Increased Risk Of Hip Fracture Research Articles

The association of type 2 diabetes-related characteristics with fracture risk at different sites.

To determine the association of diabetes-related characteristics with fractures at different sites in individuals with type 2 diabetes (T2D). We conducted a cohort study using the Clinical Practice Research Datalink (CPRD) GOLD. Patients aged over 30 years with T2D were identified within the CPRD. Patients were followed from the start of diabetes treatment until the end of data collection, death, or the occurrence of a fracture. Cox proportional hazards models were used to estimate the hazard ratios for the association of the individual characteristics (diabetes duration, glycated haemoglobin [HbA1c] level, and microvascular complications) with fracture risk, adjusted for demographics, comorbidities and comedication. A diabetes duration of >10 years was associated with an increased risk of any fracture and major osteoporotic fractures (MOFs), while a diabetes duration of >8 years was associated with an increased hip fracture risk, compared to a duration <2 years. An HbA1c level <6% was associated with an increased fracture risk compared to HbA1c values of 6% to <7%. The presence of one or two microvascular complications was associated with an increased risk of any fracture and MOFs and the presence of two microvascular complications was associated with an increased hip fracture risk, compared to no microvascular complications. In conclusion, our study shows that a diabetes duration of 10 years or more, strict glycaemic control resulting in HbA1c levels below 6%, and/or the presence of at least one microvascular complication increased the risk of any fracture, hip fractures, MOFs, and humerus fractures, but not ankle, scapula or skull fractures.

The association of microvascular disease and endothelial dysfunction with vertebral trabecular bone mineral density : The MESA study.

Microvascular diseases of the eye, kidney, and brain are associated with endothelial dysfunction and increased hip fracture risk. To explore the basis for higher hip fracture risk, we comprehensively examined whether markers of microvascular disease and/or endothelial dysfunction are related to trabecular bone mineral density (BMD), a proximate risk factor for osteoporotic fractures. Among 6814 participants in the Multi-Ethnic Study of Atherosclerosis study (MESA), we derived thoracic vertebral trabecular BMD from computed tomography of the chest and measured urine albumin to creatinine ratios (UACR), retinal arteriolar and venular widths, flow mediated dilation (FMD) of the brachial artery after 5min of ischemia; and levels of five soluble endothelial adhesion markers (ICAM-1, VCAM-1, L-selectin, P-selectin, and E-selectin). Linear regression models were used to examine the association of trabecular BMD with markers of microvascular disease and with markers of endothelial dysfunction. We observed no significant associations of UACR, retinal arteriolar or venular widths, or FMD with BMD. We also observed no statistically significant association of spine trabecular BMD with levels of endothelial adhesion markers. Men and women had largely similar results. We conclude that there is little evidence to connect thoracic spine trabecular BMD to microvascular disorders or to endothelial dysfunction among multi-ethnic middle-aged and older adults. Other factors beyond trabecular BMD (e.g., bone quality or predisposition to falling) may be responsible for the associations of microvascular disease with osteoporotic fractures.

Hip fractures in patients with primary aldosteronism – a Swedish nationwide study

SummaryIn this large population-based matched cohort study, patients with primary aldosteronism were at increased risk of hip fracture, particularly subgroups traditionally considered at higher risk of osteoporosis such as women, patients older than 56 years at diagnosis, patients with established cardiovascular disease at diagnosis, and patients treated with MRA.PurposePrevious studies suggest that primary aldosteronism (PA) is associated with dysregulated bone homeostasis. The aim of this study was to evaluate the incidence of hip fractures in patients with PA.MethodsWe studied a nationwide cohort of 2419 patients with PA (1997–2019) and 24 187 age and sex matched controls from the general population. Hip fractures were identified by ICD codes in the Swedish National Patient Register. We estimated hazard ratios (HRs) for incident hip fractures, adjusted for prior fractures, socioeconomic factors, diabetes, osteoporosis, hyperparathyroidism, and cardiovascular disease (CVD). Pairwise subgroup comparisons were performed by age (18–56 and > 56 years), sex, CVD at baseline, and treatment for PA.ResultsDuring a mean follow up of 8 ± 5 years, 64 (2.6%) patients had a hip fracture after being diagnosed with PA, compared to 401 (1.7%) controls. After adjustments, PA was associated with a 55% increased risk of hip fracture compared to controls (HR 1.55 [1.18–2.03]). HRs were increased in women (HR 1.76 [95% CI 1.24–2.52]), patients aged > 56 years (HR 1.62 [95% CI 1.21–2.17]), and patients with CVD at diagnosis (HR 2.15 [95% CI 1.37–3.37]). PA patients treated with adrenalectomy did not have higher risk than controls (HR 0.84 [95% CI 0.35–2.0]), while patients treated with mineralocorticoid receptor antagonists (MRA) retained a greater risk (HR 1.84 [95% CI 1.20–2.83]).ConclusionPA is associated with increased hip fracture risk, especially in women, patients diagnosed after the age of 56 years and patients with established CVD at diagnosis. Also, patients treated with MRA seem to have an increased risk of hip fractures, while adrenalectomy may be protective.

The medication-based Rx-Risk Comorbidity Index and risk of hip fracture - a nationwide NOREPOS cohort study

BackgroundFew previous studies have assessed overall morbidity at the individual level with respect to future risk of hip fracture. The aim of this register-based cohort study was to examine the association between morbidity measured by the medication-based Rx-Risk Comorbidity Index (Rx-Risk) and the risk of first hip fracture.MethodsIndividual-level data on medications dispensed from pharmacies (2005–2016) was retrieved from the Norwegian Prescription Database and used to calculate Rx-Risk for each calendar year. Information on first hip fractures (2006–2017) was obtained from a nationwide hip fracture database. Individuals ≥ 51 years who filled at least one prescription during the study period comprised the population at risk. Using Rx-Risk as a time-varying exposure variable, relative risk estimates were obtained by a negative binomial model.ResultsDuring 2006–2017, 94,104 individuals sustained a first hip fracture. A higher Rx-Risk was associated with increased risk of hip fracture within all categories of age and sex. Women with the highest Rx-Risk (> 25) had a relative risk of 6.1 (95% confidence interval (CI): 5.4, 6.8) compared to women with Rx-Risk ≤ 0, whereas the corresponding relative risk in women with Rx-Risk 1–5 was 1.4 (95% CI: 1.3, 1.4). Similar results were found in men. Women > 80 years with Rx-Risk 21–25 had the highest incidence rate (514 (95% CI: 462, 566) per 10, 000 person years). The relative increase in hip fracture risk with higher Rx-Risk was most pronounced in the youngest patients aged 51–65 years.ConclusionsRx-Risk is a strong predictor of hip fracture in the general outpatient population and may be useful to identify individuals at risk in a clinical setting and in future studies.

A new hip fracture risk index derived from FEA-computed proximal femur fracture loads and energies-to-failure.

Quantitative CT-based patient-specific finite element (FE) analysis (FEA) incorporates bone geometry and bone density in the proximal femur to compute the force (fracture load) and energy necessary to break the proximal femur in a particular loading condition. The fracture loads and energies-to-failure are individually associated with incident hip fracture, and provide different structural information about the proximal femur. We used principal component analysis (PCA) to develop a global FEA-computed fracture risk index that incorporates the FEA-computed yield and ultimate failure loads and energies-to-failure in four loading conditions of 110 hip fracture subjects and 235 age- and sex-matched control subjects from the AGES-Reykjavik study. Using a logistic regression model, we compared the prediction performance for hip fracture based on the stratified resampling. We referred the first principal component (PC1) of the FE parameters as the global FEA-computed fracture risk index, which was the significant predictor of hip fracture (p-value < 0.001). The area under the receiver operating characteristic curve (AUC) using PC1 (0.776) was higher than that using all FE parameters combined (0.737) in the males (p-value < 0.001). The global FEA-computed fracture risk index increased hip fracture risk prediction accuracy in males.

Large-scale circulating proteome association study (CPAS) meta-analysis identifies circulating proteins and pathways predicting incident hip fractures.

Hip fractures are associated with significant disability, high cost, and mortality. However, the exact biological mechanisms underlying susceptibility to hip fractures remain incompletely understood. In an exploratory search of the underlying biology as reflected through the circulating proteome, we performed a comprehensive Circulating Proteome Association Study (CPAS) meta-analysis for incident hip fractures. Analyses included 6430 subjects from two prospective cohort studies (Cardiovascular Health Study and Trøndelag Health Study) with circulating proteomics data (aptamer-based 5K SomaScan version 4.0 assay; 4979 aptamers). Associations between circulating protein levels and incident hip fractures were estimated for each cohort using age and sex-adjusted Cox regression models. Participants experienced 643 incident hip fractures. Compared with the individual studies, inverse-variance weighted meta-analyses yielded more statistically significant associations, identifying 23 aptamers associated with incident hip fractures (conservative Bonferroni correction 0.05/4979, P < 1.0 × 10-5). The aptamers most strongly associated with hip fracture risk corresponded to two proteins of the growth hormone/insulin growth factor system (GHR and IGFBP2), as well as GDF15 and EGFR. High levels of several inflammation-related proteins (CD14, CXCL12, MMP12, ITIH3) were also associated with increased hip fracture risk. Ingenuity pathway analysis identified reduced LXR/RXR activation and increased acute phase response signaling to be overrepresented among those proteins associated with increased hip fracture risk. These analyses identified several circulating proteins and pathways consistently associated with incident hip fractures. These findings underscore the usefulness of the meta-analytic approach for comprehensive CPAS in a similar manner as has previously been observed for large-scale human genetic studies. Future studies should investigate the underlying biology of these potential novel drug targets.

Higher serum free thyroxine levels are associated with increased risk of hip fractures in older men.

Overt and subclinical hyperthyroidism are associated with an increased fracture risk, but whether thyroid hormones are associated with fracture risk in individuals with normal thyroid-stimulating hormone (TSH) has mostly been investigated in women. Therefore, we investigated if serum levels of free thyroxine (FT4) or TSH are associated with fracture risk in Swedish men. We followed (median 12.2yr) elderly men (n = 1825; mean age 75, range 69-81yr) participating in the Gothenburg and Malmö subcohorts of the prospective, population-based MrOS-Sweden study. The statistical analyses included Cox proportional hazards regression. Men receiving levothyroxine treatment were excluded. In our total cohort, serum FT4 (per SD increase) was associated with increased risk of major osteoporotic fractures (MOFs; n = 479; fully adjusted hazard ratio [HR] 1.14, 95% CI, 1.05-1.24) and hip fractures (n = 207; HR 1.18, 95% CI, 1.04-1.33). Also, in men with normal TSH (n = 1658), FT4 (per SD increase) was significantly associated with increased risk of MOF and hip fractures. Furthermore, men in the highest FT4 quartile had a 1.5-fold increase in hip fracture risk compared with men in the three lower FT4 quartiles, both in the total population and in men with normal TSH (fully adjusted: HR 1.45, 95% CI, 1.04-2.02 and HR 1.51, 95% CI, 1.07-2.12, respectively). In contrast, the risk of MOF was not statistically different in the highest FT4 quartile compared with the three lower FT4 quartiles. Finally, serum TSH was not associated with fracture risk after full adjustment for covariates. In conclusion, serum FT4, but not serum TSH, is a predictor of hip fracture risk in elderly Swedish men. Additionally, there was an association between FT4 (per SD increase) and the risk of MOF.

Impact of sodium‐glucose cotransporter‐2 inhibitors on the risk of hip fracture in older patients in Japan using a nationwide administrative claims database: A matched case–control study

Some clinical trials have shown that sodium-glucose cotransporter-2 (SGLT2) inhibitors are associated with fracture risk. However, this notion remains controversial. This study aimed to evaluate hip fracture risk after the use of SGLT2 inhibitors while controlling for factors that may affect fracture risk. Furthermore, hip fracture risk is evaluated in relation to the SGLT2 inhibitors component and its concomitant use with other antidiabetic agents. Using large-scale real-world data, this case-control study investigated hospitalized patients between January 2018 and December 2020. Patients were aged 65-89 years and had beenprescribed with SGLT2 inhibitors at least twice. Patients with hip fracture (cases) and those without (controls) were identified via 1:3 matching according to sex, age (±3 years), hospital size classification, and number of concomitant antidiabetic agents. Exposure to SGLT2 inhibitors of the cases and controls was compared with the use of multivariate conditional logistic regression. After matching, 396 cases and 1081 controls were identified. The adjusted odds ratio for patients receiving treatment with SGLT2 inhibitors was 0.83 (95% confidence interval: 0.55-1.26), indicating no increase in hip fracture risk. Additionally, no increased risk was observed with respect to SGLT2 inhibitors by component or concomitant use with other antidiabetic agents. Our study showed that SGLT2 inhibitors do not increase hip fractures in older patients. However, because the risk assessment of SGLT2 inhibitors by component and their concomitant use with other antidiabetic agents is based on a limited number of patients, it is important to interpret the results with caution. Geriatr Gerontol Int 2023; ••: ••-••.

Association between changes in depressive symptoms and hip fracture among middle-aged and older Chinese individuals: a prospective cohort study

BackgroundAlthough studies have shown that depressive symptoms are associated with an increased risk of hip fracture (HF). Depressive symptoms are dynamic, and it is unclear whether HF risk persists if depressive symptoms remit. This study aims to examine the associations between changes in depressive symptoms and HF risk.MethodsData were from the China Health and Retirement Longitudinal Study from 2011 to 2018. Depressive symptoms were measured using the 10-item version of the Center for Epidemiological Studied Depression scale (cutoff ≥ 10). Changes in depressive symptoms were classified into four groups by two successive surveys (stable low/no, recent-onset, recently remitted, and stable high depressive symptoms). Multivariable logistic regressions were performed to assess whether changes in depressive symptoms were associated with HF incidents reported through 2018, adjusting for age, sex, educational level, marital status and other potential confounding factors.ResultsIn total, 8574 participants were included, 265 (3.1%) of whom had reported HF incidents in the subsequent 5-year period. Participants with recent-onset (OR = 1.97, 95% CI = 1.40–2.77) or stable high (OR = 2.15, 95% CI = 1.53–3.02) symptoms had a higher risk of HF than those with stable low/no depressive symptoms, whereas those with improved depressive symptoms (OR = 1.27, 95% CI = 0.89–1.82) had no elevation in HF risk.ConclusionStable high and recent-onset depressive symptoms were associated with increased HF risk, and no elevated HF risk was observed if symptoms remitted, suggesting that strategies to reduce depressive symptoms may be beneficial for HF prevention.

ODP127 Trabecular Bone Score and Advanced Glycation End Products In Adults with Type 1 Diabetes

Abstract Background Individuals with type 1 diabetes (T1D) have a two- to threefold increase in fracture risk at any site, and up to a sevenfold increase in hip fracture risk compared to those without diabetes. Reduced bone quality appears to contribute to the increased fracture risk observed in this population. Advanced glycation end products (AGEs) tissue accumulation, which reflects long-term glycemic control, may influence bone quality in T1D. Objective We aimed to determine if skin AGEs, as a surrogate marker for bone AGEs, are associated with vertebral trabecular bone score (TBS),anindex of bone microarchitecture derived from lumbar spine dual-energy X-ray absorptiometry (DXA) images and evaluating bone quality. Methods We present preliminary data from subjects with T1D who participated in a cross-sectional study aiming at comparing the prevalence of vertebral fractures between adult subjects with T1D from two tertiary care centers and age-, sex- and BMI-matched controls without diabetes. TBS and bone mineral density (BMD) were assessed using DXA. Skin AGEs were measured by skin autofluorescence. Simple and multiple linear regression analyses were used to explore the factors associated with TBS. Results One hundred and six subjects with T1D (52.8% women; mean age 42.7±14.7 years; mean BMI 26.9±5.6 kg/m 2; mean diabetes duration 27.6±12.3 years; 48.1% with a microvascular complication; mean HbA 1C in the preceding 3 years 7.5±0.9%; mean skin AGEs 2.15±0.54 units; mean TBS 1.428±0.113) were included. Higher skin AGEs were associated with a lower TBS in simple regression analysis (p=0. 012). In multiple linear regression, older age, male sex, higher BMI, current smoking, higher serum calcium, lower lumbar spine and femoral neck BMD, but not skin AGEs, were significantly associated with a lower TBS (model adjusted R 2 =0.65). Conclusion In this population with relatively well-controlled T1D, skin AGEs were not independently associated with TBS. Presentation: No date and time listed

25-OH vitamin D threshold for optimal bone mineral density in elderly patients with chronic kidney disease.

Introduction: Vitamin D deficiency is common in chronic kidney disease (CKD) and is associated with lower bone mineral density (BMD), decreased muscle strength, and increased hip fracture risk. Guidelines have suggested targeting 25-OH vitamin D (25(OH)D) levels between 20 and 30ng/ml. However, vitamin D metabolism is altered in CKD, and threshold levels for optimal BMD are unknown. Methods: We included 1097 patients with hip fractures. CKD was defined as estimated glomerular filtration rate <60ml/min/1.73m (Mucsi et al., Clin. Nephrol., 2005, 64(4), 288-294) and low BMD defined as T score ≤ -2.5 at femoral neck. We assessed the association of 25(OH)D with low BMD in patients with and without CKD: using the conventional threshold 25(OH)D < 30ng/dl, as well as a new threshold. Results: CKD was present in 479 (44%) patients. Using a threshold of 25(OH)D < 30ng/ml, there were no significant differences in patients with CKD and low BMD when compared to the other groups. We identified 27ng/ml as a better threshold with the Youden index. Using 25(OH)D < 27ng/ml as a threshold, 360 of 482 patients (74.7%) with low 25(OH)D had low BMD, compared to only 185/276 (67%) of patients with adequate vitamin D, p = 0.02, which was irrespective of the presence or absence of CKD. Furthermore, patients with CKD and 25(OH)D < 27ng/ml had a higher odds ratio of mortality upon follow-up, 1.61, 95% CI: 1.08-2.39, compared to those with CKD and 25(OH)D ≥ 27ng/ml. Conclusion: We find that 25(OH)D < 27ng/ml is associated with low BMD in patients with and without CKD. Further prospective studies targeting vitamin D repletion to at least 27ng/ml and the outcome of hip fractures will be useful to validate these findings.

Characteristics of fallers who later sustain a hip fracture: a NOREPOS study

SummaryFall prevention programs have shown inconclusive results concerning hip fracture reduction. We found that fallers with poor health, low societal participation, and use of psychotropics/painkillers had a threefold to fivefold increased hip fracture risk compared to non-fallers without these risk factors. This may help target fall prevention towards high-risk individuals.IntroductionTo investigate whether self-reported information on health, societal participation, and drug use in older people, easily obtainable by health care providers, contribute to predict future hip fracture beyond self-reported falls.MethodsWe used data from 3801 women and 6439 men aged 70–79 years participating in population-based studies in five counties in Norway 2000–2003. Height and weight were measured. Socioeconomic status, lifestyle, health status, and history of falling were self-reported through questionnaires. Falls last year were dichotomized into one or more versus no falls. Hip fractures were identified by linkage to hospital data with follow-up through 2013. Hazard ratios (HR) with 95% confidence intervals (95% CI) for hip fracture by combinations of risk factors with history of falling were estimated using Cox proportional hazards regression.ResultsMore women (32.4%) than men (27.7%) reported one or more falls during the previous year, and 17.9% of women (n = 682) and 8.9% of men (n = 572) suffered a hip fracture during median 11.6 years of follow-up. Poor health, low societal participation, and use of psychotropics/analgesics among fallers were strong predictors of hip fracture. The presence of all three risk factors and history of falling was associated with HR 2.92 (95% CI 2.10–4.05) for hip fracture in women and HR 4.60 (95% CI 2.71–7.81) in men compared to non-fallers without these factors.ConclusionOur study indicates that self-assessment of health, information about activities outside home, and drug use among fallers far better identify high risk of hip fracture in older people than information about falls alone.

Increased Cortical Porosity, Reduced Cortical Thickness, and Reduced Trabecular and Cortical Microhardness of the Superolateral Femoral Neck Confer the Increased Hip Fracture Risk in Individuals with Type 2 Diabetes.

Individuals with diabetes mellitus type 2 (T2DM) have approximately 30% increased risk of hip fracture; however, the main cause of the elevated fracture risk in those subjects remains unclear. Moreover, micromechanical and microarchitectural properties of the superolateral femoral neck—the common fracture-initiating site—are still unknown. We collected proximal femora of 16 men (eight with T2DM and eight controls; age: 61 ± 10 years) at autopsy. After performing post-mortem bone densitometry (DXA), the superolateral neck was excised and scanned with microcomputed tomography (microCT). We also conducted Vickers microindentation testing. T2DM and control subjects did not differ in age (p = 0.605), body mass index (p = 0.114), and femoral neck bone mineral density (BMD) (p = 0.841). Cortical porosity (Ct.Po) was higher and cortical thickness (Ct.Th) was lower in T2DM (p = 0.044, p = 0.007, respectively). Of trabecular microarchitectural parameters, only structure model index (p = 0.022) was significantly different between T2DM subjects and controls. Control group showed higher cortical (p = 0.002) and trabecular bone microhardness (p = 0.005). Increased Ct.Po and decreased Ct.Th in T2DM subjects increase the propensity to femoral neck fracture. Apart from the deteriorated cortical microarchitecture, decreased cortical and trabecular microhardness suggests altered bone composition of the superolateral femoral neck cortex and trabeculae in T2DM. Significantly deteriorated cortical microarchitecture of the superolateral femoral neck is not recognized by standard DXA measurement of the femoral neck.

Peptic Ulcer Disease and Risk of Hip Fracture: A General Population-based Cohort Study.

Previous studies reported proton pump inhibitor (PPI) use may increase the risk of fracture; however, the findings may be susceptible to indication bias because peptic ulcer disease (PUD), 1 major indication for PPIs, may affect skeletal health. Determining whether PUD would increase hip fracture risk may help identify high-risk populations and explore risk factors. We conducted a cohort study using data from The Health Improvement Network (THIN) in the United Kingdom. THIN contains patient information such as disease diagnosis and medicine prescriptions. Up to 5 non-PUD individuals (n = 138 265) were matched to each case of incident PUD (n = 27 653) by age, sex, and body mass index. We examined the association between PUD and hip fracture by a multivariable Cox proportional hazard model. We repeated the same analysis among individuals with incident PUD and gastroesophageal reflux disease (GERD) (n = 27 160), another disease with similar indication for PPIs, as a positive control exposure. Over a mean of 5.6 years of follow-up, hip fracture occurred in 589 individuals with PUD and 2015 individuals without PUD (3.8 vs 2.6/1000 person-years), with a multivariable-adjusted hazard ratio (HR) being 1.44 (95% confidence interval [CI], 1.31-1.58). The association persisted among subgroups stratified by sex and age. In positive control exposure analysis, the hip fracture risk was also higher in PUD than GERD (3.8 vs 2.4/1000 person-years; multivariable-adjusted HR = 1.65; 95% CI, 1.45-1.7). This general population-based cohort study suggests, after controlling for acid-lowering medication and other potential risk factors, PUD is independently associated with an increased risk of hip fracture.

Anaemia Is Associated with an Increased Risk of Fractures, a Systematic Review, and Meta-Analysis

Background: Anaemia and osteoporotic fractures are both major health problems among older adults worldwide. Objectives: Previous studies suggest that anaemia may be associated with elevated fracture risk among older adults; however, the exact relationship between them is unknown. We aimed to investigate the association between anaemia and fracture risk. Methods: A comprehensive literature search was performed in four medical databases. We included articles that were published from inception to February 18, 2021. Odds ratios (ORs), hazard ratios (HRs) with 95% confidence intervals (CIs), and original raw incidences from studies comparing fracture rates in anaemic versus non-anaemic patients were extracted and pooled with the random-effects model. I2 test was used to assess heterogeneity. Risk of bias assessment was performed using the Quality of Prognostic Studies tool. PROSPERO: CRD42021241109. Results: A total of 13 studies were identified; 8 of them were included in the quantitative synthesis. Anaemia was found to be a risk factor for fracture compared to non-anaemia. Anaemia increased hip fracture risk in both older men (HR = 1.71; CI: 1.46–2.00, p< 0.001, I2 = 83.2%) and women (HR = 1.31; CI: 1.13–1.52, p< 0.001), but the fracture risk was more increased among men. There was also an increased chance of hip fracture in the presence of anaemia in populations, including both older men and women (OR = 1.64; CI: 1.35–2.01, p< 0.001, I2 = 61.1%). Anaemia was also associated with increased vertebral (HR = 1.21; CI: 1.04–1.40, p = 0.012) and all-type (HR = 1.49; CI: 1.19–1.86, p< 0.001) fracture risk in older men. Conclusion: Our results suggest that there is a significant relationship between anaemia and fracture risk in older adults. This association is stronger among older men than women and differs in the different types of fractures.

Gamma-glutamyl-transferase is associated with incident hip fractures in women and men ≥ 50years: a large population-based cohort study.

We herein examined a possible relation between serum levels of GGT and hip fracture risk in women and men aged ≥ 50years, which has not been investigated before. In this population-based prospective cohort study, approximately 41,000 women and nearly 33,000 men ≥ 50years participating in a medical prevention program 1985-2005 in western Austria were followed up for the occurrence of osteoporotic hip fractures during 2003-2013. ICD-10 based discharge diagnoses for hip fracture included S72.0, S72.1, and S72.2 available from all regional hospitals. GGT-related hip fracture risk was ascertained at each participant´s first and last examination during the prevention program. In a subset of 5445 participants, alcohol consumption could be included as a covariate. In men, hip fracture risk rose significantly by 75% and 86% for every tenfold increase of GGT measured at the first and last examination, respectively, and in women, hip fracture risk rose by 22% from the last examination. Elevated GGT (≥ 36 U/l in women, ≥ 56 U/l in men) at the first examination was associated with increased hip fracture risk only in men (HR 1.51, 95% CI 1.25-1.82), and at the last examination in both women (HR 1.14, 95% CI 1.02-1.28) and men (HR 1.61, 95% CI 1.33-1.95). Alcohol consumption had no significant influence on GGT-mediated hip fracture risk in women and men. Our findings identified an association of elevated GGT and hip fracture in women and men ≥ 50years and suggest GGT as a candidate serum marker of long-term hip fracture risk in an elderly population.

Parametric Study of Hip Fracture Risk Using QCT-Based Finite Element Analysis

Various parameters such as age, height, weight, and body mass index (BMI) influence the hip fracture risk in the elderly which is the most common injury during the sideways fall. This paper presents a parametric study of hip fracture risk based on the gender, age, height, weight, and BMI of subjects using the subject-specific QCT-based finite element modelling and simulation of single-leg stance and sideways fall loadings. Hip fracture risk is estimated using the strain energy failure criterion as a combination of bone stresses and strains leading to more accurate and reasonable results based on the bone failure mechanism. Understanding the effects of various parameters on hip fracture risk can help to prescribe more accurate preventive and treatment plans for a community based on the gender, age, height, weight, and BMI of the population. Results of this study show an increase in hip fracture risk with the increase of age, body height, weight, and BMI in both women and men under the single-leg stance and the sideways fall configurations.

Dietary patterns and hip fracture in the Adventist Health Study 2: combined vitamin D and calcium supplementation mitigate increased hip fracture risk among vegans

Concerns regarding the adequacy of vegetarian diets with respect to fracture risk continue. We aimed to explore the influence of 5 previously defined dietary patterns on hip fracture risk and whether this association is modified by concomitant calcium and vitamin D supplementation. The Adventist Health Study 2 is a prospective cohort study in which participants were enrolled during 2002-2007; proportional hazards regression analyses were used to estimate fracture risk. Participants reside throughout the United States and Canada. A total of 34,542 non-Hispanic white peri- and postmenopausal women and men 45 y and older responded to the biennial hospital history form and were followed for a median of 8.4 y. The study identified 679 incident hip fractures during 249,186 person-years of follow-up. Fracture risk varied according to dietary pattern, with a clear effect modification by concurrent supplementation with both vitamin D and calcium. In multivariable models, including adjustment for calcium and vitamin D supplementation, female vegans had 55% higher risk of hip fracture (HR: 1.55; 95% CI: 1.06, 2.26) than nonvegetarians (NVEGs), whereas there was no association between diet pattern and hip fracture risk in men. When further stratifying females on supplement use with both vitamin D and calcium, vegans taking both supplements were at no greater risk of hip fracture than the subjects with other dietary patterns including the NVEGs. Without combined supplementation of both vitamin D and calcium, female vegans are at high risk of hip fracture. However, with supplementation the excessive risk associated with vegans disappeared. Further research is needed to confirm the adequacy of a vegan diet supplemented with calcium and vitamin D with respect to risk of fracture.

Mechano-structural alteration in proximal femora of individuals with alcoholic liver disease: Implications for increased bone fragility.

Although increased hip fracture risk is noted in patients with alcoholic liver disease (ALD), their femoral microstructural and mechanical properties were not investigated previously. The present study aimed to analyze the associations between subregional deteriorations in femoral mechano-structural properties and clinical imaging findings to explain increased femoral fracture risk among ALD patients. This study analyzed proximal femora of 33 male cadaveric donors, divided into ALD (n=13, 57±13years) and age-matched control group (n=20, 54±13years). After pathohistological verification of ALD stage, DXA and HSA measurements of the proximal femora were performed, followed by micro-CT and Vickers microindentation of the superolateral neck, inferomedial neck, and intertrochanteric region. Bone mineral density and cross sectional area of the femoral neck were deteriorated in ALD donors, compared with healthy controls (p<0.05). Significant ALD-induced degradation of trabecular and cortical microstructure and Vickers microhardness reduction were noted in the analyzed femoral regions (p<0.05). Still, the most prominent ALD-induced mechano-structural deterioration was noted in intertrochanteric region. Additionally, more severe bone alterations were observed in individuals with an irreversible stage of ALD, alcoholic liver cirrhosis (ALC), than in those with an initial ALD stage, fatty liver disease. Observed osteodensitometric and mechano-structural changes illuminate the basis for increased femoral fracture risk in ALD patients. Additionally, our data suggest bone strength reduction that may result in increased susceptibility to intertrochanteric femoral fracture in men with ALD. Thus, femoral fracture risk assessment should be advised for all ALD patients, especially in those with ALC.

Factors Associated With Low Bone Mineral Density in Adults With Type 1 Diabetes: A Cross-Sectional Study

Context: Individuals with type 1 diabetes (T1D) have a two- to threefold increase in fracture risk at any site, and up to a sevenfold increase in hip fracture risk compared to those without diabetes. The mechanisms accounting for this bone fragility are not yet fully understood. Objectives: 1) To determine factors associated with low bone mineral density (BMD) in patients with T1D; 2) To assess the association between skin advanced glycation end products (AGEs) and low BMD in patients with T1D. Methods: These are preliminary data from patients with T1D included in a cross-sectional study aiming at comparing the prevalence of vertebral fractures between adult patients with T1D from two tertiary care centers and age- and sex-matched controls without diabetes. Patients were eligible if they were aged ≥20 years and had a diagnosis of T1D for at least 5 years. Patients were classified as having a low BMD if Z-score was ≤-2.0 at any site (lumbar spine, femoral neck, total hip, radius) in patients aged <50 years or if T-score was ≤-1.0 at any site in patients aged ≥50 years or in postmenopausal women. Skin AGEs (surrogate marker of overall including bone AGEs) were measured by skin autofluorescence (AGE Reader ®). Unpaired t-tests or Chi-squared tests were used to compare characteristics between patients with or without a low BMD. Variables associated with a low BMD were determined by univariate analysis and were subsequently included in a multivariate logistic regression analysis if p<0.1 in the univariate analysis. All variables were tested for multicollinearity. Results: 106 patients with T1D were included (mean age 45.2±15.0 years; mean BMI 26.3±5.1 kg/m2; 54.7% women; mean duration of diabetes 28.2±13.6 years; 44.3% with a microvascular complication). Mean HbA1C over the past 3 years was 7.5±0.8%. A third of the patients (31.1%) had a low BMD (3 patients using Z-score; 30 patients using T-score). Patients with a low BMD were older (58.3 vs 39.3 years, p<0.001), had a lower mean HbA1C over the past 3 years (7.3% vs 7.6%, p=0.047), a longer diabetes duration (36.1 vs 24.6 years, p<0.001), higher skin AGEs (2.50 vs 2.03, p<0.001), a higher prevalence of microvascular complications (63.6% vs 37.7%, p=0.02) and a higher prevalence of abnormal albumin to creatinine ratio (ACR ≥2.0) on the day of assessment (38.7% vs 11.8%, p=0.003). In multivariate regression analysis, age (p<0.001), abnormal ACR (p=0.003) and lower mean HbA1C over the past 3 years (p=0.02) remained significantly associated with a low BMD. Skin AGEs were correlated with age (r=0.56) and diabetes duration (r=0.47). Conclusion: In this population with T1D, a low BMD was independently associated with older age, abnormal ACR and, unexpectedly, with a lower mean HbA1C over the past 3 years, but not with skin AGEs.