Determinants of bone loss across multiple functional declines a call˸ for an integrated insight : Characterization of the determinants of bone loss in Chronic Kidney Disease and in obese patients undergoing bariatric surgery

Le vieillissement est caractérisé par le déclin multiple d'organes dont les évaluations et les événements à prévenir peuvent être communs, bien qu'en compétition. L'ostéoporose est caractérisée par une diminution de la densité et de la résistance osseuse prédisposant aux fractures. Son déclin est associé à un déclin des fonctions musculaires et à une réaction paradoxale du tissu adipeux. L'insuffisance rénale chronique prédispose aux fractures par fragilité et influe aussi sur la performance physique. Dans un premier article de revue de la littérature, nous avons étudié les liens et les chevauchements entre ces concepts pour mieux comprendre les phénomènes de vieillissement. Ainsi, on constate un manque de caractérisation des déterminants de la perte osseuse chez le sujet insuffisant rénal non dialysé. Dans le deuxième article, nous avons exploré les déterminants de la densité minérale osseuse (DMO) chez des sujets insuffisants rénaux non dialysés. Nous avons étudié la cohorte NephroTest, une cohorte multicentrique de suivi longitudinal de l'évolution de la fonction rénale (grâce à des débits de filtration glomérulaires mesurés). Au total, 858 patients avaient au moins une évaluation de DMO. Nous avons retrouvé en transversal que la Parathormone (PTH) & les phosphates étaient plus élevés, et la DMO plus basse à tous les sites de mesure. Ceci, de manière proportionnelle à la sévérité de la maladie rénale. Le suivi longitudinal de près de 4,3 ans en moyenne nous a permis de mettre en évidence que le déclin osseux chez l'insuffisant rénal non dialysé n'était visible qu'au site du poignet, ce qui correspond au site le plus cortical. Les déterminants qui étaient à l'inclusion associés à une DMO basse dans ce modèle linéaire mixte étaient : le sexe, le tabagisme, un indice de masse corporelle (IMC) bas et des PTH hautes. Dans la recherche de facteurs prédictifs d'une perte osseuse longitudinale, nous avons montré que ni la PTH initiale ni le stade initial de sévérité de maladie rénale chronique ne permettaient de prédire les changements de DMO. Cependant les modifications de DMO étaient associées à l'indice de masse corporel initial. Pour le troisième article de cette thèse, nous avons étudié une population d'obèses opérés de chirurgie bariatrique afin de savoir si celle-ci avait un effet à long terme sur leur DMO. Nous avons étudié une cohorte monocentrique de patients opérés de chirurgie bariatrique de manière transversale, à une longue distance de leur chirurgie. Des 159 patients obèses avec DMO, nous avons analysé 131 sujets ayant été opérés (51,8 ans, 87,8% de femmes). Ils étaient en moyenne à 6,8 ans de la chirurgie. Parmi eux, on dénombre 90 by-pass gastriques et 41 sleeve-gastrectomies. La perte de poids moyenne était de - 12,9 %. Les patients aux IMC les plus élevés avaient les DMO les plus hautes et des CRP plus élevées. L'analyse univariée a permis de montrer que les DMO étaient plus basses en cas de by-pass gastrique (p65 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 chronic kidney disease (CKD) which promote fractures and falls. Our first article is a narrative review, where we aimed to highlight the need for a global approach for musculoskeletal and kidney aging. We tried to understand the outcomes in bone loss, loss of renal function and the overlap of these issues on fracture risk, bone mineral density (BMD) and aging understanding. We observed a lack of characterization in determinants of bone loss in non dialysis CKD patients. The second article tried to fill the gap in understanding longitudinal parameters impacting BMD. In the NephroTest cohort, we measured BMD with circulating biomarkers and standardized measured glomerular filtration rate (mGFR) in a subset of patients with CKD stage 1 to 5 followed during 4.3 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-yo) had at least 1 and 477 had at least 2 BMD measures. 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. The third work consisted in the cross-sectional analysis of a monocenter cohort of bariatric patients in which we aimed to characterize long-term BMD determinants. A total of 131 patients (91 gastric-bypass (RYGB), 40 Sleeve gastrectomy (SG)) underwent BMD (51.8-yo, 87.8% women). In this long-term (>2-y) analysis, average weight loss was - 12.9 %. In late stages of obesity, we observed higher BMD and a CRP regardless the BS procedure. In the univariate analysis, BMD was significantly lower in the RYGB group (p<.001) at all sites despite the same body composition. Moreover, RYGB patients had higher serum parathyroid hormone and phosphate concentrations. Only 10.1% of patients showed vascular calcifications limiting lumbar spine BMD interpretation with no difference between BS groups. BMD was also not impacted by the extent of weight loss. In the multivariate analysis (104 participants), ferritin and uric acid remain the only markers explaining BMD after adjustment on age, BMI, ethnicity, sex and type of procedure. These models predict BMD with a stronger relationship at the total hip and the femoral neck rather than at the lumbar spine (adjusted R²= 0.440; 0.435 and 0.199 respectively). None of the vitamin was involved as explanatory factor for BMD in the final model. Serum Zinc showed a positive trend with the total hip and the femoral neck BMD. This persistent difference in BMD between procedures highlight that the trajectory in bone loss could be deeply impacted whatever was the control of bone and mineral parameters. All these situations highlighted that the relevance of routine bone parameters in explaining BMD remain irrelevant as compared to clinical markers such as age, sex and BMI. Further studies should focus on the study of concomitant multiple decline with a longitudinal insight

Longitudinal Bone Loss Occurs at the Radius in CKD

International audienceIntroduction: 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 51Cr-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

Longitudinal Bone Loss Occurs at the Radius in CKD

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 51Cr-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

Corticosteroid Therapy in COVID-19 Associated With In-hospital Mortality in Geriatric Patients: A Propensity Matched Cohort Study

International audienceBackground: 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