Incident Major Osteoporotic Fracture Research Articles

Fracture Risk Prediction Using the Fracture Risk Assessment Tool in Individuals With Cancer

The Fracture Risk Assessment Tool (FRAX) is a fracture risk prediction tool for 10-year probability of major osteoporotic fracture (MOF) and hip fracture in the general population. Whether FRAX is useful in individuals with cancer is uncertain. To determine the performance of FRAX for predicting incident fractures in individuals with cancer. This retrospective population-based cohort study included residents of Manitoba, Canada, with and without cancer diagnoses from 1987 to 2014. Diagnoses were identified through the Manitoba Cancer Registry. Incident fractures to March 31, 2021, were identified in population-based health care data. Data analysis occurred between January and March 2023. FRAX scores were computed for those with bone mineral density (BMD) results that were recorded in the Manitoba BMD Registry. This study included 9877 individuals with cancer (mean [SD] age, 67.1 [11.2] years; 8693 [88.0%] female) and 45 877 individuals in the noncancer cohort (mean [SD] age, 66.2 [10.2] years; 41 656 [90.8%] female). Compared to individuals without cancer, those with cancer had higher rates of incident MOF (14.5 vs 12.9 per 1000 person-years; P < .001) and hip fracture (4.2 vs 3.5 per 1000 person-years; P = .002). In the cancer cohort, FRAX with BMD results were associated with incident MOF (HR per SD increase, 1.84 [95% CI, 1.74-1.95]) and hip fracture (HR per SD increase, 3.61 [95% CI, 3.13-4.15]). In the cancer cohort, calibration slopes for FRAX with BMD were 1.03 for MOFs and 0.97 for hip fractures. In this retrospective cohort study, FRAX with BMD showed good stratification and calibration for predicting incident fractures in patients with cancer. These results suggest that FRAX with BMD can be a reliable tool for predicting incident fractures in individuals with cancer.

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

Sarcopenia increases fracture risk. If the risk persists after starting osteoporosis medication, patients may need to be encouraged to pursue strategies to prevent loss of lean mass. To estimate the effects of loss in appendicular lean mass (ALM) or total body lean mass (TBLM) on subsequent fracture risk and effect modification with anti-osteoporosis medication use. We conducted a registry-based cohort study linked to population-based data. We identified individuals ≥ 40years of age with two DXA assessments ≥ 1year apart and minimum 0.5years of observation. ALM and TBLM were estimated from weight, sex, and percent fat from DXA (R2 = 0.91 and 0.84 vs total body DXA, respectively). We report hazard ratios (HR) from Cox regression models estimating time to first incident major osteoporotic fracture (MOF) and hip fracture, adjusted for fracture risk; osteoporosis medication was included as an interaction term and used to stratify analyses. We included 21,249 individuals (mean 67 [SD 10] years, 95% female, 37% on osteoporosis medication). The mean follow-up was 7years (SD 4). A total of 1868 and 548 people had incident MOF and hip fracture, respectively. People with prior ALM loss (HR per SD 1.09, 95% CI 1.04-1.15) or TBLM loss (HR per SD 1.09, 95% CI 1.42-1.14) had a higher risk of MOF. Hip fracture risk was greater in people with prior ALM loss (HR per SD 1.22, 95% CI 1.12-1.33) and TBLM loss (HR per SD 1.26, 95% CI 1.16-1.38). There were no interactions with anti-osteoporosis medication use (all p > 0.3). When restricted to people on anti-osteoporosis medication, each SD in ALM or TBLM loss was associated with 8-9% increased MOF risk and 18-23% increased hip fracture risk. Loss of lean mass is associated with increased fracture risk among individuals on anti-osteoporosis medication. Patients should be encouraged to pursue strategies to prevent sarcopenia.

The Effect of Smoking Cessation versus Current Smoking on Fracture Risk: The Manitoba BMD Registry

Current tobacco smoking is included in FRAXTM calculator for fracture risk assessment. It is unknown whether previous smoking increases the risk of fracture. The current analysis was performed to compare incident fracture risk associated with current smoking, smoking cessation and non-smoking. The study population comprised 18,115 individuals aged 40 years and older (mean age 68.8 years, 95.1% female) from a large clinical registry of DXA tests for the Province of Manitoba, Canada, with two consecutive visits (mean interval 4.4 years) where current smoking was recorded. Smokers (N=1620) were defined as those reporting current smoking at visit 2 (index date), non-smokers (N=15,942) as answering no to current smoking at both visits, and ex-smokers (N=553) as answering yes to current smoking at visit 1 but no at visit 2. Incident fractures were identified through healthcare data linkage. Compared with non-smokers, risk for any incident fracture (primary outcome) was significantly greater in current smokers (hazard ratio [HR] 1.41, 95% CI 1.19-1.67 adjusted for age/sex; HR 1.22, 95% CI 1.03-1.44 full adjusted) and ex-smokers (HRs 1.56, 95% CI 1.19-2.024 and 1.42, 95% CI 1.09-1.86, respectively). Similar directions and magnitudes of effect were seen for incident major osteoporotic fractures and hip fractures (secondary outcomes), with point estimates for ex-smokers that were close to current smokers. In summary, recent smoking cessation was associated with ongoing increased short-term fracture risk similar to current smoking. Larger studies are needed to better define the time course of fracture risk after smoking cessation.

An electronic health record (EHR)-based risk calculator can predict fractures comparably to FRAX: a proof-of-concept study.

Fracture risk calculators, such as the Fracture Risk Assessment Tool, or FRAX, typically lie outside the clinician workflow. Conversely, the electronic health record (EHR) is at the center of the clinical workflow, and many variables in the EHR could predict fractures without having to verbally ascertain FRAX risk factors. We sought to evaluate the utility of EHR variables to predict fractures and, as a proof of concept, to create an EHR-based fracture risk model. Routine clinical data from 24,189 subjects presenting to primary care from 2010 to 2018 was utilized. Major osteoporotic fractures (MOFs) were captured by physician diagnosis codes. Data was split into training (n = 18,141) and test sets (n = 6048). We fit Cox regression models for candidate risk factors in the training set, and then created a global model using a backward stepwise approach. We then applied the model to the test set and compared the discrimination and calibration to FRAX. We found variables related to vital signs, utilization, diagnoses, medications, and laboratory values to be associated with incident MOF. Our final model included 19 variables, including age, BMI, Parkinson's disease, chronic kidney disease, and albumin levels. When applied to the test set, we found the discrimination (AUC 0.73 vs. 0.70, p = 0.08) and calibration were comparable to FRAX. Routinely collected data in EHR systems can generate adequate fracture predictions without the need to verbally ascertain fracture risk factors. In the future, this could allow for automated fracture prediction at the point of care to improve osteoporosis screening and treatment rates.

Non-osteoporotic fractures are associated with increased risk of subsequent major osteoporotic fractures

SummaryWe studied the association between non-osteoporotic fractures and future major osteoporotic fractures, using UK health records. Non-osteoporotic fractures were found to increase the risk of major osteoporotic fractures, although to a lesser extent than osteoporotic fractures. This highlights the importance of considering all previous fractures in assessing future fracture risk.PurposePrevious studies demonstrated that osteoporotic fractures—minor and major—increase the risk for future major osteoporotic fractures; we test whether non-osteoporotic fractures are also associated with such increased risk.MethodsThe study is a retrospective cohort study using UK primary care electronic health records. Exposure groups were defined according to fracture location prior to the year 2011 (index date): major, minor, and non-osteoporotic. The outcome of incident major osteoporotic fractures following the index date was compared between the exposure groups and the general population.ResultsThe general study population included 1,951,388 patients. The exposure groups included 39,931 patients with a prior major osteoporotic fracture, 19,397 with a prior minor osteoporotic fracture, and 50,115 patients with a prior non-osteoporotic fracture. The standardized Incidence Rate Ratio for future major osteoporotic fractures was 2.73 (95% confidence interval: 2.64–2.82), 2.43 (2.32–2.54), and 1.83 (1.74–1.92), respectively.ConclusionNon-osteoporotic fractures are significantly associated with increased risk for future major osteoporotic fractures relative to the general population, yet to a lesser extent compared to major and minor osteoporotic fractures.

Effect of abdominal tissue thickness on trabecular bone score and fracture risk in adults with diabetes: the Manitoba BMD registry.

Individuals with type 2 diabetes have lower trabecular bone score (TBS) and increased fracture risk despite higher bone mineral density. However, measures of trabecular microarchitecture from high-resolution peripheral computed tomography are not lower in type 2 diabetes. We hypothesized that confounding effects of abdominal tissue thickness may explain this discrepancy, since central obesity is a risk factor for diabetes and also artifactually lowers TBS. This hypothesis was tested in individuals aged 40years and older from a large DXA registry, stratified by sex and diabetes status. When DXA-measured abdominal tissue thickness was not included as a covariate, men without diabetes had lower TBS than women without diabetes (mean difference -0.074, P < .001). TBS was lower in women with versus without diabetes (mean difference -0.037, P < .001), and men with versus without diabetes (mean difference -0.007, P = .042). When adjusted for tissue thickness these findings reversed, TBS became greater in men versus women without diabetes (mean difference +0.053, P < .001), in women with versus without diabetes (mean difference +0.008, P < .001), and in men with versus without diabetes (mean difference +0.014, P < .001). During mean 8.7years observation, incident major osteoporotic fractures were seen in 7048 (9.6%). Adjusted for multiple covariates except tissue thickness, TBS predicted fracture in all subgroups with no significant diabetes interaction. When further adjusted for tissue thickness, HR per SD lower TBS remained significant and even increased slightly. In conclusion, TBS predicts fractures independent of other clinical risk factors in both women and men, with and without diabetes. Excess abdominal tissue thickness in men and individuals with type 2 diabetes may artifactually lower TBS using the current algorithm, which reverses after accounting for tissue thickness. This supports ongoing efforts to update the TBS algorithm to directly account for the effects of abdominal tissue thickness for improved fracture risk prediction.

Simultaneous automated ascertainment of prevalent vertebral fracture and abdominal aortic calcification in clinical practice: role in fracture risk assessment.

Whether simultaneous automated ascertainments of prevalent vertebral fracture (auto-PVFx) and abdominal aortic calcification (auto-AAC) on vertebral fracture assessment (VFA) lateral spine bone density (BMD) images jointly predict incident fractures in routine clinical practice is unclear. We estimated the independent associations of auto-PVFx and auto-AAC primarily with incident major osteoporotic and secondarily with incident hip and any clinical fractures in 11 013 individuals (mean [SD] age 75.8 [6.8] years, 93.3% female) who had a BMD test combined with VFA between March 2010 and December 2017. Auto-PVFx and auto-AAC were ascertained using convolutional neural networks (CNNs). Proportional hazards models were used to estimate the associations of auto-PVFx and auto-AAC with incident fractures over a mean (SD) follow-up of 3.7 (2.2) years, adjusted for each other and other risk factors. At baseline, 17% (n = 1881) had auto-PVFx and 27% (n = 2974) had a high level of auto-AAC (≥ 6 on scale of 0 to 24). Multivariable-adjusted hazard ratios (HR) for incident major osteoporotic fracture (95% CI) were 1.85 (1.59, 2.15) for those with compared with those without auto-PVFx, and 1.36 (1.14, 1.62) for those with high compared with low auto-AAC. The multivariable-adjusted HRs for incident hip fracture were 1.62 (95% CI, 1.26 to 2.07) for those with compared to those without auto-PVFx, and 1.55 (95% CI, 1.15 to 2.09) for those high auto-AAC compared with low auto-AAC. The 5-year cumulative incidence of major osteoporotic fracture was 7.1% in those with no auto-PVFx and low auto-AAC, 10.1% in those with no auto-PVFx and high auto-AAC, 13.4% in those with auto-PVFx and low auto-AAC, and 18.0% in those with auto-PVFx and high auto-AAC. While physician manual review of images in clinical practice will still be needed to confirm image quality and provide clinical context for interpretation, simultaneous automated ascertainment of auto-PVFx and auto-AAC can aid fracture risk assessment.

Risks of incident major osteoporotic fractures following SARS-CoV-2 infection among older individuals: a population-based cohort study in Hong Kong.

Population-based epidemiological studies on post-acute phase coronavirus 2019 (COVID-19)-related fractures in older adults are lacking. This study aims to examine the risk of incident major osteoporotic fractures following SARS-CoV-2 infection among individuals aged ≥50, compared to individuals without COVID-19. It was a retrospective, propensity-score matched, population-based cohort study of COVID-19 patients and non-COVID individuals identified from the electronic database of the Hong Kong Hospital Authority from January 2020 to March 2022. The primary outcome was a composite of major osteoporotic fractures (hip, clinical vertebral, and upper limb). COVID-19 patients were 1:1 matched to controls using propensity-score according to age, sex, vaccination status, medical comorbidities and baseline medications. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression models. A total of 429 459 COVID-19 patients were included, 1:1 matched to non-COVID individuals. Upon median follow-up of 11months, COVID-19 patients had higher risks of major osteoporotic fractures (5.08 vs 3.95 per 1000 persons; HR 1.22 95%CI [1.15-1.31]), hip fractures (2.71 vs 1.94; 1.33 [1.22-1.46]), clinical vertebral fractures (0.42 vs 0.31; 1.29 [1.03-1.62]), and falls (13.83 vs 10.36; 1.28 [1.23-1.33]). Subgroup analyses revealed no significant interaction. In acute (within 30days) and post-acute phases (beyond 30days) following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, we consistently observed a significant increase in fractures and falls risks. Our study demonstrated increased risk of major osteoporotic fractures after SARS-CoV-2 infection in both acute and post-acute phases in older adults, partly due to increased fall risk. Clinicians should be aware of musculoskeletal health of COVID-19 survivors.

FRAX predicts cardiovascular risk in women undergoing osteoporosis screening: the Manitoba bone mineral density registry.

Osteoporosis and cardiovascular disease (CVD) are highly prevalent in older women, with increasing evidence for shared risk factors and pathogenesis. Although FRAX was developed for the assessment of fracture risk, we hypothesized that it might also provide information on CVD risk. To test the ability of the FRAX tool and FRAX-defined risk factors to predict incident CVD in women undergoing osteoporosis screening with DXA, we performed a retrospective prognostic cohort study which included women aged 50yr or older with a baseline DXA scan in the Manitoba Bone Mineral Density Registry between March 31, 1999 and March 31, 2018. FRAX scores for major osteoporotic fracture (MOF) were calculated on all participants. Incident MOF and major adverse CV events (MACE; hospitalized acute myocardial infarction [AMI], hospitalized non-hemorrhagic cerebrovascular disease [CVA], or all-cause death) were ascertained from linkage to population-based healthcare data. The study population comprised 59 696 women (mean age 65.7 ± 9.4yr). Over mean 8.7yr of observation, 6021 (10.1%) had MOF, 12 277 women (20.6%) had MACE, 2274 (3.8%) had AMI, 2061 (3.5%) had CVA, and 10 253 (17.2%) died. MACE rates per 1000 person-years by FRAX risk categories low (10-yr predicted MOF <10%), moderate (10%-19.9%) and high (≥20%) were 13.5, 34.0, and 64.6, respectively. Although weaker than the association with incident MOF, increasing FRAX quintile was associated with increasing risk for MACE (all P-trend <.001), even after excluding prior CVD and adjusting for age. HR for MACE per SD increase in FRAX was 1.99 (95%CI, 1.96-2.02). All FRAX-defined risk factors (except parental hip fracture and lower BMI) were independently associated with higher non-death CV events. Although FRAX is intended for fracture risk prediction, it has predictive value for cardiovascular risk.

Fracture prediction in rheumatoid arthritis: validation of FRAX with bone mineral density for incident major osteoporotic fractures

Abstract Objectives FRAX uses clinical risk factors, with or without BMD, to calculate 10-year fracture risk. RA is a risk factor for osteoporotic fracture and a FRAX input variable. FRAX predates the current era of RA treatment. We examined how well FRAX predicts fracture in contemporary RA patients. Methods Administrative data from patients receiving BMD testing were linked to the Manitoba Population Health Research Data Repository. Observed cumulative 10-year major osteoporotic fracture (MOF) probability was compared with FRAX-predicted 10-year MOF probability with BMD for assessing calibration. MOF risk stratification was assessed using Cox regression. Results RA patients (n = 2099, 208 with incident MOF) and non-RA patients (n = 2099, with 165 incident MOF) were identified. For RA patients, FRAX-predicted 10-year risk was 13.2% and observed 10-year MOF risk was 13.2% (95% CI 11.6, 15.1). The slope of the calibration plot was 0.67 (95% CI 0.53, 0.81) in those with RA vs 0.98 (95% CI 0.61, 1.34) in non-RA patients. Risk was overestimated in RA patients with high FRAX scores (&amp;gt;20%), but FRAX was well calibrated in other groups. FRAX stratified risk in those with and without RA [hazard ratio (HR) 1.52 (95% CI 1.25, 1.72) vs 2.00 (95% CI 1.73, 2.31)], with slightly better performance in the latter (P for interaction = 0.004). Conclusions FRAX predicts fracture risk in contemporary RA patients but may slightly overestimate risk in those already at high predicted risk. Thus the current FRAX tool continues to be appropriate for fracture risk assessment in RA patients.

Effect of BMI-Discordant Abdominal Tissue Thickness on Fracture Probability: A Registry-Based Study.

FRAX, which is used to assess fracture probability, considers body mass index (BMI), but BMI may not reflect individual variation in body composition and distribution. We examined the effect of BMI-discordant abdominal thickness on FRAX-derived fracture probability for major osteoporotic fracture (MOF) and hip fracture. We studied 73,105 individuals, mean age 64.2 years. During mean 8.7 years, 7048 (9.6%) individuals sustained incident MOF, including 2155 (3.0%) hip fractures. We defined abdominal thickness index (ATI) as the difference between abdominal thickness measured by dual-energy X-ray absorptiometry (DXA) and thickness predicted by BMI using sex-stratified regression. ATI was categorized from lower (<-2 cm, -2 to -1 cm) to higher (1-2 cm, >+2 cm) with referent around zero (-1 to +1 cm). Adjusted for FRAX probability, increasing ATI was associated with incident MOF and hip fracture (p < 0.001). For the highest ATI category, MOF risk was increased (hazard ratio [HR] = 1.23, 95% confidence interval [CI] 1.12-1.35) independent of FRAX probability. Similar findings were noted for hip fracture probability (HR = 1.28, 95% CI 1.09-1.51). There was significant age-interaction with much larger effects before age 65 years (HR = 1.44, 95% CI 1.23-1.69 for MOF; 2.29, 95% CI 1.65-3.18 for hip fracture). In contrast, for the subset of individuals with diabetes, there was also increased risk for those in the lowest ATI category (HR = 1.73, 95% CI 1.12-2.65 for MOF; 2.81, 95% CI 1.59-4.97 for hip fracture). Calibration plots across ATI categories demonstrated deviation from the line of identity in women (calibration slope 2.26 for MOF, 2.83 for hip fracture). An effect of ATI was not found in men, but this was inconclusive as the sex-interaction terms did not show significant effect modification. In conclusion, these data support the need to investigate increased abdominal thickness beyond that predicted by BMI and sex as a FRAX-independent risk factor for fracture. © 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).

Excess mortality following a first and subsequent osteoporotic fracture: a Danish nationwide register-based cohort study on the mediating effects of comorbidities

ObjectivesThis study aimed to examine the risk of mortality following incident and subsequent osteoporotic fractures, the effect of different fracture type combinations, and the mediating role of postfracture morbidity in...

Sex- and Age Group-Specific Fracture Incidence Rates Trends for Type 1 and 2 Diabetes Mellitus.

The incidence of major osteoporotic fractures has declined in men and women in Western countries over the last two decades. Although fracture risk is higher in persons with diabetes mellitus, trends of fractures remain unknown in men and women with diabetes. We investigated the trends in fracture incidence rates (IRs) in men and women with type 1 diabetes mellitus (T1D) and type 2 diabetes mellitus (T2D) in Denmark between 1997 and 2017. We identified men and women aged 18+ years who sustained a fracture (excluding skull and facial fractures) between 1997 and 2017 using the Danish National Patient Registry. We calculated sex-specific IRs of fractures per 10,000 person-years separately in persons with T1D, T2D, or without diabetes. Furthermore, we compared median IRs of the first 5 years (1997-2002) to the median IRs of the last 5 years (2012-2017). We identified 1,235,628 persons with fractures including 4863 (43.6% women) with T1D, 65,366 (57.5% women) with T2D, and 1,165,399 (54.1% women) without diabetes. The median IRs of fractures declined 20.2%, 19.9%, and 7.8% in men with T1D, T2D, and without diabetes, respectively (p-trend <0.05). The median IRs decreased 6.4% in women with T1D (p-trend = 0.35) and 25.6% in women with T2D (p-trend <0.05) but increased 2.3% in women without diabetes (p-trend = 0.08). Fracture IRs decreased in men with both diabetes types and only in women with T2D, highlighting the need for further attention behind the stable trend observed in women with T1D. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Enhancement of Hip X-ray with Convolutional Autoencoder for Increasing Prediction Accuracy of Bone Mineral Density.

It is very important to keep track of decreases in the bone mineral density (BMD) of elderly people since it can be correlated with the risk of incidence of major osteoporotic fractures leading to fatal injuries. Even though dual-energy X-ray absorptiometry (DXA) is the one of the most precise measuring techniques used to quantify BMD, most patients have restricted access to this machine due to high cost of DXA equipment, which is also rarely distributed to local clinics. Meanwhile, the conventional X-rays, which are commonly used for visualizing conditions and injuries due to their low cost, combine the absorption of both soft and bone tissues, consequently limiting its ability to measure BMD. Therefore, we have proposed a specialized automated smart system to quantitatively predict BMD based on a conventional X-ray image only by reducing the soft tissue effect supported by the implementation of a convolutional autoencoder, which is trained using proposed synthesized data to generate grayscale values of bone tissue alone. From the enhanced image, multiple features are calculated from the hip X-ray to predict the BMD values. The performance of the proposed method has been validated through comparison with the DXA value, which shows high consistency with correlation coefficient of 0.81 and mean absolute error of 0.069 g/cm2.

OR13-02 Ethnic Variation In Non-vertebral Major Osteoporotic Fractures Among US Asian/Pacific Islander Men

Abstract Disclosure: C.E. Chu: None. M. Chandra: None. N.P. Gordon: None. D.W. Zeltser: None. C. Lee: None. J.A. Darbinian: None. J.C. Lo: None. Background: Our recent characterization of hip fracture incidence among Asian/Pacific Islander (PI) adults compared Chinese, Japanese, Filipino, and South Asian adults and found that South Asian men had a higher incidence of hip fracture compared to Chinese men, but Japanese and Filipino men did not. However, published data pertaining to major osteoporotic fracture (MOF) risk remain limited. We now further examine the incidence of non-vertebral MOF among Asian/PI men, including findings by Asian subgroup. METHODS: We used data from a previously reported retrospective cohort of 188,328 Asian/PI men in an integrated healthcare delivery system who were age ≥50y during 2000-2019. Asian/PI subgroups examined included 41,862 Chinese, 45,779 Filipino, 13,322 South Asian, and 7,838 Japanese men (the four largest Asian/PI subgroups among men and women), with the remaining 79,527 Asian/PI men comprising 8,293 Vietnamese, 3,500 other Southeast Asian, 6,629 Native Hawaiian/PI (NHPI), 3,132 Korean, 451 Central Asian, and 57,522 of multiple or unspecified Asian/PI ethnicity. Incident non-vertebral MOF was defined as the first hip, humerus, or wrist fracture identified by ICD diagnosis codes during follow up to 2021. Age adjusted fracture incidence [with 95% CI] was calculated using weights from the 2010 US Census. Log-Poisson regression was used to determine fracture incidence rate ratios (IRR) with Chinese adults as reference, adjusting for age and calendar year. RESULTS: Among 188,328 Asian/PI men (aged 55.3 ± 7.8 years at entry), 1501 experienced hip (43.3%), humerus (16.3%), or wrist (37.4%) fracture, or &amp;gt;1 of these non-vertebral MOFs (3.0%) during follow-up, with mean age 71.0 ± 13.0 years at the time of incident fracture. The age-adjusted incidence of non-vertebral MOF for Asian/PI men was 1.18 [1.12-1.25] per 1000 person-years overall but varied among the major Asian/PI subgroups: 1.19 [1.08-1.29] for Chinese, 1.00 [0.88-1.12] for Filipino, 1.51 [1.28-1.77] for Japanese, and 2.01 [1.67-2.41] for South Asian men per 1000 person-years. Compared to Chinese men, the IRR for non-vertebral MOF were 0.83 [0.72-0.95] for Filipino, 1.21 [1.01-1.44] for Japanese, and 1.84 [1.54-2.20] for South Asian, and 0.89 [0.77-1.03] for all other Asian/PI men, including those with unspecified ethnicity. Conclusions: The majority of non-vertebral MOF occurred at the hip and wrist among men. When comparing fracture incidence across major Asian/PI subgroups, the largest difference in non-vertebral MOF incidence was seen among South Asian men compared to their Chinese counterparts, consistent with previous hip fracture findings. Japanese men also had somewhat higher incidence of MOF, while Filipino men had lower incidence. Future studies are needed to examine whether differences are evident in other Asian/PI subgroups and whether there are differences in clinical outcome after non-vertebral MOF fracture. Presentation: Friday, June 16, 2023

FRAX® Adjustment Using Renormalized Trabecular Bone Score (TBS) from L1 Alone may be Optimal for Fracture Prediction: The Manitoba BMD Registry

Lumbar spine trabecular bone score (TBS) used in conjunction with FRAX® improves 10-year fracture prediction. The derived FRAX risk adjustment is based upon TBS measured from L1-L4, designated TBSL1-L4-FRAX. In prior studies, TBS measurements that include L1 and exclude L4 give better fracture stratification than L1-L4. We compared risk stratification from TBS-adjusted FRAX using TBS derived from different combinations of upper lumbar vertebral levels renormalized for level-specific differences in individuals from the Manitoba Bone Density Program aged >40 years with baseline assessment of TBS and FRAX. TBS measurements for L1-L3, L1-L2 and L1 alone were calculated after renormalization for level-specific differences. Corresponding TBS-adjusted FRAX scores designated TBSL1-L3-FRAX, TBSL1-L2-FRAX and TBSL1-FRAX were compared with TBSL1-L4-FRAX for fracture risk stratification. Incident major osteoporotic fractures (MOF) and hip fractures were assessed. The primary outcome was incremental change in area under the curve (ΔAUC). The study population included 71,209 individuals (mean age 64 years, 89.8% female). Before renormalization, mean TBS for L1-3, L1-L2 and L1 was significantly lower and TBS-adjusted FRAX significantly higher than from using TBSL1-L4. These differences were largely eliminated when TBS was renormalized for level-specific differences. During mean follow-up of 8.7 years 6745 individuals sustained incident MOF and 2039 sustained incident hip fractures. Compared with TBSL1-L4-FRAX, use of FRAX without TBS was associated with lower stratification (ΔAUC = −0.009, p < 0.001). There was progressive improvement in MOF stratification using TBSL1-L3-FRAX (ΔAUC = +0.001, p < 0.001), TBSL1-L2-FRAX (ΔAUC = +0.004, p < 0.001) and TBSL1-FRAX (ΔAUC = +0.005, p < 0.001). TBSL1-FRAX was significantly better than all other combinations for MOF prediction (p < 0.001). Incremental improvement in AUC for hip fracture prediction showed a similar but smaller trend. In conclusion, this single large cohort study found that TBS-adjusted FRAX performance for fracture prediction was improved when limited to the upper lumbar vertebral levels and was best using L1 alone.

FRAX Adjustment by Trabecular Bone Score with or Without Bone Mineral Density: The Manitoba BMD Registry

Trabecular bone score (TBS), a texture measure derived from spine dual-energy x-ray absorptiometry (DXA) images, is a FRAX®-independent risk factor for fracture. The TBS adjustment to FRAX assumes the presence of femoral neck BMD in the calculation. However, there are many individuals in whom hip DXA cannot be acquired. Whether the TBS-adjustment would apply to FRAX probabilities calculated without BMD has not been studied. The current analysis was performed to evaluate major osteoporotic fracture (MOF) and hip fracture risk adjusted for FRAX with and without femoral neck BMD. The study cohort consisted of 71,209 individuals (89.8% female, mean age 64.0 years). During mean follow-up 8.7 years, 6743 (9.5%) individuals sustained one or more incident MOF, of which 2037 (2.9%) sustained a hip fracture. Lower TBS was significantly associated with increased fracture risk when adjusted for FRAX probabilities, with a slightly larger effect when BMD was not included. Inclusion of TBS in the risk calculation gave a small but significant increase in stratification for fracture probabilities estimated with and without BMD. Calibration plots showed very minor deviations from the line of identity, indicating overall good calibration. In conclusion, the existing equations for incorporating TBS in FRAX estimates of fracture probability work similarly when femoral neck BMD is not used in the calculation. This potentially extends the range of situations where TBS can be used clinically to those individuals in whom lumbar spine TBS is available but femoral neck BMD is not available.

Clinical significance of serum cystatin C-to-creatinine ratio as a surrogate marker for incident osteoporotic fracture predictions.

Detection of appropriate indicators is valuable for preventing incidental osteoporotic fractures. We statistically evaluated the significance of serum cystatin C-to-creatinine ratio (CysC/Cr) as a surrogate marker for incident major osteoporotic fractures (MOF) prediction. Eligible patients with simultaneous measurement of CysC/Cr and bone mineral density in the lumbar spine and proximal femur were selected, and their fracture histories until 5 years after baseline were observed in the retrospective area cohort data. Patients who were followed up until termination or the first osteoporotic fracture were included, and loss of follow-up or death was excluded. Candidate risk factors for osteoporotic fractures were tested for risk ratios using a cox regression analysis. Receiver operating characteristic tests were performed on factors with significantly higher risk ratios and evaluated with Kaplan-Meier survival analysis to determine the hazard ratios of the factors. A total of 175 patients of whom 28 had incident MOF, 38 men, and 137 women, were enrolled. The mean age was 70.2 years. A significantly higher risk ratio was shown in the presence of prevalent MOF, hyper fall-ability, lifestyle-related diseases, chronic kidney diseases ≥ Grade3a, and higher CysC/Cr. All parameters had cutoff indices and showed significantly higher hazard ratios. These results suggested that CysC/Cr may be a predictive marker of incident osteoporotic fractures. It might work as a screening tool for MOF risk.

The Influence of Anti-Citrullinated Polypeptide Antibodies on Bone Mineral Density Decrease and Incident Major Osteoporotic Fractures in Patients with Rheumatoid Arthritis: A Retrospective Case-Control Study

Background: Effects of anti-citrullinated polypeptide antibodies (ACPA) on the bone mineral density (BMD) reduction and incidence of major osteoporotic fractures (MOF) in patients with rheumatoid arthritis (RA) were evaluated using a retrospective longitudinal case-control study. Methods: Patients with RA who were examined using dual-energy X-ray absorptiometry and simultaneously treated for more than 5 years were recruited. BMD absolute value and Z-scores at initial measurements (baseline) and changes of these values from baseline were assessed, and associations between BMD and candidate risk factors including ACPA positivity and serum titer levels were statistically evaluated. Additional statistical evaluations of ACPA positivity in regard to the incidence of MOF were tested. Results: A total of 222 patients were included. Higher ACPA titers correlated significantly with lower BMD and Z-scores at baseline using a multivariate model (p &lt; 0.05). ACPA positivity correlated significantly with lower values and an annual decrease in the Z-score in total hip at follow-up using a univariate model (p &lt; 0.05), whereas no significant correlation was found using a multivariate model. Z-scores in the ACPA-positive group were significantly lower than those of the ACPA-negative group (p &lt; 0.05). However, ACPA-positivity demonstrated no higher risk for incident MOF. Conclusions: The presence of ACPA is a potential risk of BMD loss however weak.

Bone density and trabecular bone score to predict fractures in adults aged 20-39years: a registry-based study.

Trabecular bone score (TBS), a bone texture measurement, is associated with fracture risk independent of bone mineral density (BMD) in older adults. In adults aged 20-40years, TBS remains stable and its role in fracture risk assessment is unclear. We utilized the Manitoba Bone Density Registry to explore the relationship of fracture risk with BMD and TBS in younger adults. Women and men aged 20-39years referred for DXA testing were studied. Incident major and any fractures were captured from health records. Categories based on WHO BMD T-score classification and TBS tertile were considered using Cox regression models to estimate covariate-adjusted (including sex) hazard ratios (aHR, 95%CI) for incident fracture by category, and each SD decrement in BMD and TBS. The study included 2799 individuals (77% female, mean age 32years). Mean (SD) minimum T-score was - 0.9 (1.1) and TBS 1.355 (0.114); 7% had osteoporosis and 13% were in the lowest TBS tertile. Incident major osteoporotic fracture (MOF) and any fracture risk was elevated in those with osteopenia (aHRs 1.20/1.45) and osteoporosis (aHRs 4.60/5.16). Fracture risk was unrelated to TBS tertile. Each SD decrement in BMD was associated with increased MOF risk (aHR 1.64) and any fracture (aHR 1.71); lower TBS was unrelated to fractures. In young adults, low BMD, but not low TBS, was predictive of MOF and any fracture. Routine clinical TBS measurement is not recommended for young adults. Further study is indicated to evaluate whether TBS is beneficial in subsets of younger adults.