Risk factors for imminent fractures: a substudy of the FRISBEE cohort.

Multiple factors increase the risk of an imminent fracture, including a recent fracture, older age, osteoporosis, comorbidities, and the fracture site. These findings could be a first step in the development of a model to predict an imminent fracture and select patients most at need of immediate treatment. INTRODUCTION: The risk of a recurrent fragility fracture is maximal during the first 2 years following an incident fracture. In this prospective cohort study, we looked at the incidence of recurrent fractures within 2 years after a first incident fracture and we assessed independent clinical risk factors (CRFs) increasing this imminent fracture risk. METHODS: A total of 3560 postmenopausal women recruited from 2007 to 2013 were surveyed yearly for the occurrence of fragility fractures. We identified patients who sustained a fracture during the first 2 years following a first incident fragility fracture. We quantified the risk of a new fracture and assessed independent CRFs, associated with an imminent fracture at various sites. RESULTS: A recent fracture was a significant CRF for an imminent fracture (OR (95% CI): 3.7 (2.4-5.7) [p < 0.0001]). The incidence of an imminent fracture was higher in subjects above 80 years (p < 0.001). Other CRFs highly predictive in a multivariate analysis were osteoporosis diagnosis (p < 0.01), a central fracture as the index fracture (p < 0.01), and the presence of comorbidities (p < 0.05), with likelihood ratios of 1.9, 1.9, and 2.2, respectively. An imminent fracture was better predicted by a central fracture (p < 0.01) than by a major osteoporotic fracture. The hazard ratio was the highest for a central fracture. CONCLUSION: In patients with a recent fracture, older age, osteoporosis, comorbidities, and fracture site were associated with an imminent fracture risk. These findings could be a first step in the development of a model to predict an imminent fracture and select patients most at need of immediate and most appropriate treatment.

MOF/Hip Fracture Ratio in a Belgian Cohort of Post-menopausal Women (FRISBEE): Potential Impact on the FRAX® Score.

The ratio between major osteoporotic fractures (MOFs) and hip fractures in the Belgian FRAX® tool to predict fractures is currently based on Swedish data. We determined these ratios in a prospective cohort of Belgian postmenopausal women. 3560 women, aged 60-85 years (70.1 ± 6.4 years), were included in a prospective study from 2007 to 2013 and surveyed yearly (FRISBEE). We analyzed the number of validated incident fractures until October 2020 by age and sites and compared the MOFs/hip ratios in this cohort with those from the Swedish databases. We registered 1336 fractures (mean follow-up of 9.1 years). The MOFs/hip ratios extracted from the FRISBEE cohort were 10.7 [95% CI: (5.6-20.5)], 6.4 [4.7-8.7], and 5.0 [3.9-6.5] for women of 60-69, 70-79, and 80-89 years old, respectively. These ratios were 1.7-1.8 times higher for all age groups than those from the Swedish data, which decreased from 6.5 (60-64 years group) down to 1.8 (85-89 age group). The overall MOFs/hip ratio in Frisbee was 6.0 [5.9-6.1], which was higher than any Swedish ratio between 65 and 85 years. Nevertheless, the decrease of the ratios with age paralleled that observed in Sweden. In this Brussels prospective cohort, MOFs/hip ratios were 1.7-1.8 times those observed in Sweden currently used for MOFs prediction in the Belgian FRAX® version. This discrepancy can greatly modify the estimation of the risk of MOFs, which is among the main criteria used to recommend a pharmacological treatment for osteoporosis in several countries.

Osteoporosis treatment gap in a prospective cohort of volunteer women.

Despite the availability of efficient drugs to prevent osteoporotic fractures, only a minority of women receives osteoporosis therapy after a fracture. The high treatment gap in our cohort consisted of unselected volunteer patients highlights the urgent need of additional education, especially for the medical profession, regarding the risk-benefit balance of treatment. INTRODUCTION: Despite the availability of efficient drugs to prevent osteoporotic fractures, only a minority of women receives osteoporosis therapy after a fracture, with a treatment gap around 80%. This can have dramatic consequences for patients and the healthcare systems. METHODS: In this study based on longitudinal data from the FRISBEE (Fracture RIsk Brussels Epidemiological Enquiry) cohort of 3560 volunteer women aged 60 to 85 years, we evaluated the 1-year treatment gap after a first major incident fragility fracture. RESULTS: There were 386 first validated fragility fractures, 285 major osteoporotic fractures (MOF) and 101 "other major" fractures. The rate of untreated patients was 85.0% (82.8% for MOF versus 91.0 % for "other major" fracture sites) (p = 0.04), with a lower rate for spine (70.5%) and hip (72.5%) versus shoulder (91.6%) and wrist (94.1%) (p < 0.0001). More specifically, the treatment gap for patients with osteoporosis, defined by a T-score < - 2.5 SD was 74.6% versus 76.5% for patients with osteoporosis defined by the presence of hip, shoulder, or spine fractures, independently of DXA results. When considering age groups, the rate of untreated women was 87.9% for women 60-70 years old, 88.2% between 70 and 80 years and 77.8% above 80 years (p = 0.03), with a greater difference between women who were younger or older than 80 years at inclusion: 88.1% versus 77.8% (p = 0.009). A diagnosis of osteoporosis (p = 0.01) and age (p = 0.03) were the only clinical risk factors (CRFs) significantly associated with treatment initiation. CONCLUSIONS: This study highlights the urgent need of additional education, especially for the medical profession, regarding the risk-benefit balance of treatment.

Discriminating value of HR-pQCT for fractures in women with similar FRAX scores: A substudy of the FRISBEE cohort.

Areal bone mineral density (aBMD) has a low sensitivity to identify women at high fracture risk. The FRAX algorithm, by combining several clinical risk factors, might improve fracture prediction compared to aBMD alone. Several micro-architectural and biomechanical parameters which can be measured by high-resolution peripheral quantitative computed tomography (HR-pQCT) are associated with fracture risk. HR-pQCT in combination or not with finite element analysis (FEA) may be used to improve bone strength prediction. Our aim was to assess whether HR-pQCT measurements (densities, cortical and trabecular microarchitecture, biomechanical proprieties assessed by FEA) had an added value in predicting fractures in a subgroup of women belonging to the Belgian FRISBEE cohort. One hundred nineteen women who sustained a fracture (aged 60 to 85 years) during the initial follow-up of our cohort had a radius and tibia examination by HR-pQCT and were compared with controls matched for their FRAX score at baseline. We found that low distal radius total (OR = 1.41 [1.07-1.86] per SD, p < 0.05) and trabecular densities (OR = 1.45 [1.10-1.90], p < 0.01), trabecular number (OR = 1.32 [1.01-1.72], p < 0.05), intra individual distribution of separation (OR = 0.73 [0.54-0.99], p < 0.05) as several FEA parameters were significantly associated with fractures. At the distal tibia, impaired cortical density (OR = 1.32 [1.03-1.70] per SD, p < 0.05) and thickness (OR = 1.29 [1.01-1.63], p < 0.05) and apparent modulus (OR = 1.30 [1.01-1.66], p < 0.05) were significantly correlated with fractures. A low ultra distal radial aBMD (UDR) measured at the time of HR-pQCT was significantly associated with fractures (OR = 1.67 [1.22-2.28], p < 0.01). Women from both groups were followed further after the realization of the HR-pQCT and 46 new fractures were registered. In this second part of the study, low UDR aBMD (OR = 1.66 [1.18-2.35], p < 0.01), total (OR = 1.48 [1.08-2.03], p < 0.05), cortical (OR = 1.40 [1.04-1.87], p < 0.05) and trabecular (OR = 1.37 [1.01-1.85], p < 0.05) densities or apparent modulus (OR = 1.49 [1.07-2.05], p < 0.05) at the radius were associated with a significant increase of fracture risk. At the tibia, only the cortical density was significantly associated with the fracture risk (OR = 1.34 [1.02-2.76], p < 0.05). These results confirm the interest of HR-pQCT measurements for the evaluation of fracture risk, also in women matched for their baseline FRAX score. They also highlight that UDR aBMD contains pertinent information.

What is the validity of self-reported fractures?

We assessed the validity of self-reported fractures, over a median follow-up period of 6.2 years, in a well characterized population-based cohort of 3560 postmenopausal women, aged 60-85 years, from the Fracture Risk Brussels Epidemiological Enquiry (FRISBEE) study. Incident low-traumatic (falls from a standing height or less) or non-traumatic fractures, including peripheral fractures, were registered during each annual follow-up telephone interview. A self-reported fracture was considered as a true positive if it was validated by written reliable medical reports (radiographs, CT scans or surgical report). False positives fractures were considered to be those for which the radiology report indicated that there was no fracture at the reported site. Among self-reported fractures, false positive rates were 14.4% for all fractures. The rate of false positives of 11.2% (n = 48/429) was not negligible for the four classical major osteoporotic fractures (MOFs: hip, clinical spine, forearm or shoulder fractures). In terms of fracture site, we found the lowest false positive rate (4.4%) at the hip, and the highest (16.8%) at the spine, with the proximal humerus and the wrist in between, at about 10% each. The global rates of false positives were 12.5% (n = 22/176) for other major fractures and 22.3% (n = 49/220) for minor fractures. Younger subjects, individuals with fractures at sites other than the hip, with a lower education level, or with a higher BMI were more likely to report false positive fractures. Our data indicate that the inaccuracy of self-reported fractures is clinically relevant for several major fractures, which could influence any fracture risk prediction model.

Does the Prediction Accuracy of Osteoporotic Fractures by BMD and Clinical Risk Factors Vary With Fracture Site?

Several clinical risk factors (CRFs) have been shown to predict the risk of fragility fractures independently of BMD, but their accuracy in the prediction of a particular fracture site has not been extensively studied. In this study based on longitudinal data from the FRISBEE cohort (Fracture Risk Brussels Epidemiological Enquiry), we evaluated if CRFs are specific for sites of incident osteoporotic fractures during follow-up. We recruited 3560 postmenopausal women, aged 60 to 85 years, from 2007 to 2013, and surveyed yearly for the occurrence of fragility fractures during 6.2 years (median). We analyzed the association between CRFs included in the FRAX (fracture risk assessment tool) model or additional CRFs (falls, sedentary lifestyle, early untreated menopause, diabetes, use of selective serotonin reuptake inhibitors or proton pump inhibitors) and the first incident validated major osteoporotic fracture (MOF; n = 362; vertebra, hip, shoulder, and wrist) or other major fractures (n = 74; ankle, pelvis/sacrum, elbow, knee, long bones). Uni- and multivariate analyses using the Cox proportional hazards model were used. For MOFs considered together, the risk of fracture was highly associated in uni- and multivariate analyses (p<0.01) with osteoporosis (T-score < -2.5), prior fracture, age, BMD (assessed by DXA), and fall history (HR 2.34, 1.82,1.71, 1.38, and 1.32, respectively). For each site analyzed separately, prior OF, age, smoking, and total hip BMD remained independent predictors for hip fractures (HR 5.72, 3.98, 3.10, 2.32, and 1.92, respectively); osteoporosis, age, prior OF, glucocorticoids, and spine BMD for vertebral fracture (HR 2.08, 1.87, 1.78, 1.76, and 1.45, respectively); osteoporosis, prior OF, and femoral neck BMD (HR 1.83, 1.60, and 1.56, respectively) for wrist fracture; osteoporosis, prior OF, and spine BMD (HR 2.48, 1.78, and 1.31, respectively) for shoulder fracture; prior OF and diabetes (HR 2.62 and 2.03) for other major fractures. Thus, a prior fracture and BMD were the best predictors of fracture risk at any site. Other CRFs have a weaker predictive value, which is a function of the site of a future fracture. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

Observation of excited states in 5H.

The 5H system was produced in the 3H(t,p)5H reaction studied with a 58 MeV tritium beam at small c.m. angles. High statistics data were used to reconstruct the energy and angular correlations between the 5H decay fragments. A broad structure in the 5H missing mass spectrum showing up above 2.5 MeV was identified as a mixture of the 3/2+ and 5/2+ states. The data also present evidence that the 1/2+ ground state of 5H is located at about 2 MeV.