Summary
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.
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.
•In our cohort of volunteer women, the false positive rate of fracture was 14.4%.•The false positive rate for classical major osteoporotic fractures was 11.2%.•The false positive rate for other major fractures was 12.5%.•Inaccuracy of self-reported fractures is clinically relevant for most self-reported fractures.
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.
Summary
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.
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.
•417 women of the FRISBEE cohort, matched for FRAX, were evaluated by HR-pQCT.•Some HR-pQCT parameters, mainly at radius, are discriminating for prevalent fractures.•HR-pQCT improves the risk prediction beyond the DXA but not the FRAX score.•UDR aBMD also provides valuable information.
The space and time configurations of the dissociation of 8He into 6He+n+n, on C and Pb targets, have been explored simultaneously for the first time. The final-state interactions in the n-n and 6He-n ...channels are successfully described within a model that considers independent emission of neutrons from a Gaussian volume with a given lifetime. The dissociation on C target exhibits a dominant sequential decay through the ground state of 7He, consistent with neutrons being emitted from a Gaussian volume of r nn rms = 7.3 0.6 fm with a n-n delay in the sequential channel of 1400 400 fm/c, in agreement with the lifetime of 7He. The lower-statistics data on Pb target correspond mainly to direct breakup, and are well described using the n-n volume measured, without any n-n delay. The validity of the phenomenological model used is discussed.
Alveolar type II cells produce pulmonary surfactant and serve as the stem cell of the alveolar epithelium by proliferating and transforming into type I cells. The study of the differentiated function ...and proliferative capacity of type II cells in response to injury in vivo has been hindered by the complexity of the systemic response to injury. In vitro studies have in turn been limited by the impaired proliferative potential and loss of markers of differentiation in isolated type II cells maintained in culture. We describe an in vitro system in which type II cells proliferate spontaneously and simultaneously maintain differentiated characteristics. Other investigators have maintained slices of adult lung in culture after agarose infusion for up to 9 wk. To further develop this model for the study of epithelial cell differentiation and proliferation, we assessed epithelial differentiation, proliferative capacity, and regulation of cell-specific gene expression in slice explants of agarose-infused rat lungs. We prepared 1-mm-thick explants and maintained them in culture for up to 2 wk. Maintenance of differentiation was confirmed morphologically by light and electron microscopy, by the accumulation of epithelial cell-specific surfactant proteins, and by phospholipid analysis. Proliferative capacity was assessed by measuring 3Hthymidine incorporation in alveolar and small airway cells at baseline and in response to growth stimuli. Type II cell proliferation was inhibited in a dose-dependent manner by glucocorticoids. Glucocorticoids regulated RNA levels in explants in a manner similar to that seen in vivo and in fetal lung explants. The alveolar epithelium in adult lung slice explants maintains differentiated function and the ability to proliferate, thereby providing a useful system for the study of distal airway and alveolar cell homeostasis and response to injury.
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