Major Osteoporotic Fracture Research Articles

Early administration of romosozumab prevents rebound of bone resorption related to denosumab withdrawal in fractured post-menopausal women: a real-world prospective study.

The real-world effectiveness of switching from denosumab to romosozumab remains controversial. Sequential therapy with romosozumab was shown to be associated with inadequate suppression of bone resorption and there was anecdotal evidence of major osteoporotic fractures (MOFs) after transitioning from denosumab to romosozumab. This study evaluated the effects on bone resorption of early romosozumab administration 3 months after denosumab withdrawal in fractured women with post-menopausal osteoporosis. This prospective, single-center cohort study included 39 post-menopausal women with osteoporosis experiencing either MOFs or decrease in bone mineral density during long-term treatment with anti-resorptive drugs. Eighteen received romosozumab either 6 months (Group A) or 3 months (Group B) after their last denosumab dose, while 21 women switched from bisphosphonates to romosozumab and were enrolled as controls (Group C). Serum C-terminal telopeptide of type I collagen (CTX) levels were measured at baseline, 3 and 6 months. All women of group A and 4 out of 8 women of group B showed a clinically significant increase of CTX values (i.e., change above the least significant change) (p = 0.023), which occurred earlier in group A as compared to group B. Moreover, 9/10 women of group A and 2/8 women of group B achieved values above the mean of reference range for pre-menopausal women (p = 0.013). In group C, serum CTX values did not change significantly during the follow-up. Two women in Group A experienced MOFs during the follow-up. Early romosozumab administration after denosumab withdrawal may control bone turnover rebound and possibly prevent incidence of fractures in post-menopausal osteoporosis.

P-451. Adherence to Bone Mineral Density Screening Recommendations in Older Adults with HIV

Abstract Background HIV guidelines recommend bone mineral density (BMD) screening by dual-energy x-ray absorptiometry (DXA) for all postmenopausal women and all men ≥50 years. Uptake of these recommendations has been low. This study describes DXA screening practices among people with HIV (PWH) at highest risk for low BMD. Methods We conducted a retrospective chart review among PWH aged ≥65 or older who were seen for HIV care at the University of Colorado within the last year. First available and most recent DXA scans were collected; FRAX score was calculated to estimate 10-year risk of major osteoporotic and hip fractures. Demographics and clinical factors were also collected. Results We reviewed records of 300 PWH age 65 and older, including 243 (81%) men and 57 (19%) women. The mean age was 69.8 (SD 4.4) years, 62% were non-Hispanic white, 45% had a normal body mass index (18.5-24.9 kg/m2), and 60% reported current/prior tobacco use. 48% had a DXA scan ordered, including 53% of those with previous falls and 54% with prior fracture. Mean age at first DXA scan was 64.9 (SD 6.0) for males and 64.5 (SD 6.4) for women. Of those screened, 13% of women and 27% of men had normal BMD (T-score > -1.0); 45% of women and 53% of men had osteopenia (T-score < -1 to -2.5) and 42% of women and 20% of men had osteoporosis (T-score < -2.5). By FRAX, 10-year probability of major osteoporotic fracture was 9.8% [IQR: 5.7, 13.6] for women and 6.8% [4.7, 11.0] for men. The 10-year probability of hip fracture was 2.2% [0.8, 4.1] for women and 1.4% [0.6, 2.8] for men. Conclusion Older PWH are markedly under-screened for low BMD. There was low adherence to screening per current HIV guidelines, even among those with the highest risk. Osteopenia and osteoporosis were common, though FRAX scores suggested only moderate risk. Improved screening for reduced BMD and fracture risk in PWH is urgently needed. Disclosures Kristine M. Erlandson, MD MS, Gilead: Advisor/Consultant|Gilead: Grant/Research Support|ViiV: Advisor/Consultant

Biases in the performance of FRAX without BMD in predicting fracture risk in a multiethnic population with diabetes: the Diabetes & Aging Study.

Fracture risk calculators, such as the Fracture Risk Assessment Tool (FRAX), calculate the risk of major osteoporotic (MOF) and hip fracture, but do not account for the excess risk of fracture in people with diabetes. We examined the predictive performance of FRAX without BMD in ethnically diverse, older patients with diabetes. Patients included were between ages 65-89 from the Kaiser Permanente Northern California Diabetes Registry and not already taking osteoporosis medications. Race and ethnicity were self-identified. We calculated FRAX without BMD based on baseline characteristics and assessed how well FRAX predicted MOF and hip fracture over follow-up. Predictive performance was based on measures of discrimination (area under the receiver operator curve, AUC) and calibration (observed-to-predicted ratio, O/P). We identified 96 914 patients (47.0% female), of whom 5383 (5.6%) and 1767 (1.8%) had MOF and hip fracture, respectively, over a mean follow-up of 4.3years. The AUC for MOF and hip fracture were 0.72 and 0.77, respectively. FRAX mildly underestimated MOF and hip fracture rates (O/P 1.2 for both) overall. Discrimination was similar by race and ethnicity and diabetes duration but was worse in those over age 75 (AUC < 0.7). In some groups, there were substantial calibration errors, such as Hispanic women (O/P: 1.8 and 1.5), Black men (O/P: 1.5 and 1.8), those with duration of diabetes ≥20years (O/P: 1.6 and 1.5), and those over the age of 80 (O/P: 1.4 and 1.2) for MOF and hip fracture, respectively. While the discriminatory performance of FRAX without BMD was good overall in patients with diabetes, it underestimated risk in Hispanic women, Black men, those with long duration of diabetes, and in the oldest patients with diabetes. These algorithmic biases suggest that diabetes-specific tools may be needed to stratify fracture risk in patients with diabetes.

Hearing loss and risk of major osteoporotic fracture: a population-based cohort study in the United Kingdom

SummaryUsing the UK Clinical Practice Research Datalink, our cohort study matched 237,297 individuals with hearing loss (HL) to 829,431 without HL. The study found an 8–10% higher risk of major osteoporotic fracture in individuals with HL compared to those without. Additionally, within the HL cohort, we identified risk factors for potential inclusion in fracture risk models.PurposeAssess association between hearing loss (HL) and major osteoporotic fracture (MOF; spine, wrist/forearm, shoulder/proximal humerus, hip) in individuals aged ≥ 60 years, and risk factors for MOF in individuals with HL.MethodsFrom the UK Clinical Practice Research Datalink, our cohort study matched individuals aged ≥ 60 years diagnosed with HL (READ/ICD-10 codes; 01January2001–31December2021; index event), without secondary osteoporosis causes, with up to five individuals without HL (birth, index year, sex, general practice). Incidence rates and Cox proportional hazard ratios (HL vs. no HL; stratified by low/high fracture risk) were calculated for MOF and hip fracture; multivariate logistic regression assessed risk factors for MOF and hip fracture (HL cohort).ResultsA total of 237,297 individuals with HL matched to 829,431 without HL, with a median age of 74 and 72 years, respectively. Compared with those without HL, individuals with HL had greater frailty (severe electronic frailty index, 5.9% vs. 2.7%), higher incidence of prior falls (14.1% vs. 10.6%), longer mean follow-up with higher incidence of MOF and hip fractures (5.1 vs. 4.4 years, 20.1 and 5.32 vs. 16.58 and 4.54 per 1000 person-years, respectively) and higher risk of MOF and hip fracture (adjusted HR, 1.10 and 1.08, respectively). Significant risk factors for MOF and hip fracture included age ≥ 70 years, fracture history, falls, osteoporosis diagnosis, chronic obstructive pulmonary disorder and cardiovascular disease (HL cohort).ConclusionIn individuals with HL, we observed an 8–10% higher risk of MOF and hip fracture versus individuals without HL and identified risk factors for potential inclusion in fracture risk models.

Prediction of hip fracture by high-resolution peripheral quantitative computed tomography in older Swedish women.

The socioeconomic burden of hip fractures, the most severe osteoporotic fracture outcome, is increasing and the current clinical risk assessment lacks sensitivity. This study aimed to develop a method for improved prediction of hip fracture by incorporating measurements of bone microstructure and composition derived from high-resolution peripheral quantitative computed tomography (HR-pQCT). In a prospective cohort study of 3028 community-dwelling women aged 75 to 80, all participants answered questionnaires and underwent baseline examinations of anthropometrics and bone by dual x-ray absorptiometry (DXA) and HR-pQCT. Medical records, a regional x-ray archive, and registers were used to identify incident fractures and death. Prediction models for hip, major osteoporotic fracture (MOF), and any fracture were developed using Cox proportional hazards regression and machine learning algorithms (neural network, random forest, ensemble, and XGBoost). In the 2856 (94.3%) women with complete HR-pQCT data at 2 tibia sites (distal and ultra-distal), the median follow-up period was 8.0years, and 217 hip, 746 MOF, and 1008 any type of incident fracture occurred. In Cox regression models adjusted for age, BMI, clinical risk factors (CRF), and femoral neck bone mineral density (FN BMD) the strongest predictors of hip fracture were tibia total volumetric BMD and cortical thickness. The performance of the Cox regression-based prediction models for hip fracture was significantly improved by HR-pQCT (time-dependent AUC; area under receiver operating characteristic curve at 5years of follow-up 0.75 [0.64-0.85]), compared to a reference model including CRFs and FN BMD (AUC = 0.71 [0.58-0.81], p<.001) and a FRAX risk score model (AUC = 0.70 [0.60-0.80], p<.001). The Cox regression model for hip fracture had a significantly higher accuracy than the neural network-based model, the best-performing machine learning algorithm, at clinically relevant sensitivity levels. We conclude that the addition of HR-pQCT parameters improves the prediction of hip fractures in a cohort of older Swedish women.

Trabecular bone deficits predominate in the appendicular skeleton of midlife women living with HIV: findings from a cross-sectional study in Zimbabwe.

HIV-related mortality has fallen due to scale-up of antiretroviral therapy (ART), so more women living with HIV (WLH) now live to reach menopause. Menopausal estrogen loss causes bone loss, as do HIV and certain ART regimens. However, quantitative bone data from WLH are few in Africa. A cross-sectional study of women aged 40-60years (49% WLH) was conducted in Harare, Zimbabwe. Menopause status, fracture history, HIV status and treatment, and anthropometry were collected, and radial/tibial peripheral Quantitative Computed Tomography (pQCT) scans performed. pQCT outcomes were: distal radius and tibia trabecular volumetric bone mineral density (vBMD), total area, and compressive bone strength (BSIc); proximal radius and tibia cortical vBMD, bone mineral content (BMC), cortical thickness, bone area, and stress-strain index (SSI). Linear regression determined differences by HIV status, minimally adjusted for age and menopause status, and further adjusted for height and fat mass. Relationships between pQCT parameters and major osteoporotic fracture history were explored using univariate logistic regression. In WLH, linear regression assessed associations between HIV and ART durations on pQCT measures. 384 women mean(SD) age 49.7(5.8) years had pQCT data. WLH had lower absolute pQCT measures at all sites. Overall, HIV-related deficits were robust to adjustment for age, menopause status, height, and fat mass: WLH had lower trabecular vBMD (radius -7.3 [-12.5; -2.0]%, tibia -5.4 [-9.1; -1.7]%), and cortical vBMD (radius -3.5 [-5.9; -1.1]%, tibia -1.1[-1.6; -0.5]%). Strength estimates were lower in WLH and of similar magnitude at the radius and tibia. Longer HIV duration was associated with lower radius bone area, BMC, estimates of bone strength, independent of ART duration. Trabecular deficits predominate in WLH, though with age cortical compartment bone loss may increase in importance. This is particularly concerning as these differences were observed at the radius, a common site of postmenopausal osteoporotic fracture.

Associations between bone material strength index and FRAX scores.

Impact microindentation (IMI) measures bone material strength index (BMSi) in vivo. However, its ability to predict fractures is still uncertain. This study aimed to determine the association between BMSi and 10year fracture probability, as calculated by the FRAX algorithm. BMSi was measured using the OsteoProbe in 388 men (ages 40-90yr) from the Geelong Osteoporosis Study. The probabilities for a major osteoporotic fracture (MOF) and hip fracture (HF) were calculated using the Australian FRAX tool. Hip (HF) and major osteoporotic (MOF) fracture probabilities were computed with and without the inclusion of femoral neck bone mineral density (BMD). For each participant, four 10year probability scores were therefore generated: (i) HF-FRAXnoBMD; (ii) HF-FRAXBMD; (iii) MOF-FRAXnoBMD; (iv) MOF-FRAXBMD. BMSi was negatively correlated with age (r = -0.114, p = 0.025), no associations were detected between BMSi and femoral neck BMD (r = + 0.035, p = 0.507). BMSi was negatively correlated with HF-FRAXnoBMD (r = -0.135, p = 0.008) and MOF-FRAXnoBMD (r = -0.153, p = 0.003). These trends held true for HF-FRAXBMD (r = -0.087, p = 0.094) and MOF-FRAXBMD (r = -0.111, p = 0.034), but only the latter reached significance. BMSi captures the cumulative effect of clinical risk factors in the FRAX algorithm, suggesting that it could provide additional information that may be useful in predicting risk of fractures. Further studies are warranted to establish its efficacy in predicting fracture risk.

Fracture Risk Assessment in the 2023 Osteoporosis Canada Guideline.

Radiologists and other diagnostic imaging specialists play a pivotal role in the management of osteoporosis, a highly prevalent condition of reduced bone strength and increased fracture risk. Bone mineral density (BMD) measurement with dual-energy X-ray absorptiometry (DXA) is a critical component of identifying individuals at high risk for fracture. Strategies to prevent fractures are consolidated in the Osteoporosis Canada clinical practice guideline which was updated in 2023. In this guideline, treatment recommendations are based upon a consideration of fracture history, 10-year major osteoporotic fracture (MOF) risk, and BMD T-score in conjunction with age. The current review aims to familiarize radiologists and other diagnostic imaging specialists with the reporting requirements needed to support implementation of this guideline using the FRAX™ risk calculation tool. Fortunately, for specialists already familiar with the Canadian Association of Radiologists and Osteoporosis Canada (CAROC) tool, the transition to FRAX-based reporting is readily accommodated in a radiology workflow.

Assessment of fracture risk with FRAX and FRAXplus.

FRAX®, a risk calculator that provides individualized 10-year probabilities of hip and major osteoporotic fracture, has been widely used for fracture risk assessment since its launch in 2008. It is now incorporated into very many guidelines worldwide to inform osteoporosis management. In this review, we explore the development of FRAX and how it enhances fracture risk prediction as compared to use of bone mineral density alone, as well as approaches to utilizing FRAX in determining intervention and assessment thresholds. We also discuss the limitations of FRAX and the arithmetic adjustments that have been proposed to address these. The introduction of FRAXplus® includes these adjustments on a web-based platform for ease of application to enhance treatment decisions in osteoporosis.

A real-world analysis of 1,823 hospitalized osteoporotic fractures in Northeast China.

There are limited real-world data evidence assessing the clinical characteristics of hospitalized osteoporotic fractures in China. To investigate the clinical characteristics of hospitalized major osteoporotic fractures in Northeast China. We identified hospitalized fracture patients aged 50 and over from the First Affiliated Hospital of Jinzhou Medical University between January 1, 2018, and December 31, 2022. Major osteoporotic fractures including hip, vertebral, forearm and wrist, and humerus were diagnosed based on x-ray reports extracted from the electronic medical records (EMR). The cause of fracture, comorbidities, surgical methods, and anti-osteoporotic medications (AM) use were extracted from EMR. The study population included 1823 fracture patients, 510 males and 1313 females. Over half of fracture patients were aged over 70 years. Hip fractures accounted for 68.4% of all fractures in males and 57.9% in females. For those with hip fractures, the most common sites were the femoral neck (62.9%) and intertrochanteric (35.3%). Most fractures were due to falls (81.0% in males and 80.2% in females). The two most common comorbidities for males and females were hyperlipemia (45.9% vs. 47.1%) and hypertension (38.2% vs. 41.6%). Only 4.7% males and 8.6% females were treated with AM. Hip fractures, especially femoral neck fractures, accounted for the majority of osteoporotic fractures in a tertiary public hospital in Northeast China. Common comorbidities in these fracture patients were hyperlipemia and hypertension. There was a very low rate of AM use among these patients.

Are balance and lower extremity muscle strength correlated with fracture risk independent of bone mineral density in postmenopausal women?: A cross-sectional study.

Postmenopausal women are at increased risk of fractures due to reduced bone mineral density (BMD) and impaired physical function. While fracture risk assessment tools like FRAX include clinical factors and BMD, they exclude functional measures such as balance and muscle strength, which are critical for fall prevention. This study aimed to evaluate the correlation between two functional tests- the 30-Second Sit to Stand Test (30STS) and the One Leg Stance Test (OLST)- and fracture risk, independent of BMD in postmenopausal women aged 50-70. This cross-sectional study included 156 postmenopausal women aged 50-70. Fracture risk was assessed using FRAX. Postural balance was evaluated using the OLST, while lower extremity muscle strength was measured with the 30STS. Both tests were analyzed for correlations with 10-year risks of major osteoporotic fractures (MOF), hip fractures, femoral neck BMD, and T-score at the lumbar spine and femoral neck. Participants were grouped based on OLST (<10 s) and 30STS (<15 repetitions) cut-offs, and fracture risks were compared. OLST and 30STS scores were significantly negatively correlated with 10-year hip fracture risk (r = -0.347, p < 0.001 and r = -0.197, p = 0.014, respectively). A significant negative correlation was also observed between OLST scores and 10-year MOF risk (r = -0.245, p = 0.002). Participants with OLST <10 s had significantly higher 10-year hip and MOF risks, while those with 30STS <15 had significantly higher 10-year hip fracture risk only. No correlation was found with femoral neck BMD. LST and 30STS are associated with fracture risk independent of BMD in postmenopausal women aged 50-70. These practical tests may help identify individuals at higher fracture risk and support early interventions.

Cost-effectiveness of FRAX®-based intervention thresholds for management of osteoporosis in Indian women: a Markov microsimulation model analysis.

Osteoporosis represents a significant public health challenge in India, with an increasing economic burden due to the aging population. This study evaluated the cost-effectiveness of using fracture risk assessment tool (FRAX®)-based intervention thresholds (ITs) for managing osteoporosis with generic alendronate in Indian women. A Markov microsimulation model, adapted to the Indian healthcare context, was used to simulate the costs and quality-adjusted life years (QALYs) associated with different treatment strategies. The one-time gross domestic product (GDP) per capita (estimated at INR 1,97,468/QALY gained) was used as the cost-effectiveness threshold. The model revealed that generic alendronate is cost-effective for major osteoporotic fracture (MOF) ITs beginning at age 60years with full adherence-incremental cost-effectiveness ratio (ICER) of INR 102,151 per QALY gained, and age 65 with real-world adherence-ICER of INR 28,203 per QALY gained (conversion rate used is 1 US dollar (USD) = INR 83.97 and 1 EURO = INR 92.70). Hip fracture (HF) ITs showed similar cost-effectiveness at ages 60 (ICER of INR 67,144) and was the dominant strategy (i.e., more QALYs for lower costs) at ≥ 65years. Fixed ITs of 14% for MOF and 3.5% for HF proved cost-effective across all age groups (dominant strategy for ages ≥ 65years). Limitations of our study include the reliance on fracture incidence data from Singaporean Indians and variability in fracture prevalence across India. The results support the integration of FRAX®-based fixed ITs from the age of 50years and age-based ones from the age of 65years in India to optimize resource allocation and improve osteoporosis management.

Comment on: Among people on osteoporosis medication, loss of appendicular or total body lean mass is an independent risk factor for hip and major osteoporotic fractures

Comment on: Among people on osteoporosis medication, loss of appendicular or total body lean mass is an independent risk factor for hip and major osteoporotic fractures

Correlation between vascular endothelial function and bone mineral density in type 2 diabetes mellitus patients with MAFLD

Objective The relationship between vascular endothelial function and bone mineral density (BMD) in T2DM patients with metabolic dysfunction associated fatty liver (MAFLD) is still unclear. This study aims to analyse the correlation between vascular endothelial function and BMD or fracture risk in T2DM patients with MAFLD. Methods A total of 872 T2DM patients aged ≥50 years were enrolled and divided into two groups according to the diagnostic criteria of MAFLD: MAFLD (+) and MAFLD (−). Flow-mediated dilation (FMD) was measured by high-resolution ultrasound to reflect vascular endothelial function. BMD was measured by dual-energy X-ray bone densitometry, and FRAX scores were calculated for 10-year hip fracture risk (HF1) and major osteoporotic fracture risk (MOF). Results After multivariate adjustment, there was no significant correlation between FMD and BMD in MAFLD (−) group (p > 0.05). In MAFLD (+) and FMD < 4% group, FMD was positively correlated with WB, LS, and FN BMD, while FMD was negatively correlated with fracture risk and osteoporotic fracture history, and this correlation was only observed in female patients. However, FMD was not correlated with BMD and fracture risk and osteoporotic fracture history in 4%≤FMD ≤ 7% and FMD > 7% groups. Conclusions The association of FMD with BMD in T2DM patients with MAFLD varies according to FMD level. The decrease of FMD is associated with reduced BMD and increased fracture risk in female patients with FMD < 4% group. FMD may be an influential factor for the occurrence and development of osteoporosis, and has some clinical value in early diagnosis of osteoporosis in T2DM patients with MAFLD.

Potential impact of obstetric history on postmenopausal fragility fracture risk: A reassessment of the Fracture Risk Assessment Tool.

This study aimed to evaluate the impact of integrating obstetric parameters into the Fracture Risk Assessment Tool (FRAX) on the precision of risk assessment. In this retrospective study, patients who experienced postmenopausal fragility fractures of the distal radius, proximal femur, or lumbar vertebrae between January 1, 2021, and December 31, 2023, were included. Obstetric histories, along with standard FRAX parameters, were obtained by phone interviews. Based on the FRAX major osteoporotic fracture risk score calculated without bone mineral density, patients were classified into high-, intermediate-, and low-risk group categories. Differences in age at menarche, age at menopause, lactation duration, gravidity, and parity were analyzed across risk categories. A total of 328 patients (mean age: 64.5±5.8 years; range, 55 to 75 years) were included. The mean FRAX score was 16±8.8 (range, 3 to 58), and 85, 191, and 52 patients were classified as high-, intermediate-, and low-risk, respectively. A positive correlation was observed between FRAX scores and both later age at menarche and earlier menopause (p<0.001 and p=0.008, respectively). The mean age at menopause was significantly different between the high- and low-risk groups (46.4 vs. 49.3 years, p=0.016). The intermediate-risk group was also evaluated, showing no significant differences in obstetric parameters compared to the low-risk group (p>0.05). Although late menarche is not explicitly included in FRAX, its association with higher fracture risk was evident. The established influence of early menopause on FRAX scores supports its role in fracture risk estimation. However, the inclusion of additional obstetric parameters did not enhance the predictive accuracy of FRAX in this cohort.

Effectiveness of Bisphosphonates in Young Adults with Fragility Fractures: Representative Population-Based Cohort Study.

Fragility fractures in young adults present significant clinical challenges due to the limited evidence on the effectiveness of bisphosphonates in preventing subsequent fractures. To evaluate the effectiveness of bisphosphonate therapy in reducing the fracture risk among premenopausal women with a history of osteoporotic fractures. A population-based retrospective cohort study was conducted using data from the National Health Insurance Service-National Sample Cohort (NHIS-NSC) in South Korea, covering the years 2003 to 2014. A nationwide healthcare setting utilizing a representative cohort database. Among 2,087 premenopausal women with osteoporotic fractures, participants were propensity score-matched based on age and body mass index at a 1:3 ratio, resulting in 132 bisphosphonate users and 396 non-users. Bisphosphonate treatment. The incidence of osteoporotic fractures. Bisphosphonate users had a significantly lower risk of major osteoporotic fractures (HR 0.618, 95% CI 0.396 - 0.963) compared to non-users. Ibandronate users showed significant reductions in both major osteoporotic (HR 0.376, 95% CI 0.164 - 0.861) and nonvertebral fractures (HR 0.214, 95% CI 0.052 - 0.877). Also, longer duration of bisphosphonate use (≥180 days) was associated with a significantly lower risk of major osteoporotic and nonvertebral fractures (HR 0.528, 95% CI 0.300 - 0.929; HR 0.409, 95% CI 0.187 - 0.895, respectively). Bisphosphonate therapy significantly reduces fracture risk in premenopausal women with previous osteoporotic fractures, especially at higher cumulative doses. These findings support considering bisphosphonates as a treatment option in premenopausal women at high risk of fractures.

Age at First Fracture and Later Fracture Risk in Older Adults Undergoing Osteoporosis Assessment

Fragility fractures are often defined as those that occur after a certain age (eg, 40-50 years). Whether fractures occurring in early adulthood are equally associated with future fractures is unclear. To examine whether the age at which a prior fracture occurred is associated with future fracture risk. This observational, population-based cohort study included individuals from the Manitoba Bone Mineral Density Registry with a first bone mineral density (BMD) measurement between January 1, 1996, and March 31, 2018, with and without prior fracture in adulthood. Data analysis was completed between April 1, and May 31, 2023. Individuals with fractures before their first dual-energy x-ray absorptiometry were stratified by the age at first fracture (10-year intervals from 20-29 to ≥80 years of age). Incident fractures occurring after dual-energy x-ray absorptiometry (index date) and before March 31, 2021, were identified using linked provincial administrative health data. The cohort included 88 696 individuals (80 066 [90.3%] female; mean [SD] age, 64.6 [11.0] years) with a mean (SD) femoral neck T score of -1.4 (1.0). A total of 21 105 individuals (23.8%) had sustained a prior fracture at a mean (SD) age of 57.7 (13.6) years (range, 20.0-102.4 years) at the time of first prior fracture. During a mean (SD) of 9.0 (5.5) years of follow-up, incident fractures occurred in 13 239 individuals (14.6%), including 12 425 osteoporotic fractures (14.0%), 9440 major osteoporotic fractures (MOFs) (10.6%), and 3068 hip fractures (3.5%). The sex- and age-adjusted hazard ratios for all incident fractures, osteoporotic fractures, and MOFs, according to age at first fracture, were all significantly elevated, with point estimates ranging from 1.55 (95% CI, 1.28-1.88) to 4.07 (95% CI, 2.99-5.52). After adjusting for the additional covariates, the effect estimates were similar and remained significantly elevated, with point estimates ranging from fully adjusted hazard ratios of 1.51 (95% CI, 1.42-1.60) to 2.12 (95% CI, 1.67-2.71) across age categories. Sensitivity analyses examining age at last prior fracture and in those with multiple prior fractures showed similar results. In this cohort study, fractures in adulthood were associated with future fractures regardless of the age at which they occurred. Thus, fractures in early adulthood should not be excluded when assessing an individual's ongoing fracture risk.

Erythropoietin treatment and osteoporotic fracture risk in hemodialysis patients: A nationwide population-based study

ObjectivesConcerns about erythropoietin (EPO) therapy for anemia in patients with end-stage renal disease (ESRD) contributing to potential bone loss and increased fracture risks are growing. This study investigated the impact of EPO administration on the risk of common osteoporotic fractures in ESRD patients. MethodsThis population-based retrospective cohort study compared EPO users and non-EPO users among ESRD patients undergoing hemodialysis, diagnosed with ESRD between 2000 and 2014 identified from the National Health Insurance Research Database of Taiwan. The cohorts were matched at a propensity score ratio of 1:1, resulting in equal sample sizes of 2839. Variables related to comorbidities were considered. ResultsEPO users exhibited higher cumulative incidences of major osteoporotic fractures, hip fractures, spine fractures, and wrist fractures compared with the non-EPO user (all P < 0.001). In adjusted Cox regression models, higher adjusted subdistribution hazard ratios (aSHRs) were observed for major osteoporotic fractures (2.41, 95% confidence interval [CI] = 2.01–2.89), osteoporotic hip fractures (2.19, 95% CI = 1.69–2.85), spine fractures (2.50, 95% CI = 1.87–3.34), and wrist fractures (2.34, 95% CI = 1.44–3.78) in EPO users than in non-EPO users. The risk of major osteoporotic fractures significantly increased with increasing EPO doses (P for trend < 0.0001), and a similar trend was observed for the risks of osteoporotic spine and wrist fractures. ConclusionsOur findings suggest that EPO treatment in patients with ESRD undergoing hemodialysis is associated with an increased risk of osteoporotic fractures.

Discriminatory Accuracy of Fracture Risk Assessment Tool in Asian Populations: A Systematic Review and Meta-Analysis.

This review explores the discriminative ability of fracture risk assessment tool (FRAX) in major osteoporotic fracture (MOF) and hip fracture (HF) risk prediction and the densitometric diagnosis of osteoporosis in Asian populations. We systematically searched the EMBASE, Cochrane, and PubMed databases from the earliest indexing date to January 2024. Studies were included if FRAX was used to identify future osteoporotic fractures or a densitometric diagnosis of osteoporosis in an Asian population and reported the area under the curve (AUC) values. Meta-analyses were conducted after quality assessment for AUC with 95% confidence intervals across the following categories: standard FRAX without/with bone mineral density (BMD), adjusted FRAX, and BMD alone for fracture prediction, as well as standard FRAX for densitometric diagnosis of osteoporosis. A total of 42 studies were included. The AUC values for predicting fracture risk using FRAX-MOF with BMD (0.73 [0.70-0.77]) was highest compared to FRAX-MOF without BMD (0.72 [0.66-0.77]), and adjusted FRAX-MOF (0.71 [0.65-0.77]). The AUC values for predicting fracture risk using FRAX-HF with BMD (0.77 [0.71-0.83]) was highest compared to FRAX-HF without BMD (0.72 [0.65-0.80]), and adjusted FRAX-HF (0.75 [0.63-0.86]). The AUC values for BMD alone (0.68 [0.62-0.73]) was lowest for fracture prediction. The AUC values for identifying a densitometric diagnosis of osteoporosis was 0.77 [0.70-0.84] and 0.76 [0.67-0.86] using FRAX-MOF and FRAX-HF, respectively. FRAX with BMD tends to perform more reliably in predicting HF compared to MOF in Asia. However, its accuracy in predicting fracture risk in Asian populations can be improved through region-specific, long-term epidemiological data.

Systemic immune-inflammatory index predicts fragility fracture risk in postmenopausal anemic females with type 2 diabetes mellitus: evidence from a longitudinal cohort study

BackgroundChronic low-grade inflammation is related to bone metabolism in patients with type 2 diabetes mellitus (T2DM). However, credible data indicating the relationship between inflammation and fragility fracture risk in postmenopausal anemic females with T2DM are sparse. The current study sought to investigate the relationships between the systemic immune-inflammatory index (SII) and fragility fracture events, as well as the future 10-year fragility fracture probability evaluated using the fracture risk assessment tool (FRAX) in postmenopausal females with T2DM.MethodsAccording to the tertiles of SII, 423 postmenopausal females with T2DM were divided into three groups: low-level (≤ 381.32, n = 141), moderate-level (381.32–629.46, n = 141), and high-level (≥ 629.46, n = 141). All participants were followed up for 7 years with a median of 46.8 months (1651 person-years). The association between SII and fragility fracture risk was assessed.ResultsOf 423 subjects, 75 experienced a fragility fracture event. Spearman partial correlation analysis revealed that SII was negatively related to bone mineral density (BMD) and was positively associated with the future 10-year probability of major osteoporotic fracture (MOF) and hip fracture (HF). Restricted cubic spline (RCS) analysis revealed a positive correlation between SII and fragility fracture risk in an approximately inverted J-shaped dose–response pattern (P for overall < 0.0001). Multivariate Cox regression analysis demonstrated that patients with a high SII presented a greater risk of fragility fractures (P = 0.011). Stratified analysis revealed that fragility fractures in the high-level SII were predominantly associated with anemia with an increase of 4.15 times (P = 0.01). Kaplan‒Meier analysis indicated a greater cumulative incidence of fragility fractures in patients with a high SII (log-rank, all P = 0.0012). Receiver operating characteristic (ROC) analysis indicated an optimal SII cut-off value of 537.34, with an area under the curve (AUC) of 0.646, a sensitivity of 60%, and a specificity of 64.1% (P < 0.001).ConclusionThe SII revealed a significant positive association with a real-world fragility fracture event and a future 10-year fragility fracture probability in postmenopausal females with T2DM, particularly evident in individuals with anemia. Therefore, monitoring the SII and hemoglobin in postmenopausal older women with T2DM is helpful in routine clinical practice to identify individuals at high risk for fragility fractures and to promptly execute appropriate fracture intervention procedures.