Search

ContextFRAX® estimates 10-year fracture probability from osteoporosis-specific risk factors. Medical comorbidity indicators are associated with fracture risk but whether these are independent from those in FRAX is uncertain.ObjectiveWe hypothesized Johns Hopkins Aggregated Diagnosis Groups (ADG®) score or recent hospitalization number may be independently associated with increased risk for fractures.MethodsThis retrospective cohort study included women and men age ≥ 40 in the Manitoba BMD Registry (1996-2016) with at least 3 years prior health care data and used linked administrative databases to construct ADG scores along with number of hospitalizations for each individual. Incident Major Osteoporotic Fracture and Hip Fracture was ascertained during average follow-up of 9 years; Cox regression analysis determined the association between increasing ADG score or number of hospitalizations and fractures.ResultsSeparately, hospitalizations and ADG score independently increased the hazard ratio for fracture at all levels of comorbidity (hazard range 1.2-1.8, all P < 0.05), irrespective of adjustment for FRAX, BMD, and competing mortality. Taken together, there was still a higher than predicted rate of fracture at all levels of increased comorbidity, independent of FRAX and BMD but attenuated by competing mortality. Using an intervention threshold of major fracture risk >20%, application of the comorbidity hazard ratio multiplier to the patient population FRAX scores would increase the number of treatment candidates from 8.6% to 14.4%.ConclusionBoth complex and simple measures of medical comorbidity may be used to modify FRAX-based risk estimates to capture the increased fracture risk associated with multiple comorbid conditions in older patients.

Summary: In a combined analysis of 25,389 postmenopausal women aged 50–79 years, enrolled in the two Women’s Health Initiative hormone therapy trials, menopausal hormone therapy vs. placebo reduced the risk of fracture regardless of baseline FRAX fracture probability and falls history. Introduction: The aim of this study was to determine if the anti-fracture efficacy of menopausal hormone therapy (MHT) differed by baseline falls history or fracture risk probability as estimated by FRAX, in a combined analysis of the two Women’s Health Initiative (WHI) hormone therapy trials. Methods: A total of 25,389 postmenopausal women aged 50–79 years were randomized to receive MHT (n = 12,739) or matching placebo (n = 12,650). At baseline, questionnaires were used to collect information on falls history, within the last 12 months, and clinical risk factors. FRAX 10-year probability of major osteoporotic fracture (MOF) was calculated without BMD. Incident clinical fractures were verified using medical records. An extension of Poisson regression was used to investigate the relationship between treatment and fractures in (1) the whole cohort; (2) those with prior falls; and (3) those without prior falls. The effect of baseline FRAX probability on efficacy was investigated in the whole cohort. Results: Over 4.3 ± 2.1 years (mean ± SD), MHT (vs. placebo) significantly reduced the risk of any clinical fracture (hazard ratio [HR] 0.72 [95% CI, 0.65–0.78]), MOF (HR 0.60 [95% CI, 0.53–0.69]), and hip fracture (0.66 [95% CI, 0.45–0.96]). Treatment was effective in reducing the risk of any clinical fracture, MOF, and hip fracture in women regardless of baseline FRAX MOF probability, with no evidence of an interaction between MHT and FRAX (p > 0.30). Similarly, there was no interaction (p > 0.30) between MHT and prior falls. Conclusion: In the combined WHI trials, compared to placebo, MHT reduces fracture risk regardless of FRAX probability and falls history in postmenopausal women.

Supplementary Figure 2. Expresssion of MHC class I and activating receptor ligands on RMA and RMA-S.

Natural killer (NK) cells are most efficient if their targets do not express self MHC class I, because NK cells carry inhibitory receptors that interfere with activating their cytotoxic pathway. Clinicians have taken advantage of this by adoptively transferring haploidentical NK cells into patients to mediate an effective graft-versus-leukemia response. With a similar rationale, antibody blockade of MHC class I–specific inhibitory NK cell receptors is currently being tested in clinical trials. Both approaches are challenged by the emerging concept that NK cells may constantly adapt or “tune” their responsiveness according to the amount of self MHC class I that they sense on surrounding cells. Hence, these therapeutic attempts would initially result in increased killing of tumor cells, but a parallel adaptation process might ultimately lead to impaired antitumor efficacy. We have investigated this question in two mouse models: inhibitory receptor blockade in vivo and adoptive transfer to MHC class I–disparate hosts. We show that changed self-perception via inhibitory receptors in mature NK cells reprograms the reactivity such that tolerance to healthy cells is always preserved. However, reactivity against cancer cells lacking critical MHC class I molecules (missing self-reactivity) still remains or may even be increased. This dissociation between activity against healthy cells and tumor cells may provide an answer as to why NK cells mediate graft-versus-leukemia effects without causing graft-versus-host disease and may also be utilized to improve immunotherapy. Cancer Immunol Res; 4(2); 113–23. ©2015 AACR.

Supplementary Materials and Methods and Supplementary Figure Legends

Supplementary Figure 1. Spleen cell number after inhibitory receptor blockade.

Supplementary Figure 3. In vivo receptor occupancy after monovalent 5E6 treatment.

Supplementary Figure 4. Gating strategy used in responsiveness analysis (results shown in Figure 2).

Fractures of the proximal femur (FPF) are one of the most serious complications of osteoporosis, which has important medical, social and economic consequences. It is well known that their incidence gradually increases with age and depends on the sex, but such epidemiological studies in Ukraine are limited. This article presents the results of the first Ukrainian multicenter epidemiological study STOP (System of Registration of Osteoporotic fractures in Ukrainian Population) in terms of the incidence of FPF in persons aged 40 years and older. It was established that the FPF incidence in Ukrainian population increases with age. The study demonstrated higher rates of FPF incidence in men younger than 55 years with subsequent prevalence rates in women. The index of the overall FPF incidence was similar to that of neighboring countries (Poland and Romania). As FPF is a serious health problem in Ukraine and all over the world, the regional epidemiological data on their incidence is an important basis for the development of a national system for the prevention and treatment of osteoporosis and its complications.

The Fracture Risk Assessment Tool (FRAX®) was created to predict major osteoporotic fractures (MOF) and hip fractures in the general population. Whether FRAX accurately predicts fractures in men with prostate cancer is unknown. Our objective was to assess the performance of FRAX for predicting incident fractures in men with prostate cancer. Men from the Manitoba Bone Mineral Density (BMD) Registry (1996-2018) with prostate cancer diagnoses in the 3 years prior to dual-energy X-ray absorptiometry (DXA) were identified. FRAX scores with and without BMD were calculated. From population-based healthcare data we identified incident MOF, hip fracture, any osteoporotic fracture and death from the date of BMD testing to March 31, 2018. Cox regression was performed to estimate hazard ratios (HRs) with 95% confidence intervals (95% CIs) per standard deviation increase in FRAX score. Observed 10-year probability (estimated with competing risk of mortality) was compared with 10-year FRAX-predicted fracture probability to assess calibration. The study population included 684 men with prostate cancer (mean age 74.6 years) and 8608 men without prostate cancer (mean age 65.5 years). FRAX stratified risk for MOF (HR 1.91, 95% CI 1.48-2.45 with BMD; HR 1.96, 95% CI 1.43-2.69 without BMD) and hip fracture (HR 3.37, 95% CI 1.90-6.01 with BMD; HR 4.58, 95% CI 2.17-9.67 without BMD) in men with prostate cancer. There was no effect modification observed with prostate cancer status or current androgen deprivation therapy. Observed 10-year fracture probability in men with prostate cancer showed good agreement with FRAX with and without BMD included in the calculation (observed/predicted calibration ratios MOF 0.97, hip 1.00 with BMD; MOF 0.92, hip 0.93 with BMD). In conclusion, FRAX reliably predicts incident fractures in men with prostate cancer. © 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).

FRAX® — метод (алгоритм) оцінки 10-річного ризику переломів стегнової кістки та інших основних остеопоротичних переломів, до яких відносять переломи стегнової, променевої, плечової кісток й клінічно значущі переломи тіл хребців, в осіб віком 40 років і більше. Алгоритм розроблений на підставі використання показників віку, індексу маси тіла й різних клінічних факторів ризику переломів із врахуванням показника мінеральної щільності кісткової тканини шийки стегнової кістки або без нього. На сьогодні алгоритм FRAX включений у більшість європейських та американських рекомендацій щодо профілактики й лікування остеопорозу. Стаття присвячена результатам розробки й адаптації української моделі FRAX. У червні 2016 року завдяки співробітникам Українського науково-медичного центру проблем остеопорозу та ДУ «Інститут геронтології імені Д.Ф. Чеботарьова НАМН України» з’явилась можливість заповнювати опитувальник українською мовою, а в жовтні завдяки авторам статті на офіційному інтернет-ресурсі FRAX з’явилася нова українська модель. Її створення базується на результатах епідеміологічних досліджень, проведених останніми роками членами Української асоціації остеопорозу, співробітниками Українського науково-медичного центру проблем остеопорозу за підтримки Української асоціації травматологів-ортопедів (зокрема у м. Вінниці (1997–2002) та м. Ужгороді і Вінницькому районі (дослідження СТОП, 2011–2012)). Українська модель FRAX є першою вітчизняною моделлю прогнозування ризику основних остеопоротичних переломів й переломів стегнової кістки. Вона створена на основі оригінальної методики FRAX, яка була розроблена співробітниками Центру метаболічних захворювань кісток при ВООЗ. Усе вищезазначене робить українську модель FRAX® унікальною методикою для оцінки ризику остеопоротичних переломів та обґрунтовує необхідність широкого її впровадження в клінічну практику.

Background. Nowadays, FRAX® algorithm is an informative method for evaluation of the risk of osteoporotic fractures, implemented in European and American guidelines for osteoporosis management. However, there are differences in “intervention thresholds” for antiosteoporotic treatment, which depend on the country, the model of health care system and the reimbursement for treatment. Ukrainian version of FRAX appeared in Ukraine in 2016, but the thresholds for intervention have not yet been developed. The purpose of the study was to determine the “thresholds” for the pharmacological treatment of osteoporosis and for additional diagnostic examination of Ukrainian population using national FRAX model. Materials and methods. 3790 outpatients aged 40–90 years (mean age 61.9 ± 10.0 years) were examined. The development of the “thresholds” for intervention and additional assessment of the bone using dual-energy X-ray densitometry (DXA) based on the methodology adopted by the Natio­nal Osteoporosis Guideline Group in UK, which is further used in European guidelines. Results. There was an increase of the “thre­shold” for pharmacological intervention (“upper threshold”) with age from 6.6 % at the age of 40 to 13 % at the age of 75–85 years. The “lower threshold” (threshold for additional examination) increased significantly from 2.4 % at the age of 40 to 6.9 % in wo­men aged 85 years. The evaluation strategy begins with an analysis of the history of low-traumatic fracture. In its presence, a decision to start antiosteoporotic treatment without DXA should be made. In patients without history of fracture, calculation of fracture risk according to FRAX is required. When the risk exceeds the limit of the “upper threshold” antiosteoporotic treatment without DXA is recommended, when its values below the limit of “lower thre­shold” — additional examination or treatment is not required. In case of intermediate risk of fracture a DXA should be conducted with a reassessment of fracture risk and management tactics. Conclusions. The effectiveness of FRAX principles which uses in European guideline, but with particularities of the epidemiology of osteoporotic fractures in Ukraine, has been proved. Although this approach is cost-effective in other countries, its use in Ukraine may differ and may need to be further explored with an economic assessment of costs and benefits.

Assessment and treatment pathways using FRAX-based intervention thresholds in Chile can be used to identify patients at high risk of fracture and avoid unnecessary treatment in those at low fracture risk.The aim of the present study was to explore treatment paths and characteristics of women eligible for treatment in Chile based on major osteoporotic fracture (MOF) probabilities derived from FRAX®.Intervention and assessment thresholds were derived using methods adopted by the National Osteoporosis Guideline Group for FRAX-based guidelines in the UK but based on the epidemiology of fracture and death in Chile. Age-dependent and hybrid assessment and intervention thresholds were applied to 1998 women and 1122 men age 50 years or more drawn from participants in the National Health Survey 2016-2017.Approximately 12% of men and women had a prior fragility fracture and would be eligible for treatment for this reason. Using age-dependent thresholds, an additional 2.6% of women (0.3% of men) were eligible for treatment in that MOF probabilities lay above the upper assessment threshold. A BMD test would be recommended in 5% of men and 38% of women. With hybrid thresholds, an additional 13% of women (3.6% of men) were eligible for treatment and BMD recommended in 11% of men and 42% of women.The application of hybrid intervention thresholds ameliorates the disparity in fracture probabilities seen with age-dependent thresholds. Probability-based assessment of fracture risk, including the use of the hybrid intervention thresholds for Chile, is expected to help guide decisions about treatment.

The Fracture Risk Assessment Tool (FRAX®) combines clinical risk factors and optionally femoral neck bone density to estimate major osteoporotic fracture (MOF) and hip fracture probability. Hip dual-energy X-ray absorptiometry (DXA) simultaneously measures the trochanter and total hip, but these regions are not considered by FRAX. Our aim was to determine whether discordance in trochanter and total hip bone density (defined as ≥1 T-score difference from the femoral neck) affects fracture risk adjusted for fracture probability. Using the Manitoba bone density registry, we identified 84,773 women and men age 40 years or older undergoing baseline hip DXA. The outcomes were incident MOF and hip fracture. Cox regression hazard ratios (HRs) with 95% confidence intervals (CIs) adjusted for baseline fracture probability were used to test the association between hip T-score discordance and incident fractures. Hip T-score discordance affected more than one in five subjects (trochanter lower in 3.9%, higher in 14.2%; total hip lower in 0.3%, higher in 14.9%). After mean 8.8 years there were 8444 incident MOF including 2664 hip fractures. Discordantly lower trochanter and lower total hip T-score (≥1 below femoral neck) was associated with increased risk for MOF (adjusted HRs 1.47 and 1.60) and hip fracture (HRs 1.85 and 2.12), while discordantly higher trochanter and total hip T-score (≥1 above femoral neck) was associated with lower risk for MOF (HRs 0.83 and 0.71) and hip fracture (HRs 0.79 and 0.68). In models that examined the trochanter and total hip simultaneously, discordantly lower trochanter T-score was associated with increased incident MOF and hip fracture risk (HRs 1.43 and 1.79) whereas discordantly higher total hip T-score was associated with lower risk (HRs 0.73 and 0.75). In conclusion, trochanter and total hip regions frequently show T-scores that are discordant with the femoral neck. This information strongly affects incident fracture risk independent of fracture probability scores computed with femoral neck bone density. © 2022 American Society for Bone and Mineral Research (ASBMR).

Summary: The Danish Fracture Risk Evaluation Model (FREM) was found to predict fracture risk independent of 10-year fracture probability derived with the FRAX® tool including bone mineral density from DXA. Introduction: FREM was developed from Danish public health registers without DXA information to identify high imminent risk of major osteoporotic fracture (MOF) and hip fracture (HF), while FRAX® estimates 10-year fracture probability from clinical risk factors and femoral neck bone mineral density (BMD) from DXA. The FREM algorithm showed significant 1- and 2-year fracture risk stratification when applied to a clinical population from Manitoba, Canada. We examined whether FREM predicts 10-year fracture risk independent of 10-year FRAX probability computed with BMD. Methods: Using the Manitoba BMD Program registry, we identified women and men aged ≥ 45 years undergoing baseline BMD assessment. We calculated FREM and FRAX scores, and identified incident fractures over 10 years. Hazard ratios (HRs) for incident fracture were estimated according to FREM quintile, adjusted for FRAX probability. We compared predicted with observed 10-year cumulative fracture probability estimated with competing mortality. Results: The study population comprised 74,446 women, mean age 65.2 years; 7945 men, mean age 67.5 years. There were 7957 and 646 incident MOF and 2554 and 294 incident HF in women and men, respectively. Higher FREM scores were associated with increased risk for MOF (highest vs middle quintile HRs 1.49 women, 2.06 men) and HF (highest vs middle quintile HRs 2.15 women, 2.20 men) even when adjusted for FRAX. Greater mortality with higher FREM scores attenuated its effect on 10-year fracture probability. In the highest FREM quintile, observed slightly exceeded predicted 10-year probability for MOF (ratios 1.05 in women, 1.49 in men) and HF (ratios 1.29 in women, 1.34 in men). Conclusions: Higher FREM scores identified women and men at increased fracture risk even when adjusted for FRAX probability that included BMD; hence, FREM provides additional predictive information to FRAX. FRAX slightly underestimated 10-year fracture probability in those falling within the highest FREM quintile.

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been reported to have weak but beneficial effects on bone health, including fracture risk, but many epidemiological studies are likely confounded. We explored the relationship between NSAIDs and fracture risk in a post hoc analysis of a well-documented, randomized, placebo-controlled study of the bisphosphonate, clodronate, in which treatment reduced osteoporotic fracture risk by 23%. Concurrent medication use at baseline was used to identify those prescribed oral NSAIDs. Only verified, incident fractures were included in the analysis. A total of 1082 (20.8%) women reported use of NSAIDs at baseline. They were slightly, but significantly, younger (mean 79 versus 80 years, p = 0.004), heavier (mean 66.7 versus 64.7 kg, p

Dual-energy X-ray absorptiometry (DXA)-derived appendicular lean mass/height2 (ALM/ht2) is the most commonly used estimate of muscle mass in the assessment of sarcopenia, but its predictive value for fracture is substantially attenuated by femoral neck (fn) bone mineral density (BMD). We investigated predictive value of 11 sarcopenia definitions for incident fracture, independent of fnBMD, fracture risk assessment tool (FRAX®) probability, and prior falls, using an extension of Poisson regression in US, Sweden, and Hong Kong Osteoporois Fractures in Men Study (MrOS) cohorts. Definitions tested were those of Baumgartner and Delmonico (ALM/ht2 only), Morley, the International Working Group on Sarcopenia, European Working Group on Sarcopenia in Older People (EWGSOP1 and 2), Asian Working Group on Sarcopenia, Foundation for the National Institutes of Health (FNIH) 1 and 2 (using ALM/body mass index [BMI], incorporating muscle strength and/or physical performance measures plus ALM/ht2), and Sarcopenia Definitions and Outcomes Consortium (gait speed and grip strength). Associations were adjusted for age and time since baseline and reported as hazard ratio (HR) for first incident fracture, here major osteoporotic fracture (MOF; clinical vertebral, hip, distal forearm, proximal humerus). Further analyses adjusted additionally for FRAX-MOF probability (n = 7531; calculated ± fnBMD), prior falls (y/n), or fnBMD T-score. Results were synthesized by meta-analysis. In 5660 men in USA, 2764 Sweden and 1987 Hong Kong (mean ages 73.5, 75.4, and 72.4 years, respectively), sarcopenia prevalence ranged from 0.5% to 35%. Sarcopenia status, by all definitions except those of FNIH, was associated with incident MOF (HR = 1.39 to 2.07). Associations were robust to adjustment for prior falls or FRAX probability (without fnBMD); adjustment for fnBMD T-score attenuated associations. EWGSOP2 severe sarcopenia (incorporating chair stand time, gait speed, and grip strength plus ALM) was most predictive, albeit at low prevalence, and appeared only modestly influenced by inclusion of fnBMD. In conclusion, the predictive value for fracture of sarcopenia definitions based on ALM is reduced by adjustment for fnBMD but strengthened by additional inclusion of physical performance measures.

Objectives Severe chronic obstructive pulmonary disease affects and changes the lives of both affected persons and next of kin. There is a need for support and a sense of coherence to manage the life situation and minimize the symptom and caregiver burden. The aim of this study was to diverge or converge views of symptom burden, caregiver burden, the need for support, and sense of coherence in persons with chronic obstructive pulmonary disease and their next of kin to gain a deeper and broader knowledge and understanding. Methods A mixed methods study with data from interviews and four validated questionnaires from persons affected by chronic obstructive pulmonary disease in GOLD stages III and IV and their next of kin. Results Questionnaires from 112 persons affected by chronic obstructive pulmonary disease, and 71 next of kin, together with 25 and 21 interviews, show that; there is a difference between estimated symptoms and caregiver burden and experiences expressed in their own words. There is also a defect regarding meaningfulness, comprehensibility, and manageability affecting daily life. Symptoms and caregiver burden, together with the sense of coherence, strengthen the need for support. Discussion The complexity of the life situation leads to a need for supportive interventions to strengthen internal and external resources.

In the Women's Health Initiative (WHI), we investigated associations between baseline dual-energy X-ray absorptiometry (DXA) appendicular lean mass (ALM) and risk of incident fractures, falls, and mortality (separately for each outcome) among older postmenopausal women, accounting for bone mineral density (BMD), prior falls, and Fracture Risk Assessment Tool (FRAX® ) probability. The WHI is a prospective study of postmenopausal women undertaken at 40 US sites. We used an extension of Poisson regression to investigate the relationship between baseline ALM (corrected for height2 ) and incident fracture outcomes, presented here for major osteoporotic fracture (MOF: hip, clinical vertebral, forearm, or proximal humerus), falls, and death. Associations were adjusted for age, time since baseline and randomization group, or additionally for femoral neck (FN) BMD, prior falls, or FRAX probability (MOF without BMD) and are reported as gradient of risk (GR: hazard ratio for first incident fracture per SD increment) in ALM/height2 (GR). Data were available for 11,187 women (mean [SD] age 63.3 [7.4] years). In the base models (adjusted for age, follow-up time, and randomization group), greater ALM/height2 was associated with lower risk of incident MOF (GR = 0.88; 95% confidence interval [CI] 0.83-0.94). The association was independent of prior falls but was attenuated by FRAX probability. Adjustment for FN BMD T-score led to attenuation and inversion of the risk relationship (GR = 1.06; 95% CI 0.98-1.14). There were no associations between ALM/height2 and incident falls. However, there was a 7% to 15% increase in risk of death during follow-up for each SD greater ALM/height2 , depending on specific adjustment. In WHI, and consistent with our findings in older men (Osteoporotic Fractures in Men [MrOS] study cohorts), the predictive value of DXA-ALM for future clinical fracture is attenuated (and potentially inverted) after adjustment for femoral neck BMD T-score. However, intriguing positive, but modest, associations between ALM/height2 and mortality remain robust. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

The incidence of hip and major osteoporotic fracture was increased in patients with primary hyperparathyroidism even in patients not referred for parathyroidectomy. The risk of death was also increased which attenuated an effect on fracture probabilities. The findings argue for widening the indications for parathyroidectomy in mild primary hyperparathyroidism.Primary hyperparathyroidism (PHPT) is associated with an increase in the risk of fracture. In FRAX, the increase in risk is assumed to be mediated by low bone mineral density (BMD). However, the risk of death is also increased and its effect on fracture probability is not known.The aim of this study was to determine whether PHPT affects hip fracture and major osteoporotic fracture risk independently of bone mineral density (BMD) and whether this and any increase in mortality affects the assessment of fracture probability.A register-based survey of patients with PHPT and matched controls in Denmark were identified from hospital registers. The incidence of death, hip fracture, and major osteoporotic fracture were determined for computing fracture probabilities excluding time after parathyroidectomy. The gradient of risk for fracture for differences in BMD was determined in a subset of patients and in BMD controls. The severity of disease was based on serum calcium and parathyroid hormone levels.We identified 6884 patients with biochemically confirmed PHPT and 68,665 matched population controls. On follow-up, excluding time after parathyroidectomy in those undergoing surgery, patients with PHPT had a higher risk of death (+52%), hip fracture (+48%), and major osteoporotic fracture (+36%) than population controls. At any given age, average 10-year probabilities of fracture were higher in patients with PHPT than population controls. The gradient of fracture risk with differences in BMD was similar in cases and controls. Results were similar when confined to patients not undergoing parathyroidectomy. Fracture probability decreased with the severity of disease due to an increase in mortality rather than fracture risk.The risk of hip and other major osteoporotic fracture is increased in PHPT irrespective of the disease severity. Fracture probability was attenuated due to the competing effect of mortality. The increased fracture risk in patients treated conservatively argues for widening the indications for parathyroidectomy in mild PHPT.

Summary Hip fracture data were retrieved from electronical medical records for the years 2017–2019 in the State of Qatar and used to create a FRAX® model to facilitate fracture risk assessment. Hip fracture rates were comparable with estimates from Saudi Arabia, Abu Dhabi, and Kuwait but fracture probabilities varied due to differences in mortality. Objective This paper describes the epidemiology of osteoporotic fractures in the State of Qatar that was used to develop the country-specific fracture prediction FRAX® tool. Methods Hip fracture data were retrieved from electronic medical records for the years 2017–2019 in the State of Qatar. The age and sex specific incidence of hip fracture in Qatari residents and national mortality rates were used to create a FRAX® model. Fracture probabilities were compared with those from neighboring countries having FRAX models. Results Hip fracture rates were comparable with estimates from Saudi Arabia, Abu Dhabi and Kuwait. In contrast, probabilities of a major osteoporotic fracture or hip fracture were lower in Qatar than in Kuwait but higher than those in Abu Dhabi and Saudi Arabia due to differences in mortality. Conclusion The FRAX model should enhance accuracy of determining fracture probability among the Qatari population and help guide decisions about treatment.

Tetropium gabrieli is native to the European Alps where it breeds in European larch and may be an important pest during drought periods by killing trees. It has spread to larch plantations in several European countries including Sweden.In trapping studies conducted in Sweden, we tested whether T. gabrieli was attracted to E-fuscumol, E,Z-fuscumol, E,Z-fuscumol acetate and the host volatile combination of alpha-pinene plus ethanol. We also compared its response with those of the native congeners, T. fuscum and T. castaneum.All three Tetropium species were caught in significantly higher numbers in traps baited with E-fuscumol plus host volatiles than in traps baited with host volatiles alone or in unbaited traps.There was no difference in catch of any Tetropium species between traps baited with E-fuscumol plus host volatiles versus traps baited with E,Z-fuscumol plus host volatiles, but the latter treatment caught more T. fuscum and T. castaneum than did E,Z-fuscumol acetate plus host volatiles.The addition of E-fuscumol to host volatile-baited traps significantly reduced mean catch of T. gabrieli, significantly increased mean catch of T. castaneum, and had no significant effect on catch of T. fuscum. Mean catch of all three species was significantly greater in traps baited with E-fuscumol alone than in traps baited with host volatiles alone.All three species were caught from May to August. The median date of captures was about 2 weeks earlier for T. fuscum compared with the other two species.

The risk for hip and vertebral fracture was determined in 10,752 patients diagnosed with myeloproliferative neoplasms (MPN) in Sweden 1995–2015. The mean follow-up time were 6.34 years. Five percent developed hip fracture and 1.3% a vertebral fracture. There was a significant increased risk for fracture among the MPN patients compared with the Swedish population. The ratio of observed (obs) and expected (exp) number of hip fracture in all MPN patients, polycythemia vera (PV), essential thrombocythemia and MPN undetermined (MPNu) was 1.20 (95% confidence interval (CI): 1.10–1.31), 1.37 (95% CI: 1.19–1.58), 1.02 (95% CI: 0.87–1.19), and 1.28 (95% CI: 1.07–1.52), respectively. Corresponding figures for vertebral fractures were 1.94 (95% CI: 1.64–2.29), 2.09 (95% CI: 1.56–2.75), 1.50 (95% CI: 1.06–2.07) and 2.47 (95% CI: 1.77–3.35), respectively. Patients with MPN had an increased risk of hip and vertebral fracture, especially patients with PV and MPNu in comparison with the entire Swedish population.

Purpose Sleep-disordered breathing, SDB, in children is associated with morbidity that can result in caregivers having to stay at home from work. The aim of this study was to investigate whether the number of days when caregivers are reimbursed, temporary parental benefit (TPB) to stay at home from work to care for their sick child is increased among children with SDB before and after tonsil surgery. Methods This is a retrospective, cross-sectional study of children (n = 440), aged 2–11 years, that underwent tonsil surgery for SDB in day surgery at Sahlgrenska University Hospital in 2014 and 2015. TPB, was provided by the Swedish Social Insurance Agency. The expected days of TPB in the general population of the region were calculated. The number of days with TPB was compared 2 years before and 2 years after surgery and compared with the expected days of TPB. Results Two years before surgery, the children had no more days of TPB than expected. Two years after surgery, the children with SDB had 4.8 more days with TPB (p Conclusion Children with SDB who had tonsil surgery had no more days of parental benefits 2 years before and 2 years after surgery than expected. SDB is associated with increased morbidity, but it does not appear to cause caregivers to stay at home in the majority of children.

Increased bone loss has been noted in lymphoma patients; however, the incidence of hip fracture is not known. The aim of our study was to explore the risk for hip fracture in patients with lymphoma compared with the entire Swedish population. The risk of hip fracture was determined in a retrospective population cohort study of adult Swedish lymphoma patients (n = 37,236), diagnosed 1995–2015 and compared with the entire Swedish population during the same period. The incidence of hip fracture in lymphoma patients was higher in women than in men, increased by age, and decreased by calendar year as also demonstrated in the total population. 2.2% of the men and 4.7% of women with lymphoma sustained a hip fracture. For the total group of females, the hazard ratio (HR) was 1.19 (95% CI 1.11–1.28) and for men, the hazard ratio was 1.06 (95% CI 0.97–1.17) compared with the Swedish population. The HR for hip fracture (2016) was 2.80 (95% CI 1.20–6.53), 2.04 (95% CI 1.30–3.20), 1.56 (95% CI 1.21–2.01), 1.08 (95% CI 0.89–1.30), and 1.07 (95% CI 0.92–1.25) in females aged 40, 50, 60, 70, and 80 years, respectively. Corresponding figures for men were not significant in 2016. Unmarried men with lymphoma had a two times higher risk for hip fracture (HR 2.02 95% CI 1.63–2.50) compared with married men. Patients with lymphoma had an increased risk of hip fracture, especially younger women and unmarried men. The incidence of hip fracture is decreased by calendar year in the lymphoma patients and the entire Swedish population.

Background Fibroblast growth factor 19 (FGF19) is produced in the small intestine and is involved in suppression of hepatic bile acid (BA) synthesis. FGF19 is also expressed in the liver and serum levels are elevated in adults with cholestatic liver disease. This may reflect a rescue mechanism to dampen liver injury caused by increased intrahepatic BAs. Objectives To examine circulating FGF19 at early stages of biliary atresia and at short-term follow-up post-Kasai portoenterostomy (KPE) in relation to noncholestatic infants. The relationship between FGF19, BAs and markers for BA synthesis and hepatic gene expression of factors involved in BA metabolism were also evaluated. Methods Liver tissue, portal and peripheral blood samples were obtained from fifteen patients at KPE; additional blood was collected 4-6 months after surgery. Two control groups were included; to examine possible changes related to surgery and to compare FGF19 in biliary atresia to noncholestatic infants. Results Circulating FGF19 levels correlated to its hepatic gene expression at time of KPE in biliary atresia and levels were elevated compared to noncholestatic infants. At follow-up, FGF19 levels were markedly reduced, and the decline coincided with reductions in bilirubin and conjugated chenodeoxycholic acid and with increased levels of the BA synthesis marker C4. Conclusion Elevated circulating FGF19 in biliary atresia is of hepatic origin and reduced following KPE. Changes in serum FGF19 may reflect the level of restoration of the enterohepatic circulation, and this warrants further long-term studies on the role of FGF19 in the cholestatic liver.

FRAX estimates 10-year fracture major osteoporotic fracture (MOF) and hip fracture probability from multiple risk factors. FRAX does not consider prior fracture site or time since fracture. Fracture risk is greater in the initial 2-year post-fracture period (imminent risk), implying that FRAX may underestimate risk in this setting. We used the population-based Manitoba Bone Mineral Density (BMD) Program registry to examine the effect of fracture recency and site on incident fracture risk predictions using FRAX. We identified women aged 40 years or older with baseline BMD and FRAX scores. Observed fracture outcomes to 10 years were compared with predicted 10-year fracture probability stratified by prior fracture status: none, recent (2 years [median 0.3 years]), and remote (≥2 years [median 10.6 years]). For women with recent fractures, we also examined proposed multipliers to adjust FRAX for the effect of fracture recency and site. The cohort comprised 33,465 women aged 40 to 64 years (1897 recent fracture, 2120 remote fracture) and 33,806 women aged ≥65 years (2365 fracture, 4135 remote fracture). Observed fracture probability was consistent with predicted probability in most analyses. In women aged 40 to 64 years, there was a significant effect of recent vertebral and humerus fracture on MOF (observed to predicted 1.61 and 1.48, respectively), but these effects were still lower than the proposed multipliers (2.32 and 1.67, respectively). No significant effect of fracture recency was found after hip or forearm fracture in either age group. Our findings contribute to accumulating evidence of the importance of recent fracture. The effect of fracture recency was not consistent across fracture sites and with a lower magnitude than previously reported. Further quantification of effect size and specificity in additional independent cohorts is warranted to validate and refine recent-fracture multipliers in fracture risk assessment. © 2022 American Society for Bone and Mineral Research (ASBMR).

Research has identified several aspects that influence students' transition to mathematics studies at university, but these aspects have often been studied separately. Our study contributes to the field's understanding of the transition between upper secondary and university mathematics by taking a multifaceted perspective not previously explored. We analyse experiences and attainment in mathematics of 154 engineering students with respect to known aspects of this transition, and our results show that it is important to consider several aspects together in order to understand the full complexity of the transition. It is revealed that students with previous experiences of university studies, when compared with new first year undergraduates, perceive a larger difference between studying mathematics at the upper secondary level and university. Our results also show that the engineering students enrolled in distance programmes experience larger differences between secondary and tertiary levels than engineering students enrolled in campus programmes. Furthermore, our analyses show that students' success in mathematics is related to their perceptions of the rift experienced in the transition. In all, our results highlight the importance of taking a student perspective in the development of explanatory and useful models of students' transition between upper secondary and university mathematics.

Summary The adoption of the management pathway proposed by the National Osteoporosis Guideline Group (NOGG), UK applied using the Austrian FRAX® tool in a referral population of Austrian women categorises 22–29% of women age 40 years or more eligible for treatment of whom 28–34% are classified at very high risk. Purpose The aim of this study is to provide a reference document for the further development of existing guidelines for the management of osteoporosis in Austria, considering FRAX-based intervention thresholds for high and very high fracture risk. Methods The model development was based on two Austrian hospital referral cohorts. Baseline information was collected to compute the 10-year probability (using the Austrian FRAX model) of a major osteoporotic fracture (MOF) and hip fracture both with and without the inclusion of femoral neck bone mineral density (BMD). Assessment thresholds for BMD testing were defined, as well as intervention thresholds. In addition, thresholds that characterise men and women at high and very high fracture risk were established. The management pathway followed that currently recommended by the UK National Osteoporosis Guideline Group (NOGG). Results The two cohorts comprised a total of 1306 women and men with a mean age of 66.7 years. Slightly more than 50% were eligible for treatment by virtue of a prior fragility fracture. In those women without a prior fracture, 22% (n = 120) were eligible for treatment based on MOF probabilities. Of these, 28% (n = 33) were found to be at very high risk. When both MOF and hip fracture probabilities were used to characterise risk, 164 women without a prior fracture were eligible for treatment (29%). Of these, 34% (n = 56) were found to be at very high risk. Fewer men without prior fracture were eligible for treatment compared with women. Conclusion The management pathway as currently outlined is expected to reduce inequalities in patient management. The characterisation of very high risk may aid in the identification of patients suitable for treatment with osteoanabolic agents.

Summary In women of ages 75–80 years, a low one leg standing time (OLST) was associated with an increased risk of incident fractures, independently of bone mineral density and clinical risk factors. OLST contributed substantially to fracture probability, indicating that the test should be considered when evaluating fracture risk in older women. Introduction Physical function and risk of falls are important risk factors for fracture. A few previous studies have suggested that a one leg standing time (OLST) less than 10 s predicts fracture risk, but the impact of OLST, in addition to known clinical risk factors, for fracture probability is unknown. The aim of this study was to determine the independent contribution of OLST to fracture probability in older women. Methods The Sahlgrenska University Hospital Prospective Evaluation of Risk of Bone Fractures (SUPERB) is a prospective population-based study of 3028 women 75–80 years old, recruited from the greater Gothenburg area in Sweden. At baseline, information on risk factors was collected using questionnaires, bone mineral density was measured with dual-energy X-ray absorptiometry (DXA), and OLST was performed. Results During a median follow-up of 3.6 years (IQR 1.5 years), X-ray-verified incident fractures were identified using health records. OLST was available in 2405 women. OLST less than 10 s was associated with an increased risk for incident hip fracture (Hazard Ratio (HR) 3.02, 95% Confidence Interval (CI) [1.49–6.10]), major osteoporotic fracture (HR 95% CI 1.76 [1.34–1.46]), and nonvertebral fracture (HR 95% CI 1.61 [1.26–2.05]) in Cox regression analyses adjusted for age, height, and weight. Depending on BMD, the 4-year fracture probability increased by a factor of 1.3 to 1.5 in a 75-year-old woman with a low OLST (