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Pierre-Emmanuel Cailleaux, Martine Cohen-Solal Inserm UMR-S 1132 Bioscar, Université Paris Cité - Hôpital Lariboisiere, Paris, F-75010, FranceCorrespondence: Martine Cohen-Solal, Inserm UMR-S 1132 (Université Paris Cité), Hôpital Lariboisière, 2 rue Ambroise Paré, Paris, F-75010, France, Tel/Fax +33-1-49-95-63-58, Email martine.cohen-solal@inserm.frAbstract: Aging represents a major concern, with a two-fold increase in individuals > 65 years old by 2040. Older patients experience multiple declines in condition, with overlapping concerns. Fractures, frailty and falls remain underestimated events in routine practice. They are shared by numerous conditions and diseases, such as osteoporosis, sarcopenia and undernutrition, which mostly feature low evolution and are silent. In this review, we focused on musculoskeletal decline in older individuals who also have chronic kidney disease (CKD), which promotes fractures and falls. We aimed to highlight the need for a global approach for musculoskeletal and kidney aging. Although strategies limiting falls remain controversial, the need for an early diagnosis can limit these declines and allow for specific treatment of bone fragility in addition to non-pharmacological approaches. The emergence of senolytic agents offers new hope for preventing musculoskeletal disorders. This scoping review describes these overlapping silent diseases, provides evidence for their global understanding and management, and sheds light on new therapeutic directions.Keywords: older individuals, osteoporosis, sarcopenia, kidney disease, senolytics

Context: The association of obesity with bone fragility fractures is complex and non-linear. Despite good efficacy on weight loss, bariatric surgery (BS) is also associated with bone loss. However, we lack information on risk factors of the long-term deleterious effects of BS on the skeleton., Objective: We aimed to assess the factors associated with low bone mineral density (BMD) performed a long time after Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG)., Methods: This cross-sectional study involved patients at a long distance from their BS that underwent dual-energy x-ray absorptiometry (DXA) with biological factors (vitamins, micronutrients, bone and inflammation biomarkers). Simple and multiple linear models (stepwise and parsimony approach) were developed., Results: A total of 131 patients (91 RYGB, 40 SG) underwent DXA (51.8 ± 11.08 years, 87.8% women). At a mean of 6.8 ± 3.7 years after surgery, the mean weight loss was -28.6 ± 9.6%, and only 6 patients (5.7%) had a T -score less than or equal to -2.5. On univariate analysis, BMD was lower in the RYGB than in the SG group ( P < .001) at all sites, despite similar fat and fat-free mass and weight loss. Serum parathyroid hormone and phosphate levels were higher in RYGB than SG patients. A total of 10.1% of patients showed vascular calcifications. On multivariable analysis, BMD remained different between surgery groups after adjustment for age, body mass index, ethnicity, and sex. The model-adjusted R 2 values were 0.451 for the total hip; 0.462 the femoral neck, and 0.191 the lumbar spine for the inflammation model; 0.458, 0.462, and 0.254, respectively, for the bone marker model; and 0.372, 0.396, and 0.142 for the vitamin model. Serum zinc, ferritin, and uric acid levels were the markers associated with BMD to a low extent., Conclusion: BMD differed depending on the BS procedure. A few biological markers may be associated weakly with BMD well after the surgery., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Purpose of Review: Sarcopenia is a wasting disease, mostly age-related in which muscle strength and mass decline, such as physical performance. With aging, both lower dietary protein intake and anabolic resistance lead to sarcopenia. Moreover, aging and sarcopenia display low-grade inflammation, which also worsen muscle condition. In this review, we focused on these two main targets to study dietary strategies., Recent Findings: The better understanding in mechanisms involved in sarcopenia helps building combined dietary approaches including physical activity that would slow the disease progression. New approaches include better understanding in the choice of quality proteins, their amount and schedule and the association with antioxidative nutrients., Summary: First, anabolic resistance can be countered by increasing significantly protein intake. If increasing amount remains insufficient, the evenly delivery protein schedule provides interesting results on muscle strength. Quality of protein is also to consider for decreasing risk for sarcopenia, because varying sources of proteins appears relevant with increasing plant-based proteins ratio. Although new techniques have been developed, as plant-based proteins display a lower availability, we need to ensure an adapted overall amount of proteins. Finally, specific enrichment with leucine from whey protein remains the dietary combined approach most studied and studies on citrulline provide interesting results. As cofactor at the edge between anabolic and antioxidative properties, vitamin D supplementation is to recommend. Antioxidative dietary strategies include both fibers, vitamins, micronutrients and polyphenols from various sources for positive effects on physical performance. The ω 3 -polyunsaturated fatty acids also display positive modifications on body composition. Gut microbiota modifiers, such as prebiotics, are promising pathways to improve muscle mass and function and body composition in sarcopenic patients. Nutritional interventions could be enhanced by combination with physical activity on sarcopenia. In healthy older adults, promoting change in lifestyle to get near a Mediterranean diet could be one of the best options. In sarcopenia adults in which lifestyle changes appears unprobable, specific enrichement potentialized with physical activity will help in the struggle against sarcopenia. Longitudinal data are lacking, which makes it hard to draw strong conclusions. However, the effects of a physical activity combined with a set of nutrition interventions on sarcopenia seems promising., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Fractures of the upper end of the femur (FUEF) lead to increased mortality and dependence in the elderly. However, mechanical complications after surgery persist in up to 20% of cases, which may justify a delayed resumption of full weight bearing to protect the osteosynthesis during consolidation., Hypothesis: Our hypothesis was that the late resumption of weight bearing in an elderly population after a FUEF would be limited by a higher frequency of medical complications., Methods: This was a prospective monocentric study including patients aged 80 or over with an isolated FUEF requiring osteosynthesis. The operator decided on the discharge. The primary endpoint was to show a difference in a medical complication score created for this study (APRETAR), between a group with, and a group without, weight bearing delayed by 45 days., Results: Between 2016 and 2019, 254 patients (88±5.6 years, 77.6% women) were included, and of these, 70 (27.6%) had delayed weight bearing. The mean APRETAR at 45 days was greater in the delayed weight bearing group (5.9±8.6 vs. 5.7±11.0; p<0.001). One-year mortality was 12.6% (32 patients), with no difference between the two groups (p=0.51). The level of dependence was significant (IADL at 2.2±1.7), with some comorbidities (Charlson at 2.9±2.2 and CIRS-G at 6.5±4.3) and all comparable across the two groups but with low cognitive levels, especially in the group with delayed weight bearing (MMSE 15.9±10.7 vs. 21±6.9; p<0.001)., Conclusion: This prospective study shows that delaying weight bearing in the elderly population, even for mechanical problems with FUEF, statistically increases medical complications but in a clinically acceptable manner., Level of Evidence: II, Prospective cohort study., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Background: Few data are available on the prognosis of older patients who received corticosteroids for COVID-19. We aimed to compare the in-hospital mortality of geriatric patients hospitalized for COVID-19 who received corticosteroids or not., Methods: We conducted a multicentric retrospective cohort study in 15 acute COVID-19 geriatric wards in the Paris area from March to April 2020 and November 2020 to May 2021. We included all consecutive patients aged 70 years and older who were hospitalized with confirmed COVID-19 in these wards. Propensity score and multivariate analyses were used., Results: Of the 1 579 patients included (535 received corticosteroids), the median age was 86 (interquartile range 81-91) years, 56% of patients were female, the median Charlson Comorbidity Index (CCI) was 2.6 (interquartile range 1-4), and 64% of patients were frail (Clinical Frailty Score 5-9). The propensity score analysis paired 984 patients (492 with and without corticosteroids). The in-hospital mortality was 32.3% in the matched cohort. On multivariate analysis, the probability of in-hospital mortality was increased with corticosteroid use (odds ratio [OR] = 2.61 [95% confidence interval (CI) 1.63-4.20]). Other factors associated with in-hospital mortality were age (OR = 1.04 [1.01-1.07], CCI (OR = 1.18 [1.07-1.29], activities of daily living (OR = 0.85 [0.75-0.95], oxygen saturation < 90% on room air (OR = 2.15 [1.45-3.17], C-reactive protein level (OR = 2.06 [1.69-2.51], and lowest lymphocyte count (OR = 0.49 [0.38-0.63]). Among the 535 patients who received corticosteroids, 68.3% had at least one corticosteroid side effect, including delirium (32.9%), secondary infections (32.7%), and decompensated diabetes (14.4%)., Conclusions: In this multicentric matched-cohort study of geriatric patients hospitalized for COVID-19, the use of corticosteroids was significantly associated with in-hospital mortality., (© The Author(s) 2022. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Chronic kidney disease (CKD) exposes to an increased incidence of fragility fractures. International guidelines recommend performing bone mineral density (BMD) if the results will impact treatment decisions. It remains unknown where bone loss occurs and what would preclude the longitudinal loss in patients with CKD. Here, we aimed to investigate factors influencing BMD and to analyze the longitudinal BMD changes., Methods: In the NephroTest cohort, we measured BMD at the femoral neck, total hip, lumbar spine, and proximal radius, together with circulating biomarkers and standardized measured glomerular filtration rate (mGFR) by 51 Cr-EDTA in a subset of patients with CKD stage 1 to 5 followed during 4.3 ± 2.0 years. A linear mixed model explored the longitudinal bone loss and the relationship of associated factors with BMD changes. A total of 858 patients (mean age 58.9 ± 15.2 years) had at least 1 and 477 had at least 2 BMD measures., Results: At baseline, cross-sectional analysis showed a significantly lower BMD at femoral neck and total hip and a significant higher serum parathyroid hormone (PTH) along with CKD stages. Baseline age, gender, tobacco, low body mass index (BMI), and high PTH levels were significantly associated with low BMD. Longitudinal analysis during the mean 4.3 years revealed a significant bone loss at the radius only. BMD changes at the femoral neck were associated with BMI, but not CKD stages or basal PTH levels., Conclusions: CKD is associated with low BMD and high PTH in the cross-sectional analysis. Longitudinal bone loss occurred at the proximal radius after 4.3 years., (© 2021 International Society of Nephrology. Published by Elsevier Inc.)

Competing Interests: Declaration of Competing Interest None.

Background: The evaluation process of French medical students will evolve in the next few years in order to improve assessment validity. Script concordance testing (SCT) offers the possibility to assess medical knowledge alongside clinical reasoning under conditions of uncertainty. In this study, we aimed at comparing the SCT scores of a large cohort of undergraduate medical students, according to the experience level of the reference panel., Methods: In 2019, the authors developed a 30-item SCT and sent it to experts with varying levels of experience. Data analysis included score comparisons with paired Wilcoxon rank sum tests and concordance analysis with Bland & Altman plots., Results: A panel of 75 experts was divided into three groups: 31 residents, 21 non-experienced physicians (NEP) and 23 experienced physicians (EP). Among each group, random samples of N = 20, 15 and 10 were selected. A total of 985 students from nine different medical schools participated in the SCT examination. No matter the size of the panel (N = 20, 15 or 10), students' SCT scores were lower with the NEP group when compared to the resident panel (median score 67.1 vs 69.1, p < 0.0001 if N = 20; 67.2 vs 70.1, p < 0.0001 if N = 15 and 67.7 vs 68.4, p < 0.0001 if N = 10) and with EP compared to NEP (65.4 vs 67.1, p < 0.0001 if N = 20; 66.0 vs 67.2, p < 0.0001 if N = 15 and 62.5 vs 67.7, p < 0.0001 if N = 10). Bland & Altman plots showed good concordances between students' SCT scores, whatever the experience level of the expert panel., Conclusions: Even though student SCT scores differed statistically according to the expert panels, these differences were rather weak. These results open the possibility of including less-experienced experts in panels for the evaluation of medical students.

Objective: To evaluate the prevalence of biological abnormalities leading to secondary osteoporosis in recently fractured patients., Methods: Adults older than 50, hospitalized for a non-vertebral fracture from July 2015 to October 2016, were assessed for bone fragility contributors in the orthopedics department. Bone mineral density (BMD) measurements and vertebral fracture assessment (VFA) were performed within 3 months. We assessed the prevalence of biological abnormalities in all the patients with recent fracture and in subgroups., Results: Among 439 hospitalized patients for non-vertebral low trauma fracture, 372 had biological tests (285 women, mean age 77.5 ± 13 years) and 353 (94.6%) had at least ≥ 1 biological abnormality, most frequently vitamin D insufficiency (< 75 nmol/L) (80%). Hypercalcemia was found in 22 (7.7%) patients, explained by possible primary hyperparathyroidism in 6 cases, and by the other causes of hypercalcemia including postoperative low albumin. A high PTH level was observed in 64 (20.8%) patients. We found 3 monoclonal bands. Results were similar in patients with and without vertebral fracture or osteoporosis. Finally, many biological abnormalities can be explained by the postoperative context (low TSH, hypogammaglobulinemia, low albumin, low alkaline phosphatase) and need a control., Conclusion: This study performed in patient with recent low trauma non-vertebral fractures showed that 94.6% of patients had at least one contributor to bone fragility, which was the vitamin D insufficiency in most of cases. We found a high proportion of biological abnormalities which require additional explorations but most of them can be explained by the postoperative context., (Copyright © 2019. Published by Elsevier Masson SAS.)