standard statistical tests. To assess the association between HUs and DEXA T-score, linear regression analysis was performed. Additional receiver operating characteristic analysis was performed to evaluate the ability of HUs to classify patients as osteoporotic. ResultsA total of 162 patients undergoing primary shoulder arthroplasty with both preoperative CT and DEXA scores were included. The osteoporosis cohort had significantly lower body mass index (P = .001), although no other significant differences in demographics were found between the 2 cohorts. The osteoporosis cohort was associated with significantly lower glenoid vault bone density in HUs (183 ± 104 vs. 303 ± 157, P = .004) and trended toward significantly lower proximal humeral bone density in HUs (34.3 ± 54.8 vs. 64.5 ± 58.2, P = .058). Glenoid HU threshold of 175 had an area under the curve of 0.75, with sensitivity of 80.8% and specificity of 62.5% for classifying systemic osteoporosis. HUs of both the glenoid (P = .031) and proximal humerus (P = .003) were significantly associated with femoral neck T-scores on linear regression analysis. Similarly, HUs of both the glenoid (P < .001) and proximal humerus (P = .009) were significantly associated with spine T-scores on linear regression analysis. DiscussionThis study found that glenoid vault HU is significantly associated with systemic osteoporosis and can be used as a screening tool for detecting osteoporosis preoperatively. In addition to implications for component fixation and periprosthetic fracture, local bone density evaluation on shoulder CT prior to shoulder arthroplasty represents an opportunity for osteoporosis screening.

Risk of medication-related osteonecrosis of the jaw after dental extractions in patients receiving antiresorptive agents - A retrospective study of 240 patients.

This study investigated the incidence, risk factors, and outcome of medication-related osteonecrosis of the jaw after dental extractions in patients receiving antiresorptive agents for osteoporosis or bone metastases. 240 patients with a median drug exposure of 43months were retrospectively studied. The incidence of MRONJ after dental extraction in the osteoporosis cohort was 2.7% per person-year (95% CI 1.6-4.6%) (n=13/126), and for the bone metastases cohort 26.4% per person-year (95% CI 20.4-34.2%) (n=58/114). 92% of MRONJ cases were stage 1. Dental infection as the reason for extraction increased the osteonecrosis risk in the osteoporosis (OR 22.77; 95% CI 2.85-181.62; p=0.003) and bone metastases cohorts (OR 2.72; 95% CI 1.28-5.81; p=0.010). Using leukocyte and platelet-rich fibrin reduced this risk by 84% (p=0.003), as did antibiotics use by 86-93% (p=0.013). Within the bone metastases cohort, an interval since last administration of at least 3months reduced risk of MRONJ (OR 0.83; 95% CI 0.72-0.97; p=0.018). Mucosal healing occurred in 11/13 patients (84.6%; 95% CI 54.5-98.1%) with osteoporosis and 31/58 patients (53.4%; 95% CI 40.0-66.7%) with bone metastases. In conclusion, though the MRONJ risk in this selected population taking antiresorptive agents and presenting to the Oral Maxillofacial Surgery clinic for a dental extraction is considerable and higher in those with dental infections, preventive measures such as antibiotics and use of LRPF membranes may significantly reduce that risk.

Bone density changes after five or more years of unilateral lower extremity osseointegration: Observational cohort study

ContextRehabilitation following lower extremity amputation presents multiple challenges, many related to the traditional prosthesis (TP) socket. Without skeletal loading, bone density also rapidly decreases. Transcutaneous osseointegration for amputees (TOFA) surgically implants a metal prosthesis attachment directly into the residual bone, facilitating direct skeletal loading. Quality of life and mobility are consistently reported to be significantly superior with TOFA than TP. ObjectiveTo investigate how femoral neck bone mineral density (BMD, g/cm2) changes for unilateral transfemoral and transtibial amputees at least five years following single-stage press-fit osseointegration. MethodsRegistry review was performed of five transfemoral and four transtibial unilateral amputees who had dual x-ray absorptiometry (DXA) performed preoperatively and after at least five years. The average BMD was compared using Student's t-test (significance p < .05). First, all nine Amputated versus Intact limbs. Second, the five patients with local disuse osteoporosis (ipsilateral femoral neck T-score < −2.5) versus the four whose T-score was greater than −2.5. ResultsThe average Amputated Limb BMD was significantly less than the Intact Limb, both Before Osseointegration (0.658 ± 0.150 vs 0.929 ± 0.089, p < .001) and After Osseointegration (0.720 ± 0.096 vs 0.853 ± 0.116, p = .018). The Intact Limb BMD decreased significantly during the study period (0.929 ± 0.089 to 0.853 ± 0.116, p = .020), while the Amputated Limb BMD increased a not statistically significant amount (0.658 ± 0.150 to 0.720 ± 0.096, p = .347). By coincidence, all transfemoral amputees had local disuse osteoporosis (BMD 0.545 ± 0.066), and all transtibial patients did not (BMD 0.800 ± 0.081, p = .003). The local disuse osteoporosis cohort eventually had a greater average BMD (not statistically significant) than the cohort without local disuse osteoporosis (0.739 ± 0.100 vs 0.697 ± 0.101, p = .556). ConclusionsSingle-stage press-fit TOFA may facilitate significant BMD improvement to unilateral lower extremity amputees with local disuse osteoporosis.

Association between Dairy Product intake and Risk of Osteoporotic Fractures in Postmenopausal Japanese Women: Secondary Analysis of 15-Year Follow-Up data from the Japanese Population-Based Osteoporosis (JPOS) Cohort Study.

Few prospective cohort studies have evaluated the relationship between dairy product intake frequency and risk of osteoporotic fractures in Asians. This study aimed to investigate the association between habitual dairy product intake and risk of osteoporotic fractures. Secondary analysis of prospective cohort study. Five municipalities of Japan. This study included 1,429 postmenopausal Japanese women (age ≥45 years at baseline). Baseline milk-intake frequency was obtained using nurse-administered questionnaires. Intakes of yogurt and cheese, and estimated calcium intake, were assessed using a validated food frequency questionnaire. Osteoporotic fracture was defined as a clinical fracture diagnosed using radiography. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. Over a median follow-up period of 15.1 years (interquartile range [IQR], 10.1-15.4 years; total, 18,118 person-years), 172 women sustained at least one osteoporotic fracture. The proportions of participants with milk intakes <1, 1, and ≥2 cups/d were 34.4%, 48.0%, and 17.6%, respectively. After adjustment for age, frequency of yogurt intake, frequency of cheese intake, body mass index, history of osteoporotic fractures, and frequency of natto intake, the HRs compared with that for milk intake <1 cup/d were 0.71 (95% CI: 0.51-0.98) and 0.57 (95% CI: 0.35-0.92) for 1 cup/d and ≥2 cups/d, respectively. After adjustment for bone mineral density, HR significance for milk intakes ≥2 cups/d remained significant. Yogurt and cheese intakes were not related to the risk of osteoporotic fractures. High habitual milk intake, but not a habitual yogurt or cheese intake is associated with a decreased risk of osteoporotic fractures, independent of bone mineral density, in postmenopausal Japanese women.

Comprehensive assessment of osteoporosis in lumbar spine using compositional MR imaging of trabecular bone.

To comprehensively assess osteoporosis in the lumbar spine, a compositional MR imaging technique is proposed to quantify proton fractions for all the water components as well as fat in lumbar vertebrae measured by a combination of a 3D short repetition time adiabatic inversion recovery prepared ultrashort echo time (STAIR-UTE) MRI and IDEAL-IQ. A total of 182 participants underwent MRI, quantitative CT, and DXA. Lumbar collagen-bound water proton fraction (CBWPF), free water proton fraction (FWPF), total water proton fraction (TWPF), bone mineral density (BMD), and T-score were calculated in three vertebrae (L2-L4) for each subject. The correlations of the CBWPF, FWPF, and TWPF with BMD and T-score were investigated respectively. A comprehensive diagnostic model combining all the water components and clinical characteristics was established. The performances of all the water components and the comprehensive diagnostic model to discriminate between normal, osteopenia, and osteoporosis cohorts were also evaluated using receiver operator characteristic (ROC). The CBWPF showed strong correlations with BMD (r = 0.85, p < 0.001) and T-score (r = 0.72, p < 0.001), while the FWPF and TWPF showed moderate correlations with BMD (r = 0.65 and 0.68, p < 0.001) and T-score (r = 0.47 and 0.49, p < 0.001). The high area under the curve values obtained from ROC analysis demonstrated that CBWPF, FWPF, and TWPF have the potential to differentiate the normal, osteopenia, and osteoporosis cohorts. At the same time, the comprehensive diagnostic model shows the best performance. The compositional MRI technique, which quantifies CBWPF, FWPF, and TWPF in trabecular bone, is promising in the assessment of bone quality. • Compositional MR imaging technique is able to quantify proton fractions for all the water components (i.e., collagen-bound water proton fraction (CBWPF), free water proton fraction (FWPF), and total water proton fraction (TWPF)) in the human lumbar spine. • The biomarkers derived from the compositional MR imaging technique showed moderate to high correlations with bone mineral density (BMD) and T-score and showed good performance in distinguishing people with different bone mass. • The comprehensive diagnostic model incorporating CBWPF, FWPF, TWPF, and clinical characteristics showed the highest clinical diagnostic capability for the assessment of osteoporosis.

Response to: The association between total body bone mineral density and stroke: a Mendelian randomization analyses.

We thank Dr Zheng for the comments and insight in response to our recent original article ‘Total bone mineral density (BMD) is inversely associated with stroke: a family osteoporosis cohort study in rural China’,1 in which we found that decreased total BMD may correlate with stroke risk among male participants in rural area. As a further excavation of this topic, Dr Zheng found an association of BMD with stroke risk in different age groups especially in those over 60 years old by using the Mendelian randomization method. We sincerely appreciate their effort on this topic. As we know, stroke is the second most common cause of death and the leading cause of serious long-term disability worldwide.2 As a neurovascular disease, stroke was classified into ischemic stroke and cerebral hemorrhage. In the USA, it is estimated that every 3 min 30 s, someone died of a stroke, and stroke accounted for ≈1 of every 19 deaths.3 Multifactorial including age, genetic and former diseases were reported to associate with stroke development. Among the numerous risks, age is a non-negligible factor. Approximately 10% of all strokes occur in individuals 18–50 years of age and patients with stroke >85 years of age makeup 17% of all patients with stroke.3 Thus, the influence of age should be given even more attention. In addition, Racial/ethnic differences in all types of stroke should also be considerate. Compared with the Caucasian population, Chinese populations have been reported to have a higher incidence of stroke.4 Thus when we explain the results from Genome Wide Association Study (GWAS) should with even more caution especially the cohort were from different genetic background.

The Association between Osteoporosis and Peripheral Artery Disease: A Population-Based Longitudinal Follow-Up Study in Taiwan.

Background: There are several possible links that have been used to claim that osteoporosis and peripheral artery disease (PAD) are associated; however, the solid evidence is not sufficient. This study aimed to use the Taiwan National Health Insurance Research Database (NHIRD) to determine if osteoporosis is associated with peripheral artery disease (PAD). Method: NHIRD records from 23 million patients were collected to recruit two matched cohort groups: 64,562 patients with and 64,562 patients without osteoporosis. To compare the crude hazard ratio (HR) and the incidence rate ratio between the two cohort groups for PAD, the Cox model was used. Result: With an adjusted HR of 1.18 (95% CI, 1.08–1.29), the osteoporosis cohort group had a significantly greater risk for PAD than the group without osteoporosis. The cumulative incidence of PAD in the cohort group was also statistically higher than it was in the group without osteoporosis (1.71% and 1.39%; p ≤ 0.0001, log-rank) over the 10-year follow-up period. In addition, the osteoporotic patients with ischemic stroke, chronic obstructive pulmonary disease (COPD), and congestive heart failure (CHF) had a significantly increased risk of PAD based on subgroup analysis. Conclusions: There was a positive association between osteoporosis and the development of PAD, as patients with osteoporosis had an increased incidence of PAD over time.

Assessing the incidence of osteosarcoma among teriparatide-treated patients using linkage of commercial pharmacy and state cancer registry data, contributing to the removal of boxed warning and other labeling changes.

Teriparatide, a recombinant human parathyroid hormone analogue, is associated with increased bone mineral density and a decreased risk of fractures. A dose-dependent increase in the incidence of osteosarcoma was observed in toxicology studies conducted in rats. The primary objective of this study was to estimate the incidence of osteosarcoma over a 10-year period among teriparatide-treated patients versus patients unexposed to teriparatide with osteoporosis and patients in the general population using national pharmacy dispensing data linked with data from participating state cancer registries (SCRs) in the US. Patients aged 18years or older with a dispensed teriparatide prescription formed two different cohorts: Teriparatide-Osteoporosis (Teriparatide-OP) was formed by matching teriparatide patients to unexposed patients with osteoporosis and Teriparatide-General Population (Teriparatide-GP) was formed by matching teriparatide patients to general population patients with a dispensed prescription for a medication other than teriparatide. Matching was performed using select demographics and other variables. Study cohorts were linked to SCR data to ascertain osteosarcoma status. To account for missing outcome data from non-participating SCRs, two analytic approaches were used: the first adjusted the person-time at-risk using a coverage fraction and the second restricted the analyses to patients from states with participating SCRs. There were 18 osteosarcoma cases across four study cohorts: the same three cases in the Teriparatide-OP and Teriparatide-GP cohorts, six cases in the Osteoporosis cohort, and nine cases in the General Population cohort. For the analysis using the coverage fraction the incidence rate ratio (IRR) comparing the Teriparatide-OP and Teriparatide-GP cohorts to the Osteoporosis and General Population cohorts was 1.0 (95% CI: 0.2, 4.5) and 1.3 (95% CI: 0.2, 5.1), respectively. When restricting the analysis to patients from states with participating SCRs, the IRR was 0.6 (95% CI: 0.1, 3.6) and 0.8 (95% CI 0.1, 4.0), respectively. The estimates of association between teriparatide and osteosarcoma were imprecise due to the small number of observed osteosarcoma cases. However, the incidence of osteosarcoma observed in each study cohort was within the expected range given background rates for the US general population. The evidence generated by this study, in conjunction with other real-world studies evaluating the risk of osteosarcoma, was used to support changes to the US teriparatide label (including removal of the black box warning regarding potential risk of osteosarcoma) and expand treatment options for patients with osteoporosis.

The Risk of Trigeminal Neuralgia Following Osteoporosis.

Background and objectives: Managing people with trigeminal neuralgia (TN) and osteoporosis is challenging due to their debilitating conditions. Currently, the exact association between TN and osteoporosis in patients remains unknown, although there is potential overlapping of pathophysiological mechanisms. In response, we calculated TN risk in patients who have osteoporosis. Materials and Methods: 45,393 patients aged over 50 years diagnosed with osteoporosis were matched with 45,393 non-osteoporosis patients aged over 50 years (1:1 ratio) who were used as the control group, using data from 1996 to 2010 from Taiwan’s National Health Insurance Research Database. The cumulative incidences of subsequent TN and the hazard ratio were estimated using Cox proportional hazards modeling and the Kaplan–Meier method, respectively. Results: Among the total sample, 333 patients were diagnosed with TN during the follow-up period: 205 in the osteoporosis cohort and 128 in the control cohort. Through covariate adjustment, the overall TN incidence showed a 1.80-fold increase in the osteoporosis cohort in comparison with the control cohort (0.60 vs. 0.18 per 1000 person-years, respectively). The High Charlson Comorbidity Index, hypertension, and migraines were risk factors of TN. Conclusions: Osteoporosis patients had a higher TN risk than that of the control cohort. Therefore, early recognition of pain and symptoms in osteoporotic people may help to identify possible TN patients who need prompt therapy.

Osteoporosis increases the risk of rotator cuff tears: a population-based cohort study.

Osteoporosis has been demonstrated to be a risk factor for rotator cuff retears after surgery; however, no studies have directly investigated the association between osteoporosis and the development of rotator cuff tears. To investigate whether osteoporosis is associated with an increased risk of rotator cuff tears. We conducted a population-based, matched-cohort study with a 7-year follow-uTwo matched cohorts (n = 3511 with osteoporosis and 17,555 without osteoporosis) were recruited from Taiwan's Longitudinal Health Insurance Dataset. Person-year data and incidence rates were evaluated. A multivariable Cox model was used to derive an adjusted hazard ratio (aHR) after controlling for age, sex, and various prespecified comorbidities. Age and sex were added in the model to test for interaction with osteoporosis. Women constituted 88.5% of the cohorts. During follow-up of 17,067 and 100,501 person-years for the osteoporosis and nonosteoporosis cohorts, 166 and 89 rotator cuff tears occurred, respectively. The cumulative incidence of rotator cuff tears was significantly higher in the osteoporosis cohort than in the nonosteoporosis cohort (p < 0.001, log-rank). The Cox model revealed a 1.79-fold increase in rotator cuff tears in the osteoporosis cohort, with an aHR of 1.79 (95% confidence interval, 1.55-2.05). Effect modification of sex and age on rotator cuff tears was not found in patients with osteoporosis. This population-based study supports the hypothesis that compared with individuals without osteoporosis, those with osteoporosis have a higher risk of developing rotator cuff tears.

Effect of fasting blood glucose on risk of new\u2010onset hypertension in rural Chinese population: a 15-year follow-up cohort

BackgroundThe purpose of this study was to examine the correlation between fasting blood glucose and new-onset hypertension and examine any synergistically effect modification with multiple risk factors.MethodsWe conducted post-hoc analyses of repeated-measures data in the original Dongzhi osteoporosis cohort study. In total, 3985 participants without hypertension aged 25–64 years were included in the current analyses. Generalized estimating equation models were used to assess the relationship between fasting blood glucose and risk of new-onset hypertension after adjusting for pertinent covariates and autocorrelations among siblings.Results393 men (19.4%) and 398 women (20.3%) without hypertension at the baseline developed hypertension by the end of the study period. Compared to lower baseline fasting blood glucose levels (Q1–Q3: < 5.74 mmol/L; clinical cut points: < 5.6 mmol/L), higher baseline fasting blood glucose levels (Q4: ≥ 5.74 mmol/L; clinical cut points: ≥ 5.6 mmol/L and < 7.0 mmol/L) increased the risk of new-onset hypertension significantly [(OR: 1.54, 95% CI 1.19–1.98, P < 0.001); (OR: 1.38, 95% CI 1.09–1.75, P = 0.008)] in women. Additionally, a stronger significant association was found in women with elevated fasting blood glucose on risk of new-onset of hypertension with higher total cholesterol (≥ 5.2 mmol/L) [(OR: 2.76; 95% CI: (1.54, 4.96), P < 0.001)]. However, no association was found between fasting blood glucose and risk of new-onset hypertension in men.ConclusionsHigh fasting blood glucose may be significantly associated with risk of new-onset hypertension in Chinese women, especially in women with higher total cholesterol. Further randomized studies are needed to confirm our findings.

Predictive ability of novel volumetric and geometric indices derived from dual-energy X-ray absorptiometric images of the proximal femur for hip fracture compared with conventional areal bone mineral density: the Japanese Population-based Osteoporosis (JPOS) Cohort Study.

To clarify whether volumetric and geometric indices derived from novel three-dimensional (3D) modeling of the hip using dual-energy X-ray absorptiometric (DXA) images improve hip fracture prediction relative to areal bone mineral density (aBMD). We examined 1331 women who had completed the baseline survey and at least one follow-up survey over 20 years (age 40-79 years at baseline). Each survey included aBMD measurement at the hip by DXA. Volumetric and geometric indices of the hip at baseline and the 10-year follow-up were estimated from DXA images using a 3D modeling algorithm. Incident hip fractures during the 20-year follow-up period were identified through self-report. Cox proportional hazards regression models allowing for repeated measurements of predictors and outcomes were constructed, and their predictive ability for hip fracture was evaluated using areas under receiver operating characteristic curves (AUCs) and net reclassification improvement (NRI) over aBMD at the femoral neck (FN) and total hip (TH) as references. During a median follow-up of 19.8 years, 68 incident hip fractures were identified (2.22/1000 person-years). A significantly larger AUC of trabecular volumetric BMD (vBMD) at the total hip (AUC = 0.741), femoral neck (AUC = 0.748), and intertrochanter (AUC = 0.738) and significant NRI (0.177, 0.149, and 0.195, respectively) were observed compared with FN-aBMD (AUC = 0.701), but not TH-aBMD. vBMD obtained from 3D modeling using routinely obtained hip DXA images significantly improved hip fracture risk prediction over conventional FN-aBMD, but not TH-aBMD. The Japanese Population-Based Osteoporosis (JPOS) Cohort Study was retrospectively registered as UMIN000032869 in the UMIN Clinical Trials Registry on July 1, 2018.

Temporal Trends in Prescribing of Bone-Directed Therapies in the United States, 2009–2020

Multiple new osteoporosis therapies, including some with novel mechanisms of action, have been introduced in the past decade. However, little is known about temporal trends in prescribing these new medications. Using claims data from the Clinformatics Data Mart (Optum, Inc.), we determined the number of enrolled individuals over age 50 who were prescribed any osteoporosis medication during each quarter between January 1, 2009 and March 31, 2020. Of all individuals receiving therapy, we then calculated the percent receiving each medication. In subgroup analyses, we limited the population to (1) only those with ICD codes for osteoporosis in the current or previous three quarters and without codes for active malignancy during the current or previous quarter, and (2) only those with ICD codes from an oncology provider for active malignancy likely to metastasize to bone during the current or previous quarter. In the all-user cohort, a total of 15.48 million unique prescription or medication administration claims from 1.46 million unique individuals during the study period were analyzed. Of these, 89% were women and 71% over the age of 65, with a mean age of 69. Alendronate was the most common medication used, representing >50% of all treated individuals, and its use increased over time. Percent of users receiving zoledronic acid doubled during this period but remained <5%. Use of other bisphosphonates declined steadily. By comparison, after its approval in 2010, denosumab use increased rapidly, reaching 10% of users in 2015 and 15% of users in 2018. Percent of individuals treated with raloxifene declined after 2013. Use of teriparatide, abaloparatide, and romosozumab remained less than 2% throughout the study period. Trends in the osteoporosis cohort paralleled those in the all-user cohort. In the malignancy cohort, alendronate and zoledronic acid were each used in approximately 30% of individuals at the onset of the study, and both declined over the decade. By contrast, denosumab use rapidly increased after introduction and surpassed use of either bisphosphonate by 2013. Denosumab use continued to increase over time and reached approximately 50% of all bone-directed medication use in the malignancy cohort. Use of other medications, mainly alternate bisphosphonates, was low and declined throughout the study period. In a privately insured cohort between 2009–2020, denosumab use increased significantly in both osteoporosis and malignancy populations, outpacing gains in use of other agents, despite guidelines suggesting that either bisphosphonates or denosumab could be considered first-line therapy for osteoporosis.

Hepcidin-induced reduction in iron content and PGC-1β expression negatively regulates osteoclast differentiation to play a protective role in postmenopausal osteoporosis.

As a necessary trace element, iron is involved in many physiological processes. Clinical and basic studies have found that disturbances in iron metabolism, especially iron overload, might lead to bone loss and even be involved in postmenopausal osteoporosis. Hepcidin is a key regulator of iron homeostasis. However, the exact role of hepcidin in bone metabolism and the underlying mechanism remain unknown. In this study, we found that in postmenopausal osteoporosis cohort, the concentration of hepcidin in the serum was significantly reduced and positively correlated with bone mineral density. Ovariectomized (OVX) mice were then used to construct an osteoporosis model. Hepcidin overexpression in these mice significantly improved bone mass and rescued the phenotype of bone loss. Additionally, overexpression of hepcidin in OVX mice greatly reduced the number and differentiation of osteoclasts in vivo and in vitro. This study found that overexpression of hepcidin significantly inhibited ROS production, mitochondrial biogenesis, and PGC-1β expression. These data showed that hepcidin protected osteoporosis by reducing iron levels in bone tissue, and in conjunction with PGC-1β, reduced ROS production and the number of mitochondria, thus inhibiting osteoclast differentiation and bone absorption. Hepcidin could provide new targets for the clinical treatment of postmenopausal osteoporosis.

Prescription Patterns in Patients with Chronic Obstructive Pulmonary Disease and Osteoporosis

ObjectivePatients with chronic obstructive pulmonary disease (COPD) have a higher risk of osteoporosis. Few studies have addressed the prescription patterns in osteoporosis patients with COPD. The purpose of this study was to conduct a retrospective study of the prescription patterns in patients with COPD and osteoporosis in Taiwan.MethodsThe study was conducted with data from the Taiwan National Health Insurance Research Database from January 1, 2003, to December 31, 2016. We selected the COPD population in Taiwan older than 40 years with at least one prescription for a bronchodilator. We excluded patients who had osteoporosis, fracture, asthma, or cancer before the diagnosis of COPD. After the diagnosis of COPD, patients who did not have osteoporosis were also excluded. We followed this COPD and osteoporosis cohort until they had been prescribed medication for osteoporosis.ResultsThere were 13,407 patients with COPD and osteoporosis who received osteoporosis treatment. Among the patients who received treatment, the majority were female (n = 9136), accounting for 68.14% of all treated patients. A total of 53.4% of the patients had been prescribed steroids least once within the last year before receiving a diagnosis of osteoporosis. A total of 34.61% of the patients received systemic corticosteroids with a daily dose equivalent to 5 mg of prednisolone within the 3 months prior to the diagnosis of osteoporosis. The older the patient was, the higher the probability of the prescription of medication for osteoporosis. Patients with depression had a high probability of receiving medication for osteoporosis with adjusted hazard ratio of 1.141 (95% confidence interval, 1.072–1.214).ConclusionThe rate of prescriptions for the treatment of osteoporosis in patients with COPD was low. Physicians need to be aware of this issue and treat osteoporosis more aggressively in patients with COPD.

Total bone mineral density is inversely associated with stroke: a family osteoporosis cohort study in rural China.

The relationship of osteoporosis and stroke is still not fully clarified. Apart from the well-known risk factors for stroke, bone mineral density (BMD) has gained more interest in recent years. To further elucidate the relationship between BMD and stroke risk, a prospective cohort study in the Chinese rural population was conducted. Retrospective analysis of a family osteoporosis cohort. Our subjects were selected from an osteoporosis cohort conducted in Anqing, China. All participants underwent a questionnaire assessment, clinical examinations and laboratory assessments. During the follow-up period, the number of people who had a stroke was recorded. Generalized estimating equation regression analysis was performed to determine the significance of the association between BMD and stroke. A total of 17868 people were included. A two-way interaction test of sex and BMD on stroke was significant (P = 0.002). There was a significant difference in BMD and stroke morbidity in the male group (P = 0.003). When BMD was assessed as quartiles and the lowest quartile was used as reference, a significantly lower risk for stroke was observed in Q2-4. Notably, no significant difference was observed in female participants with adjusted odds ratio (P > 0.05). The P-value for interaction was calculated. The body mass index (P = 0.014) and waist-to-hip ratio (P = 0.027) were found to be significantly associated with BMD and stroke risk in female participants. In Chinese rural areas, total BMD may negatively correlated with stroke, especially in men.