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Summary: Individuals with low socio-economic status (SES) have a higher risk of dying following hip fracture compared with individuals with high SES. Evidence on social inequalities in non-hip fractures is lacking as well as evidence on the impact of SES on health-related quality of life post fracture. Introduction: Fragility fractures, especially of the hip, cause substantial excess mortality and impairment in health-related quality of life (HRQoL). This systematic review and meta-analysis aimed to investigate the association between socio-economic status (SES) and post-fracture mortality and HRQoL. Methods: PubMed, EMBASE and CINAHL databases were searched from inception to the last week of November 2018 for studies reporting an association between SES and post-fracture mortality and/or HRQoL among people aged ≥ 50 years. Risk ratios (RRs) were meta-analyzed using a standard inverse-variance-weighted random effects model. Studies using individual-level and area-based SES measures were analyzed separately. Results: A total of 24 studies from 15 different countries and involving more than one million patients with hip fractures were included. The overall risk of mortality within 1-year post-hip fracture in individuals with low SES was 24% higher than in individuals with high SES (RR 1.24, 95% CI 1.19 to 1.29) for individual-level SES measures, and 14% (RR 1.14, 95% CI 1.09 to 1.19) for area-based SES measures. The quality of the evidence for the outcome mortality was moderate. Using individual SES measures, we estimated the excess HRQoL loss to be 5% (95% CI − 1 to 10%) among hip fracture patients with low SES compared with high SES. Conclusions: We found a consistently increased risk of post-hip fracture mortality with low SES across SES measures and across countries with different political structures and different health and social care infrastructures. The impact of SES on post-fracture HRQoL remains uncertain due to sparse and low-quality evidence. [ABSTRACT FROM AUTHOR]

The article presents a systematic review which examined the effects of equity factors to the eligibility criteria of rehabilitation intervention trials in hip fracture patients. Other topics include the founding principle of equity in access to healthcare of the National Health Service in Great Britain, as well as the factors affecting equity like age, time-dependent relationships, socioeconomic status, and gender.

Summary: Deprivation predicts increased hip fracture risk. Over 14 years, hip fracture incidence increased among men with persisting inequalities. Among women, inequalities in incidence were less pronounced; whilst incidence decreased overall, this improvement was seen marginally less in women from the most deprived areas. Hip fracture prevention programmes have not reduced inequalities. Purpose: Deprivation is associated with increased hip fracture risk. We examined the effect of area-level deprivation on hip fracture incidence in England over 14 years to determine whether inequalities have changed over time. Methods: We used English Hospital Episodes Statistics (2001/2002-2014/2015) to identify hip fractures in adults aged 50+ years and mid-year population estimates (2001-2014) from the Office for National Statistics. The Index of Multiple Deprivation measured local area deprivation. We calculated age-adjusted incidence rate ratios (IRR) for hip fracture, stratified by gender and deprivation quintiles. Results: Over 14 years, we identified 747,369 hospital admissions with an index hip fracture; the number increased from 50,640 in 2001 to 55,092 in 2014; the proportion of men increased from 22.2% to 29.6%. Whereas incidence rates decreased in women (annual reduction 1.1%), they increased in men (annual increase 0.6%) (interaction p < 0.001). Incidence was higher in more deprived areas, particularly among men: IRR most vs. least deprived quintile 1.50 [95% CI 1.48, 1.52] in men, 1.17 [1.16, 1.18] in women. Age-standardised incidence increased for men across all deprivation quintiles from 2001 to 2014. Among women, incidence fell more among those least compared to most deprived (year by deprivation interaction p < 0.001). Conclusions: Deprivation is a stronger relative predictor of hip fracture incidence in men than in women. However, given their higher hip fracture incidence, the absolute burden of deprivation on hip fractures is greater in women. Despite public health efforts to prevent hip fractures, the health inequality gap for hip fracture incidence has not narrowed for men, and marginally widened among women. [ABSTRACT FROM AUTHOR]

Summary: In this study, we report that self-perception of fracture risk captures some aspect of fracture risk not currently measured using conventional fracture prediction tools and is associated with improved medication uptake. It suggests that adequate appreciation of fracture risk may be beneficial and lead to greater healthcare engagement and treatment. Introduction: This study aimed to assess how well self-perception of fracture risk, and fracture risk as estimated by the fracture prediction tool FRAX, related to fracture incidence and uptake and persistence of anti-osteoporosis medication among women participating in the Global Longitudinal study of Osteoporosis in Women (GLOW). Methods: GLOW is an international cohort study involving 723 physician practices across 10 countries in Europe, North America and Australia. Aged ≥ 55 years, 60,393 women completed baseline questionnaires detailing medical history, including co-morbidities, fractures and self-perceived fracture risk (SPR). Annual follow-up included self-reported incident fractures and anti-osteoporosis medication (AOM) use. We calculated FRAX risk without bone mineral density measurement. Results: Of the 39,241 women with at least 1 year of follow-up data, 2132 (5.4%) sustained an incident major osteoporotic fracture over 5 years of follow-up. Within each SPR category, risk of fracture increased as the FRAX categorisation of risk increased. In GLOW, only 11% of women with a lower baseline SPR were taking AOM at baseline, compared with 46% of women with a higher SPR. AOM use tended to increase in the years after a reported fracture. However, women with a lower SPR who were fractured still reported lower AOM rates than women with or without a fracture but had a higher SPR. Conclusions: These results suggest that SPR captures some aspect of fracture risk not currently measured using conventional fracture prediction tools and is also associated with improved medication uptake. [ABSTRACT FROM AUTHOR]

Background: Osteoporosis is a major global health issue, weakening bones and increasing fracture risk. Dual-energy X-ray absorptiometry (DXA) is the standard for measuring bone mineral density (BMD) and diagnosing osteoporosis, but its costliness and complexity impede widespread screening adoption. Predictive modeling using genetic and clinical data offers a cost-effective alternative for assessing osteoporosis and fracture risk. This study aims to develop BMD prediction models using data from the UK Biobank (UKBB) and test their performance across different ethnic and geographical populations. Methods and findings: We developed BMD prediction models for the femoral neck (FNK) and lumbar spine (SPN) using both genetic variants and clinical factors (such as sex, age, height, and weight), within 17,964 British white individuals from UKBB. Models based on regression with least absolute shrinkage and selection operator (LASSO), selected based on the coefficient of determination (R2) from a model selection subset of 5,973 individuals from British white population. These models were tested on 5 UKBB test sets and 12 independent cohorts of diverse ancestries, totaling over 15,000 individuals. Furthermore, we assessed the correlation of predicted BMDs with fragility fractures risk in 10 years in a case-control set of 287,183 European white participants without DXA-BMDs in the UKBB. With single-nucleotide polymorphism (SNP) inclusion thresholds at 5×10−6 and 5×10−7, the prediction models for FNK-BMD and SPN-BMD achieved the highest R2 of 27.70% with a 95% confidence interval (CI) of [27.56%, 27.84%] and 48.28% (95% CI [48.23%, 48.34%]), respectively. Adding genetic factors improved predictions slightly, explaining an additional 2.3% variation for FNK-BMD and 3% for SPN-BMD over clinical factors alone. Survival analysis revealed that the predicted FNK-BMD and SPN-BMD were significantly associated with fragility fracture risk in the European white population (P < 0.001). The hazard ratios (HRs) of the predicted FNK-BMD and SPN-BMD were 0.83 (95% CI [0.79, 0.88], corresponding to a 1.44% difference in 10-year absolute risk) and 0.72 (95% CI [0.68, 0.76], corresponding to a 1.64% difference in 10-year absolute risk), respectively, indicating that for every increase of one standard deviation in BMD, the fracture risk will decrease by 17% and 28%, respectively. However, the model's performance declined in other ethnic groups and independent cohorts. The limitations of this study include differences in clinical factors distribution and the use of only SNPs as genetic factors. Conclusions: In this study, we observed that combining genetic and clinical factors improves BMD prediction compared to clinical factors alone. Adjusting inclusion thresholds for genetic variants (e.g., 5×10−6 or 5×10−7) rather than solely considering genome-wide association study (GWAS)-significant variants can enhance the model's explanatory power. The study highlights the need for training models on diverse populations to improve predictive performance across various ethnic and geographical groups. Yong Liu and co-workers compare Author summary: Why was this study done?: Osteoporosis diagnosis via bone mineral density (BMD) measurements by dual-energy X-ray absorptiometry (DXA) is impractical for large-scale screening, especially in resource-limited areas. Genomic data offers a cost-effective alternative for predicting disease risk, but current methods often overlook sub-significant variants and clinical factors. Most existing genomic prediction methods are based on European ancestry, with limited evaluation in other ethnic populations. What did the researchers do and find?: We developed BMD prediction models for femoral neck (FNK) and lumbar spine (SPN) using a training set of 17,964 individuals from British white ancestry in UK Biobank (UKBB), integrating clinical and genetic factors. We observed that strong correlations between predicted and true BMDs (R2≈25% for FNK-BMD and R2≈45% for SPN-BMD) and significant associations with fracture risk in European ancestry populations. And we identified the optimal P-value thresholds for FNK-BMD (5×10−6) and SPN-BMD (5×10−7), noting that these thresholds vary by trait and sample size. By applying the prediction models on 5 UKBB test sets and 12 independent cohorts of diverse ancestries, totaling over 15,000 individuals, we observed that the BMD prediction models performed well in UKBB European populations but less effectively in other ancestry groups and independent cohorts. What do these findings mean?: We show that genetic factors could improve the performance of DXA-BMD prediction. Within the same population, the predicted BMDs can help prioritize individuals at high risk of fragility fracture for tailored treatments. Genetic prediction methods need rigorous evaluation before application to different populations, emphasizing the importance of diverse population training. Study limitations include differences in the distribution of clinical factors such as sex and age between the UKBB data sets and the independent cohorts, as well as the inclusion of only single-nucleotide polymorphisms (SNPs) as genetic factors. [ABSTRACT FROM AUTHOR]

Background: Gender differences in the diagnosis and treatment of osteoporosis is a relatively common phenomenon, particularly amongst those patients under 80 years of age presenting with fragility fractures. The clinical implications of these findings are that strategies, which tend to focus on osteoporosis management in women, should also pay enough attention to osteoporosis in men. However, there have been questions whether there is a gender difference when setting intervention thresholds for osteoporosis management. This work was carried out aiming to determine the fracture probabilities calculated by FRAX at which therapeutic intervention in older men and women can be considered. Results: Assessment of fracture risk probability thresholds in men revealed that for hip fractures, ROC was 0.754 (95% CI: 0.69–0.817). The sensitivity was 80.5% for threshold probabilities of 2.5%. For the major osteoporosis fracture, ROC was 0.828 (95% CI: 0.694–0.963). The sensitivity was 87.5% for threshold probabilities of 10%. Assessment of fracture risk probability threshold in women ROC was 0.760 (95% CI: 0.691–0.83). The sensitivity was 76.1% for threshold probabilities of 3%. For major osteoporosis fracture, ROC was 0.848 (95% CI: 0.784–0.912). The sensitivity was 87.3% for threshold probabilities of 15%. Conclusion: Operational aspects of osteoporosis management should consider gender specific fracture thresholds. Interventional thresholds were found to be different in men compared to women. This helps to optimise fracture prevention in older men. [ABSTRACT FROM AUTHOR]

Glucocorticoid-induced osteoporosis (GIOP) is a side effect of glucocorticoid (GC) treatment; however, despite established prevention guidelines in various countries, a gap persists between these guidelines and clinical practice. To address this gap, we implemented a collaborative intervention between hospitals and community pharmacists, aiming to assess its effectiveness. Pharmacists recommended to the prescribing doctor osteoporosis treatment for patients who did not undergo osteoporosis treatment with a fracture risk score of ≥3 via tracing reports (TRs), between 15 December 2021, and 21 January 2022. Data were extracted from electronic medical records, including prescriptions, concomitant medications, reasons for not pursuing osteoporosis treatment, and TR contents. Of 391 evaluated patients, 45 were eligible for TRs, with 34 (75.6%) being males. Prednisolone was the most common GCs administered, and urology was the predominant treatment department. Among the 45 patients who received TRs, prescription suggestions were accepted for 19 (42.2%). After undertaking the intervention, guideline adherence significantly increased from 87% to 92.5%. This improvement indicates that TRs effectively bridged the evidence–practice gap in GIOP prevention among GC patients, suggesting their potential utility. Expansion of this initiative is warranted to further prevent GIOP. [ABSTRACT FROM AUTHOR]

(1) Background: Analysis of risk factors and prevalence of osteoporosis in an elderly population suggests a study focused on identifying and evaluating factors contributing to osteoporosis among them. (2) Methods: The aim of this paper is to analyse and compare the prevalence levels of osteoporosis in different age groups in adult women, focusing on the identification and assessment of relevant risk factors. Hypothesis of the work: There are assumed to be significant correlations between adult women age groups and osteoporosis prevalence, and these correlations are influenced by a number of risk factors, including older age, BMI, family history of fractures, and BMD bone mineral density levels. (3) Results: There is a tendency to increase the average weight with age up to the age group of 70-79 years. Mean BMI values indicate significant variation in participants weight status, with relatively high values across all age groups. Mean Tscore and Z-score values at femoral neck BMD indicate reduced bone mineral density, possibly associated with osteoporosis or osteopenia, especially in older age groups. (4) Conclusions: There is an increase in average weight with age, and BMI values are relatively high across all age groups, indicating the importance of monitoring and managing body weight to prevent complications associated with osteoporosis. [ABSTRACT FROM AUTHOR]

We aim was to present a case of severe osteoporosis with concern to an adult female who was under specific medication against the condition while she experienced inexplicable weight loss in association with an incidental fracture inconsistent with DXA changes. Challenges of the case management and decision making are further on explained. Real-life-medicine poses multiple issues that require an individual decision while respecting the standard protocols. That is why a generalized decision is rather impractical. Here we introduce the clinical case of a lady in her late 60s with a known 6-year history of osteoporosis that required several difficult decisions along surveillance: at first, zoledronic acid represented an available solution, yet after one year, BMD decreased and adjustment was done by initiating a second sequence according to the teriparatide protocol. DXA-BMD, as well as the spectrum of bone turnover markers, qualified the patient as responsive and she further continued with oral bisphosphonates while being monitored via telemedicine amid COVID-19 pandemic. After 24 more months, a second decision of zoledronic acid was done, despite prior partial response, but digestive complains restricted the oral administration of anti-osteoporotic drugs. After one more year, denosumab was initiated and consecutive follow-up is essential. At this point, another challenging aspect was revealed: the discordance between DXA - based scores increase and the presence of an incidental fracture. A supplementary investigation was considered useful (Tc-whole body scintigraphy) noting the clinical presentation with local pain, dysfunctionality, and mild weight loss that also required rehabilitation management. [ABSTRACT FROM AUTHOR]

Orthopedic patients need to perform limb immobilization for several days to several weeks due to fracture or other special circumstances. When the function of a certain part or the whole body is restricted, the activity of osteoclasts will be enhanced and its life activity will surpass that of osteoblasts, so local or even whole body bone loss will occur. Acute bone loss usually occurs within a few weeks after the immobilization of limbs. At this stage, the patient's bone mass will decrease sharply, and the patient is prone to osteoporotic refracture. After that, the bone mass will gradually recover, but the speed of bone formation and bone absorption is difficult to reach a balanced state, and the bone mass of patients will continue to decline after it has recovered to a certain degree. After acute progressive bone loss, a large number of bones were lost and the strength of bones decreased. It is often difficult to recover to the level before fracture for a long time, which undoubtedly increases the risk of osteoporosis and related refractures. According to this common phenomenon of bone loss, clinical treatment varies greatly. After a series of research and practice, clinicians summed up some rules and put forward some feasible suggestions, thus strengthening clinicians' understanding of the treatment of acute bone loss, effectively improving the treatment effect of acute bone loss, having far-reaching significance for preventing and treating osteoporosis, reducing the risk of fracture, and improving the long-term prognosis of patients. [ABSTRACT FROM AUTHOR]

This prospectively registered systematic review and meta-analysis examines whether exercise (EX) training has an additive effect to osteoanabolic and/or antiresorptive pharmacological therapy (PT) in people with osteoporosis on bone mineral density (BMD), bone turnover markers (BTMs), fracture healing, and fractures. Four databases (inception to 6 May 2022), 5 trial registries, and reference lists were searched. Included were randomized controlled trials comparing the effect of EX + PT vs. PT with regard to BMD, BTM, fracture healing, and fractures. Risk of bias was assessed using the Cochrane RoB2 and certainty of evidence by the GRADE approach. Random-effects meta-analysis with Hartung-Knapp-Sidik-Jonkman adjustment was used to estimate standardized mean differences and 95% confidence intervals. Out of 2593 records, five RCTs with 530 participants were included. Meta-analysis showed with very low certainty evidence and wide confidence intervals that EX + PT compared to PT had larger effect sizes for BMD at 12 months at the hip (SMD [95%CI]: 0.18 [− 1.71; 2.06], n = 3 studies), tibia (0.25 [− 4.85; 5.34], n = 2), lumbar spine (0.20 [− 1.15; 1.55], n = 4), and forearm (0.05 [− 0.35; 0.46], n = 3), but not femoral neck (− 0.03 [− 1.80; 1.75], n = 3). Furthermore, no improvement was revealed for BTM such as bone ALP (− 0.68 [− 5.88; 4.53], n = 3), PINP (− 0.74 [− 10.42; 8.93], n = 2), and CTX-I (− 0.69 [− 9.61; 8.23], n = 2), but with very wide confidence intervals. Three potentially relevant ongoing trials were identified via registries. No data were found for fracture healing or fracture outcomes. It remains unclear whether EX has an additive impact to PT in people with osteoporosis. High-quality, adequately powered, targetted RCTs are required. Protocol Registration: PROSPERO CRD42022336132. [ABSTRACT FROM AUTHOR]

Currently in the UK and Ireland, after a hip fracture most patients do not receive bone protection medication to reduce the risk of refracture. Yet randomised controlled trial data specifically examining patients with hip fracture have shown that intravenous zoledronate reduces refracture risk by a third. Despite this evidence, use of intravenous zoledronate is highly variable following a hip fracture; many hospitals are providing this treatment, whilst most are currently not. A range of clinical uncertainties, doubts over the evidence base and practical concerns are cited as reasons. This paper discusses these concerns and provides guidance from expert consensus, aiming to assist orthogeriatricians, pharmacists and health services managers establish local protocols to deliver this highly clinically and cost-effective treatment to patients before they leave hospital, in order to reduce costly re-fractures in this frail population. [ABSTRACT FROM AUTHOR]

Background: The diagnosis of Cushing's syndrome is challenging; however, through the clinical picture and the search for secondary causes of osteoporosis, it was possible to reach the diagnosis of the case reported. There was an independent, symptomatic ACTH hypercortisolism manifested by typical phenotypic changes, severe secondary osteoporosis and arterial hypertension in a young patient. Case presentation: A 20-year-old Brazilian man with low back pain for 8 months. Radiographs showed fragility fractures in the thoracolumbar spine, and bone densitometry showed osteoporosis, especially when evaluating the Z Score (− 5.6 in the lumbar spine). On physical examination, there were wide violaceous streaks on the upper limbs and abdomen, plethora and fat increase in the temporal facial region, hump, ecchymosis on limbs, hypotrophy of arms and thighs, central obesity and kyphoscoliosis. His blood pressure was 150 × 90 mmHg. Cortisol after 1 mg of dexamethasone (24.1 µg/dL) and after Liddle 1 (28 µg/dL) were not suppressed, despite normal cortisoluria. Tomography showed bilateral adrenal nodules with more severe characteristics. Unfortunately, through the catheterization of adrenal veins, it was not possible to differentiate the nodules due to the achievement of cortisol levels that exceeded the upper limit of the dilution method. Among the hypotheses for the differential diagnosis of bilateral adrenal hyperplasia are primary bilateral macronodular adrenal hyperplasia, McCune–Albright syndrome and isolated bilateral primary pigmented nodular hyperplasia or associated with Carney's complex. In this case, primary pigmented nodular hyperplasia or carcinoma became important etiological hypotheses when comparing the epidemiology in a young man and the clinical-laboratory-imaging findings of the differential diagnoses. After 6 months of drug inhibition of steroidogenesis, blood pressure control and anti-osteoporotic therapy, the levels and deleterious metabolic effects of hypercortisolism, which could also impair adrenalectomy in the short and long term, were reduced. Left adrenalectomy was chosen, given the possibility of malignancy in a young patient and to avoid unnecessary definitive surgical adrenal insufficiency if the adrenalectomy was bilateral. Anatomopathology of the left gland revealed expansion of the zona fasciculate with multiple nonencapsulated nodules. Conclusion: The early identification of Cushing's syndrome, with measures based on the assessment of risks and benefits, remains the best way to prevent its progression and reduce the morbidity of the condition. Despite the unavailability of genetic analysis for a precise etiological definition, it is possible to take efficient measures to avoid future damage. [ABSTRACT FROM AUTHOR]

The fracture risk assessment tool (FRAX) is a tool which calculates an individual 10-year fracture risk based on epidemiological data in patients with a risk of osteporosis. The aim of this study was to evaluate the value of FRAX to estimate the risk of postoperative periprosthetic fractures (PPF) in patients following with total hip and knee arthroplasty. 167 patients (137 periprosthetic fractures in total hip arthroplasty and 30 periprosthetic fractures in total knee arthroplasty) were included in this study. Patients' data was retrieved retrospectively. In each patient the 10-year probability of a major osteoporotic fracture (MOF) and an osteoporotic hip fracture (HF) was calculated using FRAX. According to the NOGG guideline 57% of total hip arthroplasty (THA) patients and 43.3% of total knee arthroplasty (TKA) patients were in need of osteoporosis treatment, whereas only 8% and 7% received an adequate one respectively. 56% of the patients with PPF after THA and 57% of the patients with PPF after TKA reported about a previous fracture. Significant associations between the 10-year probability of a MOF and HF calculated by FRAX and PPF in THA and TKA were seen. The results of the present study show that FRAX might have the potential to estimate the PPF in patients following THA and TKA. FRAX should be calculated before and after THA or TKA in order to assess the risk and counsel patients. The data show a clear undertreatment of patients with PPF in respect to osteoporosis. [ABSTRACT FROM AUTHOR]

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Using a sample of healthy youth (n = 466, 10 to 18 yr), we report the predictive utility of vertical jump power (VJ Power, W) for predicting bone strength. We measured VJ Power using mechanography and an indicator of bone strength, i.e., height-adjusted total bone mineral content less head (TBLH BMC, g), using DXA. Growth curve models were used to convert VJ Power to age- and sex-specific percentiles/Z-scores. Associations were examined using receiver operator characteristic curve analysis, i.e., area-under-the-curve (AUC), as well as sensitivity (Se) and specificity (Sp) for Desirable, Marginal, and Low groups based on VJ Power percentiles. The AUC was 0.84 for TBLH BMC ≤ −2.0 Z-score from VJ Power percentiles. Se for Marginal and Low groups were 71.4% and 42.9%, respectively. Sp for Marginal and Low groups were 85.2% and 95.1%, respectively. The results suggest the utility of using VJ Power percentiles for assessing bone strength. [ABSTRACT FROM AUTHOR]

Objective : Although several commercialized bone cements are used during percutaneous vertebroplasty (PVP) for patients with osteoporotic vertebral compression fracture (OVCF), there are no reports using domestic products from South Korea. In this study, we investigated the safety and efficacy of Spinofill® (Injecta Inc., Gunpo, Korea), a new polymethyl methacrylate product. Methods : A prospective, single-center, and single-arm clinical trial of 30 participants who underwent PVP using Spinofill® for painful thoracolumbar OVCF was performed with 6-months follow-up. Clinical and surgical outcomes included the Visual analog scale (VAS), Korean-Oswestry disability index (K-ODI), and Odom’s criteria, complication rate, and recurrence rate. Radiological outcomes were evaluated by measuring the findings of postoperative computed tomography and simple radiograph. Results : The pain of VAS (from 8.95±1.05 to 4.65±2.06, p<0.001) and the life quality based on K-ODI (from 33.95±5.84 to 25.65±4.79, p<0.001) improved significantly, and successful patient satisfaction were achieved in 20 patients (66.7%) 1 day after surgery. These immediate improvements were maintained or more improved during the follow-up. There was no surgery- or product-related complications, but OVCF recurred in two patients (6.7%). Favorable cement interdigitation was reported in 24 patients (80.0%), and extra-vertebral cement leakage was reported in 13 patients (43.0%). The mean vertebral height ratio (from 60.49%±21.97% to 80.07%±13.16%, p<0.001) and segmental kyphotic angle (from 11.46°±8.50° to 7.79°±6.08°, p=0.002) improved one day after surgery. However, these short-term radiological findings somewhat regressed at the end. Conclusion : The overall outcomes of PVP using Spinofill® were as favorable as those of other conventional used products. [ABSTRACT FROM AUTHOR]

Summary: Vertebral fracture (VF) is a strong predictor of subsequent fracture. In this study of older women, VF, identified by dual-energy X-ray absorptiometry (DXA) vertebral fracture assessment (VFA), were associated with an increased risk of incident fractures and had a substantial impact on fracture probability, supporting the utility of VFA in clinical practice. Purpose: Clinical and occult VF can be identified using VFA with dual-energy X-ray absorptiometry (DXA). The aim of this study was to investigate to what extent VFA-identified VF improve fracture risk prediction, independently of bone mineral density (BMD) and clinical risk factors used in FRAX. Methods: A total of 2852 women, 75–80 years old, from the prospective population-based study SUPERB cohort, were included in this study. At baseline, BMD was measured by DXA, VF diagnosed by VFA, and questionnaires used to collect data on risk factors for fractures. Incident fractures were captured by X-ray records or by diagnosis codes. An extension of Poisson regression was used to estimate the association between VFA-identified VF and the risk of fracture and the 5- and 10-year probability of major osteoporotic fracture (MOF) was calculated from the hazard functions for fracture and death. Results: During a median follow-up of 5.15 years (IQR 4.3–5.9 years), the number of women who died or suffered a MOF, clinical VF, or hip fracture was 229, 422, 160, and 124, respectively. A VFA-identified VF was associated with an increased risk of incident MOF (hazard ratio [HR] = 1.78; 95% confidence interval [CI] 1.46–2.18), clinical VF (HR = 2.88; 95% [CI] 2.11–3.93), and hip fracture (HR = 1.67; 95% [CI] 1.15–2.42), adjusted for age, height, and weight. For women at age 75 years, a VFA-identified VF was associated with 1.2–1.4-fold greater 10-year MOF probability compared with not taking VFA into account, depending on BMD. Conclusion: Identifying an occult VF using VFA has a substantial impact on fracture probability, indicating that VFA is an efficient method to improve fracture prediction in older women. [ABSTRACT FROM AUTHOR]

Background: There is an emerging interest in using automated approaches to enable the incidental identification of vertebral fragility fractures (VFFs) on existing medical images visualising the spine. Aim: To quantify values, and the degree of uncertainty associated with them, for the incidental identification of VFFs from computed tomography (CT) scans in current practice. Methods: An expert elicitation exercise was conducted to generate point estimates and measures of uncertainty for four values representing the probability of: VFF being correctly reported by the radiologist; the absence of VFF being correctly assessed by the radiologist; being referred for management when a VFF is identified; having a dual-energy X-ray absorptiometry (DXA) scan after general practitioner (GP) referral. Data from a sample of seven experts in the diagnosis and management of people with VFFs were pooled using mathematical aggregation. Results: The estimated mean values for each probability parameter were: VFF being correctly reported by the radiologist = 0.25 (standard deviation (SD): 0.21); absence of VFF being correctly assessed by the radiologist = 0.89 (0.10); being referred for management when a VFF is identified by the radiologist = 0.15 (0.12); having a DXA scan after GP referral = 0.66 (0.28). Discussion: These estimates could be used to facilitate the subsequent early economic evaluation of potential new approaches to improve the health outcomes of people with VFFs. Conclusion: In the absence of epidemiological studies, this study produced point estimates and measures of uncertainty for key parameters needed to describe current pathways for the incidental diagnosis of VFFs. [ABSTRACT FROM AUTHOR]

Introduction: Glucocorticoid-induced osteoporosis (GIOP) is associated with elevated fracture risk. Practice guidelines have been published to reduce this risk but are insufficiently followed in everyday practice. The objectives of this study were to estimate fracture incidence in patients exposed to oral glucocorticoids and to analyse the impact of glucocorticoid use on fracture incidence. Materials and methods: This retrospective cohort study was performed using the Medical Data Vision (MDV) claims database from Japan. All patients aged ≥ 18 years initiating oral glucocorticoids and fulfilling Japanese guideline criteria for starting prophylactic osteoporosis treatment between 2009 and 2019 were identified. These were matched to a cohort of unexposed controls using propensity score matching. Fracture incidence in the two cohorts were compared using a Fine-Gray proportional sub-distribution hazard model. Results: 13,090 glucocorticoid-exposed cases were compared to 13,090 unexposed controls. The 1-year fracture rate (all sites) was 9.3 [95% CI 8.8–9.8] in cases and 5.8 [5.4–6.2] in controls. One-year vertebral fracture rates were 4.3 [4.0–4.7] and 2.3 [2.1–2.6] respectively. In the multivariate analysis, the use of glucocorticoids was associated with an increase in the incidence of osteoporotic fractures (hazard ratio: 1.63 [1.51–1.76]). The glucocorticoid-associated risk tended to be higher in subgroups of patients with rheumatoid arthritis, asthma, COPD and in those aged < 65 years. Conclusion: Oral glucocorticoid use is associated with an increase in fracture incidence. It is necessary to raise awareness of GIOP and to take public health measures to change the perceptions and behaviour of doctors prescribing glucocorticoids. [ABSTRACT FROM AUTHOR]

Senile osteoporosis is a chronic skeletal disease, leading to increased bone brittleness and risk of fragile fractures. With the acceleration of population aging, osteoporosis has gradually become one of the most serious and prevalent problems worldwide. Bone formation is highly dependent on the proper osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in the bone marrow microenvironment, which is generated by the functional relationship among different cell types, including osteoblasts, adipogenic cells, and bone marrow stromal cells in the bone marrow. It is still not clear how osteoporosis is caused by its molecular mechanism. With aging, bone marrow is able to restrain osteogenesis. Discovering the underlying signals that oppose BMSC osteogenic differentiation from the bone marrow microenvironment and identifying the unusual changes in BMSCs with aging is important to elucidate possible mechanisms of senile osteoporosis. We used 3 gene expression profiles (GSE35956, GSE35957, and GSE35959) associated with osteoporosis. And a protein-protein interaction (PPI) network was also built to identify the promising gene CD137. After that, we performed in vivo experiments to verify its function and mechanism. In this experiment, we found that significant bone loss was observed in aged (18-month-old) mice compared with young (6-month-old) mice. The adipose tissue in bone marrow cavity from aged mice reached above 10 times more than young mice. Combining bioinformatics analysis and vivo experiments, we inferred that CD137 might be involved in the p53 and canonical Wnt/β-catenin signaling pathways and thereby influenced bone mass through regulation of marrow adipogenesis. Importantly, osteoporosis can be rescued by blocking CD137 signaling in vivo. Our research will contribute to our understanding not only of the pathogenesis of age-related bone loss but also to the identification of new targets for treating senile osteoporosis. [ABSTRACT FROM AUTHOR]

Background: Bisphosphonates are effective in preventing fragility fractures; however, high rates of adherence are needed to preserve clinical benefits. Objective: To investigate persistence and compliance to oral and intravenous bisphosphonates (alendronate, ibandronate, risedronate, and zoledronate). Methods: Searches of 12 databases, unpublished sources, and trial registries were conducted, covering the period from 2000 to April 2021. Screening, data extraction, and risk of bias assessment (Cochrane Collaboration risk-of-bias tool 1.0 & ROBINS-I) were independently undertaken by two study authors. Randomised controlled trials (RCTs) and observational studies that used prescription claim databases or hospital medical records to examine patients' adherence were included. Network meta-analyses (NMA) embedded within a Bayesian framework were conducted, investigating users' likelihood in discontinuing bisphosphonate treatment. Where meta-analysis was not possible, data were synthesised using the vote-counting synthesis method. Results: Fifty-nine RCTs and 43 observational studies were identified, resulting in a total population of 2,656,659 participants. Data from 59 RCTs and 24 observational studies were used to populate NMAs. Zoledronate users were the least likely to discontinue their treatment HR = 0.73 (95%CrI: 0.61, 0.88). Higher rates of compliance were observed in those receiving intravenous treatments. The paucity of data and the heterogeneity in the reported medication possession ratio thresholds precluded a NMA of compliance data. Conclusions: Users of intravenously administered bisphosphonates were found to be the most adherent to treatment among bisphosphonates' users. Patterns of adherence will permit the more precise estimation of clinical and cost-effectiveness of bisphosphonates. Trial registration: PROSPERO 2020 CRD42020177166 [ABSTRACT FROM AUTHOR]

Background. The fracture pathophysiology associated with type 2 diabetes and chronic kidney disease (CKD) is incompletely understood. We examined individual fracture predictors and prediction sets based on different pathophysiological hypotheses, testing whether any of the sets improved prediction beyond that based on traditional osteoporotic risk factors. Methods. Within the CREDENCE cohort with adjudicated fracture outcomes, we assessed the association of individual factors with fracture using Cox regression models. We used the Akaike information criteria (AIC) and Schwartz Bayes Criterion (SBC) to assess six separate variable sets based on hypothesized associations with fracture, namely, traditional osteoporosis, exploratory general population findings, cardiovascular risk, CKD-mineral and bone disorder, diabetic osteodystrophy, and an all-inclusive set containing all variables. Results. Fracture occurred in 135 (3.1%) participants over a median 2.35 [1.88–2.93] years. Independent fracture predictors were older age (hazard ratio [HR] 1.04, confidence interval [CI] 1.01–1.06), female sex (HR 2.49, CI 1.70–3.65), previous fracture (HR 2.30, CI 1.58–3.34), Asian race (HR 1.74, CI 1.09–2.78), vitamin D therapy requirement (HR 2.05, CI 1.31–3.21), HbA1c (HR 1.14, CI 1.00–1.32), prior cardiovascular event (HR 1.60, CI 1.10–2.33), and serum albumin (HR 0.41, CI 0.23–0.74) (lower albumin associated with greater risk). The goodness of fit of the various hypothesis sets was similar (AIC range 1870.92–1849.51, SBC range 1875.60–1948.04). Conclusion. Independent predictors of fracture were identified in the CREDENCE participants with type 2 diabetes and CKD. Fracture prediction was not improved by models built on alternative pathophysiology hypotheses compared with traditional osteoporosis predictors. [ABSTRACT FROM AUTHOR]

Summary : Risk of fracture due to glucocorticoid-induced osteoporosis (GIO) can be reduced by anti-osteoporosis (OP) medications. The proportion of patients on long-term glucocorticoid therapy who received anti-OP medications according to the GIO management guidelines has increased in recent years, but is still suboptimal. Introduction: Adherence of physicians to guidelines for glucocorticoid (GC)-induced osteoporosis (GIO) management is currently unclear. This study aimed to clarify the state of guideline adherence by physicians in Japan and identify factors associated with guideline adherence using a nationwide health insurance claims database (NDBJ). Methods: Patients aged ≥ 50 years who were prescribed GC for ≥ 90 days after 180 days without a GC prescription and who were followed up for osteoporosis (OP) management for the subsequent 360 days during the period spanning 2012–2018 were selected from the NDBJ. Guideline adherence was evaluated with the proportion of patients who received OP management as recommended by the Japanese guidelines. Information on previous vertebral and hip fractures, dementia, and polypharmacy was obtained. Factors associated with OP management were evaluated by logistic regression analysis. Results: A total of 512,296 patients were considered to be at high risk of fracture according to the guidelines. Proportions of patients receiving OP management (BMD testing or anti-OP medications) have increased in recent years. In 2017, 33.7% of men and 55.3% of women received OP management in the initial 90 days of GC therapy. Female sex, previous anti-OP medications, polypharmacy, and higher GC dose were significantly associated with receiving OP management, while dementia showed an inverse association. A prior history of hip fracture, a strong risk factor for future fracture, was not significantly associated with receiving OP management. Conclusions: Although guideline adherence by physicians has increased in recent years, it remains suboptimal. Further efforts to improve guideline adherence are necessary. Trial registration number: The present study is not registered. [ABSTRACT FROM AUTHOR]

Fragility fractures are painful, debilitating, often life-changing and accounted for an estimated 2.4% of pre-pandemic health care spending in the UK. Those who are older, frail and multimorbid have the highest fracture risk and therefore the most to gain from anti-osteoporosis treatments to reduce this risk. Currently, an unacceptable treatment gap exists between those eligible for and those who receive treatment. This commentary discusses the major changes to the new, National Institute for Health and Care Excellence accredited, UK National Osteoporosis Guideline Group (NOGG) guidance (published March 2022) most relevant to the management of older people's bone health. Changes include intervention thresholds; using fracture probabilities from FRAX; for patients too frail to undergo DXA; greater emphasis on vertebral fracture detection and the use of intravenous zoledronate as a first-line anti-osteoporosis therapy; the new concept of 'very high fracture risk' which should prompt consideration of use of parenteral anti-osteoporosis therapy; new guidance regarding anabolic treatment options; concerns regarding denosumab cessation; and the urgent need to get patients with a fragility fracture onto treatment to reduce re-fracture risk with follow-up to check tolerance and ensure adherence. [ABSTRACT FROM AUTHOR]

Osteoporosis care has evolved markedly over the last 50 years, such that there are now an established clinical definition, validated methods of fracture risk assessment and a range of effective pharmacological agents. Currently, bone-forming (anabolic) agents, in many countries, are used in those patients who have continued to lose bone mineral density (BMD), patients with multiple subsequent fractures or those who have fractured despite treatment with antiresorptive agents. However, head-to-head data suggest that anabolic agents have greater rapidity and efficacy for fracture risk reduction than do antiresorptive therapies. The European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) convened an expert working group to discuss the tools available to identify patients at high risk of fracture, review the evidence for the use of anabolic agents as the initial intervention in patients at highest risk of fracture and consider the sequence of therapy following their use. This position paper sets out the findings of the group and the consequent recommendations. The key conclusion is that the current evidence base supports an "anabolic first" approach in patients found to be at very high risk of fracture, followed by maintenance therapy using an antiresorptive agent, and with the subsequent need for antiosteoporosis therapy addressed over a lifetime horizon. [ABSTRACT FROM AUTHOR]

To investigate the association between different lipid measures and long-term hospitalization-required incident fracture among Iranian men and women. A total of 3309 individuals aged ≥50 years (men = 1598) were included in the study. Multivariate Cox proportional hazard analyses were performed to assess the risk of incident fracture across quintiles, considering first quintile as reference, as well as for 1-standard deviation (SD) increase in each lipid measure, i.e. total cholesterol (TC), triglycerides (TG), low- and high-density lipoprotein cholesterol (LDL-C and HDL-C, respectively), non-HDL-C, and related indices (TG/HDL-C and TC/HDL-C). Covariates included age, body mass index, current smoking, type 2 diabetes mellitus, hypertension, lipid lowering-drugs, and steroid medications (for women). During a median follow-up of 18 years, incident fracture was observed in 201 cases (men = 87). In both gender, no linear association was found between different lipid measures and incident fracture. Among men, only the fourth quartile of TG was associated with lower risk of fracture in the age-adjusted analysis with the hazard ratio (HR) and 95% confidence interval (CI) of [0.45 (0.21–0.95)]. Among women, the age-adjusted HRs and 95% CIs for the second, third, fourth, and fifth quintiles of non-HDL-C were [0.46 (0.25–0.87)], [0.73 (0.42–1.25)], [0.90 (0.54–1.51)], and [0.52 (0.29–0.95)], respectively; the corresponding values in the multivariate model were [0.48 (0.26–0.90)], [0.76 (0.4–1.32)], [0.94 (0.56–1.58)], and [0.52 (0.28–0.95)], respectively. The second quintile of LDL-C was also associated with lower risk for incident fracture in the multivariate analysis [0.53 (0.29–0.98)]. Among Iranian women, a nonlinear association between non-HDL-C and LDL-C and incident fracture was found as the second and fifth quintile of the former and the second quintile of the latter were associated with about 50% lower risk of fracture. Generally, our findings did not support harmful impact of these lipid measures on incident fracture. [ABSTRACT FROM AUTHOR]

Systemic vasculitides are a range of conditions characterized by inflammation of blood vessels which may manifest as single organ or life-threatening multisystem disease. The treatment of systemic vasculitis varies depending on the specific disease but historically has involved initial treatment with high dose glucocorticoids alone or in conjunction with other immunosuppressive agents. Prolonged glucocorticoid treatment is frequently required as maintenance treatment. Patients with small and large vessel vasculitis are at increased risk of fracture. Osteoporosis may occur due to intrinsic factors such as chronic inflammation, impaired renal function and to a large extent due to pharmacological therapy with high dose glucocorticoid or combination treatments. This review will outline the known mechanism of bone loss in vasculitis and will summarize factors attributing to fracture risk in different types of vasculitis. Osteoporosis treatment with specific consideration for patients with vasculitis will be discussed. The use of glucocorticoid sparing immunosuppressive agents in the treatment of systemic vasculitis is a significant area of ongoing research. Adjunctive treatments are used to reduce cumulative doses of glucocorticoids and therefore may significantly decrease the associated fracture risk in patients with vasculitis. Lastly, we will highlight the many unknowns in the relation between systemic vasculitis, its treatment and bone health and will outline key research priorities for this field. [ABSTRACT FROM AUTHOR]

Summary: We compared, for women in Pakistan, the utility of intervention thresholds either at a T-score ≤ − 2.5 or based on a FRAX probability equivalent to women of average body mass index (BMI) with a prior fragility fracture. Whereas the FRAX-based intervention threshold identified women at high fracture probability, the T-score threshold was less sensitive, and the associated fracture risk decreased markedly with age. Purpose: The fracture risk assessment algorithm FRAX® has been recently calibrated for Pakistan, but guidance is needed on how to apply fracture probabilities to clinical practice. Methods: The age-specific 10-year probabilities of a major osteoporotic fracture were calculated in women with average BMI to determine fracture probabilities at two potential intervention thresholds. The first comprised the age-specific fracture probabilities associated with a femoral neck T-score of − 2.5. The second approach determined age-specific fracture probabilities that were equivalent to a woman with a prior fragility fracture, without bone mineral density (BMD). The parsimonious use of BMD was additionally explored by the computation of upper and lower assessment thresholds for BMD testing. Results: When a BMD T-score ≤ − 2.5 was used as an intervention threshold, FRAX probabilities in women aged 50 years were approximately two-fold higher than in women of the same age but with no risk factors and average BMD. The relative increase in risk associated with the BMD threshold decreased progressively with age such that, at the age of 80 years or more, a T-score of − 2.5 was actually protective. The 10-year probability of a major osteoporotic fracture by age, equivalent to women with a previous fracture, rose with age from 2.1% at the age of 40 years to 17%, at the age of 90 years, and identified women at increased risk at all ages. Conclusion: Intervention thresholds based on BMD alone do not effectively target women at high fracture risk, particularly in the elderly. In contrast, intervention thresholds based on fracture probabilities equivalent to a 'fracture threshold' target women at high fracture risk. [ABSTRACT FROM AUTHOR]

Objective: to determine the causes of increased bone mineral density (BMD) based on case history, clinical and laboratory data, including the assay of hormones involved in ossification processes in children, living on radiologically contaminated territories (RCT) after the accident at the ChNPP, compared to the normative BMD patterns. Materials and methods. There were 289 children involved in the study. The 1st group included persons with a BMD above 100 IU, 2nd group - with normative BMD (100-85 IU). Family history of diseases was assessed featuring cancer and endocrine diseases, cholelithiasis, and urolithiasis. Weight of the child at birth, frequency of bone fractures, complaints about osalgia, jaw abnormalities, dental caries, presence or absence of obesity, peripheral blood count, blood biochemical parameters (total protein, creatinine, iron, alkaline phosphatase, calcium), serum pituitary thyroid-stimulating hormone and cortisol were accounted. Children's radiation doses were calculated according to the materials of the «General dosimetric certification of settlements of Ukraine that were exposed to radioactive contamination after the Chornobyl accident». Results. Higher than normative BMD values were found in children after puberty, while normative ones - in puberty (р < 0.001), regardless of gender. A direct correlation between the bone fractures frequency was established in children with increased BMD (р < 0.01). Jaw anomalies and dental caries occurred at that significantly less often than in normative BMD (р > 0.05). A direct correlation was established between the obesity and BMD (р < 0.001). Increased alkaline phosphatase activity was inversely correlated with BMD (rs = -0.21; р < 0.05). In children with elevated BMD a direct correlation was established between the level of iron and endocrine disorders in the family history (р > 0.001). Serum level of cortisol was directly correlated with dental caries (р < 0.05). In children, regardless of BMD value, a direct correlation was established between the radiation dose, age and obesity (р < 0.001). Conclusions. Higher than normative BMD is accompanied by an increased frequency of bone fractures, jaw abnormalities, metabolic changes in bone tissue and bone tissue hormonal regulation in children, which requires application of pathogenetic therapy for the osteogenesis. [ABSTRACT FROM AUTHOR]

Glucocorticoid-induced osteoporosis (GIOP) leads to fractures in up to 40% of patients with chronic glucocorticoid (GC) therapy when left untreated. GCs rapidly increase fracture risk, and thus many patients with anticipated chronic GC exposures should start anti-osteoporosis pharmacotherapy to prevent fractures. In addition to low awareness of the need for anti-osteoporosis therapy among clinicians treating patients with GCs, a major barrier to prevention of fractures from GIOP is a lack of clear guideline recommendations on when to start and stop anti-osteoporosis treatment in patients with GC use. The aim of this narrative review is to summarize current evidence and provide considerations for the duration of anti-osteoporosis treatment in patients taking GCs based on pre-clinical, clinical, epidemiologic, and pharmacologic evidence. We review the pathophysiology of GIOP, outline current guideline recommendations on initiating and stopping anti-osteoporosis therapy for GIOP, and present considerations for the duration of anti-osteoporosis treatment based on existing evidence. In each section, we illustrate major points through a patient case example. Finally, we conclude with proposed areas for future research and emerging areas of interest related to GIOP clinical management. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study is to evaluate irritable bowel syndrome (IBS) as a risk factor for osteoporosis and osteoporotic fracture in Korean women after controlling for basic confounding factors and considering detailed demographic and clinical information.Subjects and Methods: We performed a nationwide population-based retrospective cohort analysis and matched every IBS case with a non-IBS case at a 1:4 frequency ratio based on age. The population consisted of female patients with data in the Health Insurance Review and Assessment (HIRA) database from 2002 to 2010. To determine the risk of osteoporosis and osteoporotic fracture in IBS and non-IBS patients, hazard ratios (HRs) with 95% confidence intervals (CI) were estimated using Cox proportional hazards regression models, adjusting for confounding variables, such as the area of residence, health insurance type, and economic status.Results: We identified 1,017,468 patients in the HIRA database with data from 2002 to 2010 who could potentially be included in the cohort. Among these, we identified 1,545 (11.4%) women (age >19 years) with newly diagnosed IBS (IBS group). Additionally, 6,180 patients without IBS and age-matched to the IBS group were selected. Cox modeling revealed that the crude HRs for osteoporosis and osteoporotic fractures in patients with IBS were 1.476 (95% CI, 1.241-1.754) and 1.427 (95% CI, 1.086-1.876), respectively.Conclusion: Our data showed an increased incidence of osteoporosis and osteoporotic fractures in women with IBS compared with age-matched controls. [ABSTRACT FROM AUTHOR]

Summary: The National Osteoporosis Guideline Group (NOGG) has developed intervention thresholds based on FRAX® to characterise patients at high and very high risk of fracture. Introduction: Guidelines for the assessment of fracture risk have begun to categorise patients eligible for treatment into high and very high risk of fracture to inform choice of therapeutic approach. The aim of the present study was to develop intervention thresholds based on the hybrid assessment model of NOGG. Methods: We examined the impact of intervention thresholds in a simulated cross-sectional cohort of women age 50 years or more from the UK with the distribution of baseline characteristics based on that in the FRAX cohorts. The prevalence of very high risk using the hybrid model was compared with age-dependent thresholds used by the International Osteoporosis Foundation and the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (IOF/ESCEO). The appropriateness of thresholds was tested based on the populations treated with anabolic agents. Results: With an upper intervention threshold using the IOF/ESCEO criteria, 56% of women age 50 years or more would be characterised at very high risk. This compares with 36% using the IOF/ESCEO criteria and an age-specific intervention threshold over all ages. With an upper intervention threshold of 1.6 times the pre-existing intervention threshold, 10% of women age 50 years or more would be characterised at very high risk. The data from phase 3 studies indicate that most trial participants exposed to romosozumab or teriparatide would fall into the very high-risk category. Conclusions: Proposals for FRAX-based criteria for very high risk for the NOGG hybrid model categorise a small proportion of women age 50 years or more (10%) in this highest risk stratum. The level of risk identified was comparable to that of women enrolled in trials of anabolic agents. [ABSTRACT FROM AUTHOR]

Glucocorticoids are used to treat many autoimmune and inflammatory diseases. However, an adverse systemic effect is a deleterious effect on bone, which may lead to glucocorticoid-induced osteoporosis, characterized by a rapid and transient increase in bone resorption and fracture risk, which may increase rapidly within 3 months of commencing oral glucocorticoids. Therefore, early risk assessment and intervention are crucial for preventing fractures in patients receiving glucocorticoids. Recent practice guidelines recommend an assessment for fracture risk in patients beginning or receiving glucocorticoids for more than 3 months, and they have suggested fracture risk assessment tool values for identifying patients who need preventive treatment. Bisphosphonates are currently the recommended first-line therapy for the prevention and treatment of glucocorticoid-induced osteoporosis. These have been shown to increase the bone mineral density in the spine and hip and to decrease the incidence of vertebral fractures. Recently, a more potent antiresorptive agent, denosumab, has been shown to increase the bone density in patients receiving glucocorticoids. Teriparatide has been shown to have a preventive effect on vertebral fractures, but not on nonvertebral fractures. In this article we aimed to provide an update on glucocorticoid-induced osteoporosis by focusing on the assessment of its risk and treatment options. [ABSTRACT FROM AUTHOR]

Summary: Among 4238 cancer and 16,418 cancer-free individuals with incident major non-traumatic fractures (hip, clinical vertebral, forearm, humerus), post-fracture osteoporosis care was equally poor for both groups, whether assessed from bone mineral density (BMD) testing, initiation of osteoporosis therapy or either intervention (BMD testing and/or osteoporosis therapy). Introduction: Most individuals sustaining a fracture do not undergo evaluation and/or treatment for osteoporosis. Cancer survivors are at increased risk for osteoporosis and fracture. Whether cancer survivors experience a similar post-fracture "care gap" is unclear. Using population-based databases, we assessed whether cancer patients are evaluated and/or treated for osteoporosis after a major fracture. Methods: From the Manitoba Cancer Registry, we identified cancer cases (first cancer diagnosis between 1987 and 2013) and cancer-free controls with incident major non-traumatic fractures (from provincial physician billing claims and hospitalization databases). The outcomes were performance of BMD testing (from the BMD Registry), initiation of osteoporosis therapy (from drug dispensation database) or either intervention (BMD testing and/or osteoporosis therapy) in the 12 months post-fracture. Results: There were 4238 cancer and 16,418 cancer-free individuals who sustained a fracture after the index date (cancer diagnosis) and were followed for at least 1 year post-fracture. Subsequent BMD testing was performed in 11.0% of cancer cases versus 11.5% non-cancer controls (P = 0.43), osteoporosis treatment in 22.9% cancer cases versus 21.8% non-cancer controls (P = 0.15), and either testing or treatment in 28.9% cancer cases versus 28.4% non-cancer controls (P = 0.53). Predictors of BMD testing and/or initiation of therapy were similar for non-cancer and cancer patients. Post-fracture interventions were consistently used more frequently among women, older patients (age 50 years or older), those who sustained fractures in a later calendar period, and (for treatment) after vertebral fracture. Cancer-specific variables (cancer type, years from cancer diagnosis to fracture, specialty of care provider) showed only weak and inconsistent effects. Conclusions: A large care gap exists among cancer patients who sustain a fracture, similar to the general population, whereby the evaluation or treatment for osteoporosis is seldom conducted. Care maps may need to be developed for cancer populations to improve post-fracture care. [ABSTRACT FROM AUTHOR]

Summary: The multidisciplinary co-management program for geriatric patients with hip fracture is cost-effective in the Chinese population and it has the potential to be scaled up in China. Introduction: The study aimed to investigate the cost-effectiveness of a multidisciplinary co-management program for patients with hip fracture in China. Methods: Hip fracture patients who were admitted to an orthopedic hospital in Beijing were included in the multidisciplinary co-management program. The cost-effectiveness of intervention was evaluated compared to the conventional management. A Markov microsimulation model was developed to simulate lifetime costs and effectiveness. Costs including intervention, hospitalization, medications, and long-term care costs were expressed using 2019 US dollars and the healthcare perspective was adopted. Effectiveness was evaluated using both 1-year mortality-averted and quality-adjusted life years (QALYs). Costs and effectiveness were discounted at 5% per annum. The willingness-to-pay (WTP) threshold was set at $26,481 per QALY gained which was three times gross domestic product (GDP) per capita in China. One-way and probabilistic sensitivity analyses were conducted. Results: The lifetime cost for the conventional management (n = 1839) and intervention group (n = 1192) was $11,975 and $13,309 respectively. The lifetime QALYs were 2.38 and 2.45 years and the first-year mortality was 17.8% and 16.1%. The incremental cost-effectiveness ratio was $19,437 per QALY gained or $78,412 per 1-year mortality-averted. Given the Chinese WTP threshold, the intervention had a 78% chance being cost-effective. The cost-effectiveness of the intervention was sensitive to cost of intervention and the proportion of patients who underwent surgery within 48 h. Conclusions: The multidisciplinary co-management program for patients with hip fracture is cost-effective and it has the potential to be scaled up in the Chinese population. [ABSTRACT FROM AUTHOR]

Summary: The Canadian FRAX® tool used without bone mineral density (BMD) is highly sensitive for identifying individuals qualifying for pharmacotherapy based upon an intervention threshold of 20% for major osteoporotic fracture risk (MOF) computed with BMD. Introduction: This analysis was performed to inform initial BMD testing as part of Osteoporosis Canada's Guidelines Update for women and men at average risk, assuming a pharmacotherapy intervention threshold of 20% for FRAX® MOF computed with BMD. Methods: Women and men age 50 + without previous low-trauma fracture or high-risk medication use were identified in a BMD registry for the province of Manitoba, Canada. Fracture probability assessments with the Canadian FRAX® tool were computed without and with BMD (denoted MOF-clinical and MOF-BMD, respectively). Results: The study population consisted of 50,700 women (mean age 65.5 ± 9.4 years) and 4152 men (69.2 ± 10.0 years). FRAX MOF-clinical score was > 10% in 33.8% of women and 13.3% of men (P < 0.001). The median (interquartile range [IQR]) age for MOF-clinical to reach 10% in women was 70 (69–72) and 65 years (62–67) years in the absence and presence of additional FRAX clinical risk factors, respectively. In men, comparable ages were 83 years [82–86] and 76 [70–78] years. Using MOF-BMD of 20% as the intervention threshold, 4.3% of women and 0.7% of men qualified for treatment. MOF-clinical > 10% had high sensitivity to identify those qualifying for treatment (99.3% in women and 99.1% in men). An age-based rule ("BMD testing is indicated at age 70 if no additional FRAX clinical risk factors are present, or at age 65 if one or more clinical risk factors exists") gave similarly high sensitivity (women 99.9% and men > 99.9%). Conclusions: FRAX without BMD offers an effective strategy to identify individuals meeting the current Canadian treatment threshold based upon FRAX® with BMD (≥ 20%). Moreover, this can be operationalized using simple age cutoffs of 70 years in the absence of additional clinical risk factors and 65 years in the presence of additional clinical risk factors. [ABSTRACT FROM AUTHOR]

Summary: During median follow-up 6.0 years in 11,495 individuals, prior absolute and annualized measured height loss was significantly greater in those with subsequent incident fracture compared with those without incident fracture. Purpose: FRAX® accepts baseline height and weight as input variables, but does not consider change in these parameters over time. Aim: To evaluate the association between measured height or weight loss on subsequent fracture risk adjusted for FRAX scores, risk factors, and competing mortality. Methods: Using a dual-energy x-ray absorptiometry (DXA) registry for the Province of Manitoba, Canada, we identified women and men age 40 years 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. Results: The study population consisted of 11,495 individuals (average age 68.0 ± 9.9 years, 94.6% women). During median follow-up 6.0 years, 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 3.0 cm or greater more than doubled the risk for subsequent fracture. Conclusions: 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. [ABSTRACT FROM AUTHOR]

Summary: Prior high-trauma fractures identified through health services data are associated with low bone mineral density (BMD) and future fracture risk to the same extent as fractures without high-trauma. Introduction: Some have questioned the usefulness of distinguishing high-trauma fractures from low-trauma fractures. The aim of this study is to compare BMD measurements and risk of subsequent low-trauma fracture in patients with prior high- or low-trauma fractures. Methods: Using a clinical BMD registry for the province of Manitoba, Canada, we identified women and men age 40 years or older with fracture records from linked population-based healthcare data. Age- and sex-adjusted BMD Z-scores and covariate-adjusted hazard ratios (HR) with 95% confidence intervals (CI) for incident fracture were studied in relation to prior fracture status, categorized as high-trauma if associated with external injury codes and low-trauma otherwise. Results: The study population consisted of 64,428 women and men with no prior fracture (mean age 63.7 years), 858 with prior high-trauma fractures (mean age 65.1 years), and 14,758 with prior low-trauma fractures (mean age 67.2 years). Mean Z-scores for those with any prior high-trauma fracture were significantly lower than in those without prior fracture (P < 0.001) and similar to those with prior low-trauma fracture. Median observation time for incident fractures was 8.8 years (total 729,069 person-years). Any prior high-trauma fracture was significantly associated with increased risk for incident major osteoporotic fracture (MOF) (adjusted HR 1.31, 95% CI 1.08–1.59) as was prior low-trauma fracture (adjusted HR 1.55, 95% CI 1.47–1.63), and there was no significant difference between the two groups (prior trauma versus low-trauma fracture P = 0.093). A similar pattern was seen when incident MOF was studied in relation to prior hip fracture or prior MOF, or when the outcome was incident hip fracture or any incident fracture. Conclusions: High-trauma and low-trauma fractures showed similar relationships with low BMD and future fracture risk. This supports the inclusion of high-trauma fractures in clinical assessment for underlying osteoporosis and in the evaluation for intervention to reduce future fracture risk. [ABSTRACT FROM AUTHOR]

Summary: Guidance is provided in an international setting on the assessment and specific treatment of postmenopausal women at low, high and very high risk of fragility fractures. Introduction: The International Osteoporosis Foundation and European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis published guidance for the diagnosis and management of osteoporosis in 2019. This manuscript seeks to apply this in an international setting, taking additional account of further categorisation of increased risk of fracture, which may inform choice of therapeutic approach. Methods: Clinical perspective and updated literature search. Results: The following areas are reviewed: categorisation of fracture risk and general pharmacological management of osteoporosis. Conclusions: A platform is provided on which specific guidelines can be developed for national use to characterise fracture risk and direct interventions. [ABSTRACT FROM AUTHOR]

Osteoporosis is a systemic skeletal disease characterized by low bone mass and microarchitecture deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture. Several gastrointestinal disorders have been associated with osteoporosis including inflammatory bowel disease and celiac disease. Different factors can explain low bone density and fractures in these patients. [ABSTRACT FROM AUTHOR]

Summary: We compared the utility of the current Iranian guidelines that recommend treatment in women with a T-score ≤ − 2.5 SD with a FRAX-based intervention threshold equivalent to women of average BMI with a prior fragility fracture. Whereas the FRAX-based intervention threshold identified women at high fracture probability, the T-score threshold was less sensitive, and the associated fracture risk decreased markedly with age. Introduction: The fracture risk assessment algorithm FRAX® has been recently calibrated for Iran, but guidance is needed on how to apply fracture probabilities to clinical practice. Methods: The age-specific ten-year probabilities of a major osteoporotic fracture were calculated in women with average BMI to determine fracture probabilities at two potential intervention thresholds. The first comprised the age-specific fracture probabilities associated with a femoral neck T-score of − 2.5 SD, in line with current guidelines in Iran. The second approach determined age-specific fracture probabilities that were equivalent to a woman with a prior fragility fracture, without BMD. The parsimonious use of BMD was additionally explored by the computation of upper and lower assessment thresholds for BMD testing. Results: When a BMD T-score ≤ − 2.5 SD was used as an intervention threshold, FRAX probabilities in women aged 50 years was approximately two-fold higher than in women of the same age but with an average BMD and no risk factors. The relative increase in risk associated with the BMD threshold decreased progressively with age such that, at the age of 80 years or more, a T-score of − 2.5 SD was actually protective. The 10-year probability of a major osteoporotic fracture by age, equivalent to women with a previous fracture rose with age from 4.9% at the age of 50 years to 17%, at the age of 80 years, and identified women at increased risk at all ages. Conclusion: Intervention thresholds based on BMD alone do not effectively target women at high fracture risk, particularly in the elderly. In contrast, intervention thresholds based on fracture probabilities equivalent to a "fracture threshold" target women at high fracture risk. [ABSTRACT FROM AUTHOR]

Summary: Given the widespread practice of recommending drug holidays, we reviewed the impact of medication discontinuation of two common anti-osteoporosis therapies (bisphosphonates and denosumab). Trial evidence suggests the risk of new clinical fractures, and vertebral fracture increases when osteoporosis treatment with bisphosphonates or denosumab is stopped. Introduction: The aim of this paper was to review the available literature to assess what evidence exists to inform clinical decision-making with regard to drug holidays following treatment with bisphosphonates (BiP) or denosumab. Methods: Systematic review. Results: Differing pharmacokinetics lead to varying outcomes on stopping therapy. Prospective and retrospective analyses report that the risk of new clinical fractures was 20–40% higher in subjects who stopped BiP treatment, and vertebral fracture risk was approximately doubled. Rapid bone loss has been well described following denosumab discontinuation with an incidence of multiple vertebral fractures around 5%. Studies have not identified risk factors for fracture after stopping treatment other than those that provide an indication for treatment (e.g. prior fracture and low BMD). Studies that considered long-term continuation did not identify increased fracture risk, and reported only very low rates of adverse skeletal events such as atypical femoral fracture. Conclusions: The view that patients on long-term treatment with bisphosphonates or denosumab should always be offered a drug holiday is not supported by the existing evidence. Different pharmacokinetic properties for different therapies require different strategies to manage drug intermission. In contrast, long-term treatment with anti-resorptives is not associated with increased risk of fragility fractures and skeletal adverse events remain rare. [ABSTRACT FROM AUTHOR]

Summary: Change in total hip bone mineral density (BMD) provides a robust indication of anti-fracture effect during treatment monitoring in routine clinical practice, whereas spine BMD change is not independently associated with fracture risk. Purpose: 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. Methods: 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 > 40 years initiating osteoporosis treatment with two consecutive dual-energy X-ray absorptiometry (DXA) scans (mean interval 4.7 years). 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. Results: During a mean follow-up of 12.1 years, 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. Conclusions: 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. [ABSTRACT FROM AUTHOR]

Objective: Clinical trial results have shown that, in glucocorticoid‐treated patients, treatment with denosumab 60 mg subcutaneously once every 6 months (Q6M) increased spine and hip bone mineral density (BMD) at month 12 significantly more than treatment with risedronate 5 mg orally once daily (QD). The present analysis was performed to compare efficacy and characterize safety through month 24. Methods: This phase III study enrolled men and women ≥18 years old who had received ≥7.5 mg daily prednisone or equivalent for <3 months (glucocorticoid‐initiating) or for ≥3 months (glucocorticoid‐continuing) before screening. All patients <50 years old had a history of osteoporotic fracture. Glucocorticoid‐continuing patients ≥50 years old had T scores of −2.0 or less (or −1.0 or less with fracture history). Patients were randomized (1:1) to receive denosumab 60 mg subcutaneously Q6M or risedronate 5 mg orally QD for 24 months, with daily calcium and vitamin D. Results: Of 795 patients, 590 (74.2%) completed the study (in the glucocorticoid‐initiating group, 109 of 145 patients treated with denosumab and 117 of 145 patients treated with risedronate; in the glucocorticoid‐continuing group, 186 of 253 patients treated with denosumab and 178 of 252 patients treated with risedronate). Denosumab was superior to risedronate in increasing lumbar spine and total hip BMD at all time points assessed, among glucocorticoid‐initiating patients (24‐month lumbar spine: BMD increase of 6.2% versus 1.7%, respectively [P < 0.001]; 24‐month total hip: BMD increase of 3.1% versus 0.0% [P < 0.001]) and among glucocorticoid‐continuing patients (24‐month lumbar spine: BMD increase of 6.4% versus 3.2% [P < 0.001]; 24‐month total hip: BMD increase of 2.9% versus 0.5% [P < 0.001]). Adverse events, serious adverse events (including infections), and fractures were similar between treatment groups. Conclusion: Denosumab was superior to risedronate in terms of increases in spine and hip BMD through month 24, and the safety profile was similar between treatment groups. Denosumab may offer a new osteoporosis treatment option for glucocorticoid‐treated patients. [ABSTRACT FROM AUTHOR]

Glucocorticoids (GCs) are often used for improvement of quality of life, particularly in the elderly, but long-term GC use may cause harm; bone loss and fractures are among the most devastating side effects. Fracture risk is particularly high in patients with a severe underlying disease with an urgent need for treatment with high-dose GCs. Moreover, it is important to realize that these patients suffer from an augmented background fracture risk as these patients have a high presence of traditional risk factors for osteoporosis, such as high age, low body mass index (BMI), smoking and relatives with osteoporosis or hip fractures. It is thus crucial for prevention of osteoporotic fractures to use the lowest dose of GC for a short period of time to prevent fractures. Another important task is optimal treatment of the underlying disease; for instance, fracture risk is higher in patients with active rheumatoid arthritis than in patients in whom rheumatoid arthritis is in remission. Thus, fracture risk is generally highest in the early phase, when GC dosage and the disease activity of the underlying disease are high. Finally, some of the traditional risk factors can be modulated, e.g., smoking and low BMI. Life-style measures, such as adequate amounts of calcium and vitamin D and exercise therapy are also crucial. In some patients, anti-osteoporotic drugs are also indicated. In general, oral bisphosphonates (BPs) are the first choice, because of their efficacy and safety combined with the low cost of the drug. However, for those patients who do not tolerate oral BPs, alternatives ("second-line therapies") are available: BP intravenously (zoledronic acid), denosumab (Dmab), and teriparatide. Both zoledronic acid and Dmab have been proven to be superior to oral bisphosphonates like risedronate in improvement of bone mineral density. For teriparatide, vertebral fracture reduction has been shown in comparison with alendronate. Thus, to reduce the global burden of GC use and fracture risk, fracture risk management in GC users should involve at least involve life-style measures and the use of the lowest possible dose of GC. In high-risk patients, anti-osteoporotic drugs should be initiated. First choice drugs are oral BPs; however, in those with contraindications and those who do not tolerate oral BPs, second-line therapies should be started. Although this is a reasonable treatment algorithm, an unmet need is that the most pivotal (second-line) drugs are not used in daily clinical practice at the initial phase, usually characterized by high-dose GC and active underlying disease, when they are most needed. In some patients second-line drugs are started later in the disease course, with lower GC dosages and higher disease activity. As this is a paradox, we think it is a challenge for physicians and expert committees to develop an algorithm with clear indications in which specific patient groups second-line anti-osteoporotic drugs should or could be initiated as first-choice treatment. [ABSTRACT FROM AUTHOR]

Summary: There is no consensus on which tool is the most accurate to assess fracture risk. The results of this systematic review suggest that QFracture, Fracture Risk Assessment Tool (FRAX) with BMD, and Garvan with BMD are the tools with the best discriminative ability. More studies assessing the comparative performance of current tools are needed. Introduction: Many tools exist to assess fracture risk. This review aims to determine which tools have the best predictive accuracy to identify individuals at high risk of non-traumatic fracture. Methods: Studies assessing the accuracy of tools for prediction of fracture were searched in MEDLINE, EMBASE, Evidence-Based Medicine Reviews, and Global Health. Studies were eligible if discrimination was assessed in a population independent of the derivation cohort. Meta-analyses and meta-regressions were performed on areas under the ROC curve (AUCs). Gender, mean age, age range, and study quality were used as adjustment variables. Results: We identified 53 validation studies assessing the discriminative ability of 14 tools. Given the small number of studies on some tools, only FRAX, Garvan, and QFracture were compared using meta-regression models. In the unadjusted analyses, QFracture had the best discriminative ability to predict hip fracture (AUC = 0.88). In the adjusted analysis, FRAX with BMD (AUC = 0.81) and Garvan with BMD (AUC = 0.79) had the highest AUCs. For prediction of major osteoporotic fracture, QFracture had the best discriminative ability (AUC = 0.77). For prediction of osteoporotic or any fracture, FRAX with BMD and Garvan with BMD had higher discriminative ability than their versions without BMD (FRAX: AUC = 0.72 vs 0.69, Garvan: AUC = 0.72 vs 0.65). A significant amount of heterogeneity was present in the analyses. Conclusions: QFracture, FRAX with BMD, and Garvan with BMD have the highest discriminative performance for predicting fracture. Additional studies in which the performance of current tools is assessed in the same individuals may be performed to confirm this conclusion. [ABSTRACT FROM AUTHOR]

Background: Unlike public awareness around the world, osteoporosis is still underdiagnosed in most cases till bone fractures. Currently, the dual-energy X-ray absorptiometry (DEXA) is the gold standard diagnostic method of osteoporosis, but unfortunately this method is not available in all diagnostic centers, especially in developing countries. Aims: To evaluate the accuracy of tibial cortical thickness in the diagnosis of osteoporosis compared with DEXA. Materials and Methods: In this descriptive--analytic study, patients suspicious of osteoporosis who referred to Imam Khomeini Hospital, Ahvaz from 2016 --2017 were recruited. Data was collected for each patient including age, sex, radiography, and DEXA. The total thickness of the tibia cortex (sum of the two sides) was measured using knee anteroposterior radiography at 10 cm from the proximal tibial joint. The bone mineral density (BMD) was measured by DEXA method and reported as T-score. Results: In this study, 62 patients (90% female) were evaluated. The mean age of the patients was 57 years (range 45--80 years). T-score had a direct significant correlation with TCT level (r = 0.51, P < 0.0001). Also, T-score had a reverse and significant correlation with age of patients (r = −0.280, P = 0.028). The area under the curve (AUC) was 77%. Also, the sensitivity and specificity for the TCT level less than 4.37 mm (as cutoff point) was 100% and 39.1%, respectively. Conclusion: The findings of this study indicate that TCT has a direct significant correlation with the T-score obtained by the DEXA method. It has also been shown that TCT can be a relatively accurate diagnostic tool for predicting osteoporosis. [ABSTRACT FROM AUTHOR]