Incident Major Osteoporotic Fracture Research Articles

Measured height loss predicts incident clinical fractures independently from FRAX: a registry-based cohort study.

FRAX® accepts baseline height and weight as input variables, but does not consider change in these parameters over time. To evaluate the association between measured height or weight loss on subsequent fracture risk adjusted for FRAX scores, risk factors, and competing mortality. Using a dual-energy x-ray absorptiometry (DXA) registry for the Province of Manitoba, Canada, we identified women and men age 40years or older with height and weight measured at the time of two DXA scans. Cox regression analyses were performed to test for a covariate-adjusted association between prior height and weight loss with incident fractures occurring after the second scan using linked population-based healthcare data. The study population consisted of 11,495 individuals (average age 68.0 ± 9.9years, 94.6% women). During median follow-up 6.0years, records demonstrated incident major osteoporotic fracture (MOF) in 869 individuals, hip fractures in 265, clinical vertebral fractures in 207, and any fracture in 1203. Prior height loss was significantly greater in individuals with fracture compared with those without fracture, regardless of fracture site. Mortality was greater in those with prior height loss (HR per SD 1.11, 95% CI 1.06-1.17) or weight loss (HR per SD 1.26, 95% CI 1.19-1.32). Each SD in height loss was associated with increased fracture risk (MOF 12-17%, hip 8-19%, clinical vertebral 28-37%, any fracture 14-19%). Prior weight loss was associated with 21-30% increased risk for hip fracture, but did not increase risk for other fractures. Height loss of 3.0cm or greater more than doubled the risk for subsequent fracture. Prior height loss is associated with a small but significant increase in risk of incident fracture at all skeletal sites independent of other clinical risk factors and competing mortality as considered by FRAX. Prior weight loss only increases risk for subsequent hip fracture.

Combining Frailty and Trabecular Bone Score Did Not Improve Predictive Accuracy in Risk of Major Osteoporotic Fractures

It is recognized that the trabecular bone score (TBS) provides skeletal information, and frailty measurement is significantly associated with increased risks of adverse health outcomes. Given the suboptimal predictive power in fracture risk assessment tools, we aimed to evaluate the combination of frailty and TBS regarding predictive accuracy for risk of major osteoporotic fracture (MOF). Data from the prospective longitudinal study of CaMos (Canadian Multicentre Osteoporosis Study) were used for this study. TBS values were estimated using lumbar spine (L1 to L4 ) dual-energy X-ray absorptiometry (DXA) images; frailty was evaluated by a frailty index (FI) of deficit accumulation. Outcome was time to first incident MOF during the follow-up. We used the Harrell's C-index to compare the model predictive accuracy. The Akaike information criterion, likelihood ratio test, and net reclassification improvement (NRI) were used to compare model performances between the model combining frailty and TBS (subsequently called "FI + TBS"), FI-alone, and TBS-alone models. We included 2730 participants (mean age 69 years; 70% women) for analyses (mean follow-up 7.5 years). There were 243 (8.90%) MOFs observed during follow-up. Participants with MOF had significantly higher FI (0.24 versus 0.20) and lower TBS (1.231 versus 1.285) than those without MOF. FI and TBS were significantly related with MOF risk in the model adjusted for FRAX with bone mineral density (BMD) and other covariates: hazard ratio (HR) = 1.26 (95% confidence interval [CI] 1.11-1.43) for per-SD increase in FI; HR = 1.38 (95% CI 1.21-1.59) for per-SD decrease in TBS; and these associations showed negligible attenuation (HR = 1.24 for per-SD increase in FI, and 1.35 for per-SD decrease in TBS) when combined in the same model. Although the model FI + TBS was a better fit to the data than FI-alone and TBS-alone, only minimal and nonsignificant enhancement of discrimination and NRI were observed in FI + TBS. To conclude, frailty and TBS are significantly and independently related to MOF risk. Larger studies are warranted to determine whether combining frailty and TBS can yield improved predictive accuracy for MOF risk. © 2020 American Society for Bone and Mineral Research.

Do Additional Clinical Risk Factors Improve the Performance of Fracture Risk Assessment Tool (FRAX) Among Postmenopausal Women? Findings From the Women's Health Initiative Observational Study and Clinical Trials.

ABSTRACTThe ability of the fracture risk assessment tool (FRAX) to discriminate between women who do and do not experience major osteoporotic fractures (MOFs) is suboptimal. Adding common clinical risk factors may improve discrimination. We used data from the Women's Health Initiative, a prospective study of women aged 50 to 79 years at baseline (n = 99,413; n = 5722 in BMD subset) enrolled at 40 US clinical centers. The primary outcome was incident MOFs assessed annually during 10 years' follow‐up. For prediction of incident MOF, we examined the area under the receiver operatic characteristic curve (AUC) and net reclassification index (NRI) of the FRAX model alone and FRAX plus additional risk factors (singly or together: type 2 diabetes mellitus, frequent falls [≥2 falls in the past year], vasomotor symptoms, self‐reported physical function score [RAND 36‐item Health Survey subscale), and lumbar spine BMD). For NRI calculations, high risk was defined as predicted MOF risk ≥20%. We also assessed calibration as observed MOF events/expected MOF events. The AUC value for FRAX without BMD information was 0.65 (95% CI, 0.65 to 0.66). Compared with the FRAX model (without BMD), the AUC value was not improved by the addition of vasomotor symptoms, diabetes, or frequent falls, but was minimally increased by adding physical function score (AUC 0.66, 95% CI, 0.66 to 0.67). FRAX was well‐calibrated for MOF prediction. The NRI of FRAX + additional variables versus FRAX alone was 5.7% (p < 0.001) among MOF cases and −1.7% among noncases (p > 0.99). Additional variables (diabetes, frequent falls, vasomotor symptoms, physical function score, or lumbar spine BMD) did not yield meaningful improvements in NRI or discrimination of FRAX for MOFs. Future studies should assess whether tools other than FRAX provide superior discrimination for prediction of MOFs. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

High Plasma Erythropoietin Predicts Incident Fractures in Elderly Men with Normal Renal Function: The MrOS Sweden Cohort.

Preclinical studies on the role of erythropoietin (EPO) in bone metabolism are contradictory. Regeneration models indicate an anabolic effect on bone healing, whereas models on physiologic bone remodeling indicate a catabolic effect on bone mass. No human studies on EPO and fracture risk are available. It is known that fibroblast growth factor 23 (FGF23) affects bone mineralization and that serum concentration of FGF23 is higher in men with decreased estimated glomerular filtration rate (eGFR). Recently, a direct association between EPO and FGF23 has been shown. We have explored the potential association between EPO and bone mineral density (BMD), fracture risk, and FGF23 in humans. Plasma levels of EPO were analyzed in 999 men (aged 69 to 81 years), participating in the Gothenburg part of the population-based Osteoporotic Fractures in Men (MrOS) study, MrOS Sweden. The mean ± SD EPO was 11.5 ± 9.0 IU/L. Results were stratified by eGFR 60 mL/min. For men with eGFR ≥60 mL/min (n = 728), EPO was associated with age (r = 0.13, p < 0.001), total hip BMD (r = 0.14, p < 0.001), intact (i)FGF23 (r = 0.11, p = 0.004), and osteocalcin (r = -0.09, p = 0.022). The association between total hip BMD and EPO was independent of age, body mass index (BMI), iFGF23, and hemoglobin (beta = 0.019, p < 0.001). During the 10-year follow-up, 164 men had an X-ray-verified fracture, including 117 major osteoporotic fractures (MOF), 39 hip fractures, and 64 vertebral fractures. High EPO was associated with higher risk for incident fractures (hazard ratio [HR] = 1.43 per tertile EPO, 95% confidence interval [CI] 1.35-1.63), MOF (HR = 1.40 per tertile EPO, 95% CI 1.08-1.82), and vertebral fractures (HR = 1.42 per tertile EPO, 95% CI 1.00-2.01) in a fully adjusted Cox regression model. In men with eGFR<60 mL/min, no association was found between EPO and BMD or fracture risk. We here demonstrate that high levels of EPO are associated with increased fracture risk and increased BMD in elderly men with normal renal function. © 2019 American Society for Bone and Mineral Research.

Circulating amino acids are associated with bone mineral density decline and ten-year major osteoporotic fracture risk in older community-dwelling adults.

With aging, poor bone mineral density (BMD) and accelerated decrease in BMD are strong risk factors for fracture. Reports of the associations of dietary protein intake with bone strength are inconsistent, possibly owing to differences in protein sources and amino acid (AA) composition. We examined the associations of serum AA with 4-year hip BMD loss and subsequent fracture risk within 10 years in older community-dwelling adults, and further addressed whether lifestyle, dietary protein intake and its source, and body composition would affect the associations. In 1424 men and 1573 women (mean age 72 years), using binary logistic regression, higher serum valine, leucine, isoleucine and tryptophan concentrations were associated (or approaching a borderline significance in case of the last three ones) with less hip BMD decline (defined as BMD loss ≥ 2.8 times the precision error of the BMD measurement at femoral neck) in 4 years later, with the OR (95%CI) /SD of AA increase, ranging from 0.83 (0.75, 0.91) to 0.92 (0.87, 0.98) after multiple adjustments for baseline age, gender, BMI, BMD, estimated glomerular filtration rate (eGFR), dietary protein intake (animal- and plant-derived protein intakes), calcium intake, established lifestyles (physical activity level, smoking and alcohol drinking status), osteoporosis medications, and changes of body fat and lean muscle mass. Higher serum total homocysteine (tHcy) concentration was independently associated with BMD decline 4 years later (OR (95%CI) /SD of 1.16 (1.05, 1.27)). Using multivariate Cox regression, higher serum tryptophan concentration potentially predicted low risk of incident major osteoporotic fractures (MOFs) (HR/SD (95%CI)=0.86 (0.75, 0.98)) after multiple adjustments. Higher serum tHcy was associated with MOFs (HR/SD (95%CI)=1.29 (1.12, 1.50)) risk after multiple adjustments in men. These findings suggest that a specific AA profile correlates with greater BMD and lower subsequent fracture risk, independent of diet and lifestyle factors.

Clinical Performance of the Updated Trabecular Bone Score (TBS) Algorithm, Which Accounts for the Soft Tissue Thickness: The OsteoLaus Study.

Regional soft tissue may have a noise effect on trabecular bone score (TBS) and eventually alter its estimate. The current TBS software (TBS iNsight®) is based on an algorithm accounting for body mass index (BMI) (TBSv3.03 ). We aimed to explore the updated TBS algorithm that accounts for soft tissue thickness (TBSv4.0 ). This study was embedded in the OsteoLaus cohort of women in Lausanne, Switzerland. Hip and lumbar spine (LS) dual-energy X-ray absorptiometry (DXA) scans were performed using Discovery A System (Hologic). The incident major osteoporotic fractures (MOFs) were assessed from vertebral fracture assessments using Genant's method (vertebral MOF) or questionnaires (nonvertebral MOF). We assessed the correlations of bone mineral density (BMD) or TBS with body composition parameters; MOF prediction ability of both versions of TBS; and the differences between Fracture Risk Assessment Tool (FRAX) adjusted for TBSv3.03 or TBSv4.0 . In total, 1362 women with mean ± SD age 64.4 ± 7.5 years and mean ± SD BMI 25.9 ± 4.5 kg/m2 were followed for 4.4 years and 132 experienced an MOF. All the anthropometric measurements of our interest were positively correlated with LS, femoral neck, or hip BMD and TBSv4.0 ; whereas with TBSv3.03 their correlations were negative. In the models adjusted for age, soft tissue thickness, osteoporotic treatment, and LS-BMD, for each SD decline in TBSv3.03 , there was a 43% (OR 1.43; 95% CI, 1.12 to 1.83) increase in the odds of having MOF; whereas for each SD decline in TBSv4.0 , there was a 54% (OR 1.54; 95% CI, 1.18 to 2.00) increase in the odds of having an MOF. Both FRAXs were very strongly correlated and the mild differences were present in the already high-risk women for MOF. This study shows that TBSv4.0 overcomes the debatable residual negative correlation of the current TBS with body size and composition parameters, postulating itself as free from the previously acknowledged technical limitation of TBS. © 2019 American Society for Bone and Mineral Research.

How well do the FRAX (Australia) and Garvan calculators predict incident fractures? Data from the Geelong Osteoporosis Study.

This study assessed the ability of the FRAX (Australia) and Garvan calculators to predict fractures in Australian women and men. Women (n = 809) and men (n = 821) aged 50-90years, enrolled in the Geelong Osteoporosis Study, were included. Fracture risk was estimated using FRAX and Garvan calculators with and without femoral neck bone mineral density (BMD) (FRAXBMD, FRAXnoBMD, GarvanBMD, GarvannoBMD). Incident major osteoporotic (MOF), fragility, and hip fractures over the following 10years were verified radiologically. Differences between observed and predicted numbers of fractures were assessed using a chi-squared test. Diagnostics indexes were calculated. In women, 115 MOF, 184 fragility, and 42 hip fractures occurred. For men, there were 73, 109, and 17 fractures, respectively. FRAX underestimated MOFs, regardless of sex or inclusion of BMD. FRAX accurately predicted hip fractures, except in women with BMD (20 predicted, p = 0.004). Garvan underestimated fragility fractures except in men using BMD (88 predicted, p = 0.109). Garvan accurately predicted hip fractures except for women without BMD (12 predicted, p < 0.001). Fractures were underestimated primarily in the osteopenia and osteoporosis groups; MOFs in the normal BMD group were only underestimated by FRAXBMD and fragility fractures by GarvannoBMD, both in men. AUROCs were not different between scores with and without BMD, except for fragility fractures predicted by Garvan in women (0.696, 95% CI 0.652-0.739 and 0.668, 0.623-0.712, respectively, p = 0.008) and men, which almost reached significance (0.683, 0.631-0.734, and 0.667, 0.615-0.719, respectively, p = 0.051). Analyses of sensitivity and specificity showed overall that MOFs and fragility fractures were poorly predicted by both FRAX and Garvan, while hip fractures were acceptably predicted. Overall, the FRAX and Garvan calculators underestimated MOF and fragility fractures, particularly in individuals with osteopenia or osteoporosis. Hip fractures were predicted better by both calculators. AUROC analyses suggest that GarvanBMD performed better than GarvannoBMD for prediction of fragility fractures.

Which is the preferred site for bone mineral density monitoring as an indicator of treatment-related anti-fracture effect in routine clinical practice? A registry-based cohort study.

The role of monitoring bone mineral density (BMD) as an indicator of an anti-fracture effect is controversial. Discordance between the spine and hip BMD is common and creates uncertainty in clinical practice. Using a population-based BMD Registry for the Province of Manitoba, Canada, we compared change in the spine and hip BMD as an indicator of treatment-related fracture risk reduction. The study cohort included 6093 women age >40years initiating osteoporosis treatment with two consecutive dual-energy X-ray absorptiometry (DXA) scans (mean interval 4.7years). We computed change in the spine, total hip, and femur neck BMD between the first and second DXA scans as categorical (categorized as stable, detectable decrease, or detectable increase) and continuous measures. We modeled time to first incident fracture, ascertained from health services data, using Cox regression adjusted for baseline fracture probability. During a mean follow-up of 12.1years, 995 women developed incident major osteoporotic fractures (MOF) including 246 with hip fractures and 301 with clinical vertebral fractures. Women with a detectable decrease in total hip BMD compared with stable BMD experienced an increase in MOF (adjusted hazard ratio [aHR] 1.46, 95% confidence interval [CI] 1.25-1.70) while those with a detectable increase in total hip BMD experienced a decrease in MOF (aHR 0.71, 95% CI 0.61-0.83), and these results were not attenuated when adjusted for change in spine BMD. Similar results were seen for hip and clinical vertebral fracture outcomes, when BMD change was assessed as a continuous measure, and when femur neck BMD monitoring was used instead of total hip BMD monitoring. Treatment-related increases in total hip BMD are associated with lower MOF, hip, and clinical vertebral fracture risk compared with stable BMD, while BMD decreases are associated with higher fracture risk. In contrast, spine BMD change is not independently associated with fracture risk.

SAT-515 Racial-Ethnic Differences in Diabetes-Related Fracture Risk

Background: Diabetes mellitus (DM), a novel risk factor for fracture, has not been well studied among African American (AA) and Hispanic (HIS) patients, who have the highest rates of DM in the United States and have higher rates of other major DM complications. Thus, the purpose of this study was to examine DM-related fracture risk among the multi-ethnic population of a large, urban academic center. Methods: We conducted a retrospective study using the electronic medical record. 19,171 subjects with DM (7,622 Caucasians [CA], 7,468 AA and 4,081 HIS) were identified through ICD codes and compared with 26,235 reference subjects with hypertension (HTN) but without DM (15,146 CA, 8,311 AA, and 2,778 HIS). Included subjects were at least 40 years of age, had at least 180 days of follow up, and had at least 1 outpatient visit per year. Subjects with end stage renal disease, bariatric surgery, Paget’s disease, and organ transplantation were excluded. Fractures and co-morbid conditions were identified through ICD codes. Fractures of the humerus, wrist, and hip were analyzed as major osteoporotic fractures (MOF). A Cox proportional hazards model was used to assess the impact of DM on the risk of incident MOF. A random sample of 235 subjects with incident MOF codes was chosen to assess the accuracy of fracture ICD codes and demonstrated an 85% validity rate regardless of race-ethnicity or DM/HTN status. Results: The two cohorts had a total of 717 MOFs over mean 3.2 years of follow-up. Among DM patients, there were significantly more incident MOF in CA and HIS than in AA (unadjusted rates of 1.9% and 1.7% versus 1.1%, respectively, p<0.01 for both). The unadjusted rates of MOF in DM did not differ significantly from rates in the reference cohort with HTN among the same racial-ethnic group (1.8% in CA, 1.3% in HIS, 1.3% in AA). In a comprehensive model that included age, BMI, gender, race, and prior MOF, DM was not significantly associated with the incidence of MOF when the three racial-ethnic groups were analyzed together (HR 1.16, 95% CI 0.99-1.36, p=0.07). However, the effect of DM differed in AA as compared to CA and HIS (AA race by DM interaction p=0.036). DM was significantly associated with the incidence of MOF only in CA and HIS (HR 1.24, 95% CI 1.03-1.49, p=0.02) but not in AA (HR 0.92, 95% CI 0.68-1.23, p=0.56). Interestingly, the association between MOF and prior fracture was far stronger in AA (HR 10.09, 95% CI 5.14-19.81, p<0.001) than in CA and HIS (HR 2.03, 95% CI 1.01-4.09, p=0.048). Conclusion: In a comprehensive model, the presence of diabetes was associated with elevated fracture risk in Hispanics and Caucasians, but not in African Americans. Instead, prior fracture demonstrated a remarkably strong association with incident fracture in African Americans. Our findings may have significant ramifications for case detection and management of diabetes-related fracture risk in multi-ethnic populations in the United States.

Performance of FRAX and FRAX-Based Treatment Thresholds in Women Aged 40 Years and Older: The Manitoba BMD Registry

We examined among women aged ≥40 years the performance of the Fracture Risk Assessment Tool (FRAX) and FRAX-based osteoporosis treatment thresholds under the US National Osteoporosis Foundation (NOF) and UK National Osteoporosis Guideline Group (NOGG) guidelines. We used registry data for all women aged ≥40 years in Manitoba, Canada, with baseline bone mineral density (BMD) testing (n = 54,459). Incident major osteoporotic fracture (MOF), hip fracture, and clinical fracture were assessed from population-based health services data (mean follow-up 10.5 years). Age-stratified hazard ratios (HR) were estimated from Cox regression models. We assessed the sensitivity, specificity, positive predictive value (PPV), number needed to screen (NNS), and number needed to treat (NNT) to prevent a fracture (assuming 20% relative risk reduction on treatment) for osteoporosis treatment thresholds under the NOF and NOGG guidelines. Femoral neck T-score and FRAX (with and without BMD) predicted all fracture outcomes at all ages. There was good calibration in FRAX-predicted versus observed 10-year MOF and hip fracture probability. Overall sensitivity (PPV) for incident MOF was 25.7% (24.0%) for femoral neck T-score ≤ -2.5; 20.3% (26.3%) for FRAX (with BMD)-predicted 10-year MOF risk ≥20% (NOF threshold); 27.3% (22.0%) for FRAX-predicted 10-year MOF risk ≥ age-dependent cut-off (NOGG threshold), 59.4% (19.0%) for the NOF treatment algorithm; and 28.5% (18.4%) for the NOGG treatment algorithm. Sensitivity for identifying incident MOF varied by age, ranging from 0.0% to 26.3% in women 40 to 49 years old and from 49.0% to 93.3% in women aged 80+ years. The gradient of risk for fracture prediction from femoral neck T-score and FRAX (with and without BMD) as continuous measures was strong across the age spectrum. The sensitivity and PPV of the strategies based on dichotomous cut-offs are low, especially among women aged 40 to 49 years (who have lowest incidence rates). Threshold-based approaches should be reassessed, particularly in younger women. © 2019 American Society for Bone and Mineral Research.

Fracture Risk Indices From DXA-Based Finite Element Analysis Predict Incident Fractures Independently From FRAX: The Manitoba BMD Registry

Objective: Finite element analysis (FEA) is a computational method to predict the behavior of materials under applied loading. We developed a software tool that automatically performs FEA on dual-energy X-ray absorptiometry hip scans to generate site-specific fracture risk indices (FRIs) that reflect the likelihood of hip fracture from a sideways fall. This longitudinal study examined associations between FRIs and incident fractures. Methods: Using the Manitoba Bone Mineral Density (BMD) Registry, femoral neck (FN), intertrochanter (IT), and subtrochanter (ST) FRIs were automatically derived from 13,978 anonymized dual-energy X-ray absorptiometry scans (Prodigy, GE Healthcare) in women and men aged 50 yr or older (mean age 65 yr). Baseline covariates and incident fractures were assessed from population-based data. We compared c-statistics for FRIs vs FN BMD alone and fracture risk assessment (FRAX) probability computed with BMD. Cox regression was used to estimate hazard ratios and 95% confidence intervals (95% CIs) for incident hip, major osteoporotic fracture (MOF) and non-hip MOF adjusted for relevant covariates including age, sex, FN BMD, FRAX probability, FRAX risk factors, and hip axis length (HAL). Results: During mean follow-up of 6 yr, there were 268 subjects with incident hip fractures, 1003 with incident MOF, and 787 with incident non-hip MOF. All FRIs gave significant stratification for hip fracture (c-statistics FN-FRI: 0.76, 95% CI 0.73–0.79, IT-FRI 0.74, 0.71–0.77; ST-FRI 0.72, 0.69–0.75). FRIs continued to predict hip fracture risk even after adjustment for age and sex (hazard ratio per standard deviation FN-FRI 1.89, 95% CI 1.66–2.16); age, sex, and BMD (1.26, 1.07–1.48); FRAX probability (1.30, 1.11–1.52); FRAX probability with HAL (1.26, 1.05–1.51); and individual FRAX risk factors (1.32, 1.09–1.59). FRIs also predicted MOF and non-hip MOF, but the prediction was not as strong as for hip fracture. Summary: Automatically-derived FN, IT, and ST FRIs are associated with incident hip fracture independent of multiple covariates, including FN BMD, FRAX probability and risk factors, and HAL.

Accuracy of FRAX® in People With Multiple Sclerosis.

People with multiple sclerosis (MS) have a higher risk of low bone mineral density (BMD), osteoporosis, and osteoporotic fractures than healthy adults. The Fracture Risk Assessment tool (FRAX® ) has been reported to underestimate fracture risk in people with MS when BMD is unknown. We tested FRAX performance for people with MS when BMD is known, and determined if MS is a risk factor for fracture independent of FRAX score. Using population-based databases in Manitoba, Canada, we identified people with MS who underwent BMD screening after MS diagnosis (n = 744) and controls matched on age, sex, and first BMD screening date (n = 3721). We calculated FRAX 10-year probabilities at the BMD screening date, and ascertained incident major osteoporotic fractures (MOF). Using Cox proportional hazards modeling we assessed the effect of MS on the hazard of MOF, adjusting for FRAX 10-year probabilities. MS cases had a higher mean FRAX 10-year probability of MOF calculated with BMD (8.32 ± 7.53) than controls (6.98 ± 5.18; p < 0.01). MS increased the risk for MOF after controlling for FRAX 10-year probability without BMD (HR 1.67; 95% confidence interval [CI], 1.29 to 2.16), and after controlling for FRAX individual risk factors (HR 1.45; 95% CI, 1.12 to 1.89). MS remained a risk factor for MOF even when controlling for FRAX 10-year probability of MOF with BMD (HR 1.48; 95% CI, 1.14 to 1.92). The FRAX 10-year probability with and without BMD underestimated the observed 10-year MOF risk in MS cases by 3% to 5%. Calibration improved when secondary osteoporosis was used to calculate FRAX without BMD. Calibration was best when the rheumatoid arthritis input was used to calculate FRAX probability along with BMD. Using secondary osteoporosis or rheumatoid arthritis as proxies for MS improves performance of FRAX and accurately predicts MOF outcomes in those with MS. This provides clinicians with a readily available approach to improve the accuracy of fracture prediction in MS. © 2019 American Society for Bone and Mineral Research.

The Fracture Risk Assessment Tool (FRAX®) predicts fracture risk in patients with chronic kidney disease

The Fracture Risk Assessment Tool (FRAX®) was developed to predict fracture risk in the general population, but its applicability to patients with chronic kidney disease (CKD) is unknown. Using the Manitoba Bone Mineral Density (BMD) Database, we identified adults not receiving dialysis with available serum creatinine measurements and bone densitometry within 1 year. Estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. Incident major osteoporotic fractures and hip fractures were ascertained from population-based health care databases. The performance of FRAX, derived without and with BMD, was studied in relation to CKD stage. Among 10,099 subjects (mean age 64 ± 13 years, 13.0% male), 2,154 had eGFR 30-60 mL/min/1.73 m2 (CKD stage 3) and 590 had eGFR<30 mL/min/1.73 m2 (CKD stages 4-5). During a 5-year observation period, 772 individuals experienced a major osteoporotic fracture and 226 had a hip fracture. FRAX predicted risk for major osteoporotic fracture and hip fracture in all eGFR strata. For every standard deviation increase in FRAX score derived with BMD, the hazard ratio (HR) for hip fracture was 4.54 (95% confidence interval [CI] 3.57-5.77) in individuals with eGFR≥ 60 mL/min/1.73m2, 4.52 (95% CI 3.15-6.49) in individuals with eGFR 30-60 mL/min/1.73m2, and3.10 (95% CI 1.80-5.33) in individuals with eGFR <30mL/min/1.73m2.The relationship between FRAX and major osteoporotic fracture was stronger in those with CKD compared to those with preserved eGFR. These findings support the use of FRAX to risk stratify patients with non-dialysis CKD for major osteoporotic fractures and hip fractures.

Administrative healthcare data applied to fracture risk assessment.

To evaluate the discrimination of fracture risk scores defined using inputs available from administrative data for predicting incident major osteoporotic fracture (MOF) and hip fracture (HF) alone. Using the Manitoba Bone Mineral Density (BMD) Database (1997-2013), we identified 61,041 individuals aged 50years or older with healthcare coverage following their first BMD test. We calculated two-modified FRAX)scores based on administrative data: FRAX-A and FRAX-A+. The FRAX-A modification used all FRAX inputs, except for BMD, body mass index, and parental HF, while the FRAX-A+ modification using all FRAX-A inputs plus a comorbidity score, number of hospitalizations in the 3years prior to the BMD test, depression diagnosis, and dementia diagnosis. FRAX scores computed with BMD (i.e., FRAX [BMD]) and without BMD (i.e., FRAX [no-BMD]) were the comparators. During a mean of 7years of follow-up, we identified 5306 (8.7%) incident MOF and 1532 (2.5%) incident HF. The c-statistic for MOF associated with FRAX-A was lower than FRAX (BMD) (0.655 vs 0.675; P < 0.05) and comparable to FRAX (no-BMD) (0.654; P = 0.07). The c-statistic for MOF using FRAX-A+ (0.663) was lower than FRAX (BMD) but higher than FRAX (no-BMD) (both P < 0.05). For predicting incident HF, c-statistics associated with FRAX-A (0.762) and FRAX-A+ (0.767) were lower than FRAX (BMD) (0.789) and FRAX (no-BMD) (0.773; both P < 0.05). FRAX-A and FRAX-A+ showed comparable or better discrimination than FRAX without BMD for predicting incident MOF, but slightly lower discrimination for HF alone.

Socioeconomic status and risk of osteoporotic fractures and the use of DXA scans: data from the Danish population-based ROSE study.

Lower socioeconomic status is known to be associated with a range of chronic conditions and with access to health care services. The link between socioeconomic status and the use of DXA scans and osteoporotic fracture, however, needs to be explored more closely. Therefore, the aim of this study was to examine the relationship between socioeconomic status and both DXA scan utilization and major osteoporotic fractures (MOF) using a population-based cohort of Danish women and national registers. The study included 17,155 women (65-81years) sampled from the Risk-stratified Osteoporosis Strategy Evaluation study (ROSE). Information on socioeconomic background, DXA scans, and MOFs was retrieved from national registers. Competing-risk regression analyses were performed. Mean follow-up was 4.8years. A total of 4245 women had a DXA scan (24.7%) and 1719 (10.0%) had an incident MOF during follow-up. Analyses showed that women with basic education had a lower probability of undergoing DXA scans than women with further or higher education (greater than upper secondary education and vocational training education) (subhazard ratio (SHR) = 0.82; 95% CI 0.75-0.89, adjusted for age and comorbidity). Moreover, women with disposable income in the low and medium tertiles had a lower probability of undergoing DXA scans than women in the high-income tertile (SHR = 0.90; 95% CI 0.84-0.97 and SHR = 0.88, 95% CI 0.82-0.95, respectively, adjusted for age and comorbidity). No association between socioeconomic background and probability of DXA was found in adjusted analyses. The study found no differences in risk of osteoporotic fractures depending on socioeconomic status. However, women with further or higher education as well as higher income are more often DXA-scanned.

Real-world antidiabetic drug use and fracture risk in 12,277 patients with type 2 diabetes mellitus: a nested case-control study.

Patients with type 2 diabetes mellitus (T2DM) have an increased risk of fragility fractures, to which antidiabetic therapies may contribute. We aimed to characterize the risk of fracture associated with different antidiabetic treatments as usually prescribed to T2DM patients in actual practice conditions. A case-control study was nested within a cohort of incident T2DM patients registered in 2006-2012 in the Information System for Research Development in Primary Care (Catalan acronym, SIDIAP), a database which includes records for > 5.5million patients in Catalonia (Spain). Each case (incident major osteoporotic fracture) was risk-set matched with up to five same-sex controls by calendar year of T2DM diagnosis and year of birth (± 10years). Study exposure included previous use of all antidiabetic medications (alone or in combination), as dispensed in the 6months before the index date, with metformin (MTF) monotherapy, the most commonly used drug, as a reference group (active comparator). Data on 12,277 T2DM patients (2049 cases and 10,228 controls) were analyzed. Insulin use was associated with increased fracture risk (adjusted OR 1.63 (95% CI 1.30-2.04)), as was the combination of MTF and sulfonylurea (SU) (adjusted OR 1.29 (1.07-1.56)), compared with MTF monotherapy. Sensitivity analyses suggest possible causality for insulin therapy but not for the MTF + SU combination association. No significant association was found with any other antidiabetic medications. Insulin monotherapy was associated with an increased fracture risk compared to MTF monotherapy in T2DM patients. Fracture risk should be taken into account when starting a glucose-lowering drug as part of T2DM treatment.

Volumetric Bone Mineral Density and Failure Load of Distal Limbs Predict Incident Clinical Fracture Independent HR-pQCT BMD and Failure Load Predicts Incident Clinical Fracture of FRAX and Clinical Risk Factors Among Older Men.

Our objective was to determine the associations of peripheral bone strength and microarchitecture with incident clinical and major osteoporotic fracture among older men after adjusting for major clinical risk factors. We used a prospective cohort study design with data from 1794 men (mean age 84.4 years) in the Osteoporotic Fractures in Men (MrOS) study. Eligible men attended the year 14 visit, had high-resolution peripheral quantitative computed tomography (HR-pQCT) scans of the distal radius and distal or diaphyseal tibia, DXA measured BMD, and were followed for mean 1.7 years for incident fracture. Failure load was estimated using finite element analysis. We used Cox proportional hazards models with standardized HR-pQCT parameters as exposure variables. Primary outcome was clinical fracture (n = 108). Covariates included either Fracture Risk Assessment Tool (FRAX) major osteoporotic fracture probability calculated with BMD (FRAX-BMD), or individual clinical risk factors (CRF) including age, total hip BMD, race, falls, and prevalent fracture after age 50 years. Lower failure load was associated with higher risk of incident clinical fracture and incident major osteoporotic fracture. For clinical fracture with FRAX-BMD adjustment, the associations ranged from hazard ratio (HR) 1.58 (95% CI, 1.25 to 2.01) to 2.06 (95% CI, 1.60 to 2.66) per SD lower failure load at the diaphyseal tibia and distal radius. These associations were attenuated after adjustment for individual CRFs, but remained significant at the distal sites. Associations of volumetric BMD with these outcomes were similar to those for failure load. At the distal radius, lower trabecular BMD, number, and thickness, and lower cortical BMD, thickness, and area were all associated with higher risk of clinical fracture, but cortical porosity was not. Among community-dwelling older men, HR-pQCT measures including failure load, volumetric BMD, and microstructure parameters at peripheral sites (particularly distal radius) are robust independent predictors of clinical and major osteoporotic fracture. © 2018 American Society for Bone and Mineral Research.

Risk-equivalent T-score adjustment for using lumbar spine trabecular bone score (TBS): the Manitoba BMD registry.

The aim of this study is to develop an approach for using TBS in clinical practice based upon a "risk-equivalent" adjustment to the BMD T-score. We identified 45,185 women age 40years and older with baseline spine and hip DXA, TBS, and FRAX probabilities including femoral neck BMD. Incident major osteoporotic fractures (MOF, n = 3925) were identified from population-based health services data (mean follow-up 7.4years comprising 335,910 person-years). Cox proportional hazards models adjusted for age and BMI were first used to estimate the risk for MOF from BMD T-score alone, then after including TBS and a multiplicative age interaction term. From the parameter estimates, we developed a TBS offset to the BMD T-score based upon change in TBS that would give the same risk as a unit change in BMD T-score for the femoral neck, total hip, and lumbar spine. All BMD measurements, TBS, and the age interaction term independently predicted MOF (p < 0.001). Measures of risk stratification and model fit were improved for the TBS-adjusted BMD T-score versus the unadjusted BMD T-score (p < 0.001). There was a high level of agreement between MOF probability estimated from TBS-adjusted MOF FRAX probability and FRAX probability using the "risk-equivalent" femoral BMD T-score: MOF probability r2 = 0.98, slope = 1.02, intercept = - 0.3; hip probability r2 = 0.95, slope = 1.07, intercept = 0.0. The BMD-independent effect of lumbar spine TBS on fracture risk can be estimated as a simple offset to the BMD T-score.

International Classification of Diseases (ICD)-coded obesity predicts risk of incident osteoporotic fracture.

International Classification of Diseases (ICD) codes have been used to ascertain individuals who are obese. There has been limited research about the predictive value of ICD-coded obesity for major chronic conditions at the population level. We tested the utility of ICD-coded obesity versus measured obesity for predicting incident major osteoporotic fracture (MOF), after adjusting for covariates (i.e., age and sex). In this historical cohort study (2001–2015), we selected 61,854 individuals aged 50 years and older from the Manitoba Bone Mineral Density Database, Canada. Body mass index (BMI) ≥30 kg/m2 was used to define measured obesity. Hospital and physician ICD codes were used to ascertain ICD-coded obesity and incident MOF. Average cohort age was 66.3 years and 90.3% were female. The sensitivity, specificity and positive predictive value for ICD-coded obesity using measured obesity as the reference were 0.11 (95% confidence interval [CI]: 0.10, 0.11), 0.99 (95% CI: 0.99, 0.99) and 0.79 (95% CI: 0.77, 0.81), respectively. ICD-coded obesity (adjusted hazard ratio [HR] 0.83; 95% CI: 0.70, 0.99) and measured obesity (adjusted HR 0.83; 95% CI: 0.78, 0.88) were associated with decreased MOF risk. Although the area under the receiver operating characteristic curve (AUROC) estimates for incident MOF were not significantly different for ICD-coded obesity versus measured obesity (0.648 for ICD-coded obesity versus 0.650 for measured obesity; P = 0.056 for AUROC difference), the category-free net reclassification index for ICD-coded obesity versus measured obesity was -0.08 (95% CI: -0.11, -0.06) for predicting incident MOF. ICD-coded obesity predicted incident MOF, though it had low sensitivity and reclassified MOF risk slightly less well than measured obesity.

The role of previous falls in major osteoporotic fracture prediction in conjunction with FRAX in older Chinese men and women: the Mr. OS and Ms. OS cohort study in Hong Kong.

Although the association of falls with fracture has been widely explored, the impact of previous falls is not included in the FRAX algorithm currently. Our aim was to examine the FRAX-independent associations between falls in the previous year and subsequent fracture risk, as well as the conjunctive use of falls and the FRAX score for major osteoporotic fracture (MOF) prediction in older Chinese people. Four thousand community older men and women aged 65years or older were followed up for 9.9±2.7 and 8.8±1.5years, respectively. The associations between falls in the previous 1year and MOF risk by follow-up years were evaluated using the Fine and Gray model. New prediction scores were calculated by incorporating the falls and FRAX scores using the Fine and Gray model, or developed by adjusting the FRAX scores by 30% increased risk for each fall in the previous year. The predictive powers for MOF risk between the new scores and FRAX scores were evaluated by the area under the curve (AUC) and category-based net reclassification improvement index (NRI). During the follow-up period, 139 (7.0%) men and 236 (11.8%) women had at least one incident MOF. One previous fall significantly predicted the first year incident MOF in men [hazard ratio (HR) (95%CI), 3.47 (1.02, 11.80)]. Previous recurrent falls significantly predicted a 10-year incident MOF in men [HR (95%CI), 2.42 (1.30, 4.51)]. In men, the fall-adjusting FRAX scores showed significant improvement on total net reclassification of fracture (3-6%). No improved predictive accuracy shown in women. Falls in the previous year are likely to provide some predictive power to FRAX for MOF risk assessment in older Chinese men, but not women.