Introducing FREMML: a decision-support approach for automated identification of individuals at high imminent fracture risk

The FREM is a tool developed from Danish public health registers (hospital diagnoses) to identify individuals over age 45years at high imminent risk of major osteoporotic fractures (MOF) and hip fracture (HF). In this study, our aim was to examine the ability of FREM to identify individuals at high imminent fracture risk in women and men from Manitoba, Canada. We used the population-based Manitoba Bone Mineral Density (BMD) Program registry, and identified women and men aged 45years or older undergoing baseline BMD assessment with 2years of follow-up data. From linked population-based data sources, we constructed FREM scores using up to 10years of prior healthcare information. The study population comprised 74,828 subjects, and during the 2years of observation, 1612 incident MOF and 299 incident HF occurred. We found significant fracture risk stratification for all FREM scores, with AUC estimates of 0.63-0.66 for MOF for both sexes and 0.84 for women and 0.65-0.67 for men for HF. FREM performed better than age alone but not as well as FRAX® with BMD. The inclusion of physician claims data gave slightly better performance than hospitalization data alone. Overall calibration for 1-year MOF prediction was reasonable, but HF prediction was overestimated. In conclusion, the FREM algorithm shows significant fracture risk stratification when applied to an independent clinical population from Manitoba, Canada. Overall calibration for MOF prediction was good, but hip fracture risk was systematically overestimated indicating the need for recalibration.

Most patients designated as high risk of fracture using fracture risk assessment tool (FRAX) with femoral neck bone mineral density (BMD) (i.e., 10-year major osteoporotic fracture probability exceeding 20% or hip fracture exceeding 3%) have one or more T-scores in the osteoporotic range; conversely, almost no high risk patients have normal T-scores at all bone mineral density measurement sites. We determined the agreement between a FRAX designation of high risk of fracture [defined as 10-year major osteoporotic fracture probability (≥ 20%) or hip fracture probability (≥ 3%)] and the WHO categorizations of bone mineral density according to T-score. Ten-year FRAX probabilities calculated with femoral neck BMD were derived using both Canadian and US white tools for a large clinical cohort of 36,730 women and 2,873 men age 50 years and older from Manitoba, Canada. Individuals were classified according to FRAX fracture probability and BMD T-scores alone. Most individuals designated by FRAX as high risk of major osteoporotic fracture had a T-score in the osteoporotic range at one or more BMD measurement sites (85% with Canadian tool and 83% with US white tool). The majority of individuals deemed at high risk of hip fracture had one or more T-scores in the osteoporotic range (66% with Canadian tool and 64% with US white tool). Conversely, there were extremely few individuals (<1%) who were at high risk of major osteoporotic or hip fracture with normal T-scores at all BMD measurement sites. A FRAX designation of high risk of fracture is usually associated with a densitometric diagnosis of osteoporosis.

The aims of this study are to determine the proportion of patients at high risk for major osteoporotic and hip fractures in a Japanese cohort with rheumatoid arthritis (RA) and to determine if a care gap exists for high-risk patients. The Fracture Risk Assessment Tool (FRAX®) was administered to 3,970 Japanese patients with RA enrolled in the Institute of Rheumatology Rheumatoid Arthritis cohort study with (n=276) and without (n=3,694) the use of bone mineral density (BMD) measurement. The study population had a mean age of 62 years and was 84% female. Among the 1,522 patients ≥65 years of age, 661 (43%) and 1,304 (86%) were at high risk for a major osteoporotic fracture (10-year probability >20%) and hip fracture (>3%), respectively. Among patients at high risk for a major osteoporotic fracture (n=723), only 453 (63%) and 320 (44%) reported taking any osteoporosis medications and bisphosphonates, respectively. Among female patients with BMD measurements (n=262), the 10-year risk of a major osteoporotic fracture calculated with BMD was significantly higher than in those without BMD measurements (P<0.001). The FRAX identified a substantial proportion of elderly Japanese RA patients with a high risk of fractures. A substantial gap exists between fracture risk and osteoporosis treatment in Japanese RA patients, as previously reported for patients of other ethnicities. In addition, the gap may be underestimated when BMD measurements are not involved in the fracture risk assessment.

FRI0147 Serum Rankl Level and Fracture Risk Using FRAX Tool in Post-Menopausal Rheumatoid Arthritis Patients

Background Fracture risk assessment tool (FRAX) index was developed for estimating of the 10-year risk of major or hip osteoporotic fracture. To date, there is insufficient information regarding the correlation between FRAX and serum bone turnover markers (BTMs), such as soluble ligand of receptor activator of nuclear factor-κB (sRANKL), osteoprotegerin (OPG), and other molecules related with secondary osteoporosis in rheumatoid arthritis (RA). Therefore, this study is aimed at assessing the correlation between the FRAX and serum levels of sRANKL, OPG, sRANKL/OPG ratio, Dickkopf-1 (DKK-1), and sclerostin (SOST) in RA. Methods Cross-sectional study included 156 postmenopausal women with RA. Bone mineral density (BMD) was measured at lumbar spine (L1-L4) and total hip using dual-energy X-ray absorptiometry (DXA). RA patients were divided into (A) RA + osteoporosis and (B) RA without osteoporosis. FRAX scores were calculated including the total hip BMD. Serum sRANKL, OPG, DKK-1, and SOST levels were measured by ELISA. Pearson tests were used for assessing the correlation between serum levels of these molecules and FRAX scores in RA. Results The RA + osteoporosis group had elevated sRANKL levels (p = 0.005), higher sRANKL/OPG ratio (p = 0.017), decreased DKK-1 (p = 0.028), and lower SOST levels (p < 0.001). Low total hip BMD correlated with high sRANKL (p = 0.001) and sRANKL/OPG ratio (p = 0.005). Total hip and lumbar spine BMD correlated with DKK-1 (p = 0.009 and p = 0.05, respectively) and SOST levels (p < 0.001 and p < 0.001, respectively). Higher sRANKL levels and sRANKL/OPG ratio correlated with estimated 10-year risk of a major osteoporotic fractures (p = 0.003 and p = 0.003, respectively) and hip fracture (p = 0.002 and p = 0.006, respectively). High serum SOST levels were associated with a low estimated 10-year risk of a major osteoporotic fracture (p = 0.003) and hip fracture (p = 0.009). Conclusion High sRANKL levels and sRANKL/OPG ratio can be useful to detect a subgroup of RA patients who has an increased 10-year risk of major and hip osteoporotic fractures.

Risk of major osteoporotic fracture after first, second and third fracture in Swedish women aged 50 years and older.

The primary objective of this study was to determine the percentage of nursing residents at high risk of fracture as determined by FRAX score, calculated without bone mineral density (BMD) data. The secondary objective was to quantify FRAX components able to be ascertained through pharmacist chart review. Retrospective chart review. 130-bed long-term care facility in Arizona. Inclusion criteria comprised designation as a skilled nursing facility, residents older than 50 years of age, and postmenopausal, if female. Exclusion criteria comprised current osteoporosis diagnosis/treatment, and hospice. Eighty-eight residents were screened, and 52 completed the study. The FRAX clinical risk assessment tool was used without incorporation of BMD data to determine 10-year risk of major osteoporotic and hip fracture. FRAX components unable to be determined by chart review were recorded. The primary outcome measure was calculated FRAX score for each participant. The secondary outcome measure was component(s) of FRAX unable to be ascertained via chart review. 90.3% of participants had high (≥ 3%) 10-year risk of hip fracture and 55.8% had high (≥ 20%) 10-year risk of major osteoporotic fracture. FRAX components unable to be ascertained through chart review included family history of hip fracture (absent from 51.9% of charts) and/or ethanol use (absent from 3.8% of charts). Nursing facility residents are at high risk for fracture as determined by FRAX, without BMD data. The ability to determine FRAX scores via pharmacist chart review demonstrates an opportunity for pharmacist involvement in long-term care fracture risk screening.

Introduction Studies have been conducted to assess the association between the use of statin and risk of new onset osteoporosis or osteoporotic fractures, however, they have shown conflicting results. We aimed to investigate the association between statin use and the risk of major osteoporotic fractures in elderly population. Methods In this population cohort study with Korean National Health Insurance Service-Senior Cohort database, a total of 365,656 elderly (≥60 years) without previous history of osteoporosis were included. The patients who did not have a history of statin use in year 2003 were followed from January 2004 to December 2012. Incidences of major osteoporotic fractures and site specific fractures were compared using the Cox proportional hazards model with use the inverse probability weighting method. Results During years follow-up period, 54,959 major osteoporotic fractures occurred; the risk of major osteoporotic fractures was significantly reduced (OR,0.769; 95% CI,0.716-0.826) in statin users compared with that in non-users. Among subtypes of major osteoporotic fracture, a risk reduction with statin therapy was significant for both vertebral fracture (OR,0.701; 95% CI,0.641-0.767) and non-vertebral fracture (OR,0.807; 95% CI,0.726-0.898). Longer duration and higher cumulative dose of statin, defined by cumulative daily defined dose, were negatively associated with the risk of major osteoporotic fracture. Conclusion In this population-based cohort study, the use of statin was associated with significant reduction in the risk of osteoporotic fractures in elderly patients without previous history of osteoporosis. Presentation: No date and time listed

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.

SummaryThis study revealed the risk of major osteoporotic fracture in patients with sarcoidosis exposed to glucocorticoids. Current use of glucocorticoids was associated with a risk of fracture, with no difference between patients with and without sarcoidosis. Sarcoidosis per se was not associated with an increased fracture risk.IntroductionSarcoidosis is a multi-organ, chronic inflammatory, granulomatous disorder that most frequently affects the lungs, lymph nodes, skin, eyes, and liver, but may occur in any organ, including the bones. While oral glucocorticoids (GCs) are commonly used as initial treatment, little is known about the risk of major osteoporotic fractures in patients with sarcoidosis exposed to GCs.MethodsA case-control study was conducted using the Danish National Hospital Discharge Registry (NHDR) between January 1995 and December 2011. Conditional logistics regression models were used to derive adjusted odds ratios (OR) of major osteoporotic fractures in subjects with and without sarcoidosis stratified by average daily and cumulative dose exposures.ResultsA total of 376,858 subjects with a major osteoporotic fracture and the same number of subjects without this event were identified (mean age 64.2 ± 19.5 years, 69% female). In patients with sarcoidosis (n = 124), current use of GC was associated with an increased risk of major osteoporotic fracture (adjusted (adj.) OR 1.74; 95% CI 1.17–2.58), which dropped to baseline levels after discontinuation. In subjects without sarcoidosis, this risk was comparable (adj. OR 1.36; 95% CI 1.32–1.40). In sarcoidosis patients, cumulative dose 1.0–4.9 g and >10 g prednisolone equivalents were associated with increased risk of major osteoporotic fracture (adj. OR 2.75; 95% CI 1.06–7.14 and 2.22; 95% CI 1.17–4.22, respectively), whereas a cumulative dose of <1.0 g and 5.0–9.9 g was not associated with major osteoporotic fracture risk.ConclusionBoth in subjects with and without sarcoidosis, current expose to GC is associated with increased risk of major osteoporotic fractures, with no between-group difference. Sarcoidosis per se was not associated with increased fracture risk. Having sarcoidosis per se, i.e., if not treated with GC, is not a risk factor for fracture, and such patients may only need risk assessment when they commence GC therapy.

The US Preventative Services Task Force (USPSTF) recommends consideration for screening for osteoporosis in women under age 65 who have an estimated 10-year major osteoporotic fracture risk of 9.3 % or higher. We found that this threshold for osteoporosis screening in women ages 50-64 years old has a low sensitivity to detect osteoporosis. The US Preventative Services Task Force (USPSTF) recommends consideration of dual-energy X-ray absorptiometry (DXA) in women under ages 50-64 with a major osteoporotic fracture (MOF) risk of 9.3 % or higher, as estimated by the fracture risk assessment tool (FRAX) tool. We assessed the performance of the 9.3 % MOF risk threshold for detecting osteoporosis and evaluated whether DXA indication appeared appropriate, based on USPSTF criteria and other risk factors, at our institution. We performed a retrospective record review of women ages 50-64.5 years old to determine clinical factors and FRAX scores of women undergoing a DXA at our institution over a 6-month period after the USPSTF recommendations were released and evaluated the sensitivity and specificity of the 9.3 % MOF threshold to detect densitometric osteoporosis. Additionally, using the USPSTF criteria and several additional risk factors, we evaluated the extent of potentially inappropriate DXA use in women ages 50 to 64 years in a large primary care practice in an academic medical center. The analysis included 465 DXA tests. The overall sensitivity and specificity of a FRAX-calculated MOF risk ≥9.3 % was 37 and 74 %, respectively, for the detection of osteoporosis. The receiver operator characteristic curve (ROC) demonstrated an area under the curve of 0.58. Lowering the FRAX risk threshold to 5.5 % would increase the sensitivity of detecting osteoporosis in our population from 37 to 80 % while reducing the specificity from 74 to 27 %. Out of 465 DXAs, 371 (79.8 %) were classified as appropriately ordered per our pre-specified criteria. Of the 120 women with osteoporosis at the hip and/or spine based on T-score values of -2.5 or less, 14 DXAs (11.7 %) were classified as potentially inappropriate based on a FRAX-predicted MOF risk less than 9.3 % and lack of additional pre-specified risk factors. We found that the USPSTF-recommended MOF risk threshold of 9.3 % for osteoporosis screening in women ages 50-64 years old has a low sensitivity to detect osteoporosis.

Results from previous prospective studies linking serum 25-hydroxyvitamin D (25OHD) with fracture risk have been inconsistent. The present study examined the relationship between serum 25OHD and risk of incident major osteoporotic fracture (hip, spine, radius, and humerus) in older U.S. adults. The study used a pooled cohort of 4749 men and women ages 65 years and older from the third National Health and Nutrition Examination Survey (NHANES III, 1988-1994) and NHANES 2000-2004. Incident fractures were identified using linked mortality and Medicare records that were obtained for participants from both surveys. Serum 25OHD values were measured by radioimmunoassay in both surveys. Cox proportional hazards models were used to estimate the relative risk (RR) of fracture by serum 25OHD level. There were 525 incident major osteoporotic fractures (287 hip fractures) in the sample. Serum 25OHD was a significant linear predictor of major osteoporotic fracture and significant quadratic predictor of hip fracture in the total sample and among those with less than 10 years of follow-up, but it was not related to risk of either fracture type among those with ≥ 10 years of follow-up. Major osteoporotic fracture risk was increased by 26% to 27% for each SD decrease in serum 25OHD among those with less than 10 years of follow-up. Serum 25OHD was significantly related to risk of major osteoporotic fractures as a group and to hip fracture alone in this cohort of older U.S. adults from NHANES III and NHANES 2000-2004. However, the predictive utility of serum 25OHD diminished after 10 years. In addition, the relationship appeared to be linear when major osteoporotic fracture risk was considered but quadratic when hip fracture risk was assessed.

A densitometric diagnosis of osteoporosis qualifies patients to a diagnostic-therapeutic process, but densitometric evaluation may not be sufficient for osteopaenic patients. Therefore, it is essential to assess osteoporosis risk factors, fracture history, and 10-year fracture risk, and classify patients into low-, medium-, high-, or very high-risk categories. In our study, we aimed to assess the risk of fractures in patients with newly diagnosed osteopaenia and determine the percentage of patients at high and very high risk of fracture. The study included 89 postmenopausal women with newly diagnosed osteopaenia as determined by a T-score of the femoral neck and/or lumbar spine from dual-energy X-ray absorptiometry (DXA) scans between -1.0 and -2.5 standard deviations (SD). Demographic data and laboratory tests were collected. Additionally, based on the Fracture Risk Assessment Tool (FRAX-PL) calculator including bone mineral density (BMD), 10-year fracture risk was calculated for major osteoporotic fractures (FRAX MOF) and hip fractures (FRAX HF). Each patient was then classified into particular risk groups based on FRAX and modified fracture risk assessment criteria. Our study found the most common risk factors to be glucocorticoid intake (47.19%), parental hip fracture (46.07%), and smoking (39.33%). In the general population, 56.6% of subjects had at least one fracture in adulthood. The FRAX calculator showed that 39.33% of the patients had a very high risk of HF and 34.83% had a very high risk of major osteoporotic fractures (MOF). A high fracture risk for hip fractures (HF) and MOF was noted in 11.24% and 40.45% of the patients, whereas a medium and low risk of MOF was seen in 17.98% and 6.74%, respectively. Significantly more subjects (53.93%) had been classified as being at very high risk of fracture, based on the expanded criteria than on the basis of FRAX alone. Of these, 48.31% met the criteria of FRAX > 15% for MOF or > 4.5% for HF, and 7.87% had multiple (≥ 2) major fractures. Women aged 70-75 years were at the highest risk of fracture. Our findings highlight the importance of categorising fracture risk in osteopaenic patients, and show that the number of patients at very high fracture risk increases when the expanded criteria from the latest Polish guidelines are applied.

AB0855 The disparities between fracture risk assessment (FRAX) with bmd and without BMD in korean patients with ankylosing spondylitis- multicenter trial

Association of muscle health impairment and atherosclerosis with major osteoporotic fracture risk in Taiwanese Vegetarians.