Osteoporosis Study Research Articles

Prevalence of and risk factors for sarcopenia in community-dwelling people: The Vietnam Osteoporosis Study.

Sarcopenia is a geriatric disease characterized by the progressive and generalized loss of skeletal lean mass and strength with age. The prevalence of sarcopenia in the Vietnamese population is unknown. This study sought to estimate the prevalence of and risk factors for sarcopenia among community-dwelling individuals in Vietnam. This cross-sectional study is part of the ongoing Vietnam Osteoporosis Study project. The study involved 1308 women and 591 men aged 50years and older as at 2015 (study entry). Whole-body dual-energy X-ray absorptiometry was used to measure the appendicular skeletal lean mass. Anthropometric and clinical data were collected using a structured questionnaire. Sarcopenia was defined according to the criteria proposed by the Asian Working Group for Sarcopenia in 2019. Logistic regression analysis was used to determine the association between potential risk factors and sarcopenia. The prevalence of sarcopenia in women and men was 14% (n=183) and 16% (n=83), respectively. Age (odds ratio [OR] per 10years=1.37; 95% confidence interval [CI] 1.26-1.48) and being underweight (OR=1.61; 95% CI 1.00-2.58) were independently associated with increased risk of sarcopenia. The combination of low physical activity, being underweight and advancing age accounted for ~27% of sarcopenic patients. However, most of the attributable fraction was due to ageing. Sarcopenia is common in community-dwelling Vietnamese adults, particularly those with advancing age, who are underweight and with low physical activity.

Association of Bone Mineral Density and Bone Turnover Markers with the Risk of Diabetes: Hong Kong Osteoporosis Study and Mendelian Randomization.

Preclinical studies demonstrated that bone plays a central role in energy metabolism. However, how bone metabolism is related to the risk of diabetes in humans is unknown. We investigated the association of bone health (bone mineral density [BMD] and bone turnover markers) with incident type-2 diabetes mellitus (T2DM) based on the Hong Kong Osteoporosis Study (HKOS). A total of 993 and 7160 participants from the HKOS were studied for the cross-sectional and prospective analyses, respectively. The cross-sectional study evaluated the association of BMD and bone biomarkers with fasting glucose and glycated hemoglobin (HbA1c ) levels, whereas the prospective study examined the associations between BMD at study sites and the risk of T2DM by following subjects a median of 16.8 years. Body mass index (BMI) was adjusted in all full models. Mendelian randomization (MR) was conducted for causal inference. In the cross-sectional analysis, lower levels of circulating bone turnover markers and higher BMD were significantly associated with increased fasting glucose and HbA1c levels. In the prospective analysis, higher BMD (0.1 g/cm2 ) at the femoral neck and total hip was associated with increased risk of T2DM with hazard ratios (HRs) of 1.10 (95% confidence interval [CI], 1.03 to 1.18) and 1.14 (95% CI, 1.08 to 1.21), respectively. The presence of osteoporosis was associated with a 30% reduction in risk of T2DM compared to those with normal BMD (HR = 0.70; 95% CI, 0.55 to 0.90). The MR results indicate a robust genetic causal association of estimated BMD (eBMD) with 2-h glucose level after an oral glucose challenge test (estimate = 0.043; 95% CI, 0.007 to 0.079) and T2DM (odds ratio = 1.064; 95% CI, 1.036 to 1.093). Higher BMD and lower levels of circulating bone biomarkers were cross-sectionally associated with poor glycemic control. Moreover, higher BMD was associated with a higher risk of incident T2DM and the association is probably causal. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Study on the characteristics of asymptomatic incident vertebral fractures and related factors in Vietnamese people over 50 years old

Background: Vertebral fractures are the most common complication of osteoporosis, but more than two-thirds are asymptomatic. Therefore, the present study was conducted with the following objectives: (1) To describe some characteristics of incident asymptomatic vertebral fractures in adults aged 50 years and older in Vietnam; (2) To evaluate some factors related to incident asymptomatic vertebral fractures in adults aged 50 years and older in Vietnam. Materials and Methods: 455 adults aged 50 years and older volunteered to participate in the study. Cohort study of the Vietnam Osteoporosis Study (VOS) project. Results and Conclusions: In 29/455 cases of incident asymptomatic vertebral fractures followed after 2 years, the most common characteristics included: wedge fracture type (73.3%), grade 2 fracture (56.7%), and the most common locations are T12 and L1 (over 50%). Factors associated with incident vertebral fractures are advanced age and smoking. Key words: vertebral fracture, osteoporosis, bone mineral density (BMD), risk factors.

Multi-view information fusion using multi-view variational autoencoder to predict proximal femoral fracture load.

Hip fracture occurs when an applied force exceeds the force that the proximal femur can support (the fracture load or "strength") and can have devastating consequences with poor functional outcomes. Proximal femoral strengths for specific loading conditions can be computed by subject-specific finite element analysis (FEA) using quantitative computerized tomography (QCT) images. However, the radiation and availability of QCT limit its clinical usability. Alternative low-dose and widely available measurements, such as dual energy X-ray absorptiometry (DXA) and genetic factors, would be preferable for bone strength assessment. The aim of this paper is to design a deep learning-based model to predict proximal femoral strength using multi-view information fusion. We developed new models using multi-view variational autoencoder (MVAE) for feature representation learning and a product of expert (PoE) model for multi-view information fusion. We applied the proposed models to an in-house Louisiana Osteoporosis Study (LOS) cohort with 931 male subjects, including 345 African Americans and 586 Caucasians. We performed genome-wide association studies (GWAS) to select 256 genetic variants with the lowest p-values for each proximal femoral strength and integrated whole genome sequence (WGS) features and DXA-derived imaging features to predict proximal femoral strength. The best prediction model for fall fracture load was acquired by integrating WGS features and DXA-derived imaging features. The designed models achieved the mean absolute percentage error of 18.04%, 6.84% and 7.95% for predicting proximal femoral fracture loads using linear models of fall loading, nonlinear models of fall loading, and nonlinear models of stance loading, respectively. The proposed models are capable of predicting proximal femoral strength using WGS features and DXA-derived imaging features. Though this tool is not a substitute for predicting FEA using QCT images, it would make improved assessment of hip fracture risk more widely available while avoiding the increased radiation exposure from QCT.

For older individuals there is greater variance in low mean Bone Material Strength Index values obtained with the OsteoProbe

PurposeBone Material Strength Index (BMSi) quantifies the resistance of bone to a specified force in vivo at the mid tibia using impact microindentation (IMI). Anecdotal evidence suggests that within-participant variance in BMSi may be associated with the individual's mean BMSi. This study aimed to investigate associations between mean and variance of IMI measures in a population-based study. MethodsParticipants were men (n = 420) and women (n = 55) from the Geelong Osteoporosis Study who underwent BMSi measurement using the OsteoProbe at recent follow-up phases (men 2016–2022; women 2022–2023). Median age was 63.7 yr (IQR 53.0–71.8). BMSi standard deviation was skewed and therefore natural log transformed (referred to as ln-SD). Linear regression models were developed with ln-SD as the dependent variable and mean BMSi as the independent variable adjusting for sex, age, height and weight. ResultsIn unadjusted models, greater BMSi was associated with lower ln-SD (β = −1.58, p = 0.042). This association was sustained after adjustment (p = 0.013), and an interaction between BMSi and age was observed (p = 0.004). In those aged 63.7 yr and over (median age), mean BMSi was inversely associated with ln-SD (β = −3.22, p = 0.002). Sex was not identified as an effect modifier. In younger participants, no BMSi*ln-SD association was observed. ConclusionIn older men and women, there was greater variance in low BMSi values. This suggests that standard deviation of the BMSi measure may provide additional information in the assessment of bone health and is worthy of further investigation. Mini abstractIn older men and women, greater variance is observed when BMSi values are low, reflecting potential variation in the bone surface.

Patients’ preferences for fracture risk communication: the Risk Communication in Osteoporosis (RICO) study

SummaryThe RICO study indicated that most patients would like to receive information regarding their fracture risk but that only a small majority have actually received it. Patients globally preferred a visual presentation of fracture risk and were interested in an online tool showing the risk.PurposeThe aim of the Risk Communication in Osteoporosis (RICO) study was to assess patients’ preferences regarding fracture risk communication.MethodsTo assess patients’ preferences for fracture risk communication, structured interviews with women with osteoporosis or who were at risk for fracture were conducted in 11 sites around the world, namely in Argentina, Belgium, Canada at Hamilton and with participants from the Osteoporosis Canada Canadian Osteoporosis Patient Network (COPN), Japan, Mexico, Spain, the Netherlands, the UK, and the USA in California and Washington state. The interviews used to collect data were designed on the basis of a systematic review and a qualitative pilot study involving 26 participants at risk of fracture.ResultsA total of 332 women (mean age 67.5 ± 8.0 years, 48% with a history of fracture) were included in the study. Although the participants considered it important to receive information about their fracture risk (mean importance of 6.2 ± 1.4 on a 7-point Likert scale), only 56% (i.e. 185/332) had already received such information. Globally, participants preferred a visual presentation with a traffic-light type of coloured graph of their FRAX® fracture risk probability, compared to a verbal or written presentation. Almost all participants considered it important to discuss their fracture risk and the consequences of fractures with their healthcare professionals in addition to receiving information in a printed format or access to an online website showing their fracture risk.ConclusionsThere is a significant communication gap between healthcare professionals and patients when discussing osteoporosis fracture risk. The RICO study provides insight into preferred approaches to rectify this communication gap.

Metabolomic profiles associated with physical activity in White and African American adult men.

Physical activity (PA) is associated with various health benefits, especially in improving chronic health conditions. However, the metabolic changes in host metabolism in response to PA remain unclear, especially in racially/ethnically diverse populations. This study is to assess the metabolic profiles associated with the frequency of PA in White and African American (AA) men. Using the untargeted metabolomics data collected from 698 White and AA participants (mean age: 38.0±8.0, age range: 20-50) from the Louisiana Osteoporosis Study (LOS), we conducted linear regression models to examine metabolites that are associated with PA levels (assessed by self-reported regular exercise frequency levels: 0, 1-2, and ≥3 times per week) in White and AA men, respectively, as well as in the pooled sample. Covariates considered for statistical adjustments included race (only for the pooled sample), age, BMI, waist circumstance, smoking status, and alcohol drinking. Of the 1133 untargeted compounds, we identified 7 metabolites associated with PA levels in the pooled sample after covariate adjustment with a false discovery rate of 0.15. Specifically, compared to participants who did not exercise, those who exercised at a frequency ≥3 times/week showed higher abundances in uracil, orotate, 1-(1-enyl-palmitoyl)-2-oleoyl-GPE (P-16:0/18:1) (GPE), threonate, and glycerate, but lower abundances in salicyluric glucuronide and adenine in the pooled sample. However, in Whites, salicyluric glucuronide and orotate were not significant. Adenine, GPE, and threonate were not significant in AAs. In addition, the seven metabolites were not significantly different between participants who exercised ≥3 times/week and 1-2 times/week, nor significantly different between participants with 1-2 times/week and 0/week in the pooled sample and respective White and AA groups. Metabolite responses to PA are dose sensitive and may differ between White and AA populations. The identified metabolites may help advance our knowledge of guiding precision PA interventions. Studies with rigorous study designs are warranted to elucidate the relationship between PA and metabolites.

Alcohol Consumption and the Diversity of the Oral Microbiome in Postmenopausal Women

BackgroundAlcohol reduces neutrophil function and decreases salivary flow, which could affect the composition of the oral microbiome. ObjectiveWe hypothesized that the α- and β-diversity of the oral microbiome and the relative abundance of bacterial taxa would differ by frequency and type of alcohol consumption. MethodsWe used a food frequency questionnaire to assess the frequency of consumption of beer, wine, and liquor (drinks/week) in a sample of 1179 postmenopausal women in the Osteoporosis and Periodontal Disease Study. Women were categorized as nondrinkers, drinking <1 drink/wk, ≥1 to <7 drinks/wk, or ≥7 drinks/wk for total alcohol consumption and for beer, wine, and liquor consumption. The composition and diversity of the oral microbiome was assessed from subgingival plaque samples using 16S ribosomal RNA amplicon sequencing. Permutational multivariate analysis of variance (PERMANOVA) was used to examine β-diversity (between-sample diversity) in the microbiome between alcohol consumption categories. Analysis of covariance was used to examine the mean α-diversity (within-sample diversity), assessed by the Shannon index (species evenness), Chao1 index (species richness), and observed operational taxonomic unit (OTU) count and the mean relative abundance of 245 bacterial taxa across alcohol consumption categories. ResultsOver half of the participants (67%) consumed alcohol, with 14% reporting ≥1 drink/d. The β-diversity across categories of total alcohol consumption, but not categories of alcohol type, was statistically significantly different (P for PERMANOVA = 0.016). Mean α-diversity measures were statistically significantly higher (P < 0.05) in the highest category of total alcohol and wine consumption compared to nondrinkers; no significant associations were found for beer or liquor consumption. The relative abundance of 1 OTU, Selenomonassp._oral_taxon_133, was significantly lower in the highest level of total alcohol consumption compared to nondrinkers after adjustment for multiple comparisons. ConclusionsAlcohol consumption was associated with the diversity and composition of the subgingival microbiome.

Impact of Mood Disorder History and Bone Health on Cognitive Function Among Men Without Dementia.

Poor cognitive function, a major disabling condition of older age, is often considered a prodromal feature of dementia. High mortality and the lack of a cure for dementia have necessitated a focus on the identification of potentially modifiable risk factors. Mental and physical health conditions such as mood disorders and bone loss have been previously linked with poor cognition individually although their combined effect remains largely unknown. Considering the multifactorial nature of dementia pathology, we investigated whether mood disorders, bone health and their interaction are associated with cognitive function in a population-based sample of men. Four hundred and forty-two male participants were drawn from the Geelong Osteoporosis Study. Cognitive function was assessed using the CogState Brief Battery, which measured cognitive performance across four domains and was used to compute overall cognitive function. Mood disorders and hip bone mineral density (BMD) were determined using a semi-structured clinical interview and dual energy x-ray absorptiometry, respectively. Hip BMD (Bcoeff = 0.56, 95% CI: [0.07, 1.05], p = 0.025) but not mood disorder (Bcoeff = -0.50, 95% CI: [-0.20, 0.10], p = 0.529) was associated with overall cognitive function after accounting for potential confounders. Interaction effects were observed between the two exposures (Bcoeff = -1.37, 95% CI: [-2.49, -0.26], p = 0.016) suggesting that individuals without a mood disorder displayed better cognitive performance with increasing BMD, whereas those with a lifetime history of mood disorder displayed poorer cognitive function with increasing BMD. These findings highlight the importance of exploring interactions among potentially modifiable health conditions associated with cognitive function.

Opportunistic Screening of Low Bone Mineral Density From Standard X-Rays

BackgroundOsteoporosis, characterized by loss of bone mineral density (BMD), is underscreened. Osteoporosis and low bone mass are diagnosed by a BMD T-score ≤ –2.5, and between –1.0 and –2.5, respectively, at the femoral neck or lumbar vertebrae (L1-4), using dual energy x-ray absorptiometry (DXA). The ability to estimate BMD at those anatomic sites from standard radiographs would enable opportunistic screening of low BMD (T-score < –1) in individuals undergoing x-ray for any clinical indication. MethodsRadiographs of the lumbar spine, thoracic spine, chest, pelvis, hand, and knee, with a paired DXA acquired within 1 year, were obtained from community imaging centers (62,023 x-ray–DXA pairs of patients). A software program called Rho was developed that uses x-ray, age, and sex as inputs, and outputs a score of 1 to 10 that corresponds with the likelihood of low BMD. The program’s performance was assessed using receiver-operating characteristic analyses in three independent test sets, as follows: patients from community imaging centers (n = 3,729; 83% female); patients in the Canadian Multicentre Osteoporosis Study (n = 1,780; 71% female); and patients in the Osteoarthritis Initiative (n = 591; 50% female). ResultsThe areas under the receiver-operating characteristic curves were 0.89 (0.87-0.90), 0.87 (0.85-0.88), and 0.82 (0.79-0.85), respectively, and subset analyses showed similar results for each sex, body part, and race. ConclusionRho can opportunistically screen patients at risk of low BMD (at femoral neck or L1-4) from radiographs of the lumbar spine, thoracic spine, chest, pelvis, hand, or knee.

Associations Between Aldosterone-Renin-Ratio and Bone Parameters Derived from Peripheral Quantitative Computed Tomography and Impact Microindentation in Men

Components of the renin–angiotensin–aldosterone system (RAAS) are present on bone cells. One measure of RAAS activity, the aldosterone-renin-ratio (ARR), is used to screen for primary aldosteronism. Associations between ARR and bone mineral density are conflicting. This study investigated associations between ARR and peripheral quantitative computed tomography (pQCT) and impact microindentation (IMI). Male participants (n = 431) were from the Geelong Osteoporosis Study. “Likely” primary aldosteronism was defined as ARR ≥ 70 pmol/mIU. Another group, “possible” primary aldosteronism, was defined as either ARR ≥ 70 pmol/mIU or taking a medication that affects the RAAS, but not a beta blocker, and renin < 15 mU/L. Using pQCT, images at 4% and 66% of radial (n = 365) and tibial (n = 356) length were obtained. Using IMI measurements, bone material strength index (BMSi; n = 332) was determined. Associations between ARR or likely/possible primary aldosteronism and IMI or pQCT-derived bone parameters were tested using median regression. ARR and aldosterone values were not associated with any of the pQCT-derived bone variables in either unadjusted or adjusted analyses. Men with likely primary aldosteronism (n = 16), had lower adjusted total bone area (radial 66% site, − 12.5%). No associations were observed for men with possible primary aldosteronism (unadjusted or adjusted). No associations with BMSi were observed (p > 0.05). There were no associations between ARR or aldosterone and pQCT-derived bone parameters. Men with likely primary aldosteronism had lower bone area, suggesting clinically high levels of ARR may have a negative impact on bone health.

Factors associated with osteoarthritis in menopausal women: A registry study of osteoporosis sarcopenia and osteoarthritis.

Bone and muscle mass decline after menopause. The risk of osteoarthritis (OA), sarcopenia, and osteoporosis increases in later life. Our objective aimed to assess the possible factors affecting osteoarthritis in menopausal women. This is a registry study of osteoporosis, sarcopenia, and osteoarthritis. All subjects accepted bone mineral density (BMD) and body composition studies, and X-rays of both knees were performed. A medical history was taken and biochemical data were recorded. Logistic regression analyses were used to examine the associations between the presence of osteoarthritis and BMD, muscle mass, and other parameters. A total of 139 patients were enrolled. The mean age of the patients was 73.86 ± 5.83 years in the osteoarthritis group and 74.53 ± 9.90 in the non-osteoarthritis group (p = 0.663). The mean body mass index (BMI) was 24.36 ± 3.64 kg/m2 in the osteoarthritis group, compared with 23.78 ± 3.61 in the non-osteoarthritis group (p = 0.366). The lumbar spine T score was -2.06 ± 1.33 g/cm2 in the osteoarthritis group, and -1.25 ± 1.76 in the non-osteoarthritis group (p = 0.006). There were no significant differences in smoking, alcohol consumption, diabetes, hypertension, cardiovascular disease, neurological disease, and chronic kidney disease between the two groups. When we used osteoarthritis as the outcome, we found that the lumbar spine T score had a significant association with osteoarthritis, with a high T score associated with less osteoarthritis formation (p = 0.024, odds ratio (95% confidence interval) 0.06 (0-0.69)). Knee osteoarthritis was associated with lumbar spine bone density. This study provides the initial information required to develop clinical algorithms for the early identification of potential high-risk populations, as well as essential information for the development of policies for the detection and prevention of osteoarthritis in menopausal women.

A plasma protein signature associated with cognitive function in men without severe cognitive impairment

BackgroundA minimally invasive blood-based assessment of cognitive function could be a promising screening strategy to identify high-risk groups for the incidence of Alzheimer’s disease.MethodsThe study included 448 cognitively unimpaired men (mean age 64.1 years) drawn from the Geelong Osteoporosis Study. A targeted mass spectrometry-based proteomic assay was performed to measure the abundance levels of 269 plasma proteins followed by linear regression analyses adjusted for age and APOE ε4 carrier status to identify the biomarkers related to overall cognitive function. Furthermore, two-way interactions were conducted to see whether Alzheimer’s disease-linked genetic variants or health conditions modify the association between biomarkers and cognitive function.ResultsTen plasma proteins showed an association with overall cognitive function. This association was modified by allelic variants in genes ABCA7, CLU, BDNF and MS4A6A that have been previously linked to Alzheimer’s disease. Modifiable health conditions such as mood disorders and poor bone health, which are postulated to be risk factors for Alzheimer’s disease, also impacted the relationship observed between protein marker levels and cognition. In addition to the univariate analyses, an 11-feature multianalyte model was created using the least absolute shrinkage and selection operator regression that identified 10 protein features and age associated with cognitive function.ConclusionsOverall, the present study revealed plasma protein candidates that may contribute to the development of a blood-based screening test for identifying early cognitive changes. This study also highlights the importance of considering other risk factors in elucidating the relationship between biomarkers and cognition, an area that remains largely unexplored.

Social determinants of health and cognitive function: A cross-sectional study among men without dementia.

Certain age-related and medical factors have been associated with cognitive dysfunction; however, less is known regarding social determinants of health. The current study aimed to investigate associations between social determinants of health and cognitive function in a population-based sample of men without dementia. Data were drawn from the ongoing Geelong Osteoporosis Study (n=536). Cognitive function was determined using the Cog-State Brief Battery. Area-based socioeconomic status (SES) was determined using the Index of Relative Socioeconomic Advantage and Disadvantage, marital status by self-report, and social support by the Multidimensional Scale of Perceived Social Support, which considers family, friends, and significant others. Belonging to a higher SES group, being in a relationship (married/de-facto) and perceived social support from a significant other and friends were each associated with better overall cognitive function. In regard to the specific cognitive domains, higher SES was associated with better psychomotor function and visual learning, being in a relationship was associated with better working memory, and perceived social support from a significant other was associated with better attention and working memory, with perceived social support from friends associated with better psychomotor function. There were no associations detected between social support from family and any of the cognitive domains. Higher SES, being in a relationship, and greater perceived social support from a significant other and friends were associated with better cognitive function. Further studies identifying underlying mechanisms linking social factors with cognition are needed to establish prevention strategies and enhance cognitive health.

A transcriptomic study of osteoporosis induced by ketogenic diet in mice

To investigate the molecular mechanism of osteoporosis caused by ketogenic diet (KD) using transcriptomic analysis. Sixteen 8-week-old female C57BL/6J mice were divided into KD group and sham group for feeding with KD and normal diet for 3 months, respectively. Body weight, blood glucose and blood ketone levels of the mice were measured every two weeks. Microstructure of the cancellous bone in the distal femur was observed with Micro-CT. Total RNA was extracted from bone marrow cells for transcriptomic analysis and bioinformatics analysis. RT-qPCR was used to verify the expression levels of the genes with significant differential expression between the groups. KD obviously weakened the microstructure of the cancellous bone in mice. Compared with those in the sham group, the mice in KD group showed 165 differentially expressed genes (94 up-regulated and 71 down-regulated ones), including Acot1, Mpig6b, Gp9, Ppbp, Slc2a9, etc. KEGG pathway enrichment analysis showed obvious enrichment of the Apelin signaling pathway, PI3K- Akt signaling pathway and ECM-receptor interaction signal transduction pathway with greater number of differential genes. RTqPCR results showed that the 5 differential genes screened by transcriptomics were significantly upregulated in KD group, among which Acot1, Mpig6b and Ppbp were upregulated by over two folds (2.49 ± 0.665, 2.58 ± 0.470, and 2.59 ± 0.611, respectively), suggesting their involvement in KD-induced osteoporosis. The differentially expressed genes and enriched pathways identified in the mouse models provide new clues for studying the molecular mechanism and prevention of KD-induced osteoporosis.

Height Loss Is an Independent Predictor of Fracture Incidence in Postmenopausal Women: The Results from the Gliwice Osteoporosis Study (GO Study).

The aim of a longitudinal, retrospective study was to establish variables predicting fracture incidence over a decade. The study sample comprises a group of 457 postmenopausal women aged over 55 years, recruited from the database of an outpatient osteoporotic clinic. Several variables with potential influence on bone status, including the measurement of body height and hip bone densitometry, were collected. BMD at the femoral neck (FN BMD) was established using a Prodigy device (Lunar, GE, USA). Current body height was compared with the maximal historical body height in early adulthood, as reported by the patient. Three hundred and ninety-four women did not have fractures during the follow up, and 63 subjects presented fractures. Subjects with fracture had lower FN BMD with a T-score of -1.86 ± 1.04 compared to -1.44 ± 0.89 in those without fractures (p < 0.001). Mean height loss (HL) was 3.47 ± 2.11 cm in fractured subjects and 2.50 ± 2.47 cm in unfractured ones, and differed significantly, p < 0.01. Fracture incidence was significantly related to age, rheumatoid arthritis, falls, and previous fractures. In the multivariable analysis using logistic regression, FN BMD, baseline fracture, and HL were identified as the significant predictors of fractures of follow up. Osteoporotic fractures in postmenopausal women were predicted by FN BMD, prior fracture(s), and HL easily established during physical examination.

Prevalence and risk factors of osteoporosis detected by dual-energy X-ray absorptiometry among Chinese patients with primary biliary cholangitis.

Osteoporosis is an extrahepatic complication of primary biliary cholangitis (PBC) that increases the risk of fractures and mortality. However, Epidemiological studies of osteoporosis in patients with PBC in China and the Asia-Pacific region is lack. To assess the prevalence and clinical characteristics of osteoporosis in Chinese patients with PBC. This retrospective analysis included consecutive patients with PBC from a tertiary care center in China who underwent bone mineral density (BMD) assessment using dual-energy X-ray absorptiometry between January 2013 and December 2021. We defined subjects with T-scores ≤ -2.5 in any sites (L1 to L4, femoral neck, or total hip) as having osteoporosis. Demographic, serological, clinical, and histological data were collected. Independent risk factors for osteoporosis were identified by multivariate logistic regression analysis. A total of 268 patients with PBC [236 women (88.1%); mean age, 56.7 ± 10.6 years; 163 liver biopsies (60.8%)] were included. The overall prevalence of osteoporosis in patients with PBC was 45.5% (122/268), with the prevalence of osteoporosis in women and men being 47.0% and 34.4%, respectively. The prevalence of osteoporosis in postmenopausal women was significantly higher than that in premenopausal women (56.3% vs 21.0%, P < 0.001). Osteoporosis in patients with PBC is associated with age, fatigue, menopausal status, previous steroid therapy, body mass index (BMI), splenomegaly, gastroesophageal varices, ascites, Mayo risk score, histological stage, alanine aminotransferase, albumin, bilirubin, platelet and prothrombin activity. Multivariate regression analysis identified that older age, lower BMI, previous steroid therapy, higher Mayo risk score, and advanced histological stage as the main independent risk factors for osteoporosis in PBC. Osteoporosis is very common in Chinese patients with PBC, allowing for prior screening of BMD in those PBC patients with older age, lower BMI, previous steroid therapy and advanced liver disease.

Exploring participant attrition in a longitudinal follow-up of older adults: the Global Longitudinal Study of Osteoporosis in Women (GLOW) Hamilton cohort

ObjectiveWe explored the magnitude of attrition, its pattern and risk factors for different forms of attrition in the cohort from the Global Longitudinal Study of Osteoporosis in Women.DesignProspective cohort study.SettingParticipants...

PA30 The modifying effect of maternal body mass index on the influence of maternal vitamin D supplementation on offspring risk of atopic eczema

Abstract We recently published evidence from a randomized controlled trial of the protective effect of antenatal cholecalciferol supplementation on the risk of infantile atopic eczema in infants that were breastfed for &amp;gt; 1 month. Reports that cholecalciferol supplementation has a smaller effect on circulating 25-hydroxyvitamin D levels in individuals with a higher body mass index (BMI) led us to examine whether maternal BMI modifies the effect of vitamin D supplementation on offspring atopic eczema in the first 4 years of life. In the Maternal Vitamin D Osteoporosis Study, which was a double-blind, randomized, placebo-controlled trial, mothers were supplemented (from 14 weeks’ gestation until delivery) with cholecalciferol 1000 IU daily or matched placebo. Maternal characteristics, including BMI, were recorded from pre-pregnancy, and offspring atopic eczema was ascertained based on the UK Working Party Criteria for the Definition of Atopic Dermatitis at the age of 12 (n = 636), 24 (n = 611) and 48 (n = 450) months. Mothers and offspring characteristics did not differ between the intervention and placebo groups except for longer breastfeeding duration in the intervention group. Maternal pre-pregnancy BMI was found to modify the effect of intervention on offspring eczema, so associations between maternal cholecalciferol supplementation and offspring eczema were stratified by categories of BMI (&amp;lt; 25, 25–30 and &amp;gt; 30 kg m−2), with findings expressed as odds ratios (ORs). Models were adjusted for breastfeeding duration, and infant sex as sensitivity analysis showed that the intervention had an impact on male infants that were breastfed. As reported previously, the offspring of mothers who received 1000 IU cholecalciferol had lower ORs of atopic eczema at 12 months of age [OR 0.57, 95% confidence interval (CI) 0.33–0.98]; the intervention did not affect the risk of atopic eczema in offspring at 24 and 48 months. Stratified analysis demonstrated reduced odds of atopic eczema at 12 months of age in the intervention group in infants whose mothers had a BMI &amp;lt; 25 kg m−2 (OR 0.28, 95% CI 0.09–0.92) and 25–30 kg m−2 (OR 0.20, 95% CI 0.04–1.06) but not for those with a maternal BMI &amp;gt; 30 kg m−2. The risk of atopic eczema at 24 and 48 months of age in offspring in the intervention group was not modified by maternal baseline BMI, and interaction terms between intervention and BMI were not statistically significant (P &amp;gt; 0.2). These RCT findings support evidence of an attenuated effect of cholecalciferol supplementation in mothers with a higher BMI and point toward potential preventative strategies for offspring eczema where maternal cholecalciferol supplementation can be considered and doses adjusted for BMI.

#5454 DESIGN AND OPTIMIZATION OF DRUG COMBINATION THERAPIES FOR OSTEOPOROSIS VIA SIMULATIONS OF BONE TURNOVER

Abstract Background and Aims Many chronic kidney disease (CKD) patients suffer from mineral and bone disorders like osteoporosis, which also affects a huge part of the general population, predominantly postmenopausal women. For the treatment of osteoporosis, several drug types with different mechanisms of action are available, such as bisphosphonates, PTH analogs, RANKL inhibitors and sclerostin inhibitors (some of which are contraindicated for CKD patients beyond CKD stage 3). Different drugs can be given individually or combined in various ways, simultaneously or sequentially, resulting in a huge number of theoretically possible drug combinations that are practically impossible to study in clinical studies. We aimed to study using simulations whether there are combination therapies that would work considerably better than those tested and employed in clinical practice. If so, this could be beneficial for the treatment of a large number of osteoporosis patients by leading to a higher increase in bone strength and a higher reduction in bone fracture risk than standard therapies. Method We developed a physiology-based mathematical model that simulates the process of bone renewal in the human body and can predict how different osteoporosis drugs (including bisphosphonates, PTH analogs, RANKL inhibitors, and sclerostin inhibitors) affect this process, alone and in combination [1]. Results The model was validated on over 30 clinical osteoporosis studies with about 90 study arms. It predicted the time courses of bone mineral density and bone turnover markers with a high degree of accuracy based on the knowledge of the used drugs and dosing schemes alone. We used the model to study how treatment results changed when merely reshuffling the order in which different drugs were given. For example, for 3-year drug therapies involving alendronate, denosumab and romosozumab (1 year each), our simulations showed that the order in which these drugs were given can have a considerable effect on short- and long-term therapy success [1]. This is due to different drugs favorably interacting when applied in the right sequence. Conclusion Our findings indicate that some osteoporosis drug administration schemes are superior to others while relying on the exact same types and amounts of drugs. Therefore, there is a large potential to improve pharmacologic therapies of osteoporosis using physiological simulations. For renal patients beyond CKD stage 3, a restricted set of drug types may be considered to account for contraindications related to impaired renal clearance. If translated into clinical practice, findings obtained using our model could give rise to novel treatments using combinations of existing drugs for osteoporosis that lead to a lower bone fracture risk than standard treatments. Moreover, our model could serve as a basis for personalizing osteoporosis therapy to individual patients.